bluuebunny/crossref_metadata_2025 huggingface dataset:
Atherosclerosis—Know Your Risk—Is it Time for a Paradigm Shift?
Authors: Lardinois Claude K ,   Emeritus Professor, Endocrinology Division, University of Nevada School of Medicine, Reno, Nevada, US; Medical Director, American Health Care, Rocklin, California, US
Published: October 2015

Atherosclerosis is a form of arteriosclerosis characterized by the deposition of atheromatous plaques containing cholesterol and lipids on the innermost layer of the walls of large and medium-sized arteries. People with atherosclerosis have a higher risk for cardiovascular disease (CVD) and stroke. Modification of traditional risk factors, such as smoking cessation, decreasing blood pressure, and lowering of cholesterol in high-risk individuals, has resulted in reducing CVD and stroke remarkably. However, the current standard of care using traditional modifiable risk factors alone is frequently inadequate to identify some individuals with atherosclerosis. Therefore, it is important to not rely solely on risk factor modification when assessing for CVD, but also to incorporate a disease platform. A new paradigm focusing on the disease itself (atherosclerosis) is necessary. This article will review the tools necessary to identify disease and will examine why it is critical to know the cause of the disease and to develop a treatment plan to eradicate it.
A Presidential Reflection
Authors: Gharib Hossein ,   American Thyroid Association (ATA) President, Professor of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, US
Published: October 2015

I was honored to be elected in 2013 to serve as the President of the American Thyroid Association (ATA), a professional medical organization dedicated to the diagnosis and management of thyroid disorders. This brief report describes my 40-year involvement with the ATA, my experience as the president, and our accomplishments and challenges.
Pregnancy and the Antithyroid Drug Conundrum
Authors: Davies Terry F ,   Baumritter Professor of Medicine, Thyroid Research Unit, Department of Medicine, Icahn School of Medicine at Mount Sinai; James J Peters VA Medical Center, New York, US
Published: October 2015

Treating pregnant women with anti-thyroid drugs that have known teratogenic effects continues to present clinicians with multiple concerns.
Worldwide Coverage of Newborn Screening for Congenital Hypothyroidism—A Public Health Challenge
Authors: LaFranchi Stephen H ,   Professor of Pediatrics, Division of Endocrinology, Oregon Health & Science University, Portland, Oregon, US
Published: October 2015

Despite the fact that programs began detecting neonates with congenital hypothyroidism (CH) over 40 years ago, at present only 30 % of the world birth population (approximately 127 million) undergoes screening for this disorder. The estimated cost of detection by screening, $15,400 compares with a lifetime expense of $1,296,000 in developed countries. The annual cost of the 30,000 CH cases not identified and treated early is approximately $40 billion dollars. Increasing the coverage of newborn screening worldwide remains a significant public health challenge.
Validation and Multicenter Clinical Experience of the Afirma® Gene Expression Classifier
Authors: Angell Trevor E , Alexander Erik K ,   Associate Physician, Brigham and Womens Hospital; Instructor in Medicine, Harvard Medical School, US,   Chief, Thyroid Section, Brigham & Womens Hospital; Associate Professor of Medicine, Harvard Medical School, US
Published: October 2015

The current assessment of clinically relevant thyroid nodules is imprecise and nonspecific, primarily due to the presence of indeterminate cytology. This cytologic category implies a low but clinically important risk for thyroid cancer, historically prompting consideration for diagnostic thyroidectomy in most patients. Over the last 5 years, novel molecular testing options have become available and appear able to modify preoperative thyroid cancer risk and better inform clinical decisions. The Afirma® gene expression classifier (GEC) measures messenger RNA (mRNA) expression patterns in fine-needle aspiration (FNA) tissue and seeks to identify a benign signature despite indeterminate cytology. When detected, the cancer risk is low and allows for prevention of unnecessary surgeries. The results of a large, multicenter, blinded validation trial of the Afirma GEC demonstrated the test’s high negative predictive value. Subsequent independent studies of the Afirma GEC in clinical use have documented the influence these results have on preoperative management recommendations. This review summarizes the current data regarding the Afirma GEC, including the original validation trial and recent multicenter clinical experience.
Diagnosis and Management of Acromegaly in 2014 (Update from 2012)
Authors: Katznelson Laurence ,   Professor of Medicine and Neurosurgery, Stanford University, California, US
Published: October 2015

In this update to the 2012 summary, the current diagnostic and therapeutic approaches to acromegaly are reviewed. The goals of therapy are to control excess growth hormone (GH) secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk for premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Use of a somatostatin receptor ligand (SRL) preoperatively to improve surgical outcomes has not been substantiated. Medical therapy, including SRLs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with SRLs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.
Giant Hemorrhagic Prolactinoma with Sparse Prolactin Expression Presenting with Thalamic Infarction—A Case Report
Authors: GENC Ali , SUN Halil Ibrahim , KASAPOGLU Burcu , Oz Pinar , SAV Murat Aydın , PAMIR Mustafa Necmettin ,   Consultant Neurosurgeon, Acıbadem Bodrum Hospital, Department of Neurosurgery, Mugla, Turkey,   Consultant Neurosurgeon, Acıbadem University, Department of Neurosurgery, Istanbul, Turkey,   Postdoctoral Fellow, Yeditepe University, Department of Genetics, Istanbul, Turkey,   Postdoctoral Fellow, Bosphorus University, Department of Biomedical Engineering, Istanbul, Turkey,   Professor of Pathology, Acıbadem University, Department of Pathology, Istanbul, Turkey,   Professor of Neurosurgery, Acıbadem University, Department of Neurosurgery, Istanbul, Turkey
Published: October 2015

Pituitary tumors are the most common form of intracranial neoplasms. However, clinically relevant pituitary tumors presenting with disturbances of hormonal secretion or mass effect are rare and they only represent about 10 % of all surgically resected intracranial neoplasms. Prolactinomas are the most common types of pituitary adenomas. Generally, hormonal expression patterns provided by immunohistochemistry (IHC) studies are correlated with the clinical features and endocrine activity of the patients. Nonetheless, exceptions occur where the immunocytochemical staining is not concordant with the clinical picture. Pituitary adenomas presenting with apoplexy are well known. However, pituitary adenomas causing cerebral stroke and resulting in hemiplegia are unusual. Here, we report an unusual case of prolactinoma with cerebral stroke and sparse prolactin (PRL) expression. A 25-year-old woman complaining of amenorrhea, dysphasia, and left hemiplegia presented with serum PRL level in excess of 4,700 ng/ml. Pre-operational radiology images revealed a giant macroadenoma and a thalamic infarct due to carotid compression. Transcranial surgery was performed. IHC study of the adenoma revealed no hormonal expression other than sparse PRL immunoreactivity. Therefore, a sparsely granulated PRL cell adenoma was diagnosed. The patient is still under follow-up with continuing cabergoline treatment.
Impairment of Arterial Compliance in Cushing’s Syndrome
Authors: Bassareo Pier Paolo , Zedda Angela Maria , Mercuro Giuseppe ,   Chief of the Section of Paediatric Cardiology, Department of Medical Sciences M Aresu, University of Cagliari, Cagliari, Italy,   Specialist Registrar in Cardiology, Department of Medical Sciences M Aresu, University of Cagliari, Cagliari, Italy,   Professor of Cardiology, Department of Medical Sciences M Aresu, University of Cagliari, Cagliari, Italy and Medical Director of the Cardiology and Angiology Unit, University Hospital of Cagliari, Italy
Published: October 2015

Arterial stiffness may be useful for stratifying cardiovascular risk in individuals suffering from a number of pathologies, such as hypertension, diabetes, obesity, dyslipidaemia and coronary artery disease. Cushings syndrome is underpinned by a complex metabolic syndrome, which is potentially implicated in the onset of blood vessel alterations and the increase in arterial wall stiffness. The aim of this paper was to perform a review about the most important studies conducted in order to evaluate the arterial distensibility profile of subjects affected by Cushings syndrome. Increased arterial stiffness may persist even after successful cure of this disease. It is therefore of fundamental importance to identify the presence of early vascular alterations in these patients, in order to commence their treatment and thus attempt to prevent the subsequent onset of adverse cardiovascular events.
Effectiveness of Mobile Health Solutions in Lowering Glycated Hemoglobin and Resulting Economic Effects—A Review of the Current Literature
Authors: Javitt Jonathan C ,   Professor (adj.), Johns Hopkins School of Medicine, Baltimore, Maryland, US
Published: October 2015

Background: In recent years, a variety of innovative solutions have been introduced that are designed to improve adherence to blood sugar testing among patients with diabetes, lower glycated hemoglobin (HbA1c), and decrease complications associated with diabetes mellitus. The value of lowering HbA1cin preventing long-term complications of diabetes is broadly recognized. The purpose of this review is to provide an overview of the peer-reviewed literature documenting both the efficacy of mobile health (mHealth) solutions in improving adherence and lowering HbA1c, along with the impact of lowering HbA1con near-term cost and complications of diabetes. Methodology: An extensive search of Index Medicus was performed in order to identify studies documenting the effectiveness of mHealth solutions in reducing HbA1cand documenting the effectiveness of reducing HbA1cin lowering near-term medical costs. Results: Six randomized controlled trials were identified in which the use of mobile monitoring solutions for blood glucose was tested against standard care. All demonstrated a reduction in HbA1c, ranging from 0.35–1.9 percentage points. Ten studies, primarily longitudinal and retrospective in nature, were identified, which evaluated the effectiveness of HbA1creduction on reducing near-term medical costs. Overall, moderate reduction in HbA1cappears to reduce medical costs by 10 % on average in commercially insured populations and 7 % on average in Medicare-age populations. Conclusions: mHealth interventions for diabetes show promise in reducing HbA1cacross multiple settings and achieving this clinical result is likely to result in reduction of near-term medical costs.
Is It Time to Screen the General Population for Type 1 Diabetes?
Authors: Simmons Kimber M , Michels Aaron W ,   Pediatric Endocrinology and Diabetes Fellow, Childrens Hospital Colorado, Aurora, Colorado, US,   Assistant Professor of Pediatrics & Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, US
Published: October 2015

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by destruction of insulin-producing β cells in the pancreas. The incidence of T1D is increasing dramatically, and the prevalence has doubled in the last 2 decades, further increasing the morbidity and mortality associated with the disease. T1D is now predictable with the measurement of antibodies directed against β cell proteins. Islet autoantibodies (IAs) are detectable from the peripheral blood months to years before clinical diagnosis. With the presence of two or more antibodies, the risk for developing T1D is nearly 100 % given enough time. Targeted screening for T1D risk has been carried out in first-degree relatives and those with a significant genetic risk. However, more than 85 % of individuals who are diagnosed with T1D do not have a family history. In light of the predictability of T1D and recent advances in IA measurement, general population screening is on the horizon. We provide an overview of the history of general population screening and discuss the rationale for and arguments against screening the general population for T1D risk.
The Double Burden of Infectious Diseases and Diabetes—A Bidirectional Relationship
Authors: Sobngwi Eugene , Claude Mbanya Jean ,   Associate Professor, National Obesity Centre, Yaoundé Central Hospital, Yaoundé, Cameroon,   Professor of Medicine and Endocrinology, Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1 and Laboratory of Molecular Medicine and Metabolism, The Biotechnology Centre, University of Yaoundé 1, Cameroon
Published: October 2015

There is growing evidence for an etiological interaction between infectious diseases and diabetes, as well as for bidirectional influence of clinical presentation, spread, and outcomes. Some HIV treatments increase diabetes risk, and some infectious diseases may determine unique phenotypes of diabetes. Individuals who have type 2 diabetes have increased risk for tuberculosis and viral hepatitis and have poorer treatment outcomes. Joint noncommunicable diseases (NCDs) and infectious diseases clinics are the ideal method of tackling the double burden of these diseases in developing countries.
The Refractory Patient—Managing Diabetes by the Ear
Authors: Kalra Sanjay , Gupta Yashdeep ,   Department of Endocrinology, Bharti Hospital, Karnal, India,   Department of Medicine, Government Medical College, Chandigarh, India
Published: October 2015

Refractory, or difficult to control, diabetes is a commonly encountered condition in specialist practice. This editorial describes the characteristics of people with diabetes who are unable to achieve optimal glycemic control, despite aggressive drug therapy. It reflects upon the importance of bidirectional communication between patient and physician, and highlights the need for systematic history taking, empathic listening, and therapeutic patient education. The editors call for practicing diabetes therapy by the ear, in conjunction with evidence-based pharmacological therapy, to help reduce the prevalence of refractory diabetes.
GLP-1 Receptor Agonists in Type 2 Diabetes and Beyond – New Insights 2015
Authors: Gallwitz Baptist ,   Deputy Chief, Department of Medicine IV; Head of the Outpatient Clinic for Diabetes and Endocrinology, Eberhard Karls University, Germany
Published: October 2015

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were introduced for type 2 diabetes therapy nearly 10 years ago, among them shortacting compounds on the basis of the GLP-1-like peptide exendin-4 (exenatide and lixisenatide) and a long-acting GLP-1 RA based on the human GLP-1 sequence (liraglutide). Recently, two novel long-acting GLP-1 RAs on the basis of human GLP-1 sequence, for once-weekly application, have been approved for therapy of type 2 diabetes. Additionally, liraglutide has been approved for treatment of obesity at a higher dose than that used for diabetes therapy. This mini-review gives a short overview of the novel long-acting GLP-1 RAs albiglutide and dulaglutide and also reviews the studies of liraglutide in treatment of obesity leading to its approval for this use. These studies were largely presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in fall 2014.
Cushing’s Disease – Quality of Life, Recurrence and Long-term Morbidity
Authors: Huguet Isabel , Ntali Georgia , Grossman Ashley , Karavitaki Niki ,   Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, UK,   Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, UK,   Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, UK,   Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, UK
Published: October 2015

Cushings disease (CD) is a rare disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Chronic exposure to hypercortisolism leads to significant morbidities, which may be only partially reversible after remission of the disease, as well as to impairment of the health-related quality of life (HRQoL) and an increase in mortality. Transsphenoidal surgery (TSS) is the treatment of choice, and recurrence rates vary widely, confirming the need for lifelong follow-up. This review summarises the studies performed on HRQoL, recurrence rates and morbidities in patients who have CD.
Components of the Economic Burden of Serious Mental Illness in the US
Authors: Insel Thomas R , Schoenbaum Michael , Wang Philip S ,   Director,   Senior Advisor,   Deputy Director, National Insitute of Mental Health (NIMH)
Published: October 2015

Mental disorders impose considerable socioeconomic costs due to their episodic/chronic nature, their relatively early ages at onset, and the highly disabling nature of inadequately treated mental illness. Despite substantial increases in the volume of mental health treatment for disorders in the past two decades, particularly pharmacotherapies, the level of morbidity and mortality from these disorders does not appear to have changed substantially over this period. Improving outcomes will require the development and use of more efficacious treatments for mental disorders. Likewise, implementation of cost-effective strategies to improve the quality of existing care for these disabling conditions is required.
A Pathophysiological Role for Selective Alteration of the Cytokine–Chemokine Network—Inflammatory Theory in Alzheimer’s Disease
Authors: Gambi Domenico , Reale Marcella ,   Full Professor, Neurology, and Chairman, Department of Oncology and Neuroscience,   Physician, Unit of Immunodiagnostics, Department of Oncology and Neuroscience, University G D’Annunzio Chieti-Pescara
Published: October 2015

There is growing evidence that an altered metabolism of the amyloid β (Aβ) precursor protein (APP) with progressive deposition of its Aβ fragment is a crucial event in the pathogenesis of AD. Increasing evidence suggests that inflammation and alteration of the cytokine–chemokine network contributes to the pathophysiology of AD. Activated microglia produce multiple pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS); additionally, Aβ itself can stimulate microglia, astrocytes, and oligodendrocytes to secrete pro-inflammatory cytokines, chemokines, and ROS, which can lead to neuronal damage. The concomitant release of pro-inflammatory cytokines, which influence neurodegenerative pathways, and anti-inflammatory cytokines may contribute to the chronicity of the disease. It is the balance of proinflammatory products and anti-inflammatory products that may be essential in the degenerative process. Influencing this balance may help in slowing the disease. Promising results for neurological disease treatment may be achieved by targeting cytokines and chemokines in the development of antagonists and synthesis inhibitors.
Key Clinical Trials in Pharmacological Treatment of Early Parkinson’s Disease
Authors: Shah Binit , Simuni Tanya ,   Department of Neurology, Northwestern University Feinberg School of Medicine,   Department of Neurology, Northwestern University Feinberg School of Medicine
Published: October 2015

Parkinson’s disease (PD) is the second most common neurodegenerative disease and affects more than one million people in the US. The management of PD involves treatment of motor and non-motor symptoms of the disease. The armamentarium of treatment options for PD has increased substantially over the last 10 years. This article reviews recent clinical trials investigating efficacy, complications of treatment, and possible neuroprotective agents in patients with early PD.
Dual Task Interference in Parkinson’s Disease
Authors: Wu Tao , Hallett Mark ,   Associate Professor of Neurobiology, Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing,   Chief, Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health
Published: October 2015

Performing two tasks simultaneously (dual task performance) is a frequent activity in human life. Patients with Parkinson’s disease (PD) commonly have more difficulty in performing dual tasks than healthy people. To date, research on the mechanisms of dual task interference in PD remains sparse. A recent study by Wu and Hallett in 2008 investigated the central neural correlates of dual task interference in PD, and demonstrated that dual task interference in PD is due to multiple reasons. First, the limitation of capacity of attentional resources is exceeded; second, PD patients perform tasks less automatically compared with normal subjects; and third, the central executive may be defective. However, our knowledge of this phenomenon is still far from complete and needs further investigation.
Prevalence and Phenotypic Spectrum of PINK1 Mutations in Parkinson’s Disease
Authors: Ferraris Alessandro , Valente Enza Maria , Bentivoglio Anna Rita ,   IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute,   Department of Experimental Medicine, University of Rome La Sapienza,   IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute,   Department of Medical and Surgical Paediatric Sciences, University of Messina,   Department of Neurology, Catholic University, Rome
Published: October 2015

Several genes have been identified as causative of autosomal dominant or recessive forms of Parkinson’s disease (PD). Bi-allelic mutations in the PTEN-induced putative kinase 1 (PINK1) gene represent the second most frequent cause of autosomal recessive parkinsonism (ARP) after PARK2/Parkin. The typicalPINK1-associated phenotype is characterized by early age at onset, slow disease progression, and excellent and sustained response to levodopa, but in rare cases the clinical presentation can be indistinguishable from that of sporadic PD. Single heterozygous rare variants in thePINK1gene, as well as in other ARP genes, have been frequently detected both in parkinsonian patients and in healthy controls. Although their pathogenetic role is still debated, these variants have been suggested to act as minor risk factors for developing PD.
Botulinum Toxin Type A and Post-stroke Spasticity of the Upper Limbs
Authors: Ivanhoe Cindy B , Eaddy-Rose Natasha K ,   Associate Professor, Physical Medicine and Rehabilitation, Baylor College of Medicine, and Medical Director, NeuroRehabilitation Specialists,   Physician, NeuroRehabilitation Specialists
Published: October 2015

Background:Stroke is a significant contributor to morbidity and mortality in the US and other developed nations. Stroke and its side effects are the primary cause of disability in the US and worldwide. Upper limb mobility factors are particularly detrimental to activities of daily living. Successful treatments to improve post-stroke spasticity are required.Objective:To assess the relevant medical literature related to the use of botulinum toxin type A and post-stroke spasticity of the upper limb.Methods:Literature review utilizing Medline with keywords of botulinum toxin, stroke, spasticity, and upper extremity since 2003.Results:Thirteen criteria-based articles investigated botulinum toxin type and poststroke spasticity of the upper limbs. Discussion: Botulinum toxin type A is an effective agent in reducing post-stroke spasticity of the upper limbs.
Enrollment by Surrogate Authorization into Stroke Genetic Research
Authors: Chen Donna T , Meschia James F , Worrall Bradford B ,   Center for Biomedical Ethics and Humanities, University of Virginia,   Department of Public Health Sciences, University of Virginia,   Department of Psychiatry and Neurobehavioral Sciences, University of Virginia,   Cerebrovascular Division, Mayo Clinic, Jacksonville,   Department of Public Health Sciences, University of Virginia,   Department of Neurology, University of Virginia
Published: October 2015

Continued clinical and translational research is necessary to address unmet clinical needs in stroke and cerebrovascular disease. Ethical and scientific challenges confront these research efforts. Genetic stroke research faces a number of specific challenges related to the legacy of genetic exceptionalism and the reality that stroke frequently impairs decision-making capacity. Maximizing scientific rigor and protecting human subjects have frequently and often erroneously been cast as opposing efforts. In this article, we review the challenges facing stroke genetic research and propose potential approaches given the current state of guidance and regulations. We consider the rationale behind including those with decisional impairment and several options to allow participation of these individuals. Appropriate infrastructure and processes should be established to ensure that genetic information poses minimal risk to individuals, just as has been done to minimize physical risk in non-therapeutic research.
Improving Ambulation in Multiple Sclerosis
Authors: Bethoux Francois ,   Director, Rehabilitation Services, The Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic Foundation
Published: October 2015

Ambulation is frequently affected by multiple sclerosis (MS), and is one of the most valued neurological functions among individuals with MS. While walking speed and walking distance have been used for decades as indicators of disease progression, other aspects of gait disturbance are not routinely assessed, and the impact of walking limitations on the daily activities and quality of life of patients is not fully understood. Recently, rehabilitation techniques, devices, and medications that aim directly at improving walking performance have been tested in individuals with MS. At the same time, clinician-rated and patient-reported measures of ambulation are being validated in this patient population. As a consequence of these advances, clinicians can draw from a growing body of evidence to enhance decision-making and outcome measurement when trying to help MS patients fight one of the most visible consequences of their disease.
Should Monotherapy for Epilepsy Be Reconsidered?
Authors: Faught Edward ,   Professor and Vice Chairman, Department of Neurology, and Director, Epilepsy Center, University of Alabama at Birmingham
Published: October 2015

The critical goal of antiepileptic drug therapy is complete seizure control without side effects. For about half of patients, this goal is achievable with the first drug tried. Standard practice has been to switch to a second monotherapy drug if the first fails. It is time to re-think this strategy because relatively few patients achieve complete control with the second and subsequent monotherapy trials, some patients achieve complete control without intolerable side effects with combination therapy, and the new generations of drugs are easier to use in combination because they are more free of pharmacokinetic and pharmacodynamic interactions. An unanswered question is which combinations are most effective for seizure control. Not all patients are appropriate for polytherapy; some are reasonable candidates for additional monotherapy trials. However, if a polytherapy regimen is working, the wisest plan is often to continue it. Monotherapy still rules, but ‘polypharmacy’ as a pejorative term should be scrapped.
Tools for Managing Migraine
Authors: Cady Roger K , Farmer Kathleen ,   Director,   Psychologist, Headache Care Center, Springfield
Published: October 2015

Migraine diagnostic rates are less than 50%. To assist clinicians with screening, diagnosis, and management, migraine tools have been developed; this article reviews these tools. For diagnosis, ID Migraine, Impact-based Recognition, 3-Question Headache Screen, and the Menstrual Migraine Assessment Tool are summarized. Calendars and diaries are discussed as ways to help patients identify their pattern of headaches and the effectiveness of the treatment plan. Impact and disability are measured by Migraine Disability Assessment (MIDAS), Headache Impact Test 6 (HIT-6), Migraine Assessment of Current Therapy (Migraine ACT), and Staging Questionnaire. The goal of these tools is to assist migraineurs to become responsible decision-makers in terms of therapeutic choices. Tools enable individuals to see how changes in lifestyle as well as medication can lead to health between less frequent attacks of migraine.
Treatment and Management of Migraine—The Road Ahead
Authors: Hutchinson Susan L , Tepper Stewart J ,   Director and Founder, Orange County Migraine & Headache Center, and Associate Clinical Professor, Department of Family Medicine, University of Califiornia-Irvine Medical Center,   Professor of Medicine (Neurology), Cleveland Clinic Lerner College of Medicine, and Director of Research, Center for Headache and Pain, Cleveland Clinic Neurological Institute
Published: October 2015

The road ahead for migraine treatment depends on targeting pharmacological therapies to known pathophysiological mechananisms. Acute medications of the future may include calcitonin gene-related peptide antagonists, various glutamate antagonists, and serotonin 1F receptor agonists. New formulations of older medications include effervescent diclofenac, an orally inhaled dihydroergotamine, and sumatriptan iontophoretic patch and needless injection, all either approved in the US or in phase III trials. Preventive future treatments may include the use of botulinum neurotoxin type A for chronic daily headache and gabapentin enacarbil for episodic migraine, in addition to hormonal treatments and a potential for neuromodulators, but the preventive pipeline is far less developed. In the US, the United Council for Neurologic Subspecialty Board certification for headache medicine should raise quality of care and research in the future.
Functional Information on Meningiomas Through Perfusion Magnetic Resonance Imaging
Authors: Zhang Hao , Zhang Guixiang , Oudkerk Matthijs ,   Department of Radiology, Shanghai Jiaotong University Affiliated First Hospital,   Department of Radiology, University Medical Center Groningen,   Department of Radiology, University Medical Center Groningen,   Department of Radiology, Shanghai Jiaotong University Affiliated First Hospital
Published: October 2015

This article focuses on the use of perfusion magnetic resonance imaging (MRI), and in particular dynamic susceptibility contrast-enhanced MRI (DSCMRI), to assess hemodynamics in meningiomas. We first introduce the basic principles of DSC-MRI and the most popular imaging techniques and perfusion parameters for data analysis of DSC-MRI. We then review the blood supply characteristics of meningiomas and how perfusion MRI is applied in meningiomas to help the subtyping of different meningiomas and to differentiate between benign and malignant meningiomas. Our firsthand experiences are also included. We conclude that DSC perfusion MRI can provide critical information on the vascularity of meningiomas that is not available with conventional MRI. DSC perfusion MRI measurements are helpful in the pre-operative subtyping and grading of meningiomas.
Rivastigmine for the Treatment of Delirium—A Review
Authors: Oldenbeuving Annemarie W , Kort Paul LM de , Roks Gerwin ,   Physician, Department of Intensive Care, St Elisabeth Hospital, Tilburg,   Neurologist, Department of Neurology, St Elisabeth Hospital and TweeSteden Hospital, Tilburg,   Neurologist, Department of Neurology, St Elisabeth Hospital and TweeSteden Hospital, Tilburg
Published: October 2015

Delirium is a common disorder in hospitalized elderly patients. It is a complex neuropsychiatric syndrome with disturbance of consciousness, attention, cognition, and perception. Treatment is based on identification and correction of the underlying cause together with symptomatic treatment. Decreased cholinergic activity is often considered to be one of the essential features in the pathophysiology of delirium. Therefore, correction of this cholinergic deficiency appears to be a promising approach. In this article we describe the pathophysiology of delirium, the pharmacological properties of rivastigmine, and the use of rivastigmine in the prevention and symptomatic treatment of delirium.
Potentially Modifiable Risk Factors in the Development of Alzheimer’s Disease
Authors: Forstmeier Simon , Maercker Andreas ,   Senior Researcher,   Professor, Psychopathology and Clinical Intervention, University of Zurich
Published: October 2015

This article summarises empirical findings on major potentially modifiable risk factors in the development of Alzheimer’s disease (AD), drawing on data from longitudinal epidemiological studies on the incidence of AD or any-cause dementia. Risk factors investigated to date include cognitive ability, motivational ability, emotional health, physical activity, social activity and social network, vascular risk factors and nutrition. The authors find most empirical support for two main clusters of risk factors that also represent potential targets for prevention. First, an active and stimulating lifestyle including cognitive, social, and physical activities reduces the risk of AD. Second, the absence of vascular risk factors such as diabetes, hypertension, hypercholesterol and obesity reduces the risk of AD. More prevention trials are warranted to investigate the preventative effects of an active and stimulating lifestyle on the one hand, and vascular health on the other, in delaying the onset of AD or slowing its progression.
Imaging, Cognition, and Parkinson’s Disease—An Overview
Authors: Mattis Paul , Eidelberg David ,   Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Departments of Neurology and Medicine, North Shore University Hospital, Manhasset, and New York University School of Medicine,   Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Departments of Neurology and Medicine, North Shore University Hospital, Manhasset, and New York University School of Medicine
Published: October 2015

Although the clinical diagnosis of Parkinsons disease (PD) is defined by motor symptoms, cognitive dysfunction is a common manifestation of this disease and an important contributor to functional disability. Functional brain imaging tools have proved valuable in the study of cognitive impairment in PD. Recent advances in imaging methodology and analysis have provided novel insights into the pathophysiology of cognitive decline in these patients. This review summarizes how positron emission tomographic (PET) imaging of metabolic activity in the rest state has enhanced understanding of cognitive dysfunction in PD. This tool has also created the basis for an objective biomarker for use in clinical trials of new therapeutic agents for this disease manifestation. Moreover, insights gained from the use of specific radiotracers targeting the dopaminergic and cholinergic neurotransmitter systems will be discussed, as well as findings fromin vivodetection of amyloid-beta.
Maldistribution of Neurofilaments, Disease Pathogenesis, and Amyotrophic Lateral Sclerosis
Authors: Perrot Rodolphe , Julien Jean-Pierre ,   Post-doctoral Fellow,   Professor and Canada Research Chair, Department of Anatomy and Physiology, Research Center, Laval University Hospital Center
Published: October 2015

Accumulations of neuronal intermediate filaments (IFs) are a characteristic of many human neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). However, IF formation and the contribution of IF aggregates to the pathogenesis of ALS remain unclear. Here, we review the possible mechanisms underlying the formation of IF accumulations and the mouse models that have been used to investigate the role of IF proteins in ALS pathogenesis.
TDP–43, Protein Aggregation, and Amyotrophic Lateral Sclerosis
Authors: Kabashi Edor , Valdmanis Paul N , Daoud Hussein , Belzil Véronique V , Dion Patrick A , Rouleau Guy A ,   Center of Excellence in Neuromics, University of Montréal, Reserch Center, Montréal University Hospital Center, Notre-Dame Hospital,   Center of Excellence in Neuromics, University of Montréal, Reserch Center, Montréal University Hospital Center, Notre-Dame Hospital,   Center of Excellence in Neuromics, University of Montréal, Reserch Center, Montréal University Hospital Center, Notre-Dame Hospital,   Center of Excellence in Neuromics, University of Montréal, Reserch Center, Montréal University Hospital Center, Notre-Dame Hospital,   Center of Excellence in Neuromics, University of Montréal, Reserch Center, Montréal University Hospital Center, Notre-Dame Hospital,   Center of Excellence in Neuromics, University of Montréal, Reserch Center, Montréal University Hospital Center, Notre-Dame Hospital
Published: October 2015

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder and the third most common neurodegenerative cause of adult death after Alzheimers and Parkinsons diseases. TAR DNA binding protein (TDP-43) has been found to be a major component of inclusion bodies in motor neurons of ALS patients. Inclusion bodies are protein aggregates considered a pathological hallmark of neurodegeneration. Our group and eight independent research groups screened TDP-43 for mutations. Overall, 19 missense mutations and one truncating mutation were identified only in ALS patients. These mutations were not found in a considerable number of controls sequenced in several independent studies. Ten of these mutations were found in patients with a family history of ALS. To further support a pathogenic role, the mutations segregated with the disease in three families, including one family with a significant logarithm of odds (LOD) score. Nineteen of these 20 mutations are located in the C-terminus of the TDP-43 protein. These mutations could disrupt several of the already known functions of TDP-43, including nuclear localization, exon splicing, and RNA and heterogenous ribonucleoprotein particle (hnRNP) binding, or could introduce a novel gain of function that is toxic to motor neurons. In the future, animal and cellular models using these mutations should elucidate the role of TDP-43 mutations in ALS pathogenesis and could provide new means to test pharmaceutical compounds for this neurological disease.
Early Diagnosis of Post–stroke Spasticity and Treatment Options
Authors: Patel Atul T ,   Medical Director, The Rehabilitation Institute of Kansas City, and Physiatrist, Kansas City Bone and Joint Clinic
Published: October 2015

Stroke is a leading cause of long-term disability. As a consequence of stroke and associated upper motor neuron (UMN) syndrome, stroke survivors are often left with muscle overactivity, including spasticity. Post-stroke spasticity often has a negative impact on functional activities and daily living, and is frequently accompanied by pain and abnormal limb postures and contractures. Spasticity can be beneficial occasionally but usually is detrimental to a patients function. Several factors need to be considered in the evaluation and management of these patients. This article discusses the various instruments and methods of assessing patients with post-stroke spasticity, as well as the spectrum of current treatment options, including the potential side effects.
Biomarkers of Ischemic Stroke
Authors: Jickling Glen , Xu Huichun , Sharp Frank ,   Fellow,   Fellow,   Professor, Department of Neurology and MIND Institute, University of California at Davis
Published: October 2015

The diagnosis and management of patients with ischemic stroke is primarily based on clinical assessment in conjunction with imaging tests. Development of molecular biomarkers as additional tools to support a clinical diagnosis, identify patients at risk of disease, and help guide patient treatment and prognosis would be of great value. Currently, no such biomarkers are used in the management of patients with ischemic stroke; however, several promising proteomic and genomic markers have been identified, as presented in this review.
Coated–platelets in Ischemic Stroke
Authors: Prodan Calin I , Dale George L ,   Associate Professor, Veterans Affairs Medical Center, and Department of Neurology, University of Oklahoma Health Sciences Center,   Professor, Department of Medicine, University of Oklahoma Health Sciences Center
Published: October 2015

While platelets are acknowledged as critical components of ischemic stroke pathophysiology, little is known about the role of platelet reactivity or platelet subclasses in stroke. Coated-platelets are a pro-thrombotic subclass of platelets, levels of which can vary substantially among individuals. Recently, coated-platelets were observed to be elevated in cortical stroke patients and decreased in lacunar stroke patients, thereby providing for the first time a biochemical marker distinguishing these two stroke subtypes. This article reviews the primary observation as well as the clinical and epidemiological implications of this finding.
Simvastatin for the Prevention of Delayed Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage
Authors: Kronfeld Kassi , Hsiang-Yi Chou Sherry ,   Biomedical Science Program, Tufts University School of Medicine,   Staff Physician, Division of Cerebrovascular Diseases and Critical Care Neurology, Department of Neurology, Brigham and Womens Hospital, Harvard Medical School
Published: October 2015

Aneurysmal subarachnoid hemorrhage (SAH) affects over 30,000 people annually in the US and is responsible for 27% of all stroke-related potential life-years lost before 65 years of age. Delayed cerebral vasospasm, defined as the narrowing of the cerebral arteries at the base of the brain, can occur several days after the initial SAH and cause significant additional morbidity and mortality. Currently, preventive and therapeutic options for delayed cerebral vasospasm are limited and may involve high risk. Oral nimodipine is the only therapeutic agent proven to modestly improve outcome following SAH in multicenter randomized clinical trials. Statins have pleiotropic effects targeting many known pathways in cerebral vasospasm pathogenesis and show promise as potential new therapeutic agents for delayed vasospasm in preliminary animal studies, while results from human data are mixed. In this article, we review the known pathogenic mechanisms of delayed cerebral vasospasm, pre-clinical animal studies on statin use and delayed cerebral vasospasm, and results from human studies to date.
Autonomic Nervous System Monitoring of Patients with Excess Parasympathetic Responses to Sympathetic Challenges—Clinical Observations
Authors: Tobias Hal , Vinitsky Alan , Bulgarelli Robert J , Ghosh-Dastidar Samanwoy , Colombo Joe ,   Neurologist, Private Practice, Stuart, Florida,   Primary Care Physician, Private Practice, Gaithersburg, Maryland,   Director, Integrative Cardiology, Cardiology Division, Riddle Memorial Hospital,   ANSAR Medical Technologies, Inc.,   ANSAR Medical Technologies, Inc.
Published: October 2015

A common assumption regarding the autonomic nervous system is that one branch either opposes the other or does not respond during physiological challenges. Recently, this assumption has been challenged based on clinical observations of unprovoked parasympathetic (P) excess (PE) during sympathetic (S) stimulation, an abnormal response. Over a three-year period, serial autonomic profiling of 1,340 patients was performed using the P and S method, which yields independent measures of P and S activity obtained from timefrequency analyses of respiratory activity and heart rate variability (ANX 3.0, ANSAR Medical Technologies, Inc., Philadelphia, PA). Within this cohort, patients with PE reported symptoms of sleep difficulties, poor peripheral circulation, general malaise, depression, frequent headache or migraines, gastrointestinal upset, and dizziness when standing. However, they demonstrated normal heart rate and blood pressure and no other apparent causes for their symptoms. The results of this study highlight the clinical effects of PE and indicate that, depending on patient history, carvedilol may be effective for patients with cardiovascular disease (CVD) and low-dose anticholinergics for patients without CVD. In cases where end-organ effects are not yet presented, patients may be weaned from therapy once PE is resolved.
Effective Rehabilitation Methods in Patients with Multiple Sclerosis
Authors: Bennett Susan E ,   Clinical Associate Professor, Department of Rehabilitation Science and Department of Neurology, University at Buffalo, State University of New York
Published: October 2015

The role of rehabilitation in managing symptoms of multiple sclerosis (MS) and promoting functional recovery has grown exponentially over the past 12 years. Evidence now supports strength and aerobic training for individuals with mild or moderate disease. An emerging body of evidence suggests that exercise may play a role in the production of brain-derived neurotrophic factor in individuals with MS, and the combination of pharmacological management and rehabilitation may produce better outcomes than one therapeutic intervention alone. Rehabilitation and exercise should be a major focus in the comprehensive management of MS.
Natalizumab (Tysabri®)—Re-defining Efficacy in Multiple Sclerosis—Data from Clinical Trials to Post-marketing Experience
Authors: Bates David ,   Professor of Clinical Neurology, Department of Neurology, The Institute of Neuroscience, Newcastle University
Published: October 2015

Multiple sclerosis (MS) is a chronic, disabling condition with severe clinical and social consequences. Current first-line disease-modifying treatments have limited efficacy and do not halt long-term disease progression in the majority of patients. Natalizumab (Tysabri®) is the only monoclonal antibody licensed for use in relapsingremitting MS (RRMS). It is regarded by many neurologists as the most effective MS drug on the market today, and has the potential to re-define successful MS therapy. Its efficacy has been demonstrated both in large-scale clinical trials and in post-marketing settings. Beneficial effects include reduction of relapse rates and disease progression, as well as magnetic resonance imaging (MRI) measures of disease activity. Natalizumab treatment has a substantial impact on patient quality of life. Moreover, patients have shown significant improvement following natalizumab treatment, making continuing clinical remission a realistic goal in MS for the first time. However, the benefits of natalizumab must be balanced against risk. Progressive multifocal leukoencephalopathy (PML) is a rare event associated with natalizumab treatment that may be minimized with a risk management plan to educate physicians on patient selection and management.