bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer’s Disease and Adult Neurogenesis—Are Endogenous Stem Cells Part of the Solution?
Authors: Marlatt Michael W , Hoozemans Jeroen JM , Veerhuis Rob , Lucassen Paul J ,   Swammerdam Institute for Life Science—Center for Neuroscience, University of Amsterdam,   Department of Pathology, VU University Medical Center, Amsterdam,   Department of Pathology, VU University Medical Center, Amsterdam,   Alzheimer Center/Psychiatry Department and Department of Clinical Chemistry, VU University Medical Center, Amsterdam,   Swammerdam Institute for Life Science—Center for Neuroscience, University of Amsterdam
Published: October 2015

The human brain produces new neurons that mediate hippocampal plasticity but also have a potential role in hippocampal-related disorders, such as Alzheimer’s disease and dementia. Factors such as stress and aging that reduce adult neurogenesis also serve as independent risk factors for Alzheimer’s disease. Causality between loss of neurogenesis and hippocampal dysfunction has not been established; however, neurogenesis is an attractive research avenue for therapy since it is readily modifiable. Activities such as running and enrichment increase the proliferation of neural stem cells and survival of nascent neuroblasts. Adult neurogenesis may alternatively reflect capacity to overcome age-dependent insults and neurodegeneration in the hippocampus. This collectively indicates that stimulation of endogenous cells or transplantation of neural stem cells are potential pathways reversing the behavioral changes associated with neurodegenerative disorders by augmenting structural plasticity of the hippocampus. Continued research in this area and in appropriate animal models of disease is critical for evaluating whether neurogenesis-based therapeutic strategies will have the potential to aid those with degenerative conditions.
The American Parkinson Disease Association—Information and Referral Center Coordinators—Making the Connection
Authors: Diaz Donna Packo , Thomas Cathi A ,   Department of Community Health and Outreach, Hospital of Saint Raphael, New Haven,   Department of Neurology, Boston University School of Medicine
Published: October 2015

People diagnosed with Parkinson’s disease (PD) are presented with unique challenges. The American Parkinson Disease Association, Inc. (APDA) was founded in 1961 “to ease the burden, to find the cure” for PD. Headquartered in New York, the organization has a long-standing history of providing grassroots support for those dealing with PD. In 1974, APDA established the first local Information and Referral (I&R) Centers. APDA currently funds the operation of 61 I&R Centers across the continental US. To ensure the vibrant, day-to-day operation of these Centers, the APDA has a dedicated cadre of I&R Center coordinators who help ‘ease the burden’ of PD. These coordinators come from a wide variety of professional backgrounds, particularly the fields of nursing and social work. Although coordinator qualifications are diverse, universal to all is a passion to offer patients, families, and the general community a better understanding of PD, as well as the skills to successfully manage the formidable challenges presented by the disease.
Genetic Determinants of Seizures and Epilepsy
Authors: Buono Russell J , Dlugos Dennis J , Ferraro Thomas N ,   Chief, Research and Development, Research Service, Veterans Affairs Medical Center, Coatesville,   Associate Professor, Department of Pediatrics, The Children’s Hospital of Philadelphia,   Research Associate Professor, Departments of Psychiatry and Pharmacology, University of Pennsylvania
Published: October 2015

Epilepsy is a group of common neurological disorders characterized by heterogeneous clinical presentation. The etiology of epilepsy is multifactorial, involving the influence of multiple gene variants interacting with factors in the environment. Certain rare forms of epilepsy have been attributed to mutations in a single gene, and although the list of such genes that are sufficient to produce epilepsy when mutated is growing steadily, they are directly relevant to only a very small fraction of all cases of epilepsy. Genetic influences in common forms of epilepsy have been more difficult to identify and future studies will focus on strategies to hasten the discovery process. The combination of translational research involving animal models and advances in genome technology will facilitate the identification of genetic variations that influence seizure susceptibility and contribute to the risk for developing common epilepsy. Application of genetic strategies to clinically well-characterized epilepsy patients will provide the added benefit of yielding data that are also relevant to the discovery of genes that influence responsiveness to the effects of antiepileptic drugs. Thus, future research on the genetic influences in epilepsy is anticipated to provide insight into both the underlying biological basis of seizures and potential targets that may be used to develop new treatments.
The Evolution of White Matter Hyperintensities
Authors: Young Vanessa G , Kril Jillian J ,   Medical Student, University of Notre Dame, Sydney,   Professor of Neuropathology, Disciplines of Medicine and Pathology, University of Sydney
Published: October 2015

White matter hyperintensities (WMHs) are a common finding on magnetic resonance imaging (MRI) scans of elderly subjects. Despite their frequency, the clinical correlates and etiology of WMH remain controversial, with many conflicting results published. This is due, in part, to the varied populations studied. Nevertheless, the prevailing opinion is that these lesions are of vascular origin due to the strong associations with vascular risk factors and stroke. Neuropathological studies have also yielded varied results. Interestingly, while a number of associations with variables such as demyelination and gliosis have been reported, no single pathological variable has been found to account for the MRI changes. The most consistent associations are with reduced vascular integrity and increased bloodbrain barrier permeability. Further studies investigating the bloodbrain barrier may assist in elucidating the origin of these common abnormalities.
Therapeutic Exploration of Metabotropic Glutamate Receptor Antagonists in Parkinson’s Disease by Positron Emission Tomography
Authors: Sanchez-Pernaute Rosario , Brownell Anna-Liisa ,   Neurologist and Neuroscientist, Parkinson Disease Program, Inbiomed Foundation, San Sebastian,   Associate Professor and Director, Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital
Published: October 2015

Metabotropic glutamate receptors (mGluR)s are G-protein-coupled receptors that function as modulators of synaptic function and glutamate transmission. Post-synaptically localized subtype 5 mGlu5 receptors are co-localized with adenosine A2a, dopamine, and N-methyl-D-aspartate (NMDA) receptors and regulate local protein synthesis and messenger RNA (mRNA) translation at synapses, and are thus ideally positioned to control synaptic plasticity. Aberrant synaptic plasticity appears to be involved in a number of developmental and degenerative neuropsychiatric disorders, including Parkinsons disease. Pharmacological modulation of mGluR5 could potentially open new therapeutic avenues for the treatment of such disorders, for both symptomatic and neuroprotective purposes. In this review, we summarize a series ofin vivostudies we performed in order to delineate the anatomical basis and functional role of mGluR5 antagonists in Parkinsons disease models, taking advantage of high-resolution positron emission tomography (PET) and the recent development of novel specific radiopharmaceuticals. Our findings of a prevalent distribution of mGluR5 in the striatum and limbic structures and a significant binding enhancement following dopamine lesions support the role of mGlu5 receptors in modulating dopamine- and glutamate-dependent signaling and synaptic plasticity within the basal ganglia corticosubcortical loops.
Risk Scores for Predicting Post–thrombolysis Intracerebral Hemorrhage
Authors: McKinney James S , Cucchiara Brett ,   Assistant Professor of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School,   Assistant Professor of Neurology, Hospital of the University of Pennsylvania
Published: October 2015

Post-thrombolysis hemorrhage is a major concern for physicians treating acute ischemic stroke. Two scoring systems that incorporate factors associated with post-thrombolysis hemorrhage have been developed in an attempt to estimate the risk of developing post-thrombolysis hemorrhage among stroke patients. In this article we discuss these scoring systems and their utility in the clinical assessment of stroke patients.
Nanotechnology in Neurology—Current Status and Future Possibilities
Authors: Provenzale James M , Mohs Aaron M ,   Professor of Radiology, Department of Radiology, Duke University Medical Center, and Professor of Radiology, Oncology, and Biomedical Engineering, Departments of Radiology, Oncology, and Biomedical Engineering, Emory University School of Medicine,   Distinguished Fellow, Department of Biomedical Engineering, Emory-Georgia Tech Center for Cancer Nanotechnology Excellence
Published: October 2015

The field of nanomedicine is rapidly emerging and will provide many novel methods for diagnosis and treatment. In this article the applications of nanotechnology to the central nervous system (CNS) will be described. Nanotechnology provides many potential solutions to various problems encountered in CNS diseases. Specifically, nanomedicine offers the possibility of new methods of drug delivery, more sensitive and specific means for diagnosis of disease at earlier stages and assessment of treatment response, and also potential techniques for neuro-protection and neuro-engineering. In this article, information is provided on the various types of nanoparticles involved in medical applications, the principles of nanoparticle delivery and targeting, and bothin vivoandex vivouses of nanoscale materials.
Managing Chronic Moderate to Severe Pain—EMBEDA® (Morphine Sulfate and Naltrexone Hydrochloride) Extended Release Capsules for Oral Use
Authors: Gharibo Christopher ,   Medical Director of Pain Medicine, and Assistant Professor of Anesthesiology, New York UniversityHospital for Joint Diseases, and Assistant Professor of Anesthesiology, New York University School of Medicine
Published: October 2015

EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use, indicated for the management of chronic moderate to severe pain, contain extended-release pellets of morphine sulfate with a sequestered core of naltrexone, an opioid antagonist. When EMBEDA is taken orally as directed, it is bioequivalent with regard to rate and extent of plasma morphine absorption to KADIAN® (morphine sulfate extended-release) Capsules, a similar formulation without naltrexone. EMBEDA has been shown to be significantly superior to placebo in maintaining pain relief over 12 weeks and, in one of the longest durability studies, to reduce pain intensity for up to 12 months. Upon tampering by crushing EMBEDA, naltrexone is released to mitigate morphine-induced euphoria. Euphoria and drug-liking measures after oral administration of intact or crushed EMBEDA were similar, and were reduced compared with morphine sulfate solution; crushing EMBEDA did not yield more euphoria and desirability for abuse than the intact product. The most common adverse events after long-term use were constipation, nausea, and vomiting, which are typical of opioids. Over long-term use as directed, there was no evidence of naltrexone accumulation or opioid withdrawal. The impact of formulations such as EMBEDA on the abuse rate among real-world abusers requires long-term epidemiologic studies.
Advances in Our Understanding of the Pathophysiology of Alzheimer’s Disease
Authors: Green Kim N , Schreiber Steven S ,   Assistant Professor, Department of Neurobiology and Behavior, and Institute for Memory Impairments and Neurological Disorders, University of California, Irvine,   Professor, and Interim Chair, Department of Neurology, Professor of Anatomy and Neurobiology, University of California, Irvine School of Medicine, and Chief, Neurology Section, VA Long Beach Healthcare System
Published: October 2015

Alzheimers disease (AD) is the most common age-related dementia, currently affecting more than 5 million patients in the US alone, and is characterized by the presence of both extracellular plaques and intraneuronal tangles in the brain of a patient with dementia. Alois Alzheimer first described the pathology associated with the disease over 100 years ago, and during the past three decades our understanding of the disease and of potential ways to treat it has increased tremendously. In this article we describe our current understanding of both the pathophysiology of Alzheimers disease and current and future therapeutic interventions, including symptomatic relief, disease modification, and the reversal of synaptic and neuronal loss.
‘Infectious Burden’—New Insights into Stroke Prevention
Authors: Luna Jorge M , Elkind Mitchell SV ,   Graduate Research Assistant, and Doctoral Candidate,   Associate Professor of Neurology, Associate Chairman of Neurology, and Associate Professor of Epidemiology, Columbia University College of Physicians and Surgeons and Joseph Mailman School of Public Health, Columbia University
Published: October 2015

Chronic and acute infections have been implicated as risk factors that increase the risk for stroke, myocardial infarction (MI), and other vascular events. The lack of consistency among studies attempting to link exposure to infectious pathogens and stroke risk provides empiric evidence that a single pathogen is likely not responsible for stroke. Reconsidering exposure as an infectious burden (IB) aligns with our understanding that the totality of pro-inflammatory agents can contribute to atherosclerosis and vascular risk. We define IB as the cumulative life-course exposure to infectious agents that elicit strong inflammatory responses and review the varied approaches to operationalising this measure. There is promising research investigating the role of acute and chronic IB suggesting that there may be a causal role of pathogens in atherosclerotic progression and plaque destabilization to negatively affect vascular risk; however, the evidence is preliminary.
Niemann-Pick Type C Disease—Pathophysiology and Future Perspectives for Treatment
Authors: Davidson Cristin D , Walkley Steven U ,   Graduate Student,   Professor, Department of Neuroscience, Pathology, and Neurology, Albert Einstein College of Medicine
Published: October 2015

Niemann-Pick type C (NPC) disease is a rare and fatal inherited metabolic disorder that results in intracellular accumulation of cholesterol and glycolipids within the endosomal/lysosomal system. Central nervous system (CNS) involvement is especially prominent as evidenced by ataxia and progressive decline of motor skills and intellectual function. Defects in either the NPC1 or NPC2 protein, both of which are thought to be involved in the egress of cholesterol and other lipids out of the endosomal/lysosomal system, leads to NPC disease. The pathogenic cascade is not well understood, and currently there is no corrective therapy for NPC patients. However, some compounds tested in animal models of NPC disease have shown promise in slowing disease onset and progression, and administration of these drugs in combination has provided evidence of synergy and enhanced clinical benefit. This favorable outcome indicates that combinatorial therapies using small molecules likely represent the best therapeutic option available to NPC patients at this time.
Neuroimaging Advances in Stroke Rehabilitation
Authors: Seitz Rüdiger J , Lindenberg Robert , Schlaug Gottfried ,   Professor of Neurology, Department of Neurology, University Hospital Düsseldorf and Biomedical Research Centre, Heinrich-Heine-University Düsseldorf,   Instructor in Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, and University Hospital Düsseldorf,   Associate Professor of Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School
Published: October 2015

Human ischemic stroke is a multistage disorder with various routes of recovery. Neuroimaging allows researchers to explore the pathophysiology and recovery mechanismsin vivo. Based on these findings, motor recovery and chronic motor impairment after stroke have been linked to structural alterations of grey and white matter as well as functional changes in the perilesional tissue. Parameters derived from diffusion tensor imaging and functional magnetic resonance imaging can be used as surrogate markers of chronic motor impairment and predictors of functional potential for motor recovery. These parameters have the potential to tailor individual rehabilitation and stratify patients for experimental therapy studies such as invasive and non-invasive brain stimulation alone or in combination with other facilitators.
Optimal Approaches to Skin Preparation Prior to Neurosurgery
Authors: Sukul Vishad , Lynch Tamara , Loftus Christopher M ,   Resident,   Medical Student,   Professor, and Chairman, Department of Neurosurgery, Temple University School of Medicine
Published: October 2015

Surgical site infections have always been and will likely remain a significant concern for physicians around the world. When almost 40% of nosocomial surgical infections are related to the incision site, appropriate preperation of the skin becomes a particular concern. Neurosurgery is no stranger to surgical site infection. Infections of this type in the neurosurgical patient can have serious, long-lasting consequences should infection spread deeper than skin level. In this article, the current recommendations for skin preparation at the start of surgery are reviewed, taking into account specific considerations that must be made for the neurosurgical patient. In addition, the use of adjunct methods, i.e. antibiotic-impregnated drapes, and the effects of clipping versus shaving hair at the operative site are discussed.
Neuroinflammatory Cytokines—The Common Thread in Alzheimer Pathogenesis
Authors: Griffin W Sue T , Barger Steven W ,   Dillard Professor and Vice Chairman,   Professor of Geriatrics, Neurobiology and Developmental Sciences and Internal Medicine, Donald W Reynolds Department of Geriatrics and the Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, and Geriatric Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System
Published: October 2015

This article discusses the potential role of the cytokine cycle and its corollary as drivers of the relentless progression of Alzheimer’s neuropathologies, whether they are the result of gene mutations, gene polymorphisms, and/or environmental and comorbid conditions. Based on the discovery of cytokine overexpression as an accompaniment to the dementia-related glial activation, the cytokine hypothesis was proposed. This states that in response to the negative impact on neurons of known and unknown risk factors—which include genetic inheritance, comorbid and environmental factors—microglia and astrocytes become activated and produce excess amounts of the immune-modulating cytokine interleukin-1 (IL-1) and the neuritogenic cytokine S100B, respectively. Finding that these glial events occur in fetuses and neonates with Down syndrome provided the first evidence that productive immune responses by activated glia precede rather than follow overt AD-related pathology. This finding can be added to the demonstration of IL-1 induction of amyloid β (Aβ) precursor protein and astrocyte activation with excess production of neuritogenic factor S100B. This combination suggests that IL-1 and S100B overexpression would favor the Aβ production and dystrophic neurite growth necessary for laying down neuritic Aβ plaques. This, together with demonstration of IL-1 induction of excessive production of the precursors of other features common in AD prompted a corollary to the cytokine hypothesis. The corollary states that regardless of the primary cause of the neuronal insult, the result will be chronic glial activation, which in turn will result in further neuronal injury, still more glial activation with excess cytokine expression and so on. This article discusses known causes, genetic and environmental risk factors, and comorbid conditions, and the potential contribution of glial activation with excessive cytokine expression to each.
Paraneoplastic Neurologic Syndromes—An Update on Current Understanding and Future Perspectives
Authors: Grisold Wolfgang , Giometto Bruno , Oberndorfer Stefan , Vitaliani Roberta ,   Professor and Clinician, Neurology Department, KFJ Hospital, Medical University of Vienna and Ludwig Boltzmann Institute for Neuro-oncology,   Head, Department of Neurology, Ca’ Foncello Hospital, Treviso,   Clinician, Neurology Department, KFJ Hospital, Medical University of Vienna and Ludwig Boltzmann Institute for Neuro-oncology,   Consultant, Department of Neurology, Ca’ Foncello Hospital, Treviso
Published: October 2015

Paraneoplastic neurological syndromes (PNS) are remote effects of tumors on the nervous system. They can strike at single or at multiple sites of the central nervous system (CNS) and the peripheral nervous system, and often appear before the detection of cancer. PNS can be disabling and debilitating and may be either an additional burden to cancer or the cause of death. The PNS Euronetwork group has collected a series of approximately 1,000 patients in several European centers. This study is the largest systematic series of patients with PNS and, for the first time, can answer questions about the most frequent PNS, their detailed symptoms, associated antibodies, and the types of underlying tumors. The clinical course and laboratory findings for many PNS suggest an autoimmune pathogenesis; however, research into this heterogeneous immunological relationship has been evolving over recent decades. The classic syndromes are antigen-target-oriented syndromes such as myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and ion channel-mediated diseases. Onconeuronal antibodies constitute a large group of PNS, characterized by the appearance of specific antibodies, defined clinical signs and often an association with specific tumors. In recent years, a new group of antibodies directed at surface antigens as receptors has been identified. Finally, there is a long list of ‘other’ PNS, which are evident to clinicians but which have no pathogenetic explanation. Examples include the mild terminal neuropathies and sarcopenia in cancer patients. In addition to the emerging classification based on pathophysiology, other new syndromes and symptoms have appeared, including apnea in brainstem encephalitis, a neuropsychiatric spectrum of limbic encephalitis, and increased knowledge about LEMS. Two important aspects warrant attention: some PNS respond to therapy and not all paraneoplastic-like syndromes are tumor related. This view is based on the current understanding of immune pathogenesis and on the enlarged spectrum of PNS.
Laquinimod in Relapsing–Remitting Multiple Sclerosis
Authors: Jeffery Douglas R , Pharr Emily , Zeid Nuhad Abou ,   Neurologist, Advance Neurology and Pain, Cornerstone Health Care,   Resident Physician,   Assistant Professor, Department of Neurology, Wake Forest University School of Medicine
Published: October 2015

Laquinimod is a novel oral immunomodulatory agent in development for the treatment of relapsing–remitting multiple sclerosis (RRMS). It is a derivative of roquinimex that was structurally altered to maximize safety and efficacy. In animal models laquinimod was far more potent than its parent compound with no apparent propensity to induce inflammatory reactions. Laquinimod is a broad-spectrum immunomodulatory agent with a multitude of effects on the immune system but no effect on the ability of animals to mount a cellular or humoral immune response. In phase II trials selected for highly active RRMS patients, laquinimod reduced the frequency of gadolinium-enhancing lesions by 55%, significantly reduced the number of new T2 lesions, and had a trend toward an effect on reducing brain volume loss. Laquinimod was well tolerated in phase II trials and had a favorable safety profile with a paucity of adverse events. It is metabolized by the cytochrome P-450 system (CYP-3A4) and may interact with some compounds used in symptomatic therapy. With a favorable efficacy and safety profile, laquinimod is a potential first-line agent in the future treatment of RRMS.
Redefining Efficacy in Parkinson’s Disease—Early Motor Phase Treatments and the Potential for Treating during the Pre-motor Phase
Authors: Stone Jacqueline B , Jacoby Nuri , Henchcliffe Claire ,   Resident in Neurology,   Resident in Neurology,   Associate Professor in Neurology and Neuroscience, Weill Medical College of Cornell University
Published: October 2015

Until recently, Parkinsons disease (PD) treatments have overwhelmingly focused on motor rather than non-motor symptoms. Early and accurate detection of PD is considered desirable, with major research initiatives presently focused upon identifying and validating clinical batteries and biomarkers to this end. This raises the question of how the patient deemed at high risk of developing PD should be counseled and treated. Currently there are no approved treatments for pre-motor PD, and thus any pre-motor complaints are treated for specific symptom relief, such as for sleep or mood disorders. For individuals known to be at risk, for example non-manifesting gene carriers, there is likewise a lack of consensus on management, and no proven means of risk reduction. Here we examine options for early PD treatment and clinical evidence for disease modification that might favor pushing back treatment to the pre-motor stage.
Advances in the Role of Neuroimaging to Monitor Disease Progression in Parkinson’s Disease
Authors: Agarwal Pankaj A , Stoessl A Jon ,   Postdoctoral Fellow,   Director, Pacific Parkinsons Research Centre, University of British Columbia and Vancouver Coastal Health
Published: October 2015

Since structural imaging has generally failed to demonstrate consistent abnormalities in Parkinsons disease (PD), from an imaging perspective, the diagnosis has typically been based upon the demonstration of impaired striatal dopamine (DA) function. Radiotracer imaging techniques such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT) allow thein vivoassessment of nigrostriatal DA function as well as regional cerebral blood flow, glucose metabolism, and functional connectivity, and changes in these measures have been used to infer disease progression. Pre-synaptic radiotracer imaging (RTI) has shown that striatal dopaminergic hypofunction follows a negative exponential pattern with the fastest rate of decline in early disease. Moreover, while striatal subregions remain differentially affected throughout the course of disease, with the posterior putamen affected more than anterior structures, the rate of deterioration is similar in all subregions. However, although functional imaging is undoubtedly a very useful tool in the assessment of PD progression, various studies have shown discordance between clinical progression of PD and nigrostriatal degeneration estimated by PET or SPECT. Therefore, considerable caution is warranted in the interpretation of imaging findings. While a potentially invaluable complement in assessing the severity of dopaminergic dysfunction, functional imaging is not a substitute for clinical assessment and other objective measures of PD severity, and cannot be currently considered a biomarker for progression of PD.
Long-term Experience of Glatiramer Acetate (Copaxone®) in the Treatment of Clinically Isolated Syndrome and Relapsing–Remitting Multiple Sclerosis
Authors: Zwibel Howard ,   Founding Medical Director, Emeritus Neuroscience Consultants Comprehensive Care Multiple Sclerosis Center, Coral Gables
Published: October 2015

Multiple sclerosis (Ms) is a chronic, disabling condition with severe clinical and social consequences. glatiramer acetate (gA) has been widely used for more than 15 years as a first-line disease-modifying agent in the treatment of relapsingremitting Ms (rrMs). it appears to have multiple modes of action, including the induction of gA-reactive T-helper 2 (Th2) immunoregulatory cells and the stimulation of neurotrophin secretion in the central nervous system, which may promote neuronal repair. clinical trial data show that gA reduces the relapse rate in rrMs, can delay or halt disability progression, and brings about improvement in magnetic resonance imaging (Mri) measures of disease activity, including reduction of brain atrophy. early treatment with gA can reduce the risk of developing clinically definite Ms in patients with clinically isolated syndrome. furthermore, it has an excellent safety and tolerability profile. recent data from patients treated for 15 years have indicated that more than half of the patients on long-term gA therapy have stable or improved disability scores.
Intrathecal Drug Delivery for Neuropathic Pain
Authors: Jamison David E , Wilkinson Indy M , Cohen Steven P ,   Assistant Professor, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center,   Resident in Anesthesiology, National Capital Consortium,   Professor of Anesthesiology, Uniformed Services University of the Health Sciences, and Associate Professor, Johns Hopkins School of Medicine
Published: October 2015

Neuropathic pain represents a substantial burden on society. The treatment of neuropathic pain is challenging and typically involves multiple medication classes such as anticonvulsants, antidepressants, and opioids. The advent of intrathecal medication delivery in the late 1970s provided an additional option for the treatment of refractory neuropathic pain. This article presents a review of the evidence regarding intrathecal medications for neuropathic pain. There is strong evidence to support the use of intrathecal opioids in malignant pain of mixed characteristics, and moderate evidence for their use in non-malignant, neuropathic pain. The use of baclofen is strongly supported for spasticity, but there is only intermediate-level evidence for its use in neuropathic pain. With respect to clonidine and ziconotide, there is moderate evidence to support their use for neuropathic pain, although the effectiveness of the latter agent is limited by the high incidence of adverse effects. For steroids, there is weak evidence in favor of its use in neuropathic pain, predominantly in combination with opioids. The evidence is moderate to strong for the use of steroids in post-herpetic neuralgia, which must be weighed against the possibility of neurotoxicity if depot steroids are injected.
Involvement of Nutrients in the Pathogenesis or Management of Alzheimer’s Disease
Authors: Wurtman Richard J ,   Cecil H Green Distinguished Professor Emeritus, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology
Published: October 2015

The number of hippocampal and cortical synapses is diminished in early Alzheimers disease (AD) and this loss, which is well correlated with the onset of cognitive deficits, probably reflects both an acceleration in their breakdown and a slowing in their synthesis, perhaps consequent to the concurrent decrease in dendritic spines. No strategies have been identified for increasing the number of synapses. Synaptogenesis requires adequate amounts of highly specialized synaptic membrane and activation of a process for shaping this membrane, initially into dendritic spines and neurites and then into the synapses themselves. Both can be enhanced by providing, concurrently, three circulating compounds present in the dieturidine (as its monophosphate), docosahexaenoic acid (DHA), and cholinewhich can be rate-limiting precursors in membrane phosphatide synthesis. The uridine, as uridine triphosphate (UTP), also activates brain P2Y receptors, which facilitate neuronal differentiation and affect the production of synaptic proteins. In two large-scale clinical trials, patients with early AD who received the precursors and cofactors orally for up to 24 weeks exhibited significant improvements in memory indices.
Deep Brain Stimulation for Parkinson’s Disease—A Review
Authors: Honey Christopher R , Ranjan Manish ,   Associate Professor of Neurosurgery, Surgical Centre for Movement Disorders, University of British Columbia, Vancouver, Canada,   Associate Professor of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore, India
Published: October 2015

The majority of patients with Parkinsons disease (PD) can be treated with medications. As the disease progresses, however, certain symptoms may evolve that are refractory to medical therapy but ideally suited to surgical intervention. Tremor, dyskinesia and motor fluctuation can be effectively treated with deep brain stimulation (DBS). This article highlights which PD patients can benefit from DBS and summarizes how the operations are performed and what are the expected outcomes (and potential complications). The relevant literature is reviewed for experienced clinicians and our personal bias is highlighted for those new to the field (and hoping to avoid our early mistakes).
Sudden Unexpected Death in Epilepsy—An Overview of Current Understanding and Future Perspectives
Authors: Friedman Daniel , Hirsch Lawrence J ,   Assistant Professor and Epileptologist, Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Medical Center, New York, US,   Professor of Neurology and Co-Director, Comprehensive Epilepsy Center, Department of Neurology, Yale University, New Haven, Connecticut, US
Published: October 2015

Sudden unexpected death in epilepsy (SUDEP) is likely to be the most common cause of disease-related mortality in people with epilepsy. The most commonly encountered scenario is that a previously healthy person is found dead in bed by family. Patients with frequent generalized tonic-clonic seizures are at highest risk but SUDEP can occur in patients who have never had convulsions. The mechanisms of SUDEP are poorly understood but seem to be related to seizure-related cardiac, respiratory or cerebral dysfunction. Seizure control is the only clear strategy to prevent SUDEP but that is not possible in the 30 % of patients with treatment-resistant epilepsy. Understanding the pathophysiology of SUDEP may lead to prevention strategies for patients who continue to have seizures despite maximal therapy.
Management of Motor Symptoms in Multiple Sclerosis
Authors: Barros Pedro , José Sá Maria ,   Neurology Resident, Neurology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Portugal,   Neurology Resident; Senior Neurologist, Head of MS Clinic, MS Clinic, Centro Hospitalar de São João, Porto, Portugal,   Visiting Professor; Associate and Aggregate Professor of Neurology, Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal,   Neurology Resident; Senior Neurologist, Head of MS Clinic, MS Clinic, Centro Hospitalar de São João, Porto, Portugal,   Visiting Professor; Associate and Aggregate Professor of Neurology, Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal,   Senior Neurologist, Neurology Department, Centro Hospitalar de São João, Porto, Portugal
Published: October 2015

Although there has been a significant development, in recent years, regarding disease modifying treatments (DMT) in multiple sclerosis (MS), there is a continuous need to manage the wide range of symptoms associated with MS. Although surveys vary in their results, mobility is a key concern in MS patients. However, limited evidence base exist for symptomatic drug treatment and so, it is very important to consider all therapeutic options in this patients. Here we review the current evidence in the management of three of the most common and disabling motor symptoms: spasticity, tremor and gait impairment.
New Magnetic Resonance Imaging Biomarkers Advance the Characterization of Parkinson Disease
Authors: Ziegler David A , Corkin Suzanne ,   Post-doctoral Fellow, Department of Neurology and the Center for Integrative Neuroscience, University of California San Francisco, San Francisco, California, US,   Professor of Behavioral Neuroscience, Emerita, Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, US
Published: October 2015

The pathophysiology of idiopathic Parkinson disease (PD) is traditionally characterized as substantia nigra degeneration, but careful examination of the widespread neuropathologic changes suggests individual differences in neuronal vulnerability. A major limitation to studies of disease progression in PD has been that conventional magnetic resonance imaging (MRI) techniques provide relatively poor contrast for the structures that are affected by the disease, and thus are not typically used in experimental or clinical studies. Here, we review the current state of structural MRI as applied to the analysis of the PD brain. We also describe a new multispectral MRI method that provides improved contrast for the substantia nigra and basal forebrain, which we recently used to show that these structures display different trajectories of volume loss early in the disease.
Special Report—First Comprehensive Guidelines Published for Neurostimulation Therapy
Authors: Pope Jason E , Golovac Stanley , Thomson Simon , Deer Timothy R ,   Director of Intrathecal Therapeutics, Center for Pain Relief, Charleston, West Virginia, US; Medical Director, Teays Valley Center for Pain Relief, Teays Valley, West Virginia, US,   Florida Pain Specialist, Merritt Island, Florida, US,   Consultant in Pain Medicine and Neuromodulation, Basildon and Thurrock University NHS Trust, Essex and Honorary Consultant, Addenbrookes Hospital, Cambridge, UK,   President and Chief Executive Officer, Center for Pain Relief, Charleston, West Virginia, US
Published: October 2015

Neuromodulation has a growing role in the management of chronic pain. An international panel of experts has reviewed the evidence and issued guidance regarding the appropriate use of neurostimulation. It is understood that a patient-centric cadence of progression through the pain care algorithm must be considered. Neurostimulation may offer long-term cost savings and improved functional status without complications from long-term opioid use. Indications for consideration of neurostimulation include failed back surgery syndrome, complex regional pain syndrome, peripheral neuropathic pain, chronic peripheral ischemic pain, and refractory angina pectoris. Criteria crucial for success include appropriate patient selection and education, proper use of sterile facilities, attentive follow-up by the healthcare team, and provider training.
Pharmacologic Decision-making in the Treatment of Focal Epilepsy—A Critical Comparison of Antiepileptic Drugs
Authors: Benbadis Selim R , Stefan Hermann , Morita Diego , Abou-Khalil Bassel , Hogan R Edward ,   University of South Florida, Tampa, Florida, US,   University Hospital Erlangen (FAU), Erlangen, Germany,   Cincinnati Childrens Hospital Medical Center, Cincinnati, Ohio, US,   Vanderbilt University Medical Center, Nashville, Tennessee, US,   Washington University in St Louis, St Louis, Missouri, US
Published: October 2015

Physicians who treat patients with epilepsy must balance many factors when selecting the appropriate treatment for an individual patient, including seizure type, concomitant antiepileptic drug (AED) therapy, age, comorbid conditions, and even insurance coverage. Optimal management of seizures is further complicated by a continuously increasing pool of AEDs. As seizure type is a main factor in AED selection, this review will provide an evidence-based guide for physicians treating focal epilepsy. This includes a summary of efficacy, safety, and tolerability data from randomized clinical trials as well as findings related to rational polypharmacy, drugdrug interactions, comorbidities, drug administration (titration, dosing, formulation), US Food and Drug Administration (FDA)-approved indications, and cost. Following the review are four case reports that provide real-life examples of clinical challenges physicians face, particularly when dealing with special populations, which highlight the decision-making process entailed when determining the best course of treatment for patients with epilepsy.
Physical Activity in Pediatric Multiple Sclerosis—Can Lifestyle Factors Affect Disease Outcomes?
Authors: Yeh E Ann , Motl Robert ,   Associate Professor of Paediatrics (Neurology), University of Toronto; Director, Child Neurology Residency Program; Director, Paediatric MS and Demyelinating Disorders Program; Associate Scientist, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada,   Associate Professor, Department of Kinesiology and Community Health; Affiliate, Neuroscience Program; Director, Exercise Neuroscience Research Laboratory, University of Illinois at Urbana-Champaign, US
Published: October 2015

Currently, little to no information is available about interventions that can ameliorate symptoms such as depression and fatigue in children and adolescents with multiple sclerosis (MS), nor is there clear information on modifiable factors that can provide neuroprotection in this population. However, physical activity (PA) may have significant effects on disease activity, future disability, cognition, and symptoms of depression and fatigue in pediatric MS. The extent of this effect is unknown. In this paper, after providing an overview of definitions of and outcomes in pediatric MS, we provide a review of existing literature relating PA to outcomes in MS, and then turn to a review of the complex relationship between PA, neuroinflammation, and outcomes in the pediatric population.
Retinal Nerve Fiber Layer Imaging with Spectral-domain Optical Coherence Tomography (OCT)—A Review of the Cirrus HD-OCT
Authors: To Elaine , Lam Dennis , Leung Christopher Kai-shun ,   Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong,   Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong,   Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong
Published: October 2015

High-speed, high-resolution imaging of the retinal nerve fiber layer (RNFL) with spectral-domain optical coherence tomography (OCT) has become an essential tool for evaluation of glaucoma. The Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA) is a spectral-domain OCT that provides visualization of the distribution pattern and measurement of RNFL abnormalities in a 6x6mm2optic disc region. Analysis of the RNFL thickness deviation map—a color-coded map displaying areas of RNFL abnormalities—detects glaucoma with high sensitivity and specificity. Trend analysis of average and sectorial RNFL thicknesses, and event analysis of the RNFL thickness maps and the RNFL thickness profiles can be used to detect and follow diffuse and focal RNFL progression. RNFL measurement with spectral-domain OCT could provide important information for use in formulating treatment plans and evaluating disease prognosis in the management of glaucoma.
Recent Optical Coherence Tomography Imaging of Vitreomacular Disorders
Authors: Shunmugam Manoharan , Williamson MRCOphth and Tom H ,   Department of Ophthalmology, St Thomas’ Hospital, London,   Department of Ophthalmology, St Thomas’ Hospital, London
Published: October 2015

Optical coherence tomography (OCT) has become a ubiquitous and invaluable tool in the retinal clinic as it provides the examiner with a 2D cross-section of the retina; newer machines are also able to reconstruct 3D images. The greater detail afforded by OCT scanning enhances diagnostic capabilities and advances vitreoretinal research. It has proved very useful in surgical planning and provides fine anatomical retinal detail, which can aid post-operative prognostication in certain vitreoretinal disorders. OCT operates on the same physical principles as an ultrasound scan, except it uses light as the carrier signal. First-generation OCTs are capable of resolutions only between 10 and 20μm. Second-generation OCTs improved this to 5–6μm. We await the commercial availability of third-generation and full-field OCTs, which yield resolutions as low as 1–3μm.
Ganciclovir Ophthalmic Gel in the Treatment of Herpes Simplex Keratitis
Authors: Asbell Penny A ,   Professor of Ophthalmology, Director of Cornea and Refractive Services, Department of Ophthalmology, Mount Sinai School of Medicine
Published: October 2015

Herpes simplex keratitis (HSK) is the most common form of viral keratitis and is a common cause of ocular morbidity and blindness. HSK is caused by the herpes simplex virus (HSV) and occurs in patients with no previous exposure to HSV typically occurring during childhood, or in patients with latent disease bearing dormant virus in the nerve ganglia or the cornea. HSK initially presents as a cluster of small, clear vesicles in the epithelium that accumulates to form dendritic lesions which can progress to geographic ulcers, whilst further progression of infection deeper into the cornea affects the stroma. Ganciclovir (GCV) was developed for the treatment of acute superficial herpetic keratitis as a replacement for earlier, less effective, or less tolerated antiviral therapy. Studies have found topical GCV gel treatment to be safe and well tolerated with more favorable pharmacokinetics than acyclovir. The recent approval by the US Food and Drug Administration (FDA) for the clinical use of 0.15% GCV gel for treatment of HSK will provide patients and physicians with a more tolerable, convenient, and effective treatment.
Trichiasis Recurrence—Why the Surgery Part of Trachoma Control is Still Uncontrolled
Authors: West Sheila K ,   Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore
Published: October 2015

Trichiasis surgery is a pillar of the World Health Organization (WHO) strategy for trachoma control. Visual acuity improvement and symptomatic relief follow surgery for trichiasis, and non-ophthalmologists have been trained to carry out the surgery in trachoma-endemic communities. However, recurrence of trichiasis following surgery is unfortunately common, which can undermine public confidence in national trachoma programs. Recurrence of trichiasis following surgery is more likely in high-risk patients (those with previous surgery or who have severe entropion). The most common cause appears to be surgeon skill, with large variations in recurrence reported by surgeon. Proper training, standardization, certification, and supervision would reduce adverse outcomes after surgery. Ideally, recurrence should be 10% at one year, or less with post-operative use of a single dose of azithromycin. The post-operative environment, and acquisition of bacterial infection, may also play a role in recurrence of trichiasis, but it is not clear thatChlamydia trachomatisis important. Efforts to ensure good outcomes of trichiasis surgery for trachoma-endemic, and formerly endemic, countries are imperative. Even with control of active trachoma, trichiasis cases will continue to emerge for years. Detection of these cases, proper surgery, and case management are critical to achieving all the goals of the elimination of blinding trachoma.