bluuebunny/crossref_metadata_2025 huggingface dataset:
The Future of Combination Therapies of Insulin with a Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes – Is it Advantageous?
Authors: Gallwitz Baptist ,   Professor of Medicine, Department of Medicine IV, Eberhard Karls University, Tübingen, Germany
Published: October 2015

Safe and effective therapies for type 2 diabetes are needed to reduce the burden of late complications and costs associated with this chronic disease. Hypoglycaemia and body weight gain are side effects and limitations of the therapy with insulin and/or sulphonylureas. Recently, the combination of glucagon-like peptide-1 (GLP-1) receptor agonists and insulin has become available, which is associated with good efficacy and less risk for hypoglycaemia and weight gain. This editorial discusses the strategies to escalate treatment in type 2 diabetes in view of this novel combination and discusses its placement within the therapeutic algorithm of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Recent developments to simplify this combination therapy are also dealt with.
Management of Type 2 Diabetes – Methods for Addition of Prandial to Basal Insulin
Authors: Rodbard Helena W , Karolicki Boris ,   Medical Director, Endocrine and Metabolic Consultants, Rockville, Maryland, US,   Medical Director, Novo Nordisk Inc., Princeton, New Jersey, US
Published: October 2015

As glycaemic control deteriorates with the progression of type 2 diabetes, treatment guidelines advocate starting basal insulin therapy, and then progressing to a basal–bolus regimen as needed. Nevertheless, although timely intensification of therapy is important to minimise the risk of diabetic complications, considerable clinical inertia exists, not only in the initiation of insulin but also in the progression to multiple-dose insulin regimens. One barrier has been the lack of guidance about how to make the transition from basal-only to basal–bolus insulin therapy. In this review, we discuss how data from the recent FullSTEP study, along with other randomised studies, will help to bridge this gap. Prandial boluses can be added to basal insulin in a stepwise manner, using a straightforward, patient-led dose titration approach and simple estimation of which meal to add the initial prandial bolus to. Reducing the complexity of progression to multiple-dose insulin regimens and empowering patients will lessen the burden on clinicians, improve treatment satisfaction and facilitate timely implementation of treatment guidelines.
Cardiovascular Risk in Patients with Subclinical Hypothyroidism
Authors: Duntas Leonidas H , Chiovato Luca ,   Professor, Unit of Endocrinology, Metabolism and Diabetes, Evgenidion Hospital, University of Athens, Greece,   Professor, Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri Istituto di Ricovero e Cura a Carattere Scientifico, University of Pavia, Italy
Published: October 2015

Subclinical hypothyroidism (SCH) has been associated with increased cardiovascular mortality due to adverse effects mainly on lipids and blood pressure (BP). There is evidence that SCH, especially in patients with thyroid-stimulating hormone (TSH) >10mU/l, may increase cardiovascular risk. Some uncertainty exists regarding the association of SCH with BP; however, that the coexistence of SCH with BP and hypercholesterolaemia has a negative cardiovascular impact is beyond doubt. Insulin resistance, by modulating various risk factors including coagulation, may potentially increase cardiovascular risk. Periodic health examinations including screening has been advised in patients >35 years of age, while treatment with thyroxine should be tailored to each patient.
Glycemic Control and Diabetic Complications—Is the Predominant Current Rationale Rational?
Authors: Lebovitz Harold E ,   Professor of Medicine, State University of New York Health Science Center, Brooklyn, US
Published: October 2015

Although the level of glycated hemoglobin (HbA1C) reflects chronic glycemic control, treatment-induced decreases in HbA1Cin patients who have established diabetes do not always predict beneficial clinical outcomes. Clinical outcomes are dramatically influenced by the history of previous glycemic control, the extent of current clinical complications, and the side effects of therapeutic agents. Rational approaches to the intensity of glycemic control in individual patients should take these factors into consideration, as well as in setting an appropriate goal for the HbA1Ctarget.
A Call for Diabetes Self-management Education
Authors: Siminerio Linda ,   Professor of Medicine, Executive Director, University of Pittsburgh Diabetes Institute, Pittsburgh, Pennsylvania, US
Published: October 2015

It is widely accepted that diabetes self-management education (DSME) is an important component of care. It has been shown that DSME is associated with improvements in clinical, behavioral, and psychosocial outcomes. Despite proven benefits, the number of patients who receive DSME are disappointingly small. Introducing educator services in primary care has been shown to improve access and outcomes. As the diabetes epidemic continues, strategies to help patients meet targets and lower risk for complications are needed. The provision of DSME is critical in overcoming barriers to good-quality care. Those responsible for delivering good quality care need to mobilize efforts and explore avenues to meet the needs of those living with complex chronic diseases.
The Functionally Refractory Patient in Diabetes—Prevalence and Predictors within Specialist Care Registries
Authors: Aronson Ronnie ,   Executive Director, LMC Diabetes & Endocrinology, Toronto, Canada
Published: October 2015

A recent literature survey reviewed all published global registries, evaluating them for patient outcome data and characteristics. Using registry data to define the patient characteristics of refractory patients, the authors characterized the functionally refractory patient in diabetes and provided a predictive model to facilitate the recognition of such a patient in a specialist practice. At the specialist level, the authors have identified common predictive elements of a functional refractory status: insulin usage, greater number of microvascular complications, earlier age of onset and longer durations of diabetes, and greater complexity and number of therapies. This editorial provides a brief overview and commentary of the authors original descriptive literature review and findings.
Metabolic Disturbances and the Intestinal Microbiome
Authors: Meneghini Luigi F ,   Professor of Internal Medicine, UT Southwestern Medical Center; Executive Director, Global Diabetes Program for the Parkland Health and Hospital System, Dallas, Texas, US
Published: October 2015

The gut microbiome, which can be affected by dietary and other environmental conditions, appears to have an important role in health and disease. A better understanding of the impact of changes in our gut microflora, as well as the determinants of these changes, represents an opportunity to address a number of acute and chronic disease conditions through novel mechanisms and therapeutic approaches.
Which One to Endorse Among the Multitude of Lipid Guidelines?
Authors: Sonmez Alper ,   Associate Professor in Medicine, Gulhane Military Medical Academy, School of Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey
Published: October 2015

Dyslipidemia is the major risk factor for atherosclerotic cardiovascular diseases. A multitude of lipid guidelines exist, with several controversies, and the best approach in dyslipidemia management is not clear. The tools and lipoproteins used for risk assessment, whether to use a treatment target and implementing drugs other than statins are all controversial points. Until the time for the publication of an agreeable lipid guideline, physicians should choose their way by considering the advantages and disadvantages of the existing guidelines.
Transthyretin Cerebospinal Fluid Levels in Alzheimer’s Disease—Is This a Biomarker for Disease Severity?
Authors: Gloeckner Sara Friederike , Zerr Inga ,   Doctoral Student,   Professor, Department of Neurology, University Medical School, Georg August University Göttingen
Published: October 2015

Alzheimer’s disease (AD) is the most common cause of dementia. Aβ1–42, Aβ1–40, total tau, and hyperphosphorylated tau have been reported to be suitable biomarkers in the diagnosis of AD. Additionally, transthyretin has been suggested as a biomarker since it has been shown to inhibit Aβ aggregation and the formation of senile plaques. Aggregates of Aβ1–42are an important hallmark of the pathogenesis of AD. Patients with AD show significantly lower levels of transthyretin in the cerebrospinal fluid (CSF) compared with aging controls or patients with other kinds of dementia. Furthermore, some data indicate that transthyretin levels reflect disease severity in AD. In conclusion, recent work demonstrates the potential of transthyretin as an additional biomarker in the neurochemical differential diagnosis of AD.
Radiosurgery for Gliomas
Authors: Jagannathan Jay , Pouratian Nader , Sheehan Jason P ,   Resident Physician, Wayne State University,   Neurosurgeon and Assistant Professor of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles,   Associate Professor, Department of Neurological Surgery, University of Virginia Health Sciences Center
Published: October 2015

Stereotactic radiosurgery is a neurosurgical modality that involves delivering a large dose of focused radiation to a lesion while sparing the surrounding normal brain tissue. The biological properties of some gliomas, specifically relating to their oxygenation and invasiveness, can make them good targets for stereotactic radiosurgery. Although randomized controlled studies are lacking, preliminary data suggest that radiosurgery may be a viable alternative for low-grade gliomas, with improved survival and a low rate of complications. Although the prognosis for malignant gliomas is poor even after radiosurgery, it is possible the radiosurgical treatment can allow the surgeon more flexibility in terms of operative planning and subsequently result in better quality of life for patients post-operatively.
Diagnosis and Treatment of Neuromyelitis Optica
Authors: Matiello Marcelo , Weinshenker Brian G ,   Senior Research Fellow,   Professor of Neurology, Department of Neurology, Mayo Clinic, Rochester
Published: October 2015

Neuromyelitis optica (NMO), an autoimmune inflammatory disease of the central nervous system (CNS), is characterized by severe attacks of optic neuritis and myelitis. A specific immunoglobulin G1 (IgG1) autoantibody, NMO-IgG, is present in NMO patients. Its discovery facilitates the early recognition of NMO, differentiation of NMO from multiple sclerosis (MS), and recognition of a broader spectrum of manifestations of NMO. Following an attack of NMO, high-dose intravenous methylprednisolone is the treatment of choice. Plasmapheresis is recommended for attacks that do not respond to first-line treatment. For long-term relapse prevention, immunosuppressive drugs such as azathioprine, mycophenolate mofetil, rituximab, and mitoxantrone are recommended rather than the immunomodulatory agents used for MS. The study of NMO has rapidly progressed due to the successful translation of the discovery of a specific biomarker into clinical practice and basic research. The discovery of the antigenic target of NMO-IgG, the water channel aquaporin-4, improved understanding of the physiopathology of NMO and may lead to the development of new treatments.
Advances in Medical Management of Cluster Headache
Authors: Evers Stefan ,   Professor of Neurology and Clinical Neurophysiology, Department of Neurology, University of Münster
Published: October 2015

Cluster headache is a rare but extremely disabling condition. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7l/minute, 6mg subcutaneous sumatriptan, and 5mg zolmitriptan nasal spray are the drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil in a daily dose of at least 240mg (maximum dose depends on efficacy and tolerability). Although no placebo-controlled trials are available, steroids are clearly effective in cluster headache. Methylprednisone (or equivalent corticosteroid) at least 100mg orally or up to 500mg intravenously per day over five days (then tapering down) is recommended. Methysergide, lithium, and topiramate are recommended as drugs of second choice. Although in part promising, surgical procedures require further scientific evaluation before they can be recommended.
Brain Tissue Oxygen Monitoring in Children—A Review
Authors: Figaji Anthony A , (Neurosurgery) FCS ,   Head of Pediatric Neurosurgery, Red Cross War Memorial Childrens Hospital and University of Cape Town,   Head of Pediatric Neurosurgery, Red Cross War Memorial Childrens Hospital and University of Cape Town
Published: October 2015

Brain tissue oxygen monitoring is a relatively new technique for continuous measurement of focal brain tissue oxygen tension (PbtO2). There are several studies of PbtO2monitoring in adult patients but few in children. The goal is the prevention, or early detection and treatment, of secondary insults. Episodes of low PbtO2are associated with worse outcome, and treatment directed by PbtO2may benefit patients, but there is no Class I evidence as yet. What determines PbtO2is multifactorial and the underlying pathophysiological events affecting PbtO2may be complex. The clinician using this technology must understand the technical and physiological aspects, as well as the limitations, of PbtO2monitoring if there is to be any clinical benefit. However, whether PbtO2monitoring delivers overall benefit across centers of different expertise requires a randomised controlled trial. This review examines the current literature on PbtO2monitoring with a focus on children, the important technical and physiological factors, and an approach to using a PbtO2monitor.
Developments in Neurostimulation Therapy for Epilepsy
Authors: Velasco Ana Luisa ,   Head, Epilepsy Clinic, Neurology and Neurosurgery Service, General Hospital of Mexico City
Published: October 2015

Neuromodulating neural tissue instead of performing lesions is a current trend in neurosurgery. In the case of epilepsy, stimulation of the nervoussystem is under investigation, and the field is growing at a fast pace. The purpose of this article is to review the various targets that have been studiedin the search for a way to control refractory seizures. Consideration is made of why each target is chosen, patient selection, results, and adverseeffects. Cerebellar stimulation was the first proposed method; vagus nerve stimulation is currently the most widely used due to its easy technique,but the results on seizure reduction are modest. Other targets were chosen with the idea of interfering with seizure propagationthis is the casewith thalamic stimulation. Currently, studies are being performed stimulating the epileptic focus. Although there are still many controversiesregarding which is the best target and stimulating parameters, all authors agree that neuromodulation reduces seizures and has the advantage ofbeing reversible and safe.
Vigabatrin in the Treatment of Infantile Spasms
Authors: Camposano Susana E , Thiele Elizabeth A ,   Instructor of Neurology, Harvard Medical School, and Research Coordinator, Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital,   Associate Professor of Neurology, Harvard Medical School, and Director, Pediatric Epilepsy Program, and Director, Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital
Published: October 2015

Vigabatrin (VGB) is an effective treatment of infantile spasms (IS) that controls spasms of all etiologies in about 50% of patients when used asmonotherapy. In tuberous sclerosis complex, VGB controls spasms in up to 95% of patients and should be used as the drug of choice. HigherVGB doses correlate with shorter times to response and higher response rates. Its most serious side effect is retinal toxicity characterized byirreversible bilateral concentric constriction of the visual fields (BCCVF). Maximum VGB dose, total VGB dose, and duration of VGB treatmentconstitute risk factors for BCCVF. In each particular patient, dose and duration of treatment should be kept at a minimum, while ensuringeffectiveness and preventing relapse. Every effort should be made to evaluate retinal function, even though it may require specializedophthalmological services. The addition of this new US Food and Drug Administration (FDA)-approved drug as an alternative in the treatmentof IS represents a major contribution to an armamentarium that contains only one other treatment.
Chronic Stress Accelerates and Intensifies Aß-induced Alzheimer’s-disease-like Pathogenesis in Rat Models
Authors: Alkadhi Karim A ,   Professor of Pharmacology, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston
Published: October 2015

Apart from genetic factors, environmental factors such as stress may also play a critical role in the manifestation of Alzheimer’s disease (AD). We studied the impact of chronic psychosocial stress in two amyloid-beta (Aβ) rat models of AD by three approaches: learning and memory tests in the radial arm water maze, electrophysiological recordings of long-term potentiation (LTP) in anesthetized rats, and immunoblot analysis of synaptic plasticity- and cognition-related signaling molecules. The first Aβ rat model, representing established AD, was induced by continuous intracerebroventricular (ICV) infusion of a pathogenic dose of Aβ peptides via a 14-day osmotic pump. In this AD model, chronic stress intensified cognitive deficits, produced more depression of LTP, and accentuated the reduction of signaling molecule levels compared with the established model alone. The second model represents subjects that are clinically normal but are at risk for AD, and was induced by ICV infusion of a sub-threshold (sub-Aβ) dose of Aβ peptides. Chronic psychosocial stress was induced using a rat intruder model. Various tests showed that sub-Aβ rats were not significantly different from control rats. However, chronically stressed sub-Aβ rats showed more significant impairment of cognitive functions and early-phase LTP than that caused by stress alone. Molecular analysis revealed marked disturbances in the levels of essential signaling molecules in the stressed AD at-risk rats. These findings suggest that chronic stress may profoundly accelerate and intensify the impairment of cognition and synaptic plasticity in individuals at risk for AD and those with established AD, respectively. Possible mechanisms for the effect of chronic stress are discussed.
Relapsing–Remitting Multiple Sclerosis—Current Treatment Options and Perspectives for the Future
Authors: Rae-Grant Alex , Ontaneda Daniel ,   Neurologist,   Neurology Resident, Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic
Published: October 2015

Multiple sclerosis (MS) is the most prevalent demyelinating condition of the central nervous system and produces significant disability over time. For many years it was considered to be an untreatable disease, but great advances have been made in the treatment of MS in the last 20 years. There are currently six US Food and Drug Administration (FDA)-approved disease-modifying agents for the relapsing form of the disease. We review in detail these medications and the pivotal trials leading to their approval. We will briefly review non-FDA-approved medications already used in MS. We will also discuss some of the medications currently being studied in phase II and III trials that are not yet approved for use in MS.
Neuroimaging in Migraine—Recent Advances and Perspectives for the Future
Authors: Day Brian K , Dodick David W , Schwedt Todd J ,   Resident Neurologist, Department of Neurology, Washington University School of Medicine,   Professor of Neurology, Mayo Clinic,   Assistant Professor of Neurology and Anesthesiology, and Director, Washington University Headache Clinic, Washington University School of Medicine
Published: October 2015

Migraine is a very common disorder that imposes substantial individual and societal costs. A better understanding of migraine mechanisms may lead to the development of new therapies and thus improve the management of migraine patients. Magnetic resonance imaging (MRI) techniques and positron emission tomography (PET) have revolutionized our understanding of migraine pathophysiology as a primary central nervous system (CNS) disorder, advanced the search for a central migraine generator, clarified the role of cortical spreading depression (CSD) and central sensitization in the pathogenesis of migraine, and revealed some potential sites of action of migraine medications. Structural imaging has shed light on relationships between migraine and stroke, white matter lesions, iron deposition, microstructural brain damage, and other gray and white matter aberrations. Emerging neuroimaging techniques, such as arterial spin labeling (ASL) and functional connectivity MRI (fcMRI), are beginning to provide further evidence of functional brain alterations in migraine patients. Ultimately, it is hoped that advanced neuroimaging will benefit the individual migraine patient by enhancing our diagnostic abilities, allowing for development of better treatments and serving as an important tool in medical decision-making.
Technological Advances in Stroke Rehabilitation—High Tech Marries High Touch
Authors: Senelick Richard C ,   Neurologist, and Medical Director, Rehabilitation Institute of San Antonio
Published: October 2015

Until recently, the rehabilitation of stroke patients relied heavily on treatment that focused on teaching them how to compensate for their physical deficits. However, the latest neurorehabilitation studies show that the concept of neural plasticity (the ability of the brain to repair itself) can be applied effectively to the rehabilitation regimen of such patients, leading to improved outcomes and enhanced functional abilities. Stroke patients with limited voluntary movement could now benefit from technologies such as functional electrical stimulation (FES) combined with necessary repetition of functional tasks (use-dependent plasticity) to enhance the neural repair process and improve outcomes, thus enabling them to begin to overcome their previous limitations and to improve their physical capabilities.
Advances in Our Understanding of Dystonia—Pathophysiology and Treatment Options
Authors: Lubarr Naomi , Bressman Susan ,   Attending Neurologist, Division of Pediatric Neurology and Division of Movement Disorders, Department of Neurology, Beth Israel Medical Center,   Alan and Joan Mirken Chair, Department of Neurology, Beth Israel Medical Center and Professor of Neurology, Albert Einstein College of Medicine
Published: October 2015

Although the pathophysiology of dystonia remains incompletely understood, advances in two major areas of research over the past two decades have led to important insights into the mechanisms of dystonia. First, with the identification of dystonia genes, investigations using cellular and animal models of dystonia have become possible. Second, advances in functional neuroimaging have led to the possibility of identification of distinct functional, anatomic, and neurochemical abnormalities in dystonia patients. Dystonia is currently conceptualized as a neurofunctional disorder characterized by alterations at various levels and multiple points along the sensorimotor circuit. There are multiple causes of these disruptions, and lesions along different points in interconnected pathways can yield similar motor dysfunction. The existence of dystonia endophenotypes in genetic forms of dystonia suggests that it may be a ‘second hit’ disorder, in which genetically predisposed brains can be thrown into an unbalanced dystonic state by environmental or genetic factors. Ultimately, a more complete understanding of the pathophysiology of dystonia should lead to better, more rational, targeted therapies.
Update and Overview of the International League Against Epilepsy Consensus Definition of Drug-resistant Epilepsy
Authors: Hao Xiao-Ting , Kwan Patrick ,   Doctorate Student, Division of Neurology, Department of Neurology, West China Hospital, Sichuan University School of Medicine,   Associate Consultant, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital
Published: October 2015

Drug-resistant epilepsy remains a major clinical challenge. Diverse criteria have been used to define drug resistance by different researchers, making it difficult or even impossible to compare the results across different studies. To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) recently proposed a consensus definition to define drug-resistant epilepsy. This is the failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This article outlines the framework of the consensus definition, explains how to apply it in practice, and discusses the future development of its use.
Emerging Therapies in Multiple Sclerosis—New Decisions in the Formulation of Treatment Strategies
Authors: Buckle Guy J ,   Director of Clinical Care, Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, and Assistant Professor of Neurology, Harvard Medical School
Published: October 2015

The therapeutic options available to neurologists treating multiple sclerosis (MS) are profoundly changing. Hitherto, disease modifying therapies (DMTs) were entirely administered by injection and were only able to retard disease progression. The frequency of site reactions and flu-like symptoms has made adherence to treatment problematic and resulted in resistance from some patients. The recent approval of the first oral DMT in MS (fingolimod) and the development of other oral agents will provide much more attractive options to both physicians and patients and may promote earlier commencement of treatment. The development of the monoclonal antibody alemtuzumab may for the first time provide a MS treatment that will, in certain patients with relapsing disease, restore some degree of lost neurologic function. Therefore these new medications will fundamentally change the decision-making process from diagnosis to choice of treatment. However, these treatments do not address progressive disease. The challenge will be which MS patients should receive the new treatments and how much benefit such treatments will provide over current strategies.
Environmental Risk Factors for Pediatric Multiple Sclerosis
Authors: Makhani Naila , Banwell Brenda ,   Fellow, Pediatric Demyelinating Disease Program, The Hospital for Sick Children and University of Toronto,   Associate Professor of Pediatrics (Neurology), Associate Scientist, Research Institute, and Director, Pediatric Multiple Sclerosis Clinic, The Hospital for Sick Children and University of Toronto
Published: October 2015

Multiple sclerosis (MS) is a common neurologic disorder that is likely the result of aberrant immune responses to key childhood environmental exposures in genetically predisposed individuals. This article discusses the current understanding of environmental risk factors implicated in MS with a focus on pediatric research. The study of children with MS is a powerful means of understanding MS biology and is highly relevant to the development of disease prevention strategies.
Traumatic Encephalopathy Related to Sports Injury
Authors: Chin Lawrence S , Toshkezi Gentian , Cantu Robert C ,   Professor and Chair, Department of Neurosurgery, Boston University School of Medicine and Boston Medical Center,   Fellow, Department of Neurosurgery, Boston Medical Center,   Clinical Professor, Department of Neurosurgery, Boston University School of Medicine
Published: October 2015

Sports-related injuries account for 10 % of head and spinal cord injuries, and yearly 1.5 million Americans suffer traumatic brain injury (TBI) without loss of consciousness or need for hospitalization. Although once thought to be benign, there is increasing evidence that concussions or mild traumatic brain injury (MTBI) have more serious complications, particularly when they occur repeatedly. Sports-related chronic traumatic encephalopathy (CTE) manifests as a progressive worsening of cerebral neurologic symptoms, initiated and maintained from repetitive concussions. Patients with CTE present with headaches, dizziness, an unsteady gait, fatigue, and dysarthria. Neuronal loss and gliosis are the most common microscopic findings in CTE, but the pathognomonic neuropathologic sign of CTE is tau-immunoreactive neurofibrillary tangles with preferential involvement of superficial cortical layers. Because there are no known treatments for CTE, prevention of concussion and particularly avoiding repeated concussions is the only option.
Stroke Rehabilitation—An Overview of Existing Guidelines and Standards of Care
Authors: Zorowitz Richard D ,   Associate Professor of Physical Medicine and Rehabilitation, The Johns Hopkins University School of Medicine and Chairman, Department of Physical Medicine and Rehabilitation, Johns Hopkins Bayview Medical Center
Published: October 2015

Over seven million stroke survivors live in the US today. Despite the publication of the first post-stroke rehabilitation clinical practice guideline in 1995, many healthcare providers are unaware not only of stroke survivors potential for functional recovery, but also common secondary complications of stroke. This article summarizes the best available evidence-based recommendations for interdisciplinary management of the stroke survivor and caregivers from five sources: two in the US, one in Canada, and two in the UK. Unique characteristics of each guideline are described, followed by a list of common clinical recommendations found in most, if not all, of the guidelines. Despite the advances in stroke rehabilitation over the past 16 years, much research still needs to be done to improve the level of evidence in stroke rehabilitation.
Intraoperative Mapping and Monitoring of Motor Cortex—A New Paradigm
Authors: Yingling Charles D ,   Director of Education, Sentient Medical Systems, President, California Neuromonitoring Services and Clinical Professor, Otolaryngology, Stanford School of Medicine
Published: October 2015

Surgery for tumors near the sensorimotor cortex poses risks to sensory and motor pathways. Sensory pathways are monitored successfully with somatosensory-evoked potentials (SEP), but motor pathways pose different challenges. Historically, electrical stimulation with prolonged 60 Hz trains was used to map the motor cortex, but this method has a high incidence of induced seizures. Transcranial motor-evoked potentials (tcMEP) can monitor spinal motor pathways. However, transcranial stimulation is inappropriate for intracranial tumors, since the current may activate deep corticospinal fibers, bypassing a superficial injury. In contrast, brief high-frequency trains as used for tcMEP, applied directly to the cortical surface at lower intensity, avoid this problem and do not appear to induce seizures. Once the motor cortex has been mapped, an electrode can be left in place and used for continuous monitoring of corticospinal tract function during tumor resection.
Constructive Interference in Steady State Imaging in the Central Nervous System
Authors: Guimarães Gonçalves Fabrício , Faria do Amaral Lázaro Luis ,   Neuroradiology Fellow, Montreal General Hospital, McGill University Health Center,   Neuroradiologist, and Chief, Neuroradiology Department, Hospital da Real Beneficiência Portuguesa de São Paulo
Published: October 2015

Constructive interference in steady state (CISS) is a fully refocused fast-gradient echo sequence that is mainly used in the assessment of the central nervous system. The most important advantages of steady-state imaging are short acquisition times, high signal-to-noise ratio, and better contrast-to-noise ratio. Owing to its cisternographic effect, CISS is useful in the assessment of the cranial nerves, and can also be used when studying cysts, cystic masses, and neurocysticercosis and in hydrocephalus cases. CISS has been shown to be useful in spinal imaging, especially in cases of arteriovenous malformation and when it is helpful to better characterize intra- and extramedullary cystic abnormalities.
Use of the Unified Parkinson’s Disease Rating Scale Activities of Daily Living Subscale to Assess Response to Rasagiline in Early Parkinson’s Disease
Authors: Kremens Daniel E , Gilbart James ,   Assistant Professor of Neurology and Co-Director, Parkinsons Disease and Movement Disorders Center, Jefferson Medical College, Thomas Jefferson University,   Principal Medical Writer, Touch Briefings
Published: October 2015

Various assessment scales are used to measure the severity and rate of progression of Parkinsons disease (PD)for example, the Unified Parkinson's Disease Rating Scale (UPDRS) and its Activities of Daily Living (ADL) subscale. The relative merits of these scales for accurately determining the degree of disease progression have recently come under scrutiny. Analyses of data from the recent Attenuation of disease progression with Azilect given once daily (ADAGIO) trial demonstrated that patients receiving early-start rasagiline (Azilect®, Teva Neuroscience, North Wales, PA) 1 mg/day experienced slower disease progression, as assessed by their mean total UPDRS score, than patients receiving placebo followed by delayed-start rasagiline treatment. Subsequent secondary analyses showed that 1 and 2 mg/day doses of early-start rasagiline delayed the need for antiparkinsonian drugs and improved other parameters, including ADL scores and fatigue, when compared with placebo followed by delayed-start rasagiline. Furthermore, the analyses highlighted that, over time, the motor and mentation sections of the UPDRS-ADL subscale increasingly reflect the response to treatment of the early- and delayed-start rasagiline 1 mg/day patient groups. The results from the ADAGIO trial suggest that rasagiline has potential disease-modifying effects, but more clinical data are required to confirm their effect on PD progression.
Use of Melatonin to Promote Sleep in Older People
Authors: Wurtman Richard J ,   Cecil H Green Distinguished Professor Emeritus, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, US
Published: October 2015

Many older Americans purchase the hormone melatonin and take it orally, nightly, to promote sleep onset and to help them fall back asleep after the frequent nocturnal awakenings associated with aging. This need for exogenous melatonin reflects the fact that the progressive calcification of the human pineal diminishes the organs ability to secrete its hormone, so that instead of plasma melatonin levels rising normally by 10-fold or more around bedtime the rise may be only by twofold, or even less. The quantity of melatonin that most aging people need to restore nocturnal plasma melatonin levels to what they are in youthand, concurrently, to promote sleepis tiny, only about 0.20.5 mg. However, this dosage is generally unavailable, so patients may take doses 10-fold greater, or more, producing side-effects (e.g., hypothermia; hypoprolactinemia; morning grogginess) and ultimately desensitizing melatonin receptors in the brain. The reasons that low-dose melatonin is generally unavailable are described and a strategy is proposed for enabling patients to consume the correct dosage even when preparations containing that dosage cannot be obtained.
Symptomatic Treatment in Multiple Sclerosis
Authors: Bigi Sandra , Yeh E Ann ,   Clinical Research Fellow, MS and Demyelinating Disorders Program, Hospital for Sick Children, University of Toronto, Ontario, Canada,   Associate Professor of Pediatrics (Neurology), University of Toronto; Director, Pediatric MS and Demyelinating Disorders Program, Director, Pediatric Neurology Training Program, Associate Scientist, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
Published: October 2015

Multiple sclerosis (MS) is a progressive and disabling neurodegenerative disease that primarily affects young adults. Despite significant therapeutic advances in the prevention of relapses, individuals with MS experience a variety of symptoms, most notably fatigue, spasticity, depression, gait and balance difficulties, and sexual dysfunction. These symptoms may interfere with activities of daily living and have a negative impact on quality of life. This review discusses treatment options for these symptoms.
Novel Noninvasive Magnetic Resonance Imaging Methods in Cerebrovascular Disease
Authors: Donahue Manus J , Strother Megan K ,   Assistant Professor, Departments of Radiology, Neurology, Psychiatry, and Physics and Astronomy,   Associate Professor, Department of Radiology, School of Medicine, Vanderbilt University, Nashville, Tennessee, US
Published: October 2015

Neuroimaging is a critical component of patient care in multiple stages of cerebrovascular disease. Most imaging focuses on measurements of tissue or vascular structure, with comparatively less emphasis on function. Furthermore, imaging approaches that rely on exogenous contrast agents or ionizing radiation are common and provide crucial information regarding treatment decisions; however, they are suboptimal for monitoring patients longitudinally or in response to therapy due to dose restrictions and related health concerns. We review the state of noninvasive magnetic resonance imaging (MRI) approaches that have demonstrated clinical potential in patients with cerebrovascular disease, yet have not been incorporated into routine radiologic protocols at most hospitals. These approaches include blood oxygenation level-dependent (BOLD) for cerebrovascular reactivity, arterial spin labeling (ASL) for cerebral blood flow quantification, chemical exchange saturation transfer (CEST) for macromolecule, and pH determination and arterial vessel wall imaging for plaque visualization. The strengths and limitations of these approaches are presented, as well as a summary of their implementation in stroke.
Advanced Magnetic Resonance Imaging in Epilepsy
Authors: Pardoe Heath , Kuzniecky Ruben ,   Epilepsy Neuroimaging Laboratory, NYU Epilepsy Center, Department of Neurology, NYU School of Medicine, New York, New York, US,   Epilepsy Neuroimaging Laboratory, NYU Epilepsy Center, Department of Neurology, NYU School of Medicine, New York, New York, US
Published: October 2015

Magnetic resonance imaging (MRI) is the most commonly used noninvasive imaging modality for epilepsy diagnosis, etiologic classification, and management. The availability of 3T scanners and multiple channel coils mean isotropic T2-weighted MRI can also be readily obtained with a similar spatial resolution to T1w MRI. These acquisitions in combination with quantitative morphometric techniques can be used to detect subtle cortical and subcortical brain abnormalities associated with epilepsy. Functional MRI (fMRI) methods including electroencephalography (EEG)-fMRI and resting state imaging have been used to study network activity, such as language and memory in surgical candidates. Diffusion MRI can be used to map white matter pathways and provide an alternative structural view of connections between brain regions. These techniques will increase the yield of abnormalities in epilepsy patients previously considered nonlesional.
Management of Unruptured Brain Arteriovenous Malformations
Authors: Ducruet Andrew F , Friedlander Robert M ,   Assistant Professor of Neurological Surgery,   Chairman and Walter E Dandy Professor of Neurological Surgery, Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Philadelphia, US
Published: October 2015

Brain arteriovenous malformations (bAVMs) portent a lifelong risk of hemorrhage but the treatment of these lesions may also be associated with significant morbidity. Two recent high-profile studies have suggested that patients undergoing treatment of bAVMs may suffer a worse outcome than patients managed conservatively. However, both of these studies suffer from significant limitations that limit the conclusions that can be drawn. Further work, including the establishment of a prospective registry, is necessary to definitively address this matter.
Magnetic Resonance Imaging and Dopamine Transporter Single Photon Emission Tomography in Parkinson’s Disease—When Should We Use Them?
Authors: Kestenbaum Meir , Waters Cheryl ,   Movement Disorders Fellow,   Albert and Judith Glickman Professor of Neurology, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, US
Published: October 2015

Making an accurate diagnosis of Parkinsons disease (PD) is critical for patient counseling and therapeutic management. The diagnosis of PD remains primarily clinical and is based on nonspecific findings on examination. Magnetic resonance imaging and nuclear imaging of the brain can assist in making timely diagnoses and managing treatment appropriately. These tests should not be used routinely, but only in a selected subgroup of patients where the diagnosis of PD is not clear
Pain and Sensory Abnormalities in Parkinson’s Disease—An Age- and Gender-matched Controlled Pilot Study
Authors: Skallerup Andersen Maria , Karshenas Ali , Winther Bach Flemming , Gazerani Parisa ,   Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark,   Chief Physician, Department of Neurology, Aalborg University Hospital, Aalborg, Denmark,   Professor, Chief Physician, Department of Neurology, Aalborg University Hospital, Aalborg, Denmark,   Associate Professor, Center for Sensory-Motor Interaction (SMI), and Laboratory for Cancer Biology, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark
Published: October 2015

Background/aims:To test whether patients with Parkinsons disease (PD) have an altered sensory perception in response to painful and nonpainful stimuli and if the PD medications can influence the responses.Methods:PD patients (12) and healthy subjects (12) were recruited. Sensory perception was examined in forearms, low back, and hands by light brush, pinprick, cold pressure test (CPT), and pressure algometry.Results:A significant difference was found in PD patients in response to brush (p<0.05) and pinprick (p<0.001). Lower back and forearms were found to be more sensitive. Tolerance time in CPT was shorter in PD patients (p=0.016). Pressure pain threshold (PPT) before (p=0.011) and after (p=0.050) the CPT showed a higher sensitivity in the patients regardless of the site. No association was found between the sensory perception and the medications.Conclusion:PD patients demonstrated an altered perception to touch and pain stimuli with a general increased in pain intensity and independent of the PD medications.
An Evidence-based Update on Acute Endovascular Stroke Therapy
Authors: Chen Michael ,   Associate Professor of Neurology, Neurosurgery and Radiology, Department of Neurological Surgery and Neurological Sciences, Rush University Medical Center, Chicago, US
Published: October 2015

In 2015, there is now level 1 evidence from prospective randomized controlled trials proving the clinical efficacy of acute endovascular stroke therapy. Specifically, patients who would stand to benefit need to have a large vessel occlusion (LVO), need to be treated within the first 6 hours after symptom onset, and be treated by experienced neurointerventionalists who can consistently achieve high rates of Thombolysis in Cerebral Infarction (TICI) 2b/3 recanalization.
On the Brink of a New Era in Headache Medicine?
Authors: Friedman Deborah I ,   Professor, Neurology & Neurotherapeutics, Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, US
Published: October 2015

Monoclonal antibodies to calcitonin gene-related peptide, neuromodulation, and new delivery systems portend a bright future for the treatment of migraine and other headache disorders.
Nanomedicine and Optic Nerve Regeneration—Implications for Ophthalmology
Authors: Rao Rajesh C , Chen Dong Feng ,   Ophthalmology Resident, Massachusetts Eye and Ear Infirmary, and Research Fellow, Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School,   Associate Professor, Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School
Published: October 2015

The optic nerve transmits visual information from the retina to the brain. When injured in adult mammals, the optic nerve does not regenerate. Optic neuropathies such as glaucoma are a leading cause of blindness worldwide. Optic neuropathies can also occur after ischemia, inflammation, infection, neoplasia, trauma, and/or as a result of hereditary conditions. One of the most exciting therapeutic strategies to promote optic nerve regeneration is nanomedicine. Nanomedicine utilizes the assembly and manipulation of structures less than 100 nanometers in size to treat disease. Structural elements such as protein-coated nanofibers and self-assembling peptide scaffolds are designed to enhance axon regeneration. Nanoscale spheres can deliver intraocular pressure-lowering medications and therapeutic proteins. By ‘tagging’ cells with nanoparticles, stem cell transplants can be tracked and axons redirected via a magnetic field. Finally, nanoparticles with an ability to scavenge the toxic reactive oxygen species generated in hereditary and glaucomatous optic neuropathies may provide a new avenue to treat specific types of optic nerve disorders.
Toward a Genetic Understanding of Glaucoma—Breakthroughs and Challenges from Studies of Exfoliation Glaucoma
Authors: McDowell Colleen M , Anderson Michael G ,   Post-doctoral Fellow,   Department of Molecular Physiology and Biophysics,   Associate Professor,   Department of Molecular Physiology and Biophysics,   Department of Ophthalmology and Visual Sciences, University of Iowa
Published: October 2015

Glaucoma is a complex group of diseases causing progressive degeneration of the optic nerve. Despite strong evidence of hereditary contributions to glaucoma, relatively few genetic mutations associated with glaucoma risk have thus far been identified. Glaucoma likely represents a complex genetic trait influenced by multiple loci and many confounding factors, increasing the challenge in identifying glaucoma’s hereditary basis. In this article, a brief history of the search for glaucoma-causing mutations is presented, highlighting recent breakthroughs that have identified lysyl oxidase-like 1 (LOXL1) as a major genetic risk factor contributing to exfoliative glaucoma. In considering challenges that remain ahead, our central tenet is that the search for glaucoma’s genetic elements will continue to require experimental ingenuity and synergistic approaches involving animal models that render the complexity of glaucoma more tractable.