Author Interviews, Epilepsy / 21.02.2016

MedicalResearch.com Interview with: Dr. Samba Reddy, PhD, RPh, FAAPS Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center Bryan, TX 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. (more…)
Author Interviews, Epilepsy, Neurological Disorders, Stroke / 20.02.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Cleveland Clinic, Lancet, Multiple Sclerosis / 16.02.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Epilepsy, Lancet, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Neurological Disorders / 09.02.2016

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Frailty, Hip Fractures, Parkinson's, PLoS / 08.02.2016

MedicalResearch.com Interview with: 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 . (more…)
Author Interviews, Neurological Disorders, Zika / 06.02.2016

MedicalResearch.com Interview with: 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. (more…)
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.
(more…)
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. (more…)
Author Interviews, JAMA, Neurological Disorders, Parkinson's / 20.01.2016

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. (more…)
Author Interviews, Neurological Disorders, Sleep Disorders / 19.01.2016

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. (more…)
Author Interviews, Lipids, Neurological Disorders / 18.01.2016

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. (more…)
ALS, Alzheimer's - Dementia, Author Interviews, JAMA, Multiple Sclerosis, Neurological Disorders, Stem Cells / 12.01.2016

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. (more…)
Author Interviews, Beth Israel Deaconess, CT Scanning, JAMA, Neurological Disorders, Stroke / 04.01.2016

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. (more…)
Author Interviews, JAMA, Mental Health Research, MRI, Neurological Disorders / 12.12.2015

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. (more…)
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. (more…)
Author Interviews, Multiple Sclerosis / 07.12.2015

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. (more…)
Author Interviews, Lancet, Multiple Sclerosis, Pharmacology, UCLA / 07.12.2015

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. (more…)
Author Interviews, Genetic Research, Heart Disease, Neurological Disorders, NIH, Science / 05.12.2015

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.
(more…)
Author Interviews, Brain Injury, Mayo Clinic, Neurological Disorders / 02.12.2015

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. (more…)
Author Interviews, Depression, JAMA, Neurological Disorders / 18.11.2015

Claudia van Borkulo, MSc University of Groningen, University Medical Center Groningen Department of Psychiatry, Research School of Behavioural and Cognitive Neurosciences, Interdisciplinary Center for Psychopathology and Emotion Regulation, Groningen, the NetherlandsMedicalResearch.com Interview with: Claudia van Borkulo, MSc University of Groningen, University Medical Center Groningen Department of Psychiatry, Research School of Behavioural and Cognitive Neurosciences, Interdisciplinary Center for Psychopathology and Emotion Regulation, Groningen, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: We consider psychiatric disorders as complex dynamical systems in which symptoms can interact with each other. This novel network approach to psychopathology – that is new to psychiatry – implies that a more densely connected network of symptoms of a disorder might be indicative of worse prognosis. Having one symptom can easily lead to developing more symptoms in a densely connected network, in which more symptoms reinforce each other. Reversely, a symptom in a less densely connected network will rarely turn on other symptoms. A densely connected network can theoretically be related to an increased vulnerability; because of the high level of mutual reinforcement, a small external stressor can induce a quicker transition from a healthy state to a depressed state for people with a more densely connected network. In our study, we investigated the association between baseline network structure of depression symptoms and longitudinal course of depression. We compared the baseline network structure of persisters (defined as patients with MDD at baseline and depressive symptomatology at 2-year follow-up) and remitters (patients with MDD at baseline without depressive symptomatology at 2-year follow-up). While both groups have similar symptomatology at baseline, persisters have a more densely connected network compared to remitters. More specific symptom associations seem to be an important determinant of persistence of depression. (more…)
Author Interviews, Genetic Research, JAMA, Neurological Disorders / 17.11.2015

MedicalResearch.com Interview with: Kevin M. Biglan, M.D., M.P.H Professor of Neurology and the Associate Chair for Clinical Research Department of Neurology and the Center for Human Experimental Therapeutics University of Rochester School of Medicine and Dentistry Rochester, New York  Medical Research: What is the background for this study? What are the main findings? Dr. Biglan: A therapeutic goal of research in Huntington Disease (HD) is the identification of treatments that delay the progression of disease and onset of illness in individuals at risk for developing manifest HD. Designing such efficacy trials is challenging. A major hurdle is the lack of practical primary outcome measures to assess the effect of an intervention on delaying disease onset. Use of the dichotomous endpoint of clinical diagnosis as the primary outcome requires large sample sizes and long duration of follow up in order to show a significant therapeutic effect on delaying disease onset. Continuous measures that can reliably distinguish cytosine-adenine-guanine (CAG) expanded individuals in the pre-manifest period may allow for the identification of potential disease modifying therapies using relatively smaller cohorts followed for shorter periods of time. The Prospective Huntington At-Risk Observational Study (PHAROS) represents the largest observational study to clinically evaluate pre-manifest Huntington Disease wherein both research participants and investigators were unaware of Huntington Disease mutation status. Accordingly, PHAROS was uniquely designed to address, in an unbiased manner, those clinical features most associated with the CAG expansion during the prodromal phase in  Huntington Disease.  The identification of continuous outcome measures that are associated with HD in the pre-manifest period may facilitate the design and powering of future studies of potential disease modifying therapies prior to traditional motor diagnosis. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, JAMA, Neurological Disorders, Schizophrenia / 12.11.2015

MedicalResearch.com Interview with: Frederick W. Vonberg, MA, MBBS Research Fellow in Neurocritical Care Boston Children's Hospital and Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of epilepsy. Whether this link reflected an overlap in the genetics of the two conditions has remained a mystery, however. In this study, we used a recently developed computational technique to show that there is a significant positive correlation between the genetic variants that are associated with epilepsy and with those that are associated with schizophrenia. (more…)
Author Interviews, Macular Degeneration, Parkinson's / 10.11.2015

MedicalResearch.com Interview with: Brian S. McKay, Ph.D Associate Professor Department of Ophthalmology and Vision Science University of Arizona Medical Research Building, Room 212 Tucson, AZ 85724  Medical Research: What is the background for this study? Dr. McKay: AMD (age-related macular degeneration) is a disease that is race-related. White people get the disease and lose vision to AMD at much higher rate than Blacks or Hispanics. Thus, while race is complex, pigmentation may protect from the disease. With this starting point, my laboratory went after the pigmentation pathway to determine how pigment may affect photoreceptor (the retinal cells that actually catch the light) survival. The  pigmented cells in the back of the eye are the retinal pigment epithelial cells (RPE), the rest of the retina does not pigment, it is clear not brown. We discovered that when the RPE make pigment they turn on molecular pathways to foster photoreceptor survival. Next we discovered the ligand for a receptor on the RPE that was tied to governing photoreceptor survival and pigmentation. That ligand was L-DOPA. Knowing that L-DOPA is given to many aging individuals (those at risk of AMD), we developed a team to ask whether those taking L-DOPA for movement disorders are protected from AMD. (more…)
Author Interviews, Gender Differences, Neurological Disorders, Radiology / 30.10.2015

Dr-Lise-EliotMedicalResearch.com Interview with: Lise Eliot PhD Associate Professor of Neuroscience Chicago Medical School Rosalind Franklin University North Chicago, IL 60064    Medical Research: What is the background for this study? Dr. Eliot: The hippocampus participates in many behaviors that differ between men and women, such as episodic memory, emotion regulation, and spatial navigation.  Furthermore, the hippocampus is known to atrophy in diseases such as depression, anxiety disorders, and Alzheimer's disease, all of which are more prevalent in women.  It is conceivable that a premorbid difference in hippocampal volume contributes to females' greater vulnerability.  In the scientific literature, the hippocampus is often said to be proportionally larger in females than males.  We set out to test this by doing a systematic review of the literature for hippocampal volumes in matched samples of healthy males and females, measured using structural MRI data collected from over 6000 participants of all ages. (more…)
Author Interviews, Cleveland Clinic, JAMA, Multiple Sclerosis / 13.10.2015

Dr. Jeffrey Cohen MD Director Mellen Center for Multiple Sclerosis Treatment and Research Director of the Experimental Therapeutics Program Cleveland Clinic Main CampusMedicalResearch.com Interview with: Dr. Jeffrey Cohen MD Director Mellen Center for Multiple Sclerosis Treatment and Research Director of the Experimental Therapeutics Program Cleveland Clinic Main Campus MedicalResearch: What is the background for this study? What are the main findings? Dr. Cohen: Medications are a major contributor to the high cost of Multiple Sclerosis (MS) care.  As medications go off patent, there is the opportunity to develop generic versions with lower cost.  This trial was conducted after extensive in vitro and animal studies supported the equivalence of a generic glatiramer acetate to the brand drug Copaxone. The trial showed that generic and brand glatiramer acetate have equivalent efficacy as measured by MRI and clinical endpoints, safety, and tolerability. (more…)
Author Interviews, Neurological Disorders, Technology / 24.09.2015

An Do, MD Assistant Professor Department of Neurology University of California, IrvineMedicalResearch.com Interview with: An Do, MD Assistant Professor Department of Neurology University of California, Irvine Medical Research: What is the background for this study? What are the main findings? Dr. An Do: In this study, we demonstrated that it is possible for a person with paraplegia due to spinal cord injury to regain brain-controlled walking through the use of a brain-computer interface. This system records EEG signals as a person is thinking about walking. While the person is thinking about walking, EEG signals change in a manner which can be detected by a computer algorithm. Upon detecting that a person is thinking about walking from the EEG signals, the computer sends a command signal to an electrical stimulation system to stimulate the nerves in the legs to continuously generate alternating right and left stepping movements. This stepping stimulation stops when he stops thinking about walking. (more…)
Author Interviews, Imperial College, Parkinson's / 23.09.2015

Dr. Ilse S. Pienaar Honorary Lecturer in Neuroscience at Imperial College London (& Snr. Lecturer in Cellular Pathology, Northumbria University) Centre for Neuroinflammation & Neurodegeneration Division of Brain Sciences Faculty of Medicine Imperial College London Hammersmith Hospital Campus London United KingdomMedicalResearch.com Interview with: Dr. Ilse S. Pienaar Honorary Lecturer in Neuroscience at Imperial College London (& Snr. Lecturer in Cellular Pathology, Northumbria University) Centre for Neuroinflammation & Neurodegeneration Division of Brain Sciences Faculty of Medicine Imperial College London Hammersmith Hospital Campus London United Kingdom   Medical Research: What is the background for this study? What are the main findings? Dr. Pienaar: A highly heterogeneous brainstem structure, the pedunculopontine nucleus (PPN) has been deemed a promising target for the delivery of deep-brain stimulation (DBS), to alleviate aspects of Parkinson's disease (PD), especially gait and postural instability. However, optimal therapeutic targeting of the PPN has been hampered due to DBS being unable to discriminate between cell types being targeted. We optomised a novel technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADD) in a rat model of PD, by which to target only the PPN cholinergic neurons. A series of behavioral tests revealed that selective stimulation of the PPN cholinergics completely reverses gait problems and postural instability in the PD rats. (more…)
Author Interviews, Melatonin, Multiple Sclerosis / 12.09.2015

MedicalResearch.com Interview with: Dr. Mauricio F. Farez Center for Research on Neuroimmunological Diseases (CIEN) Raúl Carrea Institute for Neurological Research (FLENI) Buenos Aires, Argentina Medical Research: What is the background for this study? What are the main findings? Dr. Farez: We were intrigued by our initial observation that Multiple Sclerosis (MS) relapses have a clear seasonal occurrence with less relapses during fall and winter. We found that melatonin levels (a hormone secreted by the pineal gland in the absence of light) have an inverse correlation with Multiple Sclerosis relapses. Moreover, melatonin controls the generation of pathogenic Th17 cells, while it boosts the generation of regulatory Tr1 cells. By affecting the immune balance of those cells it may prevents the occurrence of relapse. Medical Research: What should clinicians and patients take away from your report? Dr. Farez: Melatonin and drugs alike targeting its pathways may be a future alternative in Multiple Sclerosis  treatment. Until a proper clinical trial is conducted, melatonin SHOULD NOT be used as Multiple Sclerosis therapy. I would like to emphasize this, because melatonin is a complex hormone with receptors present basically in every cell. We do not know yet the dosage and administration form needed to obtain similar effects as the one observed in our in vitro and animal studies. (more…)
Author Interviews, JAMA, Multiple Sclerosis, OBGYNE / 01.09.2015

PD Dr. Kerstin Hellwig Neurologische Abteilung Universitätsklinikum St. Josef Hospital BochumMedicalResearch.com Interview with: PD Dr. Kerstin Hellwig Neurologische Abteilung Universitätsklinikum St. Josef Hospital Bochum Medical Research: What is the background for this study? What are the main findings? Dr. Hellwig: The relapse risk is elevated in women with Multiple Sclerosis after delivery. We found that women with Multiple Sclerosis who breastfed exclusively had a significant lower relapse risk, than women who did not breastfed at all or breastfed some but not exclusively. After the introduction of supplemental feedings, the relase risk was similar between both groups. (more…)