bluuebunny/crossref_metadata_2025 huggingface dataset:
Rituximab for the Treatment of Graves’ Orbitopathy
Authors: Salvi Mario , Vannucchi Guia , Beck-Peccoz Paolo ,   Senior Research Associate,   Investigator,   Professor of Endocrinology, Department of Medical Sciences, Endocrine Unit, University of Milan and Fondazione Ca’ Granda IRCCS, Milan
Published: October 2015

The contribution of B-cells to human autoimmune disease has recently been underscored because of the therapeutic benefit of B-cell depleting therapies. B-cells are involved in the production of autoantibodies, and in CD4+ T-cell activation, control of T-cell function, and inflammation through cytokine production. B-cells are also important antigen-presenting cells. Rituximab (RTX) has been used off-label in various autoimmune disorders and has been shown to effectively deplete mature and memory CD20+ B-cells, but not long-lived plasma cells. The rationale behind the use of RTX in Graves’ disease (GD) and Graves’ orbitopathy (GO) relies on its putative effect on pathogenic autoantibodies causing hyperthyroidism. RTX in patients with active GO has been shown to have a significant effect on the inflammatory activity and severity of GO. However, caution is suggested before proposing RTX as a novel therapeutic tool in this disease until randomized controlled trials are available. Should preliminary observations be confirmed, an optimal strategy for controlling the progression of GO would be to pursue B-cell depletion shortly after diagnosis, rather than only as an alternative therapeutic option when standard immunosuppression has failed.
Recent Management Controversies in Osteoporosis
Authors: Hudec Susan M DeLange , Camacho Pauline M ,   Endocrinology Fellow, Loyola University Medical Center,   Associate Professor of Medicine and Director, Loyola University Osteoporosis and Metabolic Bone Disease Center, Loyola University Medical Center
Published: October 2015

Osteoporosis is an important health concern that leads to significant morbidity for millions of Americans. Most recently, several areas of osteoporosis treatment have been debated, including calcium and vitamin D supplementation, duration of bisphosphonate therapy, and frequency of bone mineral density measurement. This article reviews the recent studies on these controversial topics and presents the current practice guidelines.
Advances in Treatment Options for Polycystic Ovary Syndrome
Authors: Lathief Sanam , Pal Lubna ,   Resident, Internal Medicine, Hospital of Saint Raphael, New Haven, Connecticut,   Associate Professor and Director, Program for Polycystic Ovarian Syndrome and Director, Program for Reproductive Aging and Bone Health, Yale Reproductive Endocrinology, Yale University School of Medicine, New Haven, Connecticut, US
Published: October 2015

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy seen in women of reproductive age. Clinical concerns relating to PCOS range from ovulatory infertility and menstrual disorders to risk of diabetes and cardiovascular disease. Hormonal contraceptives have been the mainstay of the management of common PCOS symptoms, such as menstrual irregularity and clinical stigmata of androgen excess (i.e., hirsutism and acne). An appreciation of the relevance of metabolic pathways in the pathophysiology of PCOS is relatively recent, and has translated into an expansion of the therapeutic strategies available for the management of PCOS. Insulin sensitizers were one of the first metabolic modulators to be incorporated in the clinical management paradigm, albeit with mixed results. Recognizing that insulin resistance is central to the pathophysiology of PCOS, newer agents—e.g., thiazolidinediones— followed, with almost comparable efficacy to metformin. Statins and most recently incretins constitute novel therapies with distinct metabolic targets that seem to hold promise in the management of PCOS. In tandem with the expansion in pharmaceuticals, a host of complementary and alternative medical therapies have generated interest for purported promise in the management of PCOS, including vitamin D, acarbose, and myo-inositol. The therapeutic options for managing PCOS-related infertility have also expanded. Clomiphene citrate (CC) has long been the first-line strategy for ovulation induction in the setting of anovulatory infertility; however, aromatase inhibitors are fast gaining acceptance as an ovulation induction strategy, with results comparable or even better than those seen with CC. An increasing level of therapeutic sophistication is reflected in ovarian stimulation protocols judiciously using gonadotropins, gonadotropin-releasing hormone antagonists, the procedure of ovarian drilling, and assisted reproductive technologies within vitrooocyte maturation.
Using Professional Continuous Glucose Monitoring to Modify Eating Behavior in Patient on ‘Heart Healthy’ Diet
Authors: Wolpert Howard ,   Senior Physician, Joslin Diabetes Center, and Assistant Professor, Harvard Medical School, Boston, Massachusetts, US
Published: October 2015

Diabetes management is often complex and requires the involvement of various team members and technology for behavior change and successful outcomes. This paper shows how one provider utilized a team approach and the use of professional continuous glucose monitoring to help this patient identify needed behavior change to improve outcomes.
Fatigue in Adults with Type 2 Diabetes—An Overview of Current Understanding and Management Approaches
Authors: Fritschi Cynthia , Fink Anne M ,   Assistant Professor,   Research Associate, Department of Biobehavioral Health Science, University of Illinois at Chicago College of Nursing, Chicago, Illinois, US
Published: October 2015

Patients with type 2 diabetes often experience fatigue, which impacts their self-care and quality of life. There are few data supporting a relationship between fatigue and glucose homeostasis, but fatigue in type 2 diabetes has been associated with higher body mass index (BMI), depression, physical inactivity, sleep disturbances, and chronic low-grade inflammation. Although links between fatigue and inflammation are documented in other disease populations, little is known about inflammatory mechanisms specific to type 2 diabetes and associated treatment modalities for type 2 diabetes-related fatigue. Herein we review existing knowledge about fatigue in type 2 diabetes and potential pharmacologic and behavioral therapies.
Future Perspectives in Glucose Monitoring Sensors
Authors: Frontino Giulio , Meschi Franco , Bonfanti Riccardo , Rigamonti Andrea , Battaglino Roseila , Favalli Valeria , Bonura Clara , Ferro Giusy , Chiumello Giuseppe ,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy,   Department of Pediatrics, San Raffaele Scientific Institute, Milan, Italy
Published: October 2015

The prevalence of diabetes is increasing. Improved glucose control is fundamental to reduce both long-term micro- and macrovascular complications and short-term complications, such as diabetic ketoacidosis and severe hypoglycemia. Frequent blood glucose monitoring is an essential part of diabetes management. However, almost all available blood glucose monitoring devices are invasive. This determines a reduced patient compliance, which in turn reflects negatively on glucose control. Therefore, there is a need to develop noninvasive glucose monitoring devices that will reduce the need of invasive procedures, thus increasing patient compliance and consequently improving quality of life and health of patients with diabetes.
Use of Automated Bolus Calculators for Diabetes Management
Authors: Schwartz Frank L , Marling Cynthia R ,   Professor of Endocrinology, The Diabetes Institute, Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio, US,   Associate Professor, School of Electrical Engineering and Computer Science, Russ College of Engineering and Technology, Ohio University, Athens, Ohio, US
Published: October 2015

Less than 30 % of patients with diabetes who are on insulin therapy achieve target glycated hemoglobin (HbA1C) levels. Automated bolus calculators (ABCs) are now almost universally used for patients on insulin pump therapy to calculate pre-meal insulin doses. Use of ABCs in glucose monitors and smart phone applications have the potential to improve glucose control in a larger population of individuals with diabetes on insulin therapy by overcoming the fear of hypoglycemia and assisting those with low numeracy skills.
Glycemic Variability in Type 1 DiabetesDoes It Matter?
Authors: Schwartz Frank L , Marling Cynthia R ,   Professor of Endocrinology, The Diabetes Institute, Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio, US,   Associate Professor, School of Electrical Engineering and Computer Science, Russ College of Engineering and Technology, Ohio University, Athens, Ohio, US
Published: October 2015

Clinical assessment of glycemic variability (GV) attempts to measure factors that may be contribute to tissue damage and the complications of diabetes that are not measured in glycosylated hemoglobin (HbA1C). Physicians managing patients with diabetes immediately understand the concept of GV; however, how it is assessed in clinical research trials and whether it has any predictive power in patients with type 1 diabetes is controversial and uncertain. This review is intended to help the reader understand the various GV metrics currently being reported in the literature, the potential mechanisms by which GV may contribute to the pathogenesis of the long-term complications of diabetes, and, finally, the evidence that reducing GV is beneficial to patients with type 1 diabetes.
Obstructive Sleep Apnoea and Type 2 Diabetes
Authors: Tahrani Abd A , Ali Asad ,   NIHR Clinician Scientist, Centre of Endocrinology, Diabetes and Metabolism, University of Birmingham and Honorary Consultant Physician, Department of Diabetes and Endocrinology, Heart of England NHS Foundation Trust, Birmingham, UK,   Consultant Respiratory Physician, Department of Respiratory Medicine, University Hospital of Coventry and Warwickshire, Coventry, UK
Published: October 2015

With the growing prevalence of obesity, the burden of type 2 diabetes is increasing. Obstructive sleep apnea (OSA) is a very common medical condition that is associated with increased risk for cardiovascular disease and mortality. Obesity is a common risk factor for OSA and type 2 diabetes and hence it is not surprising that OSA and type 2 diabetes are interlinked. OSA has been shown to be an independent risk factor for the development of incident pre-diabetes/type 2 diabetes. OSA is also associated with worse glycemic control and vascular disease in patients with type 2 diabetes. However, evidence for the benefits of OSA treatment in patients with type 2 diabetes is still lacking. The aim of this article is to provide an overview of OSA, the relationships between OSA and dysglycemia and the impact of OSA in patients with type 2 diabetes, highlighting recent advances in the field.
Energy Flux and its Role in Obesity and Metabolic Disease
Authors: Hand Gregory A , Blair Steven N ,   Professor, Department of Exercise Science,   Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina, US
Published: October 2015

In order to reverse the global obesity pandemic, there is a need for an enhanced understanding of the energy dynamics that underlie the problem. To maintain a stable body weight, energy intake must, over time, match or equal energy expenditure, a concept known as energy balance. Obesity results from a positive state of energy balance (i.e. when energy intake exceeds energy expenditure). However, recent research suggests that strategies to combat obesity should focus on energy flux (the amount of calories going through a system), rather than energy balance alone. In other words, it is easier to maintain weight loss at higher levels of physical activity. Recent findings suggest that a high energy flux, maintained by increasing energy expenditure, can improve an individual’s metabolic profile without changing weight. Further understanding of this concept may help in the design of interventions to achieve and maintain a healthy weight.
A Novel Small Molecule Drug Derived from Methimazole (Phenylmethimazole) that Targets Aberrant Toll-like Receptor Expression and Signaling for the Potential Prevention or Treatment of Diabetes Mellitus and Non-alcoholic Fatty Liver Disease
Authors: McCall Kelly D , Schwartz Frank L ,   Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Diabetes Institute, Ohio University, Athens, Ohio, US,   Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Diabetes Institute, Ohio University, Athens, Ohio, US
Published: October 2015

Toll-like receptors (TLRs) are pattern-recognition receptors located on the surface or within (endosome) immune cells (dendritic), whose function is to recognize pathogens from the environment and mediate both the innate and acquired immune responses. Environmental activation of TLRs in nonimmune cells is now recognized as a significant pathway that mediates the loss of self-tolerance in autoimmune diseases, as well as inflammationinduced cell damage in many chronic diseases. We have developed a small molecule drug derived from methimazole, phenylmethimazole (C10), which interferes with the environmental induction of TLR signaling in nonimmune cells and is an active inhibitor of pathologic inflammation in many animal disease models. This article has been written to introduce clinicians to TLR function and the potential therapeutic role that their inhibition could play in many inflammatory/autoimmune diseases, including diabetes and nonalcoholic fatty liver disease (NAFLD).
Lifestyle Medicine—An Emerging New Discipline
Authors: Kushner Robert F , Mechanick Jeffrey I ,   Professor of Medicine, Northwestern University Feinberg School of Medicine; Director, Center for Lifestyle Medicine, Northwestern Medicine, Chicago, Illinois, US,   Clinical Professor of Medicine; Director, Metabolic Support, Division of Endocrinology, Diabetes, and Bone Disease, Icahn School of Medicine at Mount Sinai, New York City, New York, US
Published: October 2015

Unhealthful lifestyle behaviors are a primary source of the global burden of noncommunicable diseases (NCDs) and account for about 63 % of all global deaths. Recently, there has been an increased interest in evaluating the benefit of adhering to low-risk lifestyle behaviors and ideal cardiovascular health metrics. Although a healthful lifestyle has repeatedly been shown to improve mortality, the population prevalence of healthy living remains low. The new discipline of lifestyle medicine has recently emerged as a systematized approach for the management of chronic disease. The practice of lifestyle medicine requires skills and competency in addressing multiple health risk behaviors and improving self-management. This article focuses on the effects of a healthful lifestyle on chronic disease and defining lifestyle medicine as a unique discipline. It also reviews the role of effective providerpatient communication as an essential element for fostering behavior changethe main component of lifestyle medicine. The principles of communication and behavior change are skill based and are grounded in scientific theories and models. Communication and counseling must be contextualized to the patients economic situation, access to care, social support, culture, and health literacy.
New Agents for Multiple Sclerosis and the Difficulties that Lie Ahead
Authors: Jeffery Douglas R ,   Associate Professor, Department of Neurology, Wake Forest University Health Science Center
Published: October 2015

A host of new oral agents are being developed for use in relapsing forms of multiple sclerosis (MS). Although many of these agents may be both safe and effective, they could fail in clinical trials because the population of patients enrolled in such trials may behave in a fashion not taken into account by the statistical assumptions used in trial planning. In recent trials on study relapse, rates have been far lower than those observed in earlier clinical trials. This could decrease the power of a trial and result in failure to meet statistical significance even if the agent in question is effective. The same problem could also result in the failure of trials to meet disability outcomes. If too few patients progress on trial it may be difficult to demonstrate an effect on disability progression. The outcome of current MS clinical trials may stimulate the development of new designs and surrogate markers.
Advances in Treatment Options for High-grade Glioma—Current Status and Future Perspectives
Authors: Merrell Ryan T , Quant Eudocia C , Wen Patrick Y ,   Neuro-oncology Fellow,   Neuro-oncologist,   Neuro-oncologist,   Professor of Neurology, Harvard Medical School, and Director, Center for Neuro-oncology, Dana Farber/Brigham and Womens Cancer Center, and Director, Division of Neuro-oncology, Department of Neurology, Brigham and Womens Hospital
Published: October 2015

High-grade gliomas, including glioblastoma, anaplastic astrocytoma, anaplatic oligodendroglioma, and anaplastic oligoastrocytoma, account for the majority of malignant primary brain tumors diagnosed in adults. The prognosis for these tumors is poor despite multimodality therapy with surgery, radiation, and/or chemotherapy. This article summarizes treatment options for high-grade glioma, including standard regimens, targeted agents, and novel therapies.
Event-related Potentials and the Diagnosis of Alzheimer’s Disease— The COGNISION™ System
Authors: Casey David A ,   Associate Professor, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine
Published: October 2015

Alzheimer’s disease is a major cause of cognitive decline among older people. Current diagnostic approaches rely primarily on cognitive symptoms. Recently proposed changes in the definition of the disease place more emphasis on the use of biomarkers (such as neuroimaging or cerebrospinal fluid markers) in the hope of allowing earlier and more definitive diagnosis for research and, eventually, clinical purposes. Event-related potentials (ERP) represent another promising biomarker approach. Alzheimer’s disease has been demonstrated to have a recognizable ERP signature. Recent advances in ERP technology may make the process painless, non-invasive and portable. These advantages suggest that ERP should be further considered as a potential biomarker for Alzheimer’s disease.
Continuous Dopaminergic Stimulation in Parkinson’s Disease—What Have We Learned from Positron-emission Tomography?
Authors: Brooks David J , Pavese Nicola ,   Hartnett Professor of Neurology, and Head, Centre for Neuroscience, Department of Medicine, Imperial College London,   Senior Investigator Scientist, Medical Research Council—Neurology PET Group, and Honorary Senior Lecturer, Imperial College London
Published: October 2015

The hypothesis that pulsatile stimulation of striatal dopamine receptors in Parkinson’s disease (PD) induces molecular and physiologic changes in basal ganglia neurons and may contribute to the development of motor complications has led to the design of therapeutic strategies that provide more continuous dopaminergic stimulation. Newer agents and drug-delivery systems such as slow-release preparations, catechol-O-methyltransferase, and monoamine oxidase inhibitor agents, apomorphine, and Duodopa™ infusions represent a significant step towards less pulsatile dopaminergic administration. However, their efficacy in providing steady brain levels of dopaminergic stimulation in the short and longer term has not yet been proved in patients. This article briefly reviews and discusses the findings of published positron emission tomography (PET) studies that support or oppose the value of continuous dopaminergic stimulation in PD. The potential future value of PET for proof of mechanism in this area is also debated.
Dalfampridine Extended Release Tablets—Clinical Need and Use
Authors: Miller Aaron , Ross Amy Perrin , Gilbart James ,   Medical Director, Corinne Goldsmith Dickinson Center for Multiple Sclerosis and Professor of Neurology, Mount Sinai School of Medicine,   Neuroscience Program Co-ordinator, Department of Neurosciences, Loyola University Chicago,   Senior Medical Writer, Touch Briefings
Published: October 2015

Walking impairment is one of the most serious and frequent problems reported by multiple sclerosis (MS) patients. Treatments to restore walking ability are an unmet clinical need. Dalfampridine, a potassium channel blocker, is the first US Food and Drug Administration (FDA)-approved drug to be indicated specifically to improve walking in patients with MS. In clinical trials the drug showed improved walking speeds, demonstrating efficacy in all four types of MS. In phase III trials, dalfampridine provided significant benefits to 35–43% of treated patients. Therefore, it will be critical to manage patient expectations appropriately.
Measuring Disability Progression with the Multiple Sclerosis Functional Composite
Authors: Krysko Kristen M , O’Connor Paul W ,   Medical Student, Class of 2012, University of Toronto,   Neurologist and Director, Multiple Sclerosis Clinic and Multiple Sclerosis Research, St Michael’s Hospital and Professor of Medicine (Neurology), University of Toronto Abstract
Published: October 2015

The multiple sclerosis functional composite (MSFC) is a three-part quantitative objective measure of neurologic function, measuring leg (timed 25-foot walk [25FTW]), arm (nine-hole peg test [9HPT]), and cognitive (three-second paced auditory serial addition test [PASAT3]) function. The MSFC was developed to be a more sensitive measure of disability than the expanded disability status scale (EDSS) and has excellent reliability. Validity is supported by moderately strong correlations with EDSS, brain atrophy, and quality of life. Advantages of the MSFC include its continuous scale and inclusion of several disease dimensions. Limitations include practice effects, the lack of a visual function component, variations in reference populations, and limited understanding of clinically relevant MSFCz-score changes. MSFCz-score change has been used as a secondary end-point in MS trials, but EDSS progression remains the primary disability outcome. A new approach to MSFC data involves defining MSFC progression as worsening in an MSFC component by 15–20% over three months. With further study, this could be used as a primary disability outcome in future clinical trials.
Diagnosing Autonomic Nervous System Disorders—Existing Guidelines and Future Perspectives
Authors: Lahrmann Heinz , Rocha Isabel , Struhal Walter , Thijs Roland D , Hilz Max ,   Neurologist, Private Practice, Vienna,   Associate Professor, Unit of Autonomic Nervous System, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon,   Neurologist, Autonomic Unit, Department of Neurology and Psychiatry, General Hospital of the City of Linz,   Neurologist, Department of Neurology and Clinical Neurophysiology, Leiden University Medical Center and Department of Neurology and Clinical Neurophysiology, Dutch Epilepsy Clinics Foundation, Heemstede,   Professor of Neurology, Medicine and Psychiatry, Department of Neurology, University of Erlangen-Nuremberg and Departments of Neurology, Medicine and Psychiatry, New York University
Published: October 2015

Primary and secondary autonomic nervous system (ANS) disorders often have a severe adverse effect on the quality of life of patients. Diagnostics for ANS disorders are under represented, despite their common occurrence. Precise history taking is of key importance for ANS evaluation: it may help to rule out differential diagnoses and provide important clues to the underlying ANS disorder. In fact, in conjunction with additional bedside tests, it can achieve a clear diagnosis. The analysis of heart rate variability and the results of the standardized tests that make up the Ewing battery are important means of evaluating the parasympathetic and sympathetic nervous system. In addition, sudomotor testing can be used to evaluate cholinergic sympathetic function, and the spontaneous baroreceptor reflex can be assessed using new computerized techniques. These tests provide valuable information on cardiovascular autonomic control. This paper presents a structured review of current standard techniques for diagnosing ANS disorders.
Epilepsy and Sleep Disorders
Authors: Walker Matthew C , Eriksson Sofia H ,   Professor of Neurology, and Consultant Neurologist,   Consultant Neurologist, Department of Clinical and Experimental Epilepsy, National Hospital for Neurology and Neurosurgery, and Institute of Neurology, University College London
Published: October 2015

There is a close association between sleep and epilepsy. In some epilepsy syndromes, seizures occur predominantly (or even exclusively) during sleep or on awakening. Excessive daytime sleepiness is common in patients with epilepsy and may be due not only to medication but also to nocturnal seizures or concomitant sleep disorders. Sleep disorders such as obstructive sleep apnea can worsen epilepsy, with improvement of seizure control following appropriate treatment of the sleep disorder. Conversely, epilepsy and antiepileptic medication can worsen sleep disorders. Nocturnal epileptic seizures may be difficult to differentiate from parasomnias, in particular non-rapid eye movement parasomnias such as night terrors, sleepwalking and confusional arousals, on history alone since there are semiologic similarities between the two disorders. Schemes have been developed to facilitate differential diagnosis, although this remains a challenge even using the gold standard, video-electroencephalography telemetry.
Ischemic Stroke—Stenting versus Surgery for Carotid Disease
Authors: Pawar Swaroop , Messé Steven R ,   Fellow, Vascular Neurology,   Assistant Professor of Neurology, Department of Neurology, Hospital of the University of Pennsylvania
Published: October 2015

Extracranial internal carotid artery stenosis is one of the most common and best studied causes of stroke. Revascularization with carotid endarterectomy (CEA) has been shown to be beneficial for patients with severe stenosis associated with stroke or transient ischemic attack (TIA) and for many patients with moderate stenosis associated with stroke or TIA. CEA has also been shown to be beneficial for patients with asymptomatic severe stenosis if they have a reasonable expected lifespan and surgical risk, but the benefit is greater for men compared with women. Carotid angioplasty and stenting (CAS) has become a viable alternative procedure for carotid revascularization with less risk of major bleeding complications and cranial nerve injury. Randomized studies of CEA versus CAS have found that the endovascular approach is associated with a lower risk of myocardial infarction but a higher risk of peri-procedural stroke which has a greater impact on long-term quality of life. Thus, recommending CEA or CAS must be based upon individual patient characteristics and their preferences, but at this point it appears that most patients should still be receiving CEA if an intervention is required.
Intra-operative Imaging Techniques During Surgical Management of Gliomas
Authors: Tarapore Phiroz E , Chang Edward F , Berger Mitchel S ,   Resident,   Assistant Professor of Neurological Surgery and Physiology,   Professor and Chairman, Department of Neurological Surgery, University of California, San Francisco
Published: October 2015

The goal of glioma surgery is to maximize tumor removal while preserving existing function. Intra-operative imaging techniques play an important part in achieving this goal. This article surveys those techniques and discusses the indications, advantages, and drawbacks of each. Structural techniques such as intra-operative magnetic resonance imaging (MRI), ultrasound, diffusion tensor imaging, and 5-aminolevulinic acid staining offer anatomic information. Functional techniques such as functional MRI, magnetoencephalography, and transcranial magnetic stimulation provide information about the functionality of brain regions. When incorporated into a frameless stereotactical neuronavigation system, these modalities increase both the efficacy and safety of glioma surgery by allowing the surgeon to achieve the most extensive and safe resection possible.
Advances in Surgical Options for Medically Refractory Epilepsy
Authors: Gigante Paul R , Goodman Robert R ,   Resident, Department of Neurological Surgery, Columbia University Medical Center, New York, US,   Chairman, Department of Neurosurgery, St Luke's-Roosevelt Hospital Center and Associate Professor of Clinical Neurological Surgery, Department of Neurological Surgery, The Neurological Institute of New York, Columbia University Medical Center, New York, US
Published: October 2015

The evolution of surgical treatment for medically refractory epilepsy (MRE) has been influenced over the last decade by substantial advancements in imaging- and device-related technology, as well as an expanding assemblage of prospective data that support the utilization of surgery for MRE. These data, which have grown to include randomized trials and long-term follow up for established surgery, as well as large series for investigational procedures, have demonstrated safe, efficacious results with proper patient selection. Prospective randomized trials of three surgically implanted neuromodulatory devices, vagus nerve stimulators, deep brain stimulators, and responsive neurostimulators, have demonstrated safety and significant seizure frequency reduction. Numerous studies have provided strong evidence for the efficacy and safety of temporal lobe resective surgery and recent studies have focused on applying alternative approaches to open resective surgery for patients presumed to have a medial temporal seizure focus. These alternatives include stereotactic radiosurgery, radiofrequency ablation, and a magnetic resonance imaging (MRI)-guided laser technique for thermal ablation. Current evidence for these new surgical options for the treatment of medically refractory epilepsy will be presented and discussed.
Childhood Absence Epilepsy—A Review of Treatment Strategies and Perspectives for the Future
Authors: Rheims Sylvain , Ryvlin Philippe ,   Neurologist,   Professor, Department of Functional Neurology and Epileptology and Institute for Children and Adolescents with Epilepsy, Hospices Civils de Lyon, and INSERM U1028, CNRS UMR5292, Translational and Integrative Group in Epilepsy Research, Lyon Neuroscience Research Center, Lyon, France
Published: October 2015

Childhood absence epilepsy (CAE) is one of the most common forms of pediatric epilepsy. However, there is still a gap between the prevalence of CAE in pediatric epilepsies and the paucity of available data regarding its therapeutic management. Only nine randomized controlled trials have been published in the field over the past four decades, with many suffering from major methodologic limitations. A recent large randomized double-blind controlled trial reported that ethosuximide and sodium valproate are the most effective anti-epileptic dugs in CAE and that cognitive performance appears to be better with ethosuximide than with sodium valproate. Although lamotrigine also demonstrated anti-absence properties in the same trial, it proved to be significantly less efficacious than ethosuximide or sodium valproate. Despite these recent advances, several questions, including long-term outcomes, management of refractory CAE and treatment duration, remain unanswered and further studies are required to refine therapeutic decisions.
Management of Neuropathic Pain—Current Insights and Future Perspectives
Authors: Smith Howard S , Damla Kara Sukriye , Argoff Charles E ,   Professor and Academic Director of Pain Management, Department of Anesthesiology, Albany Medical College, New York, US,   Undergraduate Student, University of Rochester, New York, US,   Professor of Neurology and Director, Comprehensive Pain Center, Department of Neurology, Albany Medical College, New York, US
Published: October 2015

The management of neuropathic pain remains very challenging and very much an art. Despite the publication of multiple consensus guidelines on the management of neuropathic pain, a significant subpopulation of patients with neuropathic pain are not afforded adequate relief, employing various treatment algorithms with conventional pharmacologic therapeutic strategies. First-line agents for the treatment of neuropathic pain include: tricyclic antidepressants, selective serotonin/norepinephrine re-uptake inhibitors, calcium channel α2-δ ligands and, in certain cases of focal neuropathic pain, a lidocaine patch. Novel analgesics under development may include: purinergic receptor modulators, cannabinoid receptor modulators, neurokinin-1 (NK-1) receptor modulators, glial modulators, rostral ventral medulla ‘on-cell’ modulators, chemokine receptor modulators, toll-like receptor modulators, modulators of tetrahydrobiopterin synthesis, and/or chemically re-engineered conotoxins. It is hoped that future agents and/or combinations of agents may be helpful to this refractory subpopulation.
Dopamine Agonists and Impulse Control Disorders in Parkinson’s Disease
Authors: Claassen Daniel O , Kanoff Kristen , Wylie Scott A ,   Assistant Professor,   Research Assistant, Department of Neurology, Vanderbilt University, Nashville, Tennessee, US,   Assistant Professor
Published: October 2015

The emergence of the behavioral syndrome known as impulse control disorder (ICD) in Parkinsons disease (PD) has increasingly been associated with dopamine agonist (DAA) use. Clinical reports emphasize the presence of excessive, disruptive, and atypical behaviors in PD patients that resolve after discontinuation or reductions of DAA therapy. The severity of these behaviors has resulted in a heightened clinical vigilance, especially in patients prescribed DAA. This review will discuss the historical rationale for the clinical use of DAA in PD, highlighting the increased association of ICD in patients prescribed DAA therapy. The association between DAA and the emergence of ICD supports the hypothesis that altered mesocorticolimbic function, further emphasized in behavioral and imaging studies, may account for the distinct compulsive hedonic behaviors that characterize the clinical features of this disorder. While the first-line treatment option is reduction and discontinuation of DAA therapy, other therapeutic options are discussed.
Nutrition in Stroke Prevention
Authors: Spence J David ,   Professor of Neurology and Clinical Pharmacology, Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
Published: October 2015

Nutrition is far more important than most physicians and patients recognize. Maintaining a healthy weight, reducing dietary cholesterol, avoiding egg yolks, and consuming a Cretan Mediterranean diet substantially reduce the risk for stroke. Besides the very high cholesterol content of egg yolks (more than the recommended daily intake of 200 mg of cholesterol in a single large egg yolk), it is now apparent that phosphatidylcholine (lecithin, 250 mg per egg yolk) is converted by intestinal bacteria to trimethylamine, which in turn is oxidized in the liver to trimethylamine n-oxide (TMAO), which is pro-atherosclerotic in animal models and increases the risk for cardiovascular events in patients at risk for coronary disease. Unrecognized metabolic deficiency of vitamin B12 is very common, and frequently missed, because a normal serum B12 is not a reliable test for adequacy of B12. Besides neuropathy, myelopathy, and dementia, B12 deficiency increases the risk for stroke by raising levels of total homocysteine (tHcy). Despite widespread misunderstanding of the complex issues, it is increasingly clear that B vitamin therapy to reduce homocysteine does reduce the risk for stroke. However adequacy of B12 dosing and renal impairment determine the response to B vitamin therapy: cyanocobalamin is beneficial in patients with normal kidney function, but harmful in those with renal impairment (GFR<50). Methylcobalamin should be used in patients with renal impairment.
Biological Agents for Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Authors: Stübgen Joerg-Patrick ,   Professor of Clinical Neurology/Attending Neurologist, Department of Neurology and Neuroscience, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York, US
Published: October 2015

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a term for a group of acquired, immune-mediated inflammatory demyelinating disorders of the peripheral nervous system. Most patients with CIDP respond to first-line therapy with intravenous immunoglobulin (IVIG), plasmapheresis, and/or corticosteroids. Conventional immunosuppressive drugs are of no proven benefit. Biological agents directed at key aspects of the CIDP immunopathogenic pathway have gained increasing attention due to the unpredictable efficacy and overall health risks of non-targeted immunosuppressive drugs. Presently, there exists insufficient clinical experience with biological therapy to allow specific treatment recommendations for CIDP. The challenge remains to identify drug-naïve or treatment-resistant CIDP patients who will most likely respond to targeted immunotherapy.
Anesthetic Concerns for Patients Undergoing Neurosurgical Procedures Utilizing Intra-operative Magnetic Resonance Imaging
Authors: McClain Craig D , Chimbira Wilson T ,   Senior Associate in Perioperative Anesthesia, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Childrens Hospital, Boston, Massachusetts and Assistant Professor of Anesthesia, Harvard Medical School, Boston, Massachusetts, US,   Assistant Professor of Anesthesiology, Assistant Professor of Anesthesiology,
Published: October 2015

Intra-operative magnetic resonance imaging (ioMRI) is an evolving technology that offers precise intra-cranial lesion localization and intra-operative navigation by combining the high-resolution imaging capabilities of MRI with an operative suite. Developed in the 1990s, ioMRI presents caregivers with a variety of unique challenges revolving around performing surgical procedures in an operating theatre with a high-strength magnetic field. Different types of ioMRI systems exist, differentiated by the relative mobility of the patient and magnet. As with any MRI environment, safety is of paramount concern. Published safety guidelines exist from both the American College of Radiology and the American Society of Anesthesiologists. A variety of checklists can be used to enhance the safety of the ioMRI suite. There are a variety of anesthetic considerations when caring for patients in this environment including concerns related to the anesthesia equipment, the patient, and the general MRI environment. A multidisciplinary approach can encourage safety and efficiency in this unique operating room. The purpose of this review is to discuss the variety of topics that anesthesiologists need to consider using this technology, including the indications, specific equipment considerations, and unique safety aspects of caring for patients in the ioMRI suite. While performing surgery in a high-strength magnetic field environment carries its own special risks, each type of ioMRI suite presents its own unique challenges to patient safety. Although the challenges are significant, safe care and optimal outcomes are certainly possible with appropriate understanding of the factors unique to the ioMRI environment, good communication, a collaborative approach, and proper procedural planning.
Low Doses of Melatonin Promote Sleep Onset and Maintenance in Older People—An Update
Authors: Wurtman Richard J ,   Massachusetts Institute of Technology, Cambridge, Massachusetts, US
Published: October 2015

Plasma melatonin levels in young adults are about 10-fold higher during the night than during daylight hours, and these high levels promote both the onset of sleep at bedtime and the speedy resumption of sleep after premature nocturnal awakenings. With aging, melatonins nocturnal secretion from the pineal gland declines, as do plasma melatonin levels, total sleep time, and sleep efficiency. A very small dose (0.3 mg) of melatonin is usually sufficient to restore nighttime plasma melatonin levels to those characteristic of young people, and to accelerate the resumption of sleep after premature awakenings. The much larger doses that are marketed can produce side effects that are not observed when the melatonin in the plasma derives solely from its secretion by the pineal. Very high doses may also desensitize melatonins receptors in the brain, subsequently diminishing melatonins efficacy in promoting sleep. This article updates an earlier summary (Richard J Wurtman, Use of melatonin to promote sleep in older people,US Neurology, 2012;8(1):101) of melatonins utility in promoting sleep among older people.
Parkinson’s Disease Psychosis—A Symptom Complex Signaling Risk for Increased Disability and Caregiver Burden
Authors: Isaacson Stuart H ,   Director, Parkinsons Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida, US
Published: October 2015

Parkinsons disease psychosis (PDP) occurs frequently in patients with Parkinsons disease (PD) and involves a spectrum of symptoms, from mild hallucinations to those that are more disruptive, as well as delusions, particularly around spousal infidelity and theft of money or possessions. Risk factors for PDP include dopaminergic (and other) medications, cognitive disorders, sleep disorders, and duration of PD. Emerging evidence suggests that PDP also reflects underlying PD pathology. Routine querying of major PDP symptoms can hasten recognition and allow earlier diagnosis of PDP. Mild hallucinations with retained insight are frequent and may be tolerable by patients and caregivers, but symptoms that can be considered as psychosis will typically increase in frequency and severity. Increasing PDP results in patient distress, increased caregiver burden, and is a leading cause of long-term nursing home placement. PDP has also been associated with an increased risk for morbidity and mortality. Ongoing research into the prevalence, risk factors, phenomenology, pathophysiology, and emerging pharmacotherapy for PDP provides hope for improved diagnosis and management of PDP.
The Role of the Capsaicin 8 % Patch (Qutenza®) in the Treatment of Post-herpetic Neuralgia
Authors: Irving Gordon ,   Medical Director, Swedish Pain Center, Seattle, Washington, US
Published: October 2015

Post-herpetic neuralgia (PHN) occurs as a complication of acute herpes zoster. The capsaicin 8 % (w/w) dermal patch (Qutenza®) is a transient receptor potential vanilloid agonist that increases intracellular calcium concentration, triggering calcium-dependent protease enzymes to cause cytoskeletal breakdown. This action is thought to lead to loss of cellular integrity and defunctionalization of nociceptor epidermal nerve fibers. The capsaicin 8 % patch is indicated in the US for the treatment of neuropathic pain associated with PHN. In pivotal, randomized, doubleblind, multicenter trials in patients with PHN, a single 60-minute application of the capsaicin 8 % dermal patch reduced mean numeric pain rating scale scores between baseline and weeks 28 to a significantly greater extent than the low-dose comparator patch (capsaicin 0.04 % w/w). The capsaicin 8 % (w/w) dermal patch was found to be safe and generally well-tolerated. Most commonly reported side effects were local, comprising dermal irritation, erythema, and pain at the site of application. These effects were transient and mild to moderate in severity. Transient patch application-related pain was not a barrier to use and was managed with local cooling or oral analgesics in nearly all cases. Thus, the capsaicin 8 % dermal patch appears to have a good safety profile, is well tolerated, and offers effective topical therapy in some patients with PHN. This review aims to characterize the use of the capsaicin 8 % dermal patch in the treatment of PHN.
Complex Fasciculation Potentials in Amyotrophic Lateral Sclerosis
Authors: Shimizu Toshio , Bokuda Kota ,   Director and Neurologist,   Neurologist, Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
Published: October 2015

Fasciculation and fasciculation potentials (FPs) are most frequently observed in progressive motor neuron disorders, including amyotrophic lateral sclerosis (ALS). Recent diagnostic criteria, the so-called Awaji criteria, emphasize the importance of FPs in the electrodiagnosis of ALS. Although FPs are found in other benign syndromes, FPs in ALS often show a complex morphology (complex fasciculation potential [CFP]) with instability in the form of increased jitters with blocking of some components of the FPs. The criteria have raised the diagnostic significance of FPs as FPs have clinical importance in the diagnosis of ALS equivalent to spontaneous denervation potentials (fibrillation potentials and positive sharp waves). CFPs have multiple pathomechanisms, but they frequently originate from the most distal sites of the peripheral motor neurons. In addition, CFPs are strongly related to axonal membrane hyperexcitability. The increased amount of CFPs in individual patients has been reported to predict shorter survival and rapid progression of the disease. These findings suggest that CFPs have a disease-specific significance to ALS; therefore, exact documentation of CFPs in needle electromyography may contribute to correct diagnoses of ALS and early clinical trials.
Therapeutic Monoclonal Antibodies for Migraine
Authors: Silberstein Stephen ,   Professor of Neurology and Director, Jefferson Headache Center, Thomas Jefferson University, Philadelphia, US
Published: October 2015

Monoclonal antibody (mAb) treatment has revolutionized the approach to many diseases. They comprise immunoglobulin G (IgG) isotypes. Calcitonin gene-related peptide (CGRP) is important in migraine pathogenesis. Four mAbs that target either CGRP or the CGRP receptor are in development for prophylaxis of episodic migraine or chronic migraine. Preliminary data suggest that they are effective.
Achieving Best Visual Outcomes with a Monofocal Intraocular Lens
Authors: Davison James A ,   Wolfe Eye Clinic, Marshalltown, Iowa
Published: October 2015

Specific monofocal intraocular lens (IOL) design features have been integrated over time to provide improved vision performance after lens replacement surgery. Features of the AcrySof® IQ single-piece monofocal IOL (SN60WF, Alcon Laboratories) include architectural, chemical, and surface characteristics that improve performance over earlier designs. The architectural features include single-piece construction with low resistance to compression, 3D haptics for easy implantation, and predictable and stable long-term positioning. The foldable hydrophobic acrylic plastic provides efficient light focus and incorporates ultraviolet (UV) radiation and light-normalized spectrum transmission characteristics. The plastic’s surface incites minimal post-operative uveitis and capsule reaction and also resists epithelial cell proliferation. The biconvex optic is asymmetric with most of the power incorporated into the anterior surface to reduce dysphotopsia. The posterior surface has a base convexity and incorporates an aspheric modification. The optic’s square edge provides a barrier that discourages epithelial cell invasion and consequent posterior capsule opacification and need for neodymium-doped yttrium–aluminum–garnet (Nd:YAG) posterior capsulotomy, and is frosted to reduce dysphotopsia.