Author Interviews, Neurological Disorders / 21.07.2015

Dr Michael Lee PhD MPhty MChiro BSc Discipline of Physiotherapy, Faculty of Health Sciences, The University of Sydney Clinical Neurophysiologist, The Brain & Mind Research Institute, The University of Sydney Research Affiliate, Neuroscience Research Australia Neurology Research Fellow, Institute of Neurological Sciences, Prince of Wales HospitalMedicalResearch.com Interview with: Dr Michael Lee PhD MPhty MChiro BSc Discipline of Physiotherapy, Faculty of Health Sciences, The University of Sydney Clinical Neurophysiologist, The Brain & Mind Research Institute, The University of Sydney Research Affiliate, Neuroscience Research Australia Neurology Research Fellow, Institute of Neurological Sciences, Prince of Wales Hospital Medical Research: What is the background for this study? Dr. Lee: Our research team at the University of Sydney has previously shown that the functioning of peripheral nerves deteriorate following spinal cord injury (SCI). Using novel, non-invasive electrophysiological techniques (nerve excitability testing), we showed in this study that peripheral nerves below the level of spinal cord injury underwent dramatic functional reorganization. Peripheral nerve dysfunction will not only contribute to a number of undesirable medical complications including peripheral neuropathy and pain, it exacerbates muscle atrophy and can potentially limit the effectiveness of rehabilitative therapies that drive central plasticity. In this study, we were interested to see whether this secondary peripheral nerve dysfunction could be reversed with a short-term targeted peripheral nerve stimulation therapy. Medical Research: What are the main findings? Dr. Lee: We studied peripheral nerve function in both the upper (median nerve at the wrist) and lower limbs (peroneal nerve near the fibular head) in 22 patients with acute spinal cord injury (all within 6 months of injury). We then randomly assigned one upper limb and one lower limb nerve to a daily regimen of 30-min peripheral nerve stimulation for 6 week. All study participants continued with standard rehabilitation. The results from our nerve excitability studies showed that 6-weeks of daily stimulation reversed a number of nerve excitability abnormalities secondary to spinal cord injury, and in some cases normalized it to a level comparable to healthy age-matched subjects. The peripheral nerves in the opposite limbs remained dysfunctional over the 6-week period. The results of our study showed convincingly that the addition of peripheral nerve stimulation in the early stages of spinal cord injury is beneficial by ameliorating the downstream effects of spinal cord injury. Spinal cord injuries can be an unfortunate effect of being a car accident, causing serious issues for those who suffer from it whether financial or physical. Those who find themselves in this type of situation may look into contacting someone like these car accident injury lawyers near Sacramento who might be able to help them to get compensation for their accident, which could help with phisyotherapy and medical bills. (more…)
Author Interviews, Neurological Disorders, NYU, Opiods, Pain Research, Pharmacology / 25.06.2015

Dr. Mia T. Minen, MD, MPH Director, Headache Services at NYU Langone Medical Center Assistant professor, Department of Neurology MedicalResearch.com Interview with: Dr. Mia T. Minen, MD, MPH Director, Headache Services NYU Langone Medical Center Assistant professor, Department of Neurology   Medical Research: What is the background for this study? What are the main findings? Dr. Minen: We conducted a survey on opioid and barbiturate use among patients visiting a headache center to find out which medications they were receiving for treatment. There’s limited evidence that long-term use of these medications can help treat headaches or migraines, and even short-term use in small quantities can cause medication overuse headache. It is important to determine which providers start these medications so that educational interventions can be tailored to these physician specialties to try to prevent situations such as incorrect prescribing practices and medication overuse. In this sample of patients from a specialty headache center, approximately 20 percent of patients -- or 1 in 5 -- were using opioids or barbiturates, and about half had been prescribed these medications at some point in the past for their headaches. These findings show that opioids and barbiturates are commonly prescribed to patients with headaches. While two-thirds of patients found opioids or barbiturates helpful, many did not like them, were limited by side effects or did not find them to be helpful. Emergency department physicians were reported to be the most frequent first prescribers of opioids and general neurologists were the most frequent prescribers of barbiturate-containing medications. Primary care physicians were also identified as frequent first prescribers of these medications. (more…)
Author Interviews, JAMA, McGill, Parkinson's / 15.06.2015

Ron Postuma, MD, MSc Associate Professor Department of Neurology Montreal General Hospital Montreal, QuebecMedicalResearch.com Interview with: Ron Postuma, MD, MSc Associate Professor Department of Neurology Montreal General Hospital Montreal, Quebec Medical Research: What is the background for this study? What are the main findings? Dr. Postuma: The background is that we often think about Parkinson’s Disease as a single disease.  However, every clinician knows that there is a great deal of variability from patient to patient.  If we can understand the main aspects that separate patients into groups, we can target therapy better. The analysis used a semi-automated means to divide Parkinson’s patients into groups, using extensive information about motor and non-motor aspects of disease.  We found that the non-motor symptoms, especially cognition, sleep disorders, and blood pressure changes were the most powerful predictors of which group a patient would be in.  Based on these non-motor (and some motor aspects), the most accurate way to divide patients was into three groups - diffuse (many non-motor symptoms), pure motor, and intermediate (halfway between the other).  We then followed patients over time.  The diffuse group had, by far, the worse prognosis.  This was not only for the non-motor aspects, but the motor as well. (more…)
Author Interviews, Neurological Disorders, PLoS, Psychological Science / 12.06.2015

Dr. rer. nat. Kristin Prehn, Dipl.-Psych. Charité Universitätsmedizin Berlin Department of Neurology & NeuroCure Clinical Research Cente Berlin GermanyMedicalResearch.com Interview with: Dr. rer. nat. Kristin Prehn, Dipl.-Psych. Charité Universitätsmedizin Berlin Department of Neurology & NeuroCure Clinical Research Cente Berlin Germany MedicalResearch: What is the background for this study? What are the main findings? Dr. Prehn: The study is based on the theory by renowned American psychologist Lawrence Kohlberg stating that people progress through different levels of moral reasoning. At lower levels, individuals judge moral issues based on self-interest or laws and rules. Individuals at the post-conventional level also take into account deeper principles and shared ideals. The Kohlbergian theory influenced moral psychology and education for decades. No study to date, however, had investigated in which way moral development is reflected in human brain structure and function. In our study, we compared gray matter brain volume in healthy young subjects who either reached the post-conventional level or did not reach that level so far. We found that subjects at the post-conventional level showed larger volume in a specific brain region of the prefrontal cortex which is essential for moral reasoning as well as the integration of emotion and cognition during human behavior. (more…)
Author Interviews, Exercise - Fitness, Parkinson's / 03.06.2015

Dr. Lori P. Altmann Department of Speech, Language, and Hearing Sciences Center for Movement Disorders and Neurorestoration University of Florida, Gainesville, FloridaMedicalResearch.com Interview with: Dr. Lori P. Altmann Department of Speech, Language, and Hearing Sciences Center for Movement Disorders and Neurorestoration University of Florida, Gainesville, Florida Medical Research: What is the background for this study? What are the main findings? Dr. Altmann: There are a multitude of studies from our labs and others examining the effects of doing a variety of different cognitive tasks while walking or while maintaining postural control, and the results across studies are consistent—motor performance usually declines.  These “dual task effects” are exaggerated in healthy older adults, and are even more pronounced in people with Parkinson disease (PD).  Our study investigated dual task effects during cycling in healthy older adults and people with Parkinson disease.  In contrast to most studies of this type which typically contrast dual task effects of two cognitive tasks, we used an array of 12 cognitive tasks of graded difficulty, from very very easy to extremely difficult.  One of our primary goals was to establish that the dual task effects were directly related to the difficulty of the cognitive task. Our primary findings were that, instead of cycling slower when doing various cognitive task, both groups of participants sped up, and the amount they sped up was directly related to the difficulty of cognitive tasks.  In the easiest task, cycling speed increased by an average of about 25%, With some participants actually doubling their single task speed. There was no evidence that this increase in cycling speed came as a result of prioritizing cycling over the cognitive tasks, as scores on the cognitive tasks either remained the same or got slightly better.  Interestingly, people with Parkinson disease still showed faster cycling during the easiest tasks, but did not benefit as much from the dual task as the healthy adults. We attribute our findings to arousal that is triggered by both the cycling and the cognitive tasks which increases attentional resources that can be used for both motor and cognitive processing.  We believe the findings haven’t been documented before because most studies use gait or balance as the motor tasks, and these are much more difficult tasks that demand more attentional resources, leading to the typical findings of dual task costs instead of dual task benefits. The decrease in dual task benefits experienced by people with Parkinson disease, we believe, is due to the effects of Parkinson disease on neurotransmitters.  Both cognitive and physiological arousal increase the production of dopamine and norepinephrine in the brain, and disease processes in Parkinson disease interfere with production of these neurotransmitters, thus limiting arousal-based increases in attentional resources. (more…)
ALS, Author Interviews, Mayo Clinic, Science / 28.05.2015

Dr. Leonard Petrucelli Ph.D Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with: Dr. Leonard Petrucelli Ph.D Mayo Clinic Jacksonville, FL 32224 MedicalResearch: What is the background for this study? Dr. Petrucelli: According to the ALS Association, more than 30,000 Americans live with amyotrophic lateral sclerosis (ALS), a condition that destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing. After Alzheimer’s disease, frontotemporal dementia (FTD) is the most common form of early onset dementia. It is characterized by changes in personality, behavior, and language due to loss of neurons in the brain’s frontal lobe. Once considered rare, frontotemporal dementia is now thought to account for up to 10 to 15 percent of all dementia cases, according to the Alzheimer’s Association. In 2011, Mayo investigator Rosa Rademakers, Ph.D., identified the most common genetic mutation known to cause ALS and FTD, namely a repeat expansion in the gene C9ORF72. The C9ORF72 repeat expansion leads to the generation of toxic RNA species that form abnormal foci, as well as inclusions of c9RAN proteins in affected cells in the central nervous system. Prior to this research study lead by Leonard Petrucelli, Chair of the Department of Neuroscience at the Mayo Clinic Florida, no animal model existed that fully recapitulated the known clinicopathological features of what is now collectively referred to as c9FTD/ALS. Without such an animal it has remained difficult to identify important mechanisms by which the repeat expansion leads to neurodegeneration and putative therapeutic targets that may mitigate disease in patients where currently there are no curative treatments. (more…)
Author Interviews, Diabetes, Nature, Neurological Disorders, Vegetarians / 26.05.2015

Ulka Agarwal, M.D. California State University, East Bay Student Health and Counseling Services, Hayward, MedicalResearch.com Interview with: Ulka Agarwal, M.D. California State University, East Bay Student Health and Counseling Services Hayward, CA MedicalResearch: What is the background for this study? What are the main findings? Dr. Agarwal: Diabetic peripheral neuropathy affects 60 percent of patients with type 2 diabetes and can come with painful symptoms but limited treatment options. We thought a dietary intervention may help alleviate these symptoms since glycemic control plays a role in diabetes complications. To get started with the pilot, we put 17 adults on a low-fat vegan diet for 20 weeks and prescribed weekly nutrition classes. We found significant improvements in pain, measured by the Short Form McGill Pain questionnaire, the Michigan Neuropathy Screening Instrument physical assessment, and through electrochemical skin conductance in the foot. The participants also lost an average of 14 pounds. (more…)
Author Interviews, Genetic Research, Karolinski Institute, Nature, Neurological Disorders / 11.05.2015

MedicalResearch.com Interview with: Kristina Bečanovič Ph.D. Department of Clinical Neuroscience Karolinska Institutet, Stockholm, Sweden Medical Research: What is the background for this study? Dr. Bečanović: While the symptoms normally debut in middle-age, there is wide individual variation in how Huntington disease manifests itself, and even though two people carry the exact same genetic mutation that codes for the huntingtin protein, there can be up to a 20-year difference in onset of motor symptoms. This suggests that genetic variants, transcription factors and environmental factors could contribute to the observed differences in disease expressivity. As the identification of regulatory factors of the huntingtin gene would be targets for therapeutic intervention, we set out to study the regulation of the huntingtin gene as it has not been well-known which factors regulate the expression levels. We were interested in identifying both genetic variants and transcription factors that are of importance for gene regulation. We therefore used DNA from Huntington disease patients to study the regulation of the huntingtin gene promoter in cells. (more…)
Author Interviews, Emory, Neurological Disorders / 15.04.2015

Erwin G. Van Meir, PhD Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program Founding Director, Graduate Program in Cancer Biology Director, Laboratory for Molecular Neuro-Oncology Emory University School of Medicine Atlanta GA 30322MedicalResearch.com Interview with: Erwin G. Van Meir, PhD Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program Founding Director, Graduate Program in Cancer Biology Director, Laboratory for Molecular Neuro-Oncology Emory University School of Medicine Atlanta GA 30322 Medical Research: What is the background for this study? What are the main findings? Dr. Van Meir: In this study we queried the role of the BAI1 protein in normal physiology. To do this we generated a transgenic mouse, which lacks the expression of the Bai1 gene. The mice had no obvious anomalies and reproduced according to mendelian rules. Since BAI1 is strongly expressed in the brain, including in neurons, we wondered whether they might have some cognitive defect that would only be revealed under specific testing conditions. We had the mice perform in an experiment that tests their ability to orient themselves in space and memorize the location of a hidden platform in a water maze. This experiment clearly demonstrated that the Bai1 deficient mice had deficits in spatial learning and memory. We then further probed the electrophysiological, anatomical and biochemical basis of this abnormal physiologic behavior and showed that hippocampal neurons had abnormal synaptic plasticity, reduced thickness of the post synaptic density and that this was associated with an increased degradation of a key PSD protein called PSD-95. (more…)
Author Interviews, Diabetes, Neurological Disorders / 06.03.2015

Dr. John A Kessler MD The Ken and Ruth Davee Professor of Stem Cell Biology Department of Neurology Professor, Department of Pharmacology Northwestern University Feinberg School of MedicineMedicalResearch.com Interview with: Dr. John A Kessler MD The Ken and Ruth Davee Professor of Stem Cell Biology Department of Neurology Professor, Department of Pharmacology Northwestern University Feinberg School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Kessler: Painful diabetic neuropathy afflicts millions of patients. It interferes with sleep and many daily activities of living, and predisposes to depression. There is a loss of sensation in the legs which predisposes to foot/leg ulcers which may lead to amputation. The only currently available treatments, other than controlling glucose levels, are drugs including gabapentin, pregabalin, or antidepressants which have major side effects and which help only some patients. These are medications which must be taken daily or several times daily and are often poorly tolerated by patients. This study examined the effects of a nonviral gene therapy approach for using hepatocyte growth factor (HGF) to treat patients with painful diabetic neuropathy. HGF helps to support the health of neurons and it also helps to grow new blood vessels to support nerve function. Patients received two sets of treatments (injections) and were then followed for 9 months.  The treatment was exceptionally well tolerated -  literally without significant side effects. The patients had highly significant reductions in pain and improvement in the quality of life, and their ability to sense gentle pressure (touch) was improved. The benefits lasted months without additional treatment. (more…)
Author Interviews, Neurological Disorders / 04.03.2015

MedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MAMedicalResearch.com Interview with: Dr. Richard H. Myers Ph.D. Department of Neurology and Genome Science Institute Boston University School of Medicine, Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Myers:  Andy Hoss, who is a graduate student in my group is the primary investigator for this project. We are investigating changes that occur in the brain of individuals who had Huntington's disease. We were focused on studying regulatory mechanisms that control the levels of messenger RNAs (mRNAs) in the brain, since that is an area that has been implicated in this disease. MicroRNAs (miRNAs) are known to target mRNAs for degradation or to be sequestered for storage and later use. A few limited studies of microRNAs had been done, but we sought to measure the levels of all of the  miRNAs  present in the brains of persons with Huntington's disease and in controls using next-generation sequencing. (more…)
Author Interviews, Chemotherapy, JAMA, Leukemia, Neurological Disorders / 25.02.2015

William E. Evans, Pharm.D. Member, Pharmaceutical Sciences St. Jude Children’s Research HospitalMedicalResearch.com Interview with: William E. Evans, Pharm.D. Member, Pharmaceutical Sciences St. Jude Children’s Research Hospital MedicalResearch: What is the background for this study? What are the main findings? Dr. Evans: We are currently curing over 85 percent of children with acute lymphoblastic leukemia (ALL), the most common cancer in children. While we continue to focus on pushing cure rates closer to 100 percent through the development of new treatments, we are also increasingly focused on reducing the acute and chronic side effects of treatment. This is important to improve the quality of life for patients during treatment and as they become adults after being cured, because some side effects can persist for decades after treatment is completed. One of the medications that every child with acute lymphoblastic leukemia received 30-40 times during their 2+ years of treatment is vincristine. The major side effect of vincristine is peripheral neuropathy (about 25 percent of patients develop this side effect), which can cause loss of sensation, numbness, neuropathic pain and alter their motor skills including manual dexterity, balance and ability to walk properly. This can have very practical consequences, such as writing, using a smart phone, and the use of eating utensils. It can also alter their gait. Our main finding is we discovered that an inherited variant of the CEP72 gene enhanced the risk and severity of vincristine neuropathy in two groups of patients we studied. Those children who inherited two copies of the high-risk CEP72 gene (one from each parent, about 16 percent of patients) had a significantly higher likelihood (about 3.5-fold) of developing vincristine neuropathy and had a more severe form of neuropathy (about 2.5-fold higher severity). The CEP72 gene encodes a protein essential for normal microtubule formation in cells—a critical process for cell division. Vincristine inhibits this same cellular process. The inherited form of CEP72 that increases the risk and severity of vincristine neuropathy is associated with lower expression of the CEP72 protein. When coupled with vincristine treatment, CEP72 increases a cell’s sensitivity to vincristine. We were able to reproduce this in the laboratory by lowering CEP72 expression in human neurons made from induced pluripotent stem cells and in human leukemia cells, increasing the sensitivity of both to vincristine. We also showed that the leukemia cells from patients who inherited two copies of the CEP72 risk allele were more sensitive to vincristine, suggesting it may be possible to treat these patients with a lower dose of vincristine to reduce their neuropathy without compromising the treatment of their leukemia—a possibility we plan to test in our next clinical trial at St. Jude. (more…)
Author Interviews, Brain Injury, Neurology, Parkinson's / 20.02.2015

MedicalResearch.com Interview with: Line Kenborg, MSc, PhD Survivorship Unit Danish Cancer Society Research Center Copenhagen Medical Research: What is the background for this study? What are the main findings? Response: The hypothesis that head injuries increase the risk for Parkinson disease has been examined in many studies during the past decades, but the findings have been highly inconsistent. We have previously examined the hypothesis in a study based on information on head injuries and Parkinson disease from the Danish National Hospital Registry. In this study, we found a positive association between a hospital contact for a head injury in middle or late adulthood and a diagnosis of Parkinson disease. The reported association, however, was almost entirely due to injuries that occurred during the months preceding the first hospital contact for Parkinson disease. Because we used information from registries, we lacked detailed diagnostic information to distinguish Parkinson disease from other types of parkinsonism, and we had no information on milder head injuries and head injuries in early life. So we wanted to study whether head injuries throughout life increased the risk for Parkinson disease in the largest interview-based case-control study to date including patients with a verified diagnosis of Parkinson disease. The main finding of our study is that we do not find any association between head injuries and Parkinson disease. (more…)
Author Interviews, Depression, Lancet, Multiple Sclerosis / 04.02.2015

Dr Stefan M Gold Institute of Neuroimmunology and Multiple Sclerosis (INIMS) Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf Hamburg, GermanyMedicalResearch.com Interview with: Dr Stefan M Gold Institute of Neuroimmunology and Multiple Sclerosis (INIMS) Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf Hamburg, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Gold: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (brain and the spinal cord). In addition to motor symptoms such as walking impairment, patients with Multiple sclerosis frequently suffer from psychological problems including difficulties with learning and memory as well as depressed mood. Depression is particularly common in this patient group with a 3-4 fold elevated risk for developing major depressive disorder compared to the general population. Depression in Multiple sclerosis is associated with decreased quality of life, absence from work, and numerous other psychosocial problems. Despite this major impact on patients’ lives, depression in Multiple sclerosis is often not adequately diagnosed and treated: Antidepressant medication in this patient group often has side effects and the neurological problems associated with MS such as difficulties with concentration and fatigue make it particularly difficult for MS patients to complete “classical” depression treatments such as psychotherapy. The goal of our study was to make psychological treatments available for the many patients with Multiple sclerosis suffering from depression, who often have difficulties to find adequate treatment. For this study, published in The Lancet Psychiatry, we conducted a randomized controlled trial of a fully-automated, computer-based program that can be accessed directly from patients’ homes over the internet. The program called “deprexis” was developed by the Hamburg-based company GAIA and uses methods of “cognitive behavioral therapy” or “CBT”. Ninety Multiple sclerosis patients were enrolled in the trial and randomly assigned to a 3 months therapy using the deprexis program or a waitlist control group. At the end of the intervention, depression had significantly decreased in the treatment group but remained unchanged in patients who did not have access to the program. In addition, patients using the computer program also reported reduced fatigue and improved quality of life. (more…)
Author Interviews, Lancet, Neurological Disorders, Pediatrics, Respiratory / 31.01.2015

Samuel Dominguez MD Departments of Pediatric Infectious Diseases Children's Hospital Colorado and University of Colorado School of Medicine Aurora, COMedicalResearch.com Interview with: Samuel Dominguez MD Departments of Pediatric Infectious Diseases Children's Hospital Colorado and University of Colorado School of Medicine Aurora, CO Medical Research: What is the background for this study? What are the main findings? Dr. Dominguez: Due to global poliovirus eradication efforts, clusters of acute flaccid paralysis (AFP) and/or cranial nerve dysfunction in children are rare and associated with few pathogens, primarily enteroviruses and flaviviruses.  Our study reports the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of EV-D68 respiratory illness, strengthening the potential link between EV-D68 and neurologic disease in children. (more…)
Author Interviews, Neurological Disorders, Neurology, Pediatrics, Sleep Disorders / 23.01.2015

James Tao, MD, Ph.D Assistant Professor Director, EEG Lab Department of Neurology, The University of Chicago, IL.MedicalResearch.com Interview with: James Tao, MD, Ph.D Assistant Professor Director, EEG Lab Department of Neurology, The University of Chicago, IL. Medical Research: What is the background for this study? What are the main findings? Dr. Tao: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with chronic uncontrolled epilepsy. Patients often died in sleep, in bed, and unwitnessed. They were often found in prone position. These circumstances of SUDEP are remarkably similar to those of sudden infant death syndrome (SIDS). In our study, we found that 73% of 253 SUDEP patients were died in prone position. These findings suggest that sudden unexpected death in epilepsy may share the mechanisms similar to SIDS. (more…)
Author Interviews, Infections, Multiple Sclerosis / 20.01.2015

Allan G Kermode MBBS MD FRACP FRCP Clinical Professor of Neuroimmunology, Murdoch University Clinical Professor of Neurology, University of Western Australia Head, Department of Neurology and Clinical Neurophysiology SCGH Centre for Neuromuscular and Neurological Disorders Australian Neuromuscular Research Institute Sir Charles Gairdner Hospital Perth WA Australia Institute of Immunology and Infectious Diseases Murdoch University, Western AustraliaMedicalResearch.com Interview with: Allan G Kermode MBBS MD FRACP FRCP Clinical Professor of Neuroimmunology, Murdoch University Clinical Professor of Neurology, University of Western Australia Head, Department of Neurology and Clinical Neurophysiology SCGH Centre for Neuromuscular and Neurological Disorders Australian Neuromuscular Research Institute  Sir Charles Gairdner Hospital Perth WA Australia Institute of Immunology and Infectious Diseases Murdoch University, Western Australia MedicalResearch: You found that H. pylori sero-positivity was significantly lower in female patients with MS than in female healthy controls, but you didn’t find such a trend in men with Multiple Sclerosis… Briefly, what might explain this association between H. pylori and Multiple Sclerosis in women? (i.e the hygiene hypothesis I suppose?). Prof. Kemode: There are a number of possible explanations, but we believe that the most likely is that helicobacter colonisation is a surrogate marker for the baseline levels of exposure to environmental pathogens and organisms during childhood. We have argued this point of view in our manuscript. It should be emphasised that perhaps not all exposure to infectious agents need necessarily be pathogenic, and the concept of the protobiome is an important one. Every healthy (and unhealthy) individual is host to very many organisms, with the gut having the widest diversity. Other explanations for the association might include that there is some specific antigenic interaction occurring promoting specific immune tolerance to CNS antigens, but I believe that this conclusion would be drawing a very long bow with our current stage of knowledge regarding Multiple Sclerosis. MedicalResearch: Why does this relationship exist in women but not in men? (presumably, they are exposed to the same sanitation, hygiene etc.) Prof. Kemode: This is arguably one of the most fascinating observations of our study. Historically the sex ratio in Multiple Sclerosis was equal, yet in the last 100 years the prevalence of Multiple Sclerosis has increased markedly and the majority of this increase has occurred in women such that in Australia the sex ratio F:M approximates 3:1. The fact that over the same period prevalence of helicobacter in Western countries has declined markedly is a tantalising observation. At this stage scientific knowledge has not explained the changing sex ratios in Multiple Sclerosis nor can we yet explain the strong helicobacter association in females but not males in our study, but our study provides useful navigation to direct further research. (more…)
Author Interviews, Columbia, JAMA, Neurological Disorders / 19.01.2015

Jose Gutierrez MD, MPH Assistant Professor of Neurology Division of Stroke and Cerebrovascular Disease Columbia University Medical Center NY, NYMedicalResearch.com Interview with: Jose Gutierrez MD, MPH Assistant Professor of Neurology Division of Stroke and Cerebrovascular Disease Columbia University Medical Center NY, NY Medical Research: What is the background for this study? What are the main findings? Dr. Gutierrez: There is growing interest in the effects of vascular health in cognition. The prevailing thought is that vascular disease leads to worse cognition due to direct structural damage of the brain, as in the case of brain infarcts, microhemorrhages or white matter hyperintensities, which are themselves associated with traditional cardiovascular risk factors such as hypertension, diabetes, smoking etc. Arterial stiffness, particularly of the aorta, has gained interest among researchers as predictors of vascular disease and worse cognition, but it is not clear whether arterial stiffness in the absence of traditional definition of vascular disease may be associated with worse cognition. We investigated in a representative sample of the US among adults 60 years or older who underwent cognitive testing with the Digit Symbol Subtraction test and who also had other measures of vascular disease, including blood workup, blood pressure measurement and Pulse pressure. We hypothesized that indirect measures of arterial stiffness such as ABI > 1.3 or pulse pressure would be associated with worse cognition, even among those without any clinical vascular disease or traditional vascular risk factors. We Included 2573 US adults in the sample, segregated those with any self-reported vascular disease or vascular risk factors and we found that among those without vascular disease or risk factors, an ABI > 1.3 and increased intra-visit blood pressure variability were predictors of worse cognitive performance compared with those without these indicators. Among participants with both indirect markers of arterial stiffness, their cognitive performance was worse that having only one of them suggesting additive effects of these two variables. (more…)
Author Interviews, Neurological Disorders / 09.01.2015

Julio C. Martinez-Trujillo, MD, PhD Canada Research Chair in Neuroscience Associate Professor, Department of Physiology McGill University Montreal, Quebec, CanadaMedicalResearch.com Interview with: Julio C. Martinez-Trujillo, MD, PhD Canada Research Chair in Neuroscience Associate Professor, Department of Physiology McGill University Montreal, Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Martinez-Trujillo: Humans and other primates have an extraordinary ability to voluntarily and efficiently focus attention on important information while ignoring distraction. For decades it has been hypothesized that this ability relies on the evolutionary expansion of the lateral prefrontal cortex, a part of the brain located in the lateral convexity of the frontal lobe, that reaches its highest level of complexity in primates. Several studies have demonstrated that the activity of single neurons in the lateral prefrontal cortex of behaving primates is strongly modulated by allocating attention to different objects or locations. However, one fundamental outstanding question in this field of research is whether assemblies of simultaneously active lateral prefrontal cortex neurons (neuronal assembly) can generate sufficient information to implement the cognitive operation of attention. This is not trivial since when multiple neurons are simultaneously active the amount of information they generate depends on processes such as correlated noise and trial-to-trial response variability, which can substantially impair the information carried by a neuronal population. In order to investigate this issue we recorded the activity of hundreds of lateral prefrontal neurons in non-human primates while they allocated attention to one of several objects across the visual field. We input the recorded signals into a machine-learning algorithm running on a personal computer that mimicked the computations performed by a brain network of interconnected neurons. We tested the hypothesis that the computer will reliably signal where the subjects allocated attention on a computer display. Indeed, the machine could predict with 100 milliseconds resolution where the subjects directed attention on the display. This prediction was made well in advance the subjects executed any action towards the attended object. Thus, assemblies of prefrontal neurons can reliably signal the allocation of attention across the visual field within realistic timeframes. (more…)
Author Interviews, JAMA, Multiple Sclerosis / 31.12.2014

Dr. Richard Nash MD Colorado Blood Cancer InstituteMedicalResearch.com Interview with: Dr. Richard Nash MD Colorado Blood Cancer Institute   Medical Research: What is the background for this study? What are the main findings? Dr. Nash: Multiple sclerosis is an autoimmune disease of the central nervous system which causes significant disability and in some cases results in patients being wheel-chair bound or bed-ridden. It is a significant medical problem amongst young adults. We undertook this study because current Multiple sclerosis therapies were not adequate for effective long-term control of the disease in the majority of the patients. High-dose immunosuppressive therapy followed by autologous hematopoietic cell transplantation is an effective treatment for many hematological malignancies. It causes a profound immunosuppression. Based on this effect on the immunological system, we initiated a clinical trial of this treatment modified for autoimmune disorders. The study was supported by the Immune Tolerance Network and NIAID, NIH. In a phase 2 clinical trial of 25 patients all of whom were followed for at least 3 years, we demonstrated that 80% of patients had no evidence of disease activity. No other Multiple sclerosis treatments were given after the study treatment. Adverse events were similar to what we have observed for this treatment in patients with hematological malignancies. No significant acute neurological adverse events were observed. (more…)
Author Interviews, Nature, Neurological Disorders / 30.12.2014

György Buzsáki, M.D., Ph.D. Biggs Professor of Neural Sciences NYU Neuroscience Institute New York University Langone Medical Center New York, NY 10016MedicalResearch.com Interview with: György Buzsáki, M.D., Ph.D. Biggs Professor of Neural Sciences NYU Neuroscience Institute New York University Langone Medical Center New York, NY 10016 Medical Research: What is the background for the NeuroGrid device? Dr. Buzsaki: The main form of communication among neurons in the brain occurs through action potentials (‘spikes’). Understanding the mechanisms that translate spikes of individual neurons into perceptions, thoughts, and actions requires the ability to monitor large populations of neurons at the spatial and temporal resolution of their interactions. We developed a novel, organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) with neuron-size density electrodes capable of acquiring action potential of individual neurons from the surface of the brain. The NeuroGrid has several innovative characteristics that overcome limitations in current methods of surface recording: (i) light-weight and conformable architecture to establish stable electrical and mechanical contacts, thereby ensuring minimal damage to underlying tissue; (ii) efficient abiotic/biotic interface resulting in a high signal to noise ratio and the ability to resolve spikes. This is achieved by using conducting polymers as the interfacing material. Conducting polymers are mix conductors, they can conduct electronics and ionic currents hence they can efficiently transduce ion based neural activity into electronic signals (iii) scalable neuron-size density electrodes to allow isolation and characterization of multiple individual neurons’ action potential across the cortical surface. (more…)
Author Interviews, Case Western, Nature, Neurological Disorders / 26.12.2014

Bradley T. Lang, PhD Researcher, Jerry Silver Lab Department of Neurosciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with: Bradley T. Lang, PhD Researcher, Jerry Silver Lab Department of Neurosciences Case Western Reserve University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Lang: In the late 1980’s, Jerry Silver, PhD, discovered the presence of chondroitin sulfate proteoglycans in the developing nervous system, which form barriers to prevent aberrant growth. He has been building on this finding for more than 30 years, attempting to understand why the adult spinal cord is incapable of regenerating, or why axons don’t grow where they don’t. He has found that the glial scar, which surrounds the site of neural trauma, is incredibly rich in proteoglycans, which prevent regeneration in the spinal cord. In 2009 we collaborated with a group at Harvard to discover the very first receptor for chondroitin sulfate proteoglycans, protein tyrosine phosphatase-sigma, or PTPsigma. Medical Research: What are the main findings? Dr. Lang: The findings in this paper are twofold. We first describe a novel mechanism of regeneration failure, where regenerating axons become stabilized within a gradient of chondroitin sulfate proteoglycan, completely preventing motility. This finding helps explain why axons persist in the vicinity of the glial scar after injury indefinitely, with little to no regeneration potential—they are simply embedded within the scar. We were able to model this interaction in a petri dish to screen for drugs that were capable of promoting motility. The second finding in the manuscript is the discovery and characterization of a novel peptide therapeutic that binds to the receptor for chondroitin sulfate proteoglycans and releases inhibition. Most importantly, this drug was given systemically, similar to a daily insulin injection, avoiding complications due to direct nervous system infusion/injection. After several weeks of treatment (which began 1 day after injury), rats with severe spinal cord injury regained coordinated locomotion, bladder control, and/or balance. In total, 21/26 treated animals regained some function. (more…)
Author Interviews, Genetic Research, Neurological Disorders, PNAS, Scripps / 26.12.2014

Elizabeth A. Thomas, Ph.D. Associate Professor Department of Molecular and Cellular Neuroscience The Scripps Research InstituteMedicalResearch.com Interview with: Elizabeth A. Thomas, Ph.D. Associate Professor Department of Molecular and Cellular Neuroscience The Scripps Research Institute   Medical Research: What is the background for this study? What are the main findings? Response: Increasing evidence has demonstrated that epigenetic factors can profoundly influence gene expression, and in turn, influence resistance or susceptibility to disease.  Epigenetic drugs, such as histone deacetylase (HDAC) inhibitors, are finding their way into clinical practice, and are being proposed for therapeutic use in several neurological disorders.  Our previous studies have shown that selective HDAC inhibitors can cause beneficial effects in mouse models of Huntington’s disease, improving symptoms, and reducing severity of the disease.  Our current studies show that one such compound can alter DNA methylation, an epigenetic mark that can be inherited, leading to changes in gene expression that are seen in the parent mouse exposed directly to the drug, as well as in offspring from the drug-treated male mice.  Concurrent with these changes, we observed that offspring from drug-treated males shown improved disease symptoms, showing a delay in disease onset and a reduction of motor and cognitive symptoms that included improved performance in tests of balance, speed and memory. These finding have significant implications for human health as they enforce the concept that ancestral drug exposure may be a major molecular factor that can affect disease outcome in a subsequent generation.  One exciting aspect of our study is that the parental drug treatment made the offspring better, not worse, like other compounds known to cause transgenerational effects. (more…)
Author Interviews, Parkinson's / 14.12.2014

Filip Scheperjans MD Department of Neurology Helsinki University Central Hospital Department of Neurological Sciences University of Helsinki, Helsinki, FinlandMedicalResearch.com Interview with: Filip Scheperjans MD Department of Neurology Helsinki University Central Hospital Department of Neurological Sciences University of Helsinki, Helsinki, Finland Medical Research: What is the background for this study? What are the main findings? Dr. Scheperjans: In Parkinson’s disease (PD), the first neurodegenerative changes are seen in the olfactory bulb and enteric nervous system. Correspondingly, most Parkinson’s disease patients suffer from hyposmia and gastrointestinal symptoms, frequently years before motor symptoms evolve. Therefore, it has been suggested that an environmental factor acting through the nose or gut, could be involved in Parkinson’s disease. Interestingly, those two habitats are where our body gets mostly exposed to environmental agents, including microbes. Previous attempts to identify microbes related to Parkinson’s disease pointed to Helicobacter pylori and small intestinal bacterial overgrowth, but in the end had been somewhat inconclusive. But there possibly was a signal. We saw next generation sequencing approaches as a new opportunity to revisit the microbe theory in PD. Studies of gut microbiome composition in neurodegenerative disease have not been published before, although alterations in gut microbiota have been demonstrated in many other diseases and gut microbiota are in close interaction with the central nervous system. The fecal microbiome of Parkinson’s disease subjects clearly differed from that of matched controls and this difference was independent of the potential confounders that we assessed. The most significant finding was that the abundance of bacteria from the Prevotellaceae family was reduced by 78% in Parkinson’s disease patients. A low abundance of Prevotellaceae was 86% sensitive for PD, but rather unspecific. However, a combination of 4 bacterial families increased specificity for PD to 90%. So microbiome analysis performed quite well in distinguishing Parkinson’s disease patients from control subjects. Another interesting finding was that, within the Parkinson’s disease group, abundance of Enterobacteriaceae bacteria was related to the motor symptoms of patients. They were positively associated with the severity of postural instability and gait difficulty. (more…)
ALS, Author Interviews, JAMA / 16.11.2014

MedicalResearch.com Interview with: Charles Tzu Chi Lee, PhD Associate Prof., Department of Public Health Kaohsiung Medical University, Kaohsiung, Taiwan Sanmin District, Kaohsiung City Taiwan Medical Research: What is the background for this study? What are the main findings? Dr. Lee: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease and most patients die within three to five years after symptoms appear. Studies have suggested angiotensin-converting enzyme inhibitors (ACEIs) may decrease the risk for developing neurodegenerative diseases. But there was still no human study discussing ACEIs use and ALS risk in literature. The study results indicate that when compared with patients who did not use ACEIs, the risk reduction was 17 percent (adjusted odds ratio of 0.83) for the group prescribed ACEIs lower than 449.5 cumulative defined daily dose (cDDD) and 57 percent (adjusted odds ratio 0.43) for the group prescribed ACEIs greater than 449.5 cDDD. (more…)
Author Interviews, JAMA, Neurological Disorders / 14.11.2014

MedicalResearch.com Interview with: Charles Tzu Chi Lee, PhD Associate Prof., Department of Public Health Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung City 80708, Taiwan Medical Research: What is the background for this study? What are the main findings? Dr. Lee: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease and most patients die within three to five years after symptoms appear. Studies have suggested angiotensin-converting enzyme inhibitors (ACEIs) may decrease the risk for developing neurodegenerative diseases. But. there was still no human study discussing ACEIs use and ALS risk in literature. The study results indicate that when compared with patients who did not use ACEIs, the risk reduction was 17 percent (adjusted odds ratio of 0.83) for the group prescribed ACEIs lower than 449.5 cumulative defined daily dose (cDDD) and 57 percent (adjusted odds ratio 0.43) for the group prescribed angiotensin-converting enzyme inhibitors greater than 449.5 cDDD. (more…)