bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction After Posterior Cranial Fossa Surgery—Case Report of Application of a Synthetic Tissue Sealant to Augment Dural Closure
Authors: Coppa Nicholas D , Delashaw Jr Johnny B ,   Assistant Professor of Neurological Surgery,   Professor and Vice Chairman of Clinical Affairs, Department of Neurological Surgery, Oregon Health & Science University
Published: October 2015

Cerebrospinal fluid (CSF) leakage following cranial surgery is a well-described and potentially devastating complication, particularly in posteriorcranial fossa surgery. If untreated, a persistent CSF leak can evolve into wound breakdown, a surgical-site infection, and meningitis. Themorbidity of a complication following a cranial operation is harmful to the patient. Additionally, complications are a source of elevated medicalcosts. Numerous reconstruction strategies have been developed to thwart the ill effects of CSF leaks on patient outcomes and healthcarefinances. This case report illustrates the method employed at our institution to repair posterior fossa defects following surgery in thecerebellopontine angle.
Characterization of Fetal Brain Development with Diffusion Tensor Magnetic Resonance Imaging
Authors: Huang Hao ,   Assistant Professor, Advanced Imaging Research Center, University of Texas Southwestern Medical Center
Published: October 2015

Human brain anatomy is characterized by dramatic structural changes during fetal development. It is extraordinarily complex and yet its origin is asimple tubular structure. Revealing detailed anatomy at different stages of human fetal brain development not only aids in understanding this highlyordered process, but also provides clues to detect abnormalities caused by genetic or environmental factors. For example, the characterization ofwhite matter axon growth could provide important clues to understanding the inhomegeneity of white matter injuries in cerebral palsy. However,anatomical studies of human brain development during this period are surprisingly scarce, and histology-based atlases have only recently becomeavailable. Diffusion tensor imaging (DTI), a novel method of magnetic resonance imaging (MRI), is capable of delineating anatomical components withhigh contrast and revealing structures at the microscopic level. The volumetric measurement from 3D DTI data can quantify structural growth. Asdiscussed in this article, the fetal brain DTI database will be a valuable resource for human brain developmental study and will provide referencestandards for diagnostic radiology of premature newborns.
What Has Functional Magnetic Resonance Imaging Revealed Regarding the Neurobehavioral Correlates of Sleep Deprivation?
Authors: WL Chee Michael ,   Professor, Cognitive Neuroscience Laboratory, Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School Singapore
Published: October 2015

A night of total sleep deprivation can result in performance decline in several cognitive domains. Functional magnetic resonance imaging (fMRI) hashelped to reveal the neuroanatomical correlates of such changes in attention and memory, as well as in risky decision-making. Studies of sleepdeprivation have shed light on the role of sleep in the consolidation of declarative memory, which can be observed in the form of temporally specificchanges in hippocampal and neocortical activation. Sleep deprivation can also be thought of as a cognitive stress test that may afford testing ofcognitive enhancers.
Biomarkers in Alzheimer’s Disease—Perspectives for the Future
Authors: Cummings Jeffrey L ,   Director, Cleveland Clinic Lou Ruvo Center for Brain Health, and Professor of Neuro-Therapeutics, Neurological Institute, Cleveland Clinic
Published: October 2015

Alzheimers disease (AD) is characterized pathologically by the overproduction or excessive accumulation of amyloid beta protein leading to the deposition of diffuse and neuriric plaques. Hyperphosphorylation of tau protein promotes the accumulation of intracellular neurofibrillary tangles. These events comprise a pathological cascade in the AD brain that includes oxidation, inflammation, excitotoxicity, and apoptosis with activation of myriad associated intracellular pathways. Some of these neuropathological changes are detectable by biomarkers such as neuroimaging or serum or cerebrospinal fluid (CSF) measures. Magnetic resonance imaging (MRI) reveals cerebral atrophy, fluorodeoxyglucose positron emission tomography (FDG-PET) shows regional brain hypometabolism, amyloid imaging demonstrates fibrillar amyloid in plaques, and CSF measures reveal decreased levels of the amyloid protein and increased levels of total tau protein and hyperphosphorylated tau. These biomarkers provide the basis for identifying and characterizing asymptomatic pre-clinical AD pathology, minimally symptomatic prodromal AD, and AD type dementia. Biomarkers have an increasingly important role in AD care and research at all stages of disease, and promise to assist in the development of new AD therapies.
Monoamine Oxidase Type B Inhibitors in the Treatment of Early Parkinson’s Disease
Authors: Abraham Karunapuzha Cherian , Chitnis Shilpa , Dewey Richard B ,   Movement Disorders Fellow,   Assistant Professor of Neurology,   Professor of Neurology, University of Texas Southwestern Medical Center
Published: October 2015

Therapy in Parkinsons disease (PD) needs to be individualized since patients differ in symptom expression and responsiveness to pharmacotherapy. Disease-modifying drugs should be considered early in the course of the disease, but none is currently US Food and Drug Administration (FDA)-approved for this indication. Symptomatic therapies should be optimized to keep the patient independent and functioning for as long as possible. Early therapies in PD consist of dopamine agonists, monoamine oxidase type B (MAO-B) inhibitors, and, in some patients, carbidopalevodopa (depending on age and symptom severity). MAO-B inhibitors are approved by the FDA for monotherapy in treatment of early PD and as an adjunct to levodopa in advanced disease. This article focuses on the role of MAO-B enzymes in PD pathogenesis and reviews clinical evidence for the use of MAO-B inhibitors in the treatment of early PD.
Genetic Insights into Early-onset Parkinson’s Disease
Authors: Alcalay Roy N , Waters Cheryl ,   Assistant Professor,   Albert B and Judith L Glickman Professor, Division of Movement Disorders, Department of Neurology, Columbia University Medical Center
Published: October 2015

Early-onset Parkinson’s disease (EOPD) is defined as disease onset before 40 or 50 years of age. The clinical characteristics of EOPD are very similar to those of late-onset PD, but dystonia is more often a presenting symptom, dementia is rare, and disease progression may be slower. Mutations in several genes have been described in cases with EOPD, often with strong family history, including mutations in α-synuclein (SNCA),DJ-1, PTEN-induced kinase-1 (PINK-1), andATP13A2. However, the most common mutations identified in EOPD are in Parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2), and glucocerebrosidase (GBA). With the exception ofSNCAandATP13A2carriers, mutation carriers are often indistinguishable from non-carriers. Large series of EOPD cases that are not ascertained by family history estimate mutation frequency at 4–16%. Given that the frequency of positive family history is much higher, we believe that many genetic risk factors are yet to be discovered.
Multimodal Computed Tomography in Acute Ischemic Stroke
Authors: Rastogi Sachin , Liebeskind David S ,   Fellow, Neuro-interventional Radiology,   Associate Professor of Neurology, University of California, Los Angeles
Published: October 2015

Stroke is the third leading cause of death in the US, affecting 795,000 individuals annually. Currently, only a small percentage of acute stroke patients receive thrombolytic treatment. A significant limitation is the current use of strict time criteria in the decision to treat. As there are significant interindividual variations in response to an acute vascular occlusion, the goal of modern imaging such as multimodal computed tomography (CT) is to rapidly identify acute ischemic stroke patients and determine which patients are likely to benefit from treatment based on tissue perfusion status rather than time of presentation alone. Multimodal CT consists of a non-contrast head CT, CT angiogram (CTA) of the head and neck, and CT perfusion (CTP). The non-contrast head CT allows rapid triage of a patient with hemorrhagic versus ischemic stroke. The CTA allows identification of the site of vascular pathology with similar quality to digital subtraction angiography. The CTP scan allows for determination of the infarct core and surrounding ischemic penumbra, which remains at risk for infarction if perfusion is not restored. This allows the potential to prospectively treat only those patients likely to benefit from thrombolysis while protecting those patients unlikely to benefit from the risks associated with treatment.
Do New Antiepileptic Drugs with Novel Mechanisms of Action Suggest Reconsideration of Rational Polypharmacy?
Authors: Gidal Barry E ,   Professor of Pharmacy and Neurology, and Division Chair, School of Pharmacy, University of Wisconsin
Published: October 2015

Although effective control of epilepsy can be achieved by a single antiepileptic drug (AED), the condition persists in a significant number of patients despite increasing dosages with monotherapy and polytherapy. Treatment with combinations of older AEDs has been known to cause undesirable drugdrug interactions and side effects. However, there has been renewed interest in polytherapy with the advent of newer AEDs with novel mechanisms of actions that are less likely to cause adverse effects in patients. Animal seizure models are useful for determining whether AEDs will be effective in generalised or partial seizures prior to clinical studies and isobolgraphic analysis may allow for a more systematic, rational approach to predicting whether a given combination of drugs will result in a greater or lesser pharmacologic effect. Since one treatment strategy does not suit all patients, studies should focus on the tolerability and safety of specific combinations of AEDs in order to provide guidance to physicians. In summary, pharmacokinetic interactions must be taken into account in studies in humans and animals with measurement of toxicity as well as efficacy.
Chronic Post-traumatic Headache—Understanding the Complexities and Treatment Options
Authors: Solomon Seymour ,   Director Emeritus, Headache Center, Montefiore Medical Center, and Professor of Neurology, Albert Einstein College of Medicine
Published: October 2015

As there are few or no objective signs of disease and standard laboratory tests and imaging studies often appear normal, chronic post-traumatic headache (CPTH) is frequently disrespected. Confusion about its legitimacy began with its initial recognition in the mid-19th century, followed by modern attempts to establish its criteria in theInternational Classification of Headache Disorders(ICHD). There are no distinct clinical features of CPTH. Most resemble tension-type headache, but symptoms of migraine and, rarely, of other primary headaches may occur. CPTH is often associated with the post-concussion/post-traumatic stress syndrome. Anatomic, physiologic, psychologic, socioeconomic, and cultural factors may contribute to the development of CPTH. Changes in diffusion tensor imaging, a refinement of magnetic resonance imaging (MRI), have been correlated with subtle cognitive abnormalities in neuropsychologic tests of patients after mild traumatic brain injury. These studies and others may prove to be biologic markers for headache and other symptoms of the post-concussion syndrome. The therapy of CPTH is similar to that of the phenotypically primary headaches. Avoidance of analgesic overuse, prophylactic medications, and, in particular, non-pharmacologic modalities are the basic elements. Active participation by patients in headache management and an empathetic physician are essential.
Reduction of Surgical-site Infections in Neurosurgery—The Advantage of Antiseptics Combined with a Sterile Surface
Authors: Parks Patrick J , Nohra Georges K ,   Adjunct Associate Professor of Experimental and Clinical Pharmacology, University of Minnesota, and Advanced Division Scientist, Skin and Wound Care Division, 3M,   Associate Professor of Neurosurgery, Saint Joseph University, and Head, Neurosurgery Department, Notre Dame Des Secours Hospital, Byblos
Published: October 2015

Infection at the operative site is associated with high morbidity, mortality, and prolonged hospitalization. Typically, in neurosurgical cases the infection rate varies between 1 and 4%. The rise in antimicrobial resistance makes pre-operative methods to reduce surgical-site infection even more important. This is essential since hospitalized patients tend to have a higher frequency of resistant organisms, and the rise in methicillin-resistantStaphylococcus aureus(MRSA) infections has made antibiotic prophylaxis of this highly virulent organism more difficult. In this article we consider the role of pre-operative antisepsis, which aims to reduce bacterial density in the operative site, and the development of a sterile surface concept as part of an approach to reduce surgical-site infection in a neurosurgical setting. The risk for surgical-site infection is proportional to residual bacteria at the wound site, so a reduction in skin bacterial density will be associated with a concomitant reduction in surgical-site infection. The cumulativein vitroandin vivoevidence related to wound contamination and extensive clinical experience with implanted neurosurgical devices illustrate the utility of using 3MIoban2 as part of an infection prevention regimen within neurosurgery.
Update on the Surgical Management of Craniopharyngiomas
Authors: Komotar Ricardo J , Kellner Christopher P , Bruce Jeffrey N ,   Chief Resident,   Junior Resident,   Professor of Neurological Surgery, Department of Neurological Surgery, The Neurological Institute of New York, Columbia University Medical Center
Published: October 2015

Despite advances in microsurgical and skull base techniques, the surgical treatment of craniopharyngiomas continues to pose a challenge to surgeons. Controversy continues to exist between proponents of subtotal resection in conjunction with radiotherapy, who argue that this less aggressive approach can yield equivalent control rates with lower morbidity, and others who argue for the superiority of gross total resection. Regardless of whether gross total or subtotal resection is the goal, surgical planning must include a thorough endocrine and neuro-ophthamologic evaluation as well as imaging, and the approach, whether trans-sphenoidal or transcranial, must take into account the nature of the tumor and its location. In addition, optimal management of craniopharyngiomas must consist of individualized and multidisciplinary therapy including an array of subspecialty fields such as endocrinology, neuro-ophthalmology, neuropsychology, and radiation oncology.
The WalkAide® Functional Electrical Stimulation System—A Novel Therapeutic Approach For Foot Drop in Central Nervous System Disorders
Authors: Cameron Michelle H ,   Neurologist, Multiple Sclerosis Center of Excellence West, Portland Veterans Affairs Medical Center, and Assistant Professor, Department of Neurology, Multiple Sclerosis Center of Oregon, Oregon Health and Science University
Published: October 2015

Foot drop is the inability to voluntarily dorsiflex the ankle during the swing phase of gait. Foot drop decreases gait quality, limits mobility, increases fall risk, and greatly increases energy expenditure during walking. Traditionally, foot drop is treated with passive dorsiflexion support by an ankle foot orthosis (AFO) but today, functional electrical stimulation (FES) devices are available to promote comfortable, effective active dorsiflexion during gait for patients with central nervous system (CNS) causes of foot drop. The WalkAide® FES System’s unique control system, with tilt sensors to trigger electrical stimulation during swing phase, can help normalize gait and thus optimize safety, cosmesis, and energy efficiency in people with stroke, multiple sclerosis, cerebral palsy, and a wide range of other CNS disorders.
Neuromodulatory Approaches to the Management of Medically Refractory Cluster Headache
Authors: May Arne , Goadsby Peter J ,   Professor of Neurology, Department of Systems Neuroscience, University of Hamburg,   Professor of Neurology, Headache Group, Department of Neurology, University of California, San Francisco
Published: October 2015

The trigeminal autonomic cephalalgias are a group of primary headache disorders characterized by unilateral trigeminal distribution of pain that occurs in association with ipsilateral cranial autonomic features. The most prominent one is cluster headache, a dreadful disease with excrutiating pain attacks. These attacks last no longer than two hours but may occur several times per day. It is mandatory to find an efficient therapy for these patients, but some are unresponsive to all treatments. In these intractable cases invasive procedures are introduced, but the available evidence (while conflicting) illustrates that trigeminal denervation may not be effective in preventing the headache attacks or autonomic symptoms of chronic cluster headache. Modern neurostimulating approaches, such as stimulation of the greater occipital nerve and hypothalamic deep brain stimulation, supersede neurodestructive procedures. Both stimulation methods are exquisite and potentially life-saving treatment options in otherwise intractable patients, but they need to be better characterized and further long-term data are needed.
Molecular Imaging in Alzheimer’s Disease
Authors: Herholz Karl ,   Professor of Clinical Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester
Published: October 2015

The most sensitive and accurate method for molecular imaging in human Alzheimer’s disease (AD) is positron emission tomography (PET). The most widely available PET tracer, which is also used in clinical oncology, is 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG is an imaging biomarker for early and differential diagnosis of AD. Even higher molecular specificity and sensitivity for detection of AD before dementia onset is provided by high-affinity ligands for fibrillary amyloid. 11C-Pittsburgh Compound B is widely being used in research laboratories, while new 18F-labeled ligands are currently undergoing formal clinical trials as amyloid imaging agents and are expected to become commercially available for clinical use in the near future. A large variety of tracers is being developed and used in dementia research for activated microglia and multiple neurotransmitter systems to study disease pathophysiology, biological correlates of clinical symptoms, and new possibilities for treatment. Current studies in humans are investigating cholinergic, serotonergic, and dopaminergic neurotransmission.
Diagnosing Major Depression Following Moderate to Severe Traumatic Brain Injury—Evidence-based Recommendations for Clinicians
Authors: Seel Ronald T , Macciocchi Stephen , Kreutzer Jeffrey S , Kaelin Darryl , Katz Douglas I ,   Director, Brain Injury Research, Shepherd Center,   Director, Rehabilitation Psychology and Neuropsychology, Shepherd Center,   Professor of Physical Medicine and Rehabilitation, and Professor of Neurosurgery and Psychiatry, Virginia Commonwealth University Medical Center,   Medical Director, Acquired Brain Injury Program, Shepherd Center,   Associate Professor of Neurology, Department of Neurology, Boston University School of Medicine and Brain Injury Program, Braintree Rehabilitation Hospital
Published: October 2015

While major depression (MD) is the most common psychiatric disorder following traumatic brain injury (TBI), diagnosing MD can be challenging due to cognitive, emotional, and somatic symptoms that overlap with TBI and other psychiatric disorders. Current evidence suggests that the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) works well in the TBI population. The presence of ‘organic’ TBI sequelae that overlap with DSM-IV MD criteria do not appear to lead to false-positive MD diagnoses. Rumination, self-criticism, and guilt may best differentiate depressed from non-depressed persons following TBI. Anxiety, aggression, sleep problems, alcohol use, lower income levels, poor social functioning, and negative thinking are primary risk factors for the development of MD following TBI. Current evidence suggests that the Patient Health Questionnaire-9 is the best self-report scale option for depression screening after TBI. Apathy, anxiety, dysregulation, and emotional lability require careful clinical consideration when making a differential diagnosis of MD in persons with TBI. Research indicates that asking specific questions about depressed mood, loss of interest or pleasure, and psychosocial functioning yields the most accurate diagnosis. Practical recommendations are provided on how clinicians can improve MD diagnostic accuracy.
Is There an Optimal Management Regimen for Transient Ischemic Attack Patients to Best Prevent Stroke?
Authors: Chatzikonstantinou Anastasios , Hennerici Michael G ,   Neurologist and Senior Physician,   Professor of Neurology, and Chair, Department of Neurology, University Hospital of Mannheim, University of Heidelberg
Published: October 2015

Transient ischemic attacks (TIAs) are associated with a high risk of subsequent stroke and often pose a diagnostic and treatment challenge. It is important to separate TIAs from stroke as well as from TIA mimics to estimate individual stroke risk early and properly. New definitions and standards of clinical investigations are supportive: clinical parameters as symptom fluctuations, clinical scores (such as the ABCD2 score) and advanced magnetic resonance brain imaging in particular. Management should take place in a stroke-specialized center and consist of rapid assessment and identification of those patients at highest risk for subsequent strokes, including extensive brain and vascular imaging as well as cardiological assessement. Based on these work-up results, best suitable prevention should start immediately, usually consisting of antiplatelet agents, anticoagulation, statins, antihypertensive, and/or antidiabetic drugs and lifestyle modifications, including cessation of smoking. Studies have demonstrated that such an optimal management can reduce the risk of stroke following TIA by up to 80%.
Alemtuzumab—A New Efficacy Benchmark in Relapsing–Remitting Multiple Sclerosis?
Authors: Khan Omar A ,   Professor of Neurology, and Director, Multiple Sclerosis Clinical Research Center and Image Analysis Laboratory, Department of Neurology, Wayne State University School of Medicine
Published: October 2015

The disease-modifying drugs (DMDs) available for the treatment of multiple sclerosis (MS) have been used effectively for nearly two decades. These treatments delay the neurorodegenerative process, but do not restore lost neurological function. New oral DMDs are becoming available that offer improved convenience over existing injectable DMDs. Recently, several monoclonal antibody treatments have been developed for MS; the furthest developed is alemtuzumab (Campath-1H). In a landmark phase II clinical trial (CAMMS223) on patients with relapsing–remitting MS (RRMS), short cycles of alemtuzumab given at baseline, at 12 months, and optionally at 24 months, demonstrated superior and sustained efficacy in terms of relapse rates and magnetic resonance imaging (MRI) findings over the comparator compound, interferon beta-1a (IFNβ-1a), which was given subcutaneously and continuously. Most notably, the mean disability score for patients receiving alemtuzumab showed an unprecedented improvement, whereas for IFNβ-1a it deteriorated. Alemtuzumab in treating RRMS is the subject of two ongoing phase III trials, the results of which have the potential to change future treatments and prognoses for many patients.
Clinical and Ethical Issues in Palliative Care and Dementia—An Overview
Authors: Teper Emma L , Hughes Julian C ,   Specialist Registrar in Old Age Psychiatry, Gateshead Health NHS Foundation Trust,   Consultant in Old Age Psychiatry, and Honorary Professor of Philosophy of Ageing, Northumbria Healthcare NHS Foundation Trust and Institute for Ageing and Health, Newcastle University
Published: October 2015

The prevalence of dementia across Europe and the world is increasing. People die with and from dementia and, as such, advanced dementia can be considered a terminal condition. This, alongside the realization that care for people with dementia is deficient, has led to increasing interest in palliative care in dementia. Palliative care can be a rather broad term with different meanings, but nonetheless guidelines and expert opinions have been developed with the aim of improving overall care for people with dementia. Although at times the evidence on which these guidelines are based is somewhat sparse, they provide guidance in specific areas relevant to dementia. The main areas covered are pain, infection and fevers, artificial nutrition and hydration, resuscitation, and psychological, social, and spiritual needs. We shall consider the evidence on which guidance is based and then highlight a recent ethical framework developed to help thinking around the issues that arise in dementia care.
Approaches to the Diagnosis of Parkinson’s Disease during the Pre-motor Phase
Authors: Jacoby Nuri , Stone Jacqueline B , Henchcliffe Claire ,   Resident in Neurology,   Resident in Neurology,   Associate Professor in Neurology and Neuroscience, Weill Medical College of Cornell University
Published: October 2015

Parkinsons disease (PD) remains a clinical diagnosis based primarily upon motor features of tremor, rigidity, and bradykinesia. However, by the time motor symptoms occur, the underlying pathology may be widespread. Approaches using a combination of clinical batteries and sophisticated biomarker technology now hold promise for identifying individuals earlier in the course of the disease, including those at risk of PD who may not yet have manifested any motor symptoms. Non-motor symptoms, such as specific sleep disorders, olfactory dysfunction, and autonomic changes, occur during a pre-motor phase, and their use in PD risk stratification is being actively evaluated. Neuroimaging techniques, in particular those focused upon measuring dopamine transporter density, are now in use in many specialist centers, molecular markers are in development and validation phases, and the use of genomic analyses has expanded the number of loci identified as contributing to PD risk. Identifying those at risk of developing PD will aid in the clinical management of the disease, and perhaps enable the use of disease-modifying drugs at as early a stage as possible.
Interventional Neurology—Recent Advances and New Applications
Authors: Chen Michael ,   Assistant Professor of Neurology, Neurosurgery and Radiology, Rush University Medical Center
Published: October 2015

Interventional neurology refers to endovascular, catheter-based techniques using fluoroscopy and angiography to diagnose and treat vascular disease of the central nervous system. This article provides an update on the recent advances and newer applications of diagnostic cerebral angiography, acute endovascular stroke treatment, revascularization of carotid and intracranial stenosis, as well as cerebral aneurysm treatment. More importantly, however, is demonstrating not only how diagnostic cerebral catheter angiography has been redefined, but also how the associated interventional procedures have transformed the therapeutic landscape for stroke patients.
Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease
Authors: Bohnen Nicolaas I , Albin Roger L , Müller Martijn LTM , Chou Kelvin L ,   Professor, Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, and Veterans Administration, Ann Arbor,   Professor, Department of Neurology, University of Michigan, and Veterans Administration, Ann Arbor,   Research Investigator, Department of Radiology, University of Michigan,   Clinical Associate Professor, Departments of Neurology and Neurosurgery, University of Michigan
Published: October 2015

There is a need to explore non-dopaminergic approaches to treating balance and gait problems in Parkinsons disease (PD). There is emerging evidence on the role of cholinergic denervation of the pedunculopontine nucleus (PPN) thalamus system and falls in PD. Preliminary clinical trial data suggest that the subgroup of PD patients with frequent falls may be suitable candidates for future cholinergic augmentation clinical trials. Recent controlled clinical trials using methylphenidate have been unable to confirm earlier reports of improved gait in PD. Although progressive deterioration of axial motor symptoms occur with deep brain stimulation of the subthalamic nucleus or globus pallidus interna, new preliminary research suggests that other surgical stimulation sites, such as the PPN, may have a potential benefit on gait and balance impairments in PD. Continuing vigorous exercise and physical fitness should be highly encouraged to patients with PD who are at risk of physical deconditioning and fear of falling, but effective antifall physical therapy interventions remain an unmet clinical need.
Calcium Channels as a Potential Target for Neuroprotection in Parkinson’s Disease
Authors: Simuni Tanya , Surmeier D James ,   Associate Professor of Neurology and Director, Parkinson's Disease and Movement Disorders Center,   Nathan S Davis Professor and Chairman, Department of Physiology, Feinberg School of Medicine, Northwestern University
Published: October 2015

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1 % of the population above the age 65. The principal motor symptoms of PD are attributable to the preferential loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Recent studies demonstrate that dopaminergic (DA) neurons in the SNc, as well as many neurons in other regions affected by PD, have a distinctive physiologic phenotype. They are autonomous L-type Cav1.3 Ca2+channels pacemakers. Continuous Ca2+influx results in increased oxidative stress that may explain the selective vulnerability of these neurons. More importantly for PD, blocking these channels with isradipine, the most potent of the dihydropyridine (DHP) channel antagonists at L-type Ca2+channels with the Cav1.3 subunit, protects these neurons inin vitroandin vivomodels of parkinsonism. Neuroprotective effect is achieved at the serum concentrations that can be achieved with the doses approved for human use. Recent epidemiologic data also points to a reduced risk of PD with chronic use of specifically centrally acting DHP Ca2+channel antagonists. Isradipine is an approved agent for the treatment of hypertension. Our pilot data demonstrate acceptable dose-dependent tolerability of isradipine in early PD. A pilot Phase II multicenter, double-blind, placebo-controlled, safety, tolerability, and dosage finding study of isradipine in early PD has completed recruitment, with the results of the study to be available in the near future. Results of that study will inform the design of the planned Phase III pivotal efficacy trial of isradipine, as a disease modifying agent in early PD.
Non-motor Symptoms in Parkinson’s Disease
Authors: Uc Ergun Y , Tippin Jon , Chou Kelvin L , Erickson Bradley A , Doerschug Kevin C , Jimmeh Fletcher Decontee M ,   Associate Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City,   Associate Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City,   Clinical Associate Professor, Departments of Neurology and Neurosurgery, University of Michigan,   Assistant Professor, Department of Urology, University of Iowa,   Associate Professor, Department of Internal Medicine, University of Iowa,   Assistant Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City
Published: October 2015

In addition to typical motor dysfunction (parkinsonism), diverse non-motor symptoms (NMS) are frequently observed in patients with Parkinsons disease (PD). Some NMS may antedate the diagnosis of PD. Examples of NMS include cognitive impairment, autonomic dysfunction, visual dysfunction, sleep abnormalities, and psychiatric disorders. NMS are associated with wide-ranging abnormalities in extranigral dopaminergic systems and non-dopaminergic (e.g. cholinergic, noradrenergic, serotoninergic) systems. The type and severity of NMS vary based on age, disease severity, and predominant motor symptoms. NMS can be disabling and reduce quality of life. Treatment of NMS can be challenging. Some NMS are helped by dopaminergic treatment, whereas others can be induced or exacerbated by treatments that help the motor dysfunction. Physicians should probe their PD patients about their NMS and address them for better care. Clinical trials should incorporate NMS as outcomes for more meaningful conclusions on the effect of treatments under investigation.
Autoimmune Comorbid Conditions in Multiple Sclerosis
Authors: Berkovich Regina , Subhani Dawood , Steinman Lawrence ,   Assistant Professor of Clinical Neurology, Keck School of Medicine University of Southern California,   Clinical Research Assistant, University of Southern California MS Comprehensive Care Center,   Professor of Neurology and Neurological Sciences, Stanford School of Medicine
Published: October 2015

Autoimmune comorbidities occur frequently in multiple sclerosis (MS). They may arise as a consequence of a genetic susceptibility to autoimmunity. Certain pathological mechanisms are common to several autoimmune conditions. In the presence of comorbid autoimmune conditions, certain MS therapeutics may be preferable to others. Autoimmune comorbidity associated with MS could be a factor in predicting response to specific MS therapeutics. Treatment with interferon beta has been reported to precipitate immune-mediated abnormalities or to exacerbate existing autoimmune diseases. In comparison, there are fewer reported cases of treatment-associated comorbidities linked with autoimmune disease in patients taking glatiramer acetate. Knowledge of the factors influencing autoimmune comorbidities may provide insights into the complex pathogenesis of MS and help inform treatment choices.
Cambia® (Diclofenac Potassium for Oral Solution) in the Management of Acute Migraine
Authors: Kahn Kevin ,   Director, Clinical Care Center, Carolina Headache Institute
Published: October 2015

Migraine is a prevalent and disabling disorder involving central and peripheral neurologic processes that generate inflammatory mediated pain. Cambia® (diclofenac potassium for oral solution), a novel patented form of the anti-inflammatory medication diclofenac potassium, has been approved by the US Food and Drug Administration for the acute treatment of migraine. Clinical trial data have demonstrated that this formulation offers a four-fold decrease in time of onset of relief compared with conventional diclofenac, which has comparable efficacy to triptan medication. It has also proven effective in a real-world setting. Over the past few years, it has been established that migraine treatment that is administered early may prevent central sensitization and improve treatment outcomes. Given the importance of early intervention in migraine treatment, this medication offers rapid, convenient, and effective relief with a favorable side-effect profile. This review describes migraine pathophysiology, treatment rationale, clinical trial results, and real-world experience with the use of this new medication.
Peripheral Nerve Stimulation for Neuropathic Pain
Authors: Slavin Konstantin V ,   Professor, Stereotactic and Functional Neurosurgery, Department of Neurosurgery, University of Illinois at Chicago
Published: October 2015

Over the last two decades, electrical neuromodulation has become a dominant approach in surgical treatment of medically refractory neuropathic pain, essentially eclipsing multiple available neuroablative procedures. Among different types of neuromodulation, peripheral nerve stimulation (PNS) holds the unique position of being the least invasiveand at the same time the least established in terms of scientific evidence and regulatory approvals. However, it is now gaining tremendous momentum in terms of accumulation of clinical experience and development of new indications. As a matter of fact, recent European approval of PNS for treatment of chronic low back pain and intractable migraine headaches is expected to add legitimacy and marketing support to the entire field of PNS. This article provides an overview of PNS history, reviews current thoughts regarding its mechanism of action, summarizes common indications, clinical outcomes, technical procedural details, and complications, and suggests future directions for PNS development. It appears that PNS today is the most rapidly growing field of neuromodulationand that does not come as a surprise, considering its potential for treatment of very prevalent and hard-to-treat conditions, such as back pain and headaches. From the point of view of a practicing neurologist, PNS presents an attractive pain management option that combines a high level of efficacy and reproducibility of results with low invasiveness and minimal morbidity. As the worldwide experience with PNS continues to grow, one may expect to see it becoming a widely accepted treatment approach in a variety of clinical conditions.
Gamma Knife Radiosurgery for Trigeminal Neuralgia—A Review
Authors: Monaco III Edward A , Kano Hideyuki , Kooshkabadi Ali , Lunsford L Dade ,   Resident,   Research Assistant Professor,   Resident,   Professor, Department of Neurological Surgery, University of Pittsburgh Medical Center
Published: October 2015

Gamma knife radiosurgery (GKRS) evolved from the vision of Lars Leksell as a method of bloodless surgery for treating a wide variety of intracranial pathologies. Since the first GKRS procedure for trigeminal neuralgia (TN) in the early 1970s, thousands of medically refractory patients have been treated, with good results. GKRS has become a first-line treatment for medically refractory TN along with microvascular decompression and percutaneous rhizotomy. GKRS offers the advantages of minimal invasiveness and extremely low risk. When recommending a surgical treatment modality for medically refractory TN, one must consider patient preferences, procedural risks, medical comorbidities, and the success rates of the various approaches. In this context, we review the role of GKRS in the treatment of medically refractory TN.
Advanced Neuroimaging for Modern Epilepsy Surgery
Authors: Wang Doris D , Santos-Sanchez Carlos , Garcia Paul A , Chang Edward F ,   Resident, Department of Neurological Surgery and Comprehensive Epilepsy Center,   Junior Specialist, Comprehensive Epilepsy Center and Department of Neurology,   Professor of Clinical Neurology, Comprehensive Epilepsy Center and Department of Neurology,   Assistant Professor of Neurological Surgery and Physiology, Department of Neurological Surgery and Comprehensive Epilepsy Center, University of California, San Francisco
Published: October 2015

Localizing the onset of seizures to guide epilepsy surgery can be notoriously difficult. Modern neuroimaging has revolutionized the field by improving the diagnosis and treatment of epilepsy. In order to ameliorate seizures without causing new neurologic morbidity, many imaging tools have been developed to guide safe and effective resective surgery. In this article, we discuss recent advances in structural imaging using ultrahigh-field magnetic resonance imaging, metabolic functional imaging techniques of positron emission tomography and single positron emission computed tomography, and electrophysiologic imaging using magnetoencephalography. Our goal is to provide an overview of these state-of-the-art imaging modalities, their role in guiding surgery, and how they are incorporated into the pre-surgical evaluation of epilepsy.
Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis—A Medical, Sociological, and Media Controversy
Authors: Miller Aaron ,   Medical Director, Corinne Goldsmith Dickinson Center for Multiple Sclerosis and Professor of Neurology, Mount Sinai School of Medicine
Published: October 2015

In 2009, Zamboni et al. coined the term chronic cerebrospinal venous insufficiency (CCSVI). On the basis of transcranial and extra-cranial color-coded Doppler ultrasonography, they operationally defined CCSVI as occurring when at least two out of five abnormalities were present. They claimed to find CCSVI in 100 % of 109 individuals with multiple sclerosis (MS) and in none of 177 healthy controls. Zambonis group subsequently reported an uncontrolled treatment trial of cerebral venoplasty, which was termed the liberation procedure, and claimed that the procedure benefited people with MS. The Zamboni reports were received with considerable skepticism, regarding both their biological plausibility and the claims of 100 % sensitivity, specificity, positive predictive value, and negative predictive value. No investigators have subsequently been able to replicate the Zamboni observations. Although some additional reports have indicated finding venous abnormalities in more MS patients than in other groups, most have either found no association of CCSVI with MS, or else have found substantial numbers of controls, either healthy or with other neurologic disease, to have the abnormalities. The original Zamboni reports were widely publicized in the mainstream media, especially in Canada, and sparked a raging controversy in the social media. Patients clamored for trials of cerebral venoplasty and others demanded its availability or traveled around the globe to undergo the procedure. The Canadian Institutes of Health Research have now solicited proposals for a Phase I/II clinical trial. At this point, additional scientific studies, including many funded by the National Multiple Sclerosis Society and the Multiple Sclerosis Society of Canada, are moving toward completion and will hopefully allow a proper judgment of the validity of the concept of CCSVI in relationship to MS. In the meantime, it is important that physicians remain respectful of patients views, but that they are not reticent about expressing their own professional opinions based on available evidence, while emphasizing the importance of proper scientific research.
Update on Amyloid-associated Intracerebral Hemorrhage
Authors: Grysiewicz Rebbeca , Gorelick Philip B ,   Assistant Professor of Neurology, Section of Cerebrovascular Disease and Neurological Critical Care, University of Illinois College of Medicine at Chicago, Illinois, US,   Medical Director, Hauenstein Neuroscience Center, Saint Marys Health Care and Clinical Professor, Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, Michigan, US
Published: October 2015

Cerebral congophilic or amyloid angiopathy (CAA) is a clinicopathological entity that is considered a common cause of primary non-traumatic brain hemorrhage in the elderly. CAA is frequently associated with Alzheimers disease (AD) and has become a primary focus of scientific inquiry. The spectrum of intracerebral hemorrhage (ICH) that may occur in CAA includes: cerebral lobar hemorrhages, deep hemorrhages, purely subarachnoid and subdural hemorrhages and cerebral microbleeds. CAA is also associated with microinfarcts, leukoencephalopathy and superficial siderosis. This brief article will provide an update on the advances in our understanding of CAA-associated ICH with a focus on the following topics: neuropathology and mechanism of CAA-related hemorrhage; epidemiology, including genetic and other possible risk factors; clinical presentation; diagnosis, including newer imaging modalities; and prospects for prevention and treatment.
Transthyretin-associated Familial Amyloid Polyneuropathy—Current and Emerging Therapies
Authors: Nuvolone Mario , Obici Laura , Merlini Giampaolo ,   Postgraduate Researcher, Amyloidosis Research and Treatment Center, Foundation IRCCS San Matteo Hospital and Department of Molecular Medicine, University of Pavia, Institute for Advanced Studies, Pavia, Italy, and Institute of Neuropathology, University Hospital of Zürich, Switzerland,   Attending Physician and Researcher, Amyloidosis Research and Treatment Center, Foundation Scientific Institute Policlinico, San Matteo, Pavia, Italy,   Professor, Amyloidosis Research and Treatment Center, Foundation IRCCS San Matteo Hospital and Department of Molecular Medicine, University of Pavia, Italy
Published: October 2015

Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP), the most common form of systemic hereditary amyloidosis worldwide, is a late-adult-onset autosomal dominant disease caused by mutations in theTTRgene, with peaks in prevalence in endemic areas. The clinical picture is dominated by a progressive length-dependent polyneuropathy with onset in the feet with loss of temperature and pain sensations, accompanied by life-threatening autonomic dysfunction and infiltrative cardiomyopathy, as well as ocular disturbances. Variable expressivity, in terms of age of onset and involvement of extra-neurologic sites, can be due to different mutations, but is also observed among individuals with the same mutation in different countries. Therefore, diagnosis of TTR-FAP is often a challenge and must rely on careful clinical assessment combined with a multidisciplinary approach. Elimination of the synthesis of mutated TTR, through liver transplantation, may arrest the progressive neuropathy but not the cardiac and ocular involvement. Novel drugs have recently been developed based on a better understanding of the molecular mechanisms of the disease. Drugs that prevent the misfolding and deposition of mutated TTR have entered clinical trials, and one of these, tafamidis meglumine, has been approved in Europe and is now clinically available. Other medicines are now in the pipeline aimed at suppressing the expression of the mutatedTTRgene or at promoting amyloid fibril destructuration, favoring resorption of amyloid deposits. These recent advancements provide grounded hope of an imminent significant improvement in the care of this life-threatening multi-system disease.