bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Single Photon Emission Computed Tomography in Differentiating Dementia with Lewy Bodies - A Review of Neurotransmitter and Perfusion Imaging
Authors: Morgan Shirlony , Walker Zuzana ,   Specialist Registrar, Department of Mental Health Sciences, Royal Free Hampstead NHS Trust,   Senior Lecturer, University College Medical School, University College London
Published: June 2015

The accuracy of the clinical diagnosis of dementia with Lewy bodies continues to be relatively poor. Several neuroimaging techniques have been used to facilitate a more accurate diagnosis. Thus far, functional neuroimaging has provided the most help. This article concentrates on the use of single photon emission computed tomography (SPECT) and reports on the efficacy data available from studies investigating cerebral perfusion, cardiac scintigraphy and dopaminergic neurotransmission. The results from perfusion studies are inconsistent. Cardiac scintigraphy shows more promise, but it is not yet known whether co-morbid cardiac conditions, which are common in the elderly, will limit the clinical use of this method. The radioligand123I–FP-CIT binds to dopamine transporters in nigrostriatal nerve terminals and provides a way of assessing the neurodegeneration caused by Lewy body pathology. Abnormal123I–FP-CIT has been shown to have high sensitivity and specificity in an autopsy study and a large multicentre trial. This article aims to give an overview of the topic.
Functional Information on Meningiomas Through Perfusion Magnetic Resonance Imaging
Authors: Zhang Hao , Zhang Guixiang , Oudkerk Matthijs ,   Department of Radiology, Shanghai Jiaotong University Affiliated First Hospital,   Department of Radiology, University Medical Center Groningen,   Department of Radiology, University Medical Center Groningen,   Department of Radiology, Shanghai Jiaotong University Affiliated First Hospital
Published: June 2015

This article focuses on the use of perfusion magnetic resonance imaging (MRI), and in particular dynamic susceptibility contrast-enhanced MRI (DSC-MRI), to assess haemodynamics in meningiomas. We first introduce the basic principles of DSC-MRI and the most popular imaging techniques and perfusion parameters for data analysis of DSC-MRI. We then review the blood supply characteristics of meningiomas and how perfusion MRI is applied in meningiomas to help the subtyping of different meningiomas and to differentiate between benign and malignant meningiomas. Our first-hand experiences are also included. We conclude that DSC perfusion MRI can provide critical information on the vascularity of meningiomas that is not available with conventional MRI. DSC perfusion MRI measurements are helpful in the pre-operative subtyping and grading of meningiomas.
Caudal Zona Incerta as an Alternative Target for the Treatment of Tremor with Deep Brain Stimulation
Authors: Plaha Puneet , Khan Sadaquate , Javed Shazia , Gill Steven S ,   Institute of Neurosciences, Frenchay Hospital, Bristol,   Institute of Neurosciences, Frenchay Hospital, Bristol,   Institute of Neurosciences, Frenchay Hospital, Bristol,   Institute of Neurosciences, Frenchay Hospital, Bristol
Published: June 2015

Stereotactic deep brain stimulation (DBS) of the thalamus and the subthalamic region has been shown to be effective in treating medically refractory tremor over the past few decades. In this article we discuss the merits and drawbacks of stimulating each of the targets in this region, in particular the caudal zona incerta nucleus (cZI). We discuss our recent work in this field and the rationale behind choosing this nucleus to implant bilateral DBS leads for all forms of tremor.
Functional Magnetic Resonance Imaging – Implications for Detection of Schizophrenia
Authors: Demirci Oguz , Calhoun Vince D ,   The Mind Research Network, Albuquerque,   Department of Electrical and Computer Engineering, University of New Mexico
Published: June 2015

Functional magnetic resonance imaging (fMRI) is an invaluable non-invasive instrument that has been used to investigate physiological disturbances that lead to manifest psychiatric illnesses. It is hoped that efficient application of fMRI can be utilised to characterise and diagnose mental illnesses such as schizophrenia. Although there are various fMRI research studies presenting very promising diagnosis results for schizophrenia, we believe that there is much to be done to develop effective diagnostic tools for clinical purposes. We present specific examples based mostly on our past and recent work together with various examples from the recent literature. We discuss where we currently stand in the efforts of fMRI being used for diagnosis of schizophrenia, examine common possible biases and offer some solutions with the hope that fMRI can be more efficiently used in diagnostic research.
Hemicraniectomy – An Overview of Current Status and Future Considerations
Authors: Huttner Hagen B , Schwab Stefan ,   Resident,   Professor, Director and Chair, Department of Neurology, University of Erlangen
Published: June 2015

Space-occupying so-called ‘malignant’ middle cerebral artery infarction is – besides acute basilar artery occlusion – the most devastating form of ischaemic stroke. Until recently, there was no proven treatment. In 2007, results from randomised controlled trials were published providing evidence for the benefit of early hemicraniectomy with respect to mortality after three months. This article focuses on current treatment options for malignant ischaemic brain infarction, especially hemicraniectomy. Moreover, major unsolved problems and open questions regarding the disease are discussed, and a perspective is given on future clinical studies in this field.
Cost of Brain Disorders in Italy – A Review
Authors: Pugliatti Maura , Cossu Paola , Sobocki Patrik , Beghi Ettore ,   Department of Neuroscience, University of Sassari; Department of Public Health and Primary Health Care, University of Bergen,   Department of Neuroscience, University of Sassari,   Department of Learning, Informatics, Management and Ethics, Karolinska Institute,   ‘Mario Negri’ Institute, Milan
Published: June 2015

Brain disorders represent 35% of the total disease burden in Europe and 37% of the total disease burden in European regions with very low child mortality and low adult mortality; the latter group includes Italy. The negative socioeconomic impact of this burden is reflected in two fundamental issues: consumption of resources and state of health. In recent years, the European Brain Council (EBC), a co-ordinating council formed by European organisations and patient associations in neurological disorders, has encouraged and supported projects aimed at analysing the socioeconomic burden of brain disorders in Europe. Within the EBC, the pan-European study on Cost of Disorders of the Brain in Europe (CDBE) aimed at reporting the best possible estimates of the societal cost of 12 brain disorders (addiction, affective disorders, anxiety disorders, tumours, dementia, epilepsy, migraine and other headaches, multiple sclerosis, Parkinson's disease, psychotic disorders, stroke and trauma) based on the existing literature, using an ad hoc cost model. The aggregated results for Italy from the CDBE study are reviewed in this paper.
Environmental and Genetic Risk Factors for Alzheimer's Disease in Spain
Authors: Ampuero Israel , Bermejo-Pareja Félix , García Ribas Guillermo ,   Molecular Diagnostics Laboratory, Tissue Bank for Neurological Research, Madrid Centre for Biomedical Research in Neurodegenerative Diseases Network (CIBERNED), Institute of Health Carlos III,   Centre for Biomedical Research in Neurodegenerative Diseases Network (CIBERNED), Institute of Health Carlos III; Department of Neurology, University Hospital ‘12 de Octubre’,   Centre for Biomedical Research in Neurodegenerative Diseases Network (CIBERNED), Institute of Health Carlos III; Department of Neurology, University Hospital ‘Ramón y Cajal’
Published: June 2015

Alzheimer's disease is a complex neurodegenerative disorder of unknown aetiology, and an important number of cases are sporadic. To date, only some of the genetic and environmental risk factors for Alzheimer's disease have been identified. It is very important to understand the role of environmental and genetic risk factors in Alzheimer's disease in order to develop therapeutic strategies. For sporadic cases of Alzheimer's disease, many environmental and genetic risk factor modifiers have been described, but – with a few exceptions – most of them remain controversial. In this article we review some studies of these risk factors in a Spanish population to identify a few directives for future studies.
Recognising Early Symptoms of Alzheimer's Disease in Routine Clinical Practice
Authors: Knox Sean , Ritchie Craig W ,   European Medical Advisor, Eisai Europe Limited,   Senior Clinical Research Fellow, Division of Neurosciences and Mental Health, Imperial College London
Published: June 2015

The prevalence of Alzheimer's disease is expected to significantly increase over the next few decades. Recognising symptoms in the routine clinical setting can be challenging, particularly in the early stages. Memory loss that causes disruption to everyday life may be the first presenting complaint; however, more subtle changes may occur much earlier. These may include difficulty in performing complex activities of daily living, decline in objective neuropsychological testing and apathy, which may be present for a decade before a diagnosis is made. In the non-specialist setting, the Mini Mental State Examination and the clock-drawing test still predominate and there is limited scope for applying tests such as magnetic resonance imaging (MRI) scanning or plasma markers. At present we remain poor at diagnosing Alzheimer's dementia, particularly in the early stages; therefore, improved awareness of early symptoms as well as a belief in the value of early diagnosis may lead to more effective management of patients.
Transthyretin Cerebrospinal Fluid Levels in Alzheimer's Disease – Is This a Biomarker for Disease Severity?
Authors: Gloeckner Sara Friederike , Zerr Inga ,   Doctoral Student,   Professor, Department of Neurology, University Medical School, Georg-August University Göttingen
Published: June 2015

Alzheimer’s disease (AD) is the most common cause of dementia. A  β1–42, A β1–40, total tau and hyperphosphorylated tau have been reported to be suitable biomarkers in the diagnosis of AD. Additionally, transthyretin has been suggested as a biomarker as it has been shown to inhibit A  ββaggregation and the formation of senile plaques. Aggregates of A β1–42are an important hallmark of the pathogenesis of AD. Patients with AD show significantly lower levels of transthyretin in the cerebrospinal fluid (CSF) compared with ageing controls or patients with other kinds of dementia. Furthermore, some data indicate that transthyretin levels reflect disease severity in AD. In conclusion, recent work demonstrates the potential of transthyretin as an additional biomarker in the neurochemical differential diagnosis of AD.
Pathology of the Cleaved Tau Protein in the Context of Toxicity and the Formation of Neurofibrillary Tangles
Authors: Islas Gustavo Basurto , Rodríguez Siddhartha Mondragón , Binder Lester I , García-Sierra Francisco ,   PhD Student, Department of Cell Biology, Centre of Research and Advanced Studies, National Polytechnical Institute, Mexico City,   PhD Student, Department of Cell Biology, Centre of Research and Advanced Studies, National Polytechnical Institute, Mexico City,   Professor of Cell and Molecular Biology, Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine,   Professor of Cell Biology and Neuroscience, Department of Cell Biology, Centre of Research and Advanced Studies, National Polytechnical Institute, Mexico City
Published: June 2015

In Alzheimer’s disease, tau protein is abnormally processed to self-aggregate into pathologically paired helical filaments and neurofibrillary tangles. Accumulation of these structures in the somatodendritic compartment of neurons may result in pathological alterations of the cytoskeleton stability, abnormal sorting of molecules and obstruction of the intracellular transport of organelles. Initially, abnormal phosphorylation of tau was considered by many to be the major modification that alters its microtubule-binding capacity. In recent years, however, proteolytic cleavage of tau protein produced by caspases has been shown to promote the abnormal aggregation properties of tauin vitroand to produce toxic effects in cell and animal models of Alzheimer's disease. Although some of these results have been debated, truncation of tau associated with neurofibrillary tangle formation has been shown to correlate well with the clinical progression of Alzheimer’s disease. Although new alternative mechanisms of tau pathogenesis in a monomeric or oligomeric state have been proposed, the aggregated form of intact or truncated tau into insoluble polymers is still a major indicator of neuronal degeneration.
Rotigotine for the Treatment of Advanced Parkinson's Disease
Authors: Lloret Santiago Perez , Rascol Olivier ,   Department of Clinical Pharmacology and Neurosciences, Hospital and University Paul Sabatier of Toulouse, and INSERM CIC9023 and UMR 825, Toulouse; Clinical Pharmacology Centre, Raul Carrea Institute for Neurological Research, Buenos Aires,   Department of Clinical Pharmacology and Neurosciences, Hospital and University Paul Sabatier of Toulouse, and INSERM CIC9023 and UMR 825, Toulouse
Published: June 2015

Background: Rotigotine, a non-ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch is approved by the regulatory authorities for use in all stages of Parkinson’s disease (PD) in Europe and for early-stage PD in the US. For patients with advanced-stage PD and motor fluctuations, approved doses range from 4mg/24 hours to 16mg/24 hours. The rotigotine patch offers a certain number of potential advantages, including faster onset as intestinal absorption is not needed, continuous drug delivery and ease of use via application of a once-daily adhesive patch. An interesting element of this profile is continuous drug delivery, which may avoid the pulsatile dopaminergic stimulation that has been postulated to be related to the development of motor complications.Objective: The aim of this article is to review the pharmacokinetics, pharmacodynamics and clinical efficacy and tolerability of the rotigotine transdermal patch.Methods: Source material was identified using a PubMed search for the term ‘rotigotine’ in articles published up to October 2009 and a review of published congress abstracts. The review focused primarily on publications related to the rotigotine indication for advanced PD.Results and conclusions: The rotigotine transdermal patch demonstrates clinical efficacy and a tolerability profile that appears to be well within the range of that observed with other non-ergot dopamine agonists, except for local skin reactions, which are common with the rotigotine patch. The once-daily patch formulation may encourage compliance; however, as is the case for other theoretical advantages of continuous drug delivery, such as reduced emergence of motor complications and improved tolerance of peripheral adverse events, this requires further detailed study.
Dual Task Interference in Parkinson's Disease
Authors: Wu Tao , Hallett Mark ,   Associate Professor of Neurobiology, Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing,   Chief, Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health
Published: June 2015

Performing two tasks simultaneously (dual task performance) is a frequent activity in human life. Patients with Parkinson’s disease (PD) commonly have more difficulty performing dual tasks than healthy people. To date, research on the mechanisms of dual task interference in PD remains sparse. A recent study by Wu and Hallett in 2008 investigated the central neural correlates of dual task interference in PD, and demonstrated that dual task interference in PD is due to multiple reasons. First, the limitation of capacity of attentional resources is exceeded; second, PD patients perform tasks less automatically compared with normal subjects; and third, the central executive may be defective. However, our knowledge of this phenomenon is still far from complete and needs further investigation.
Subarachnoid Haemorrhage - Current Thinking and Future Strategy
Authors: Ferro José M , Canhão Patricia ,   Full Professor and Director,   Invited Professor and Consultant, Department of Neurosciences, Hospital de Santa Maria, Faculty of Medicine, University of Lisbon
Published: June 2015

Subarachnoid haemorrhage (SAH) accounts for only 5% of all strokes, but is responsible for 25% of all fatalities related to stroke. The most important vascular risk factors for SAH are hypertension, smoking and high alcohol intake. One-quarter of patients with acute SAH are not diagnosed at their first medical encounter. To identify the aneurysm causing SAH and allow urgent treatment, angiography must be performed as soon as possible. The most important neurological complications of SAH are re-bleeding, intracerebral haematoma and intraventricular haemorrhage, vasospasm, delayed cerebral ischaemia, hydrocephalus and seizures. Patients with SAH should be referred urgently to a tertiary care centre with expertise in cerebral aneurysm treatment, including endovascular, neurosurgical and neurointensive care. Currently, we can recommend that in a patient with acute aneurysmal SAH in whom both coiling and clipping are feasible, coiling is the preferred choice, if it can be performed within 72 hours after SAH. Adequate fluid replacement and calcium channel blockers are used to prevent vasospasm. Future health gains in SAH will depend on co-ordinated efforts between basic research and clinical research.
Modulation of Baroreceptor Reflex Sensitivity May Represent a New Therapeutic Target in Acute Stroke
Authors: Sykora Marek , Diedler Jennifer ,   Neurologist, Department of Neurology, Comenius University, Bratislava, and Department of Neurology, University of Heidelberg,   Clinical Fellow, Department of Neurology, University of Heidelberg
Published: June 2015

Acute stroke has been associated with several manifestations of autonomic dysfunction including cardiovascular, sudomotor, thermoregulatory, gastrointestinal and urogenital symptoms. In particular, cardiovascular autonomic impairment including blunted baroreflex has been repeatedly shown to be of prognostic importance in acute stroke. Pathophysiological mechanisms of baroreflex changes in acute stroke include lesions of the central autonomic processing with consequent sympathetic system overactivation and impairment of baroreflex functioning. Previous studies have shown that patients with shifted autonomic balance are more prone to develop cardiac complications and have increased cardiovascular morbidity and mortality. Moreover, autonomic dysregulation may play an important role in secondary brain injury after stroke. Therefore, modifying autonomic functions may have important therapeutic implications in acute stroke. In this article, the role of baroreflex impairment in acute stroke and its possible therapeutic relevance is discussed.
Diffusion- and Perfusion-weighted Magnetic Resonance (MR) Imaging and MR Angiography in Apolipoprotein E Polymorphism and Stroke
Authors: Liu Yawu , Hartikainen Päivi , Vanninen Ritva L ,   Docent in Experimental Neuroradiology, Department of Clinical Radiology,   Senior Specialist in Neurology, Department of Clinical Neurology,   Professor of Radiology, Department of Clinical Radiology, Kuopio University Hospital
Published: June 2015

Apolipoprotein E (ApoE) allele ε4 may have both adverse and beneficial effects in patients with acute stroke. ApoE allele ε4 is associated with increased vulnerability of the brain, which is reflected in relatively greater lesion growth and low threshold for the brain tissue to survive stroke and in the lack of correlation between the imaging findings and clinical outcome in ε4 carriers. Conversely, ε4 has at least a seemingly beneficial effect on the cerebral blood flow, i.e. collateral blood flow is better in ε4 carriers compared with non-carriers. In the clinical studies that focus on the relationship between harbouring ε4 and clinical outcomes in ischaemic stroke patients, the adverse and beneficial effects may be compromised. In any case, when possible, ApoE allele ε4 should be classified as a confounding factor when studying stroke either by imaging methods or clinically.
Application of Latent Curve Models in Medical Research - A Review
Authors: Pan Jun-Hao , Song Xin-Yuan , Kwok Timothy ,   Lecturer, Department of Psychology, Sun Yat-sen University, Guangzhou,   Associate Professor, Department of Statistics, Chinese University of Hong Kong,   Professor, Department of Medicine and Therapeutics, Chinese University of Hong Kong
Published: June 2015

Recently, latent curve modelling (LCM) has received increasing attention in the analysis of longitudinal data. It is a method to model individual change and to assess the effects of co-variates and the relationship among multiple outcomes. It provides an integrated and flexible approach in modelling developmental processes from both inter- and intra-individual perspectives. Similar to conventional longitudinal analysis, the main objectives of this model are to characterise changes in the response of interest over time and to examine the selected covariates that contribute to those changes. In this article the fundamental principle of LCM is briefly introduced. Several important kinds of LCM, including linear LCM, non-linear LCM, multilevel LCM and mixture LCM, together with their applications in medical research, are reviewed. We believe that this statistical technique should become more popular in medical applications, and that the medical field would benefit from increased use of this powerful and flexible statistical method.
Natalizumab (Tysabri®) - Re-defining Efficacy in Multiple Sclerosis - Data from Clinical Trials to Post-marketing Experience
Authors: Bates David ,   Professor of Clinical Neurology, Department of Neurology, The Institute of Neuroscience, Newcastle University
Published: June 2015

Multiple sclerosis (MS) is a chronic, disabling condition with severe clinical and social consequences. Current first-line disease-modifying treatments have limited efficacy and do not halt long-term disease progression in the majority of patients. Natalizumab (Tysabri®) is the only monoclonal antibody licensed for use in relapsing–remitting MS (RRMS). It is regarded by many neurologists as the most effective MS drug on the market today, and has the potential to re-define successful MS therapy. Its efficacy has been demonstrated both in large-scale clinical trials and in post-marketing settings. Beneficial effects include reduction of relapse rates and disease progression and magnetic resonance imaging (MRI) measures of disease activity. Natalizumab treatment has a substantial impact on patient quality of life. Moreover, patients have shown significant improvement following natalizumab treatment, making continuing clinical remission a realistic goal in MS for the first time. However, the benefits of natalizumab must be balanced against risk. Progressive multifocal leukoencephalopathy (PML) is a rare event associated with natalizumab treatment that may be minimised with a risk management plan to educate physicians on patient selection and management.
Improving Patient Satisfaction with Injection Devices in Multiple Sclerosis Improves Adherence
Authors: Baum Karl ,   Chief of Neurology, Hennigsdorf Hospital
Published: June 2015

Various studies have demonstrated that regular injections of interferon beta (IFN-β), whether subcutaneously or intramuscular, are effective as maintenance therapy in multiple sclerosis (MS), with acceptable safety and tolerability profiles. While tolerability and adverse events are reported to be comparable across the three most commonly available formulations of IFN-β (Betaferon®, Bayer Schering Pharma; Rebif®, Merck Serono; and Avonex®, Biogen Idec), the formulation of IFN, needle diameter and injection method have been implicated in the rate of injection-site reactions (ISRs) and injection-site pain (ISP), which can ultimately affect a patient’s adherence to therapy. Providing MS patients with information and education regarding their condition and available treatments is considered to be of high importance among patients, and the availability and support of specialist MS nurses, or even an educational website, has been associated with improved quality of life among MS patients. Recent data from European surveys of patients and nurses show consistently high satisfaction with a new Betaferon auto-injection system, which offers automatic withdrawal of the needle, reduced needle size and variable depth adjustment. IFN formulation, nursing support and use of an auto-injector can therefore have a major impact on adherence to therapy.
Pain and Quality of Life in the Treatment of Cervical Dystonia
Authors: Coelho Miguel , Valadas Anabela Ferreira , Mestre Tiago , Ferreira Joaquim J ,   Attending Neurologist,   Resident in Neurology, University Hospital of Santa Maria, and Neurological Clinical Research Unit, Institute of Molecular Medicine, Lisbon,   Resident in Neurology, University Hospital of Santa Maria, and Neurological Clinical Research Unit, Institute of Molecular Medicine, Lisbon,   Attending Neurologist
Published: June 2015

Cervical dystonia (CD) is a chronic movement disorder characterised by abnormal postures of the neck. Although muscle contractions represent the most visible disease feature, associated symptoms such as pain are frequent and relevant contributors to disability. At the same time, pain constitutes one of the most important factors in terms of poor quality of life (QoL) and is one of the more affected QoL domains in CD patients. However, the mechanism underlying the pain associated with CD remains unclear. There are no therapeutic controlled trials that have evaluated pain or QoL as primary outcomes, but the available data suggest that therapeutic interventions that improve dystonia also alleviate pain and have a beneficial effect on QoL. The management of CD should incorporate problems such as pain, depression and anxiety in order to achieve a significant decrease in the burden of disease.
Deep Brain Stimulation for Dystonia
Authors: Nandi Dipankar , O’Riordan Sean , Bain Peter G ,   Consultant Neurosurgeon and Honorary Senior Lecturer in Neurosurgery,   Consultant Neurologist,   Reader and Honorary Consultant in Clinical Neurology, Movement Disorders and Neuromodulation Group, Department of Neurosciences, Imperial College London, Charing Cross Hospital
Published: June 2015

There is now strong evidence demonstrating that bilateral globus pallidus internus (GPi) stimulation improves motor function and disability in patients with severe primary generalised, segmental or cervical dystonia. The improvement is gradual, typically occurring over a period of about six months, with pain and then phasic components dissipating before the tonic elements of dystonia. Controlled data indicate that the benefits of GPi stimulation are in the order of 40–60% and are sustained at three years. Further work is required to better understand variation in the extent of the response. The procedure is usually performed under general anaesthesia and is well tolerated, although minor and hardwarerelated complications are common. GPi stimulation can also provide useful benefit to selected patients with secondary dystonia, with encouraging results reported for tardive dystonia, myoclonic dystonia and pantothenate-kinase-associated neurodegeneration. Currently, it is not known whether the nucleus ventralis intermedius of the thalamus or GPi is the optimal target for the surgical treatment of writer’s cramp.
Treatment of Restless Legs Syndrome
Authors: Ferini-Strambi Luigi , Manconi Mauro ,   Sleep Disorders Centre, Department of Neuroscience, H San Raffaele Scientific Institute and Vita-Salute San Raffaele University,   Sleep Disorders Centre, Department of Neuroscience, H San Raffaele Scientific Institute and Vita-Salute San Raffaele University
Published: June 2015

Restless legs syndrome (RLS) is one of the most common neurological disorders. It is characterised by an urge to move the legs accompanied by uncomfortable or unpleasant sensations. Symptoms occur predominantly at rest in the evening or at night, and they are alleviated by moving the affected extremity or by walking. Although the aetiopathogenesis of RLS is still unknown, the rapid and dramatic improvement of RLS with dopaminergic compounds suggests a dopaminergic system dysfunction as a basic mechanism. Some studies have shown that rotigotine transdermal patch is efficacious for RLS treatment: using dosages between 1 and 3mg/24 hours, up to >30% of severely affected patients became symptom-free. Similar safety and tolerability to other non-ergot dopamine agonists have been reported, except for skin reactions at the application site. One of the most important problems when treating RLS patients with dopaminergic compounds is augmentation, which is a phenomenon mainly characterised by earlier onset of symptoms. Retrospective evaluation of augmentation with rotigotine showed a value of 1.5% in a six-month placebo-controlled study and of 2.9% in a one-year open trial, which is lower than the percentage observed with the other dopamine agonist compounds with shorter half-lifes.
Developments in Neurostimulation Therapy for Epilepsy
Authors: Velasco Ana Luisa ,   Head, Epilepsy Clinic, Neurology and Neurosurgery Service, General Hospital of Mexico City
Published: June 2015

Neuromodulating neural tissue instead of performing lesions is a current trend in neurosurgery. In the case of epilepsy, stimulation of the nervous system is under investigation, and the field is growing at a fast pace. The purpose of this article is to review the various targets that have been studied in the search for a way to control refractory seizures. Consideration is made of why each target is chosen, patient selection, results and adverse effects. Cerebellar stimulation was the first proposed method; vagus nerve stimulation is currently the most widely used due to its easy technique, but the results on seizure reduction are modest. Other targets were chosen with the idea of interfering with seizure propagation – this is the case with thalamic stimulation. Currently, studies are being performed stimulating the epileptic focus. Although there are still many controversies regarding which is the best target and stimulating parameters, all authors agree that neuromodulation reduces seizures and has the advantage of being reversible and safe.
Migraine and Vascular Disease
Authors: Rabe Kasja , Katsarava Zaza ,   Resident,   Consultant, Department of Neurology, University of Essen
Published: June 2015

Migraine is a common disease that is considered to be a benign disorder. However, recently evidence was produced that migraineurs, especially those with aura, have an increased risk of stroke and cardiac disease. These patients have more cardiovascular risk factors, but migraine seems to bear a risk in itself. The pathophysiology is still unknown. Patients might have endothelial dysfunction, which is associated with an increased risk of stroke and cardiac events. Other potential mechanisms include coagulation abnormalities and platelet hyperaggregability. A patent foramen ovale (PFO) that might lead to cardiac embolism is more often observed in migraineurs than in people without migraine. It is not yet known whether the disorders are genetically linked or whether a PFO is a risk factor for migraine with aura. This review examines the occurrence of stroke and cardiac events in migraineurs and discusses potential mechanisms.
Advances in Medical Management of Cluster Headache
Authors: Evers Stefan ,   Professor of Neurology and Clinical Neurophysiology, Department of Neurology, University of Münster
Published: June 2015

Cluster headache is a rare but extremely disabling condition. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7l/minute, 6mg subcutaneous sumatriptan and 5mg zolmitriptan nasal spray are the drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil in a daily dose of at least 240mg (maximum dose depends on efficacy and tolerability). Although no placebo-controlled trials are available, steroids are clearly effective in cluster headache. Methylprednisone (or equivalent corticosteroid) at least 100mg orally or up to 500mg intravenously per day over five days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as drugs of second choice. Although in part promising, surgical procedures require further scientific evaluation before they can be recommended.
Are All Gadolinium-based Contrast Agents Similar? The Importance of High Stability, High Relaxivity and High Concentration
Authors: Anzalone Nicoletta ,   Department of Neuroradiology, Scientific Institute H San Raffaele
Published: June 2015

Gadolinium-based contrast agents (GBCAs) are commonly used to enhance image acquisition via magnetic resonance imaging, but they differ in their physicochemical characteristics and therefore their function. The stability, concentration and relaxivity of a GBCA can have a major impact on clinical efficacy. Stability is related to safety. GBCAs can be categorised into three stability classes: non-ionic linear agents, ionic linear agents and macrocyclic agents, in order of increasing stability. Relaxivity and concentration are contributing factors to the level of enhancement that can be achieved with any given GBCA. Gadobutrol, gadobenate and gadoxetic acid have relatively high relaxivities. Among these compounds, only gadobutrol is commercially available at a higher concentration of 1.0M, whereas the others are used at a standard concentration of 0.5M. With high stability, relaxivity and concentration, gadobutrol has been shown in a number of clinical studies to be safe while improving image enhancement with increased conspicuity and sensitivity over other commonly used GBCAs.
nordic fMRI Solution - Products for Enhancing the Development of a Functional Imaging Clinical Practice
Authors: Elsinger Catherine , Schwarcz Attila , Dóczi Tamás ,   Chief Science Officer, NordicNeuroLab,   Neurosurgeon, and Assistant Professor of Neurosurgery, Department of Neurosurgery, Pecs University Medical School,   Neurosurgeon, Professor of Neurosurgery, and Chairman, Department of Neurosurgery, Pecs University Medical School
Published: June 2015

In the last few years we have witnessed increased adoption of functional magnetic resonance imaging (fMRI) technology in clinical settings. fMRI is rapidly gaining acceptance as a pre-operative planning tool. Functional imaging data provide critical information to the neurosurgeon for considering therapeutic approaches that might not be considered due to procedural risk. The goal is to accurately delineate tissue pathology from surrounding eloquent cortex and examine vital connections between brain regions, aiding decision-making and maintaining a balance between a more aggressive resection approach and reducing post-operative deficits. In this article we describe the solution NordicNeuroLab has developed to support this technology and illustrate the method employed in the Department of Neurosurgery at Pecs University Medical School in Hungary to assess pre-operative risk and plan surgery for patients with brain tumours.
Bone-free 3D Computed Tomography Angiography Using an Image-processing Application - Imaging Efficacy for Aneurysms Near the Skull Base and Clipped Cerebral Aneurysms
Authors: Tomura Noriaki , Koga Makoto , Otani Takahiro , Nishii Toshiaki , Takahashi Satoshi ,   Associate Professor of Radiology, and Chief of Neuroradiology,   Research Associate in Radiology,   Assistant Professor of Radiology,   Research Associate in Radiology,   Lecturer in Radiology, Akita University School of Medicine
Published: June 2015

Bone-free 3D computed tomography angiography (CTA) can be carried out to image cerebral aneurysms near the skull base when the elimination of bones is surgically required. The maximum intensity projection (MIP) images were initially obtained using the application. Further post-processing was performed to obtain the MIP and volume-rendering (VR) images. This technique did not increase radiation exposure to patients, and remnant bones in the initial MIP images automatically acquired by the application for bone elimination could be easily removed through post-processing. Although parts of vessels were sometimes removed from the image along with the bones, these could be quickly and easily recovered through post-processing. Thus, bone-free 3D CTA and conventional 3D CTA are complementary tools for imaging cerebral aneurysms near the skull base prior to surgery. This application could also eliminate clips in cases of clipped cerebral aneurysms, and it could improve the accuracy of detecting remnant necks after clipping surgery.
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: June 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 neuroophthamological evaluation as well as imaging, and the approach, whether trans-sphenoidal or transcranial, must take into account the nature of the tumour and its location. In addition, optimal management of craniopharyngiomas must consist of individualised and multidisciplinary therapy including an array of subspeciality fields such as endocrinology, neuro-ophthalmology, neuropsychology and radiation oncology.
Genetics and Molecular Biology of Alzheimer's Disease and Frontotemporal Lobar Degeneration
Authors: Galimberti Daniela , Fenoglio Chiara , Scarpini Elio ,   PhD Researcher,   Professor of Neurology, Department of Neurological Science, ‘Dino Ferrari’ Centre, University of Milan,   Professor of Neurology, Department of Neurological Science, ‘Dino Ferrari’ Centre, University of Milan
Published: June 2015

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, whereas frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a pre-senile onset. The two major neuropathological hallmarks of AD are extracellular amyloid beta plaques and intracellular neurofibrillary tangles. In FTLD the deposition of tau has been observed in a number of cases, but in several brains there is no deposition of tau but instead a positivity for ubiquitin. In some families these diseases are inherited in an autosomal dominant fashion. Genes responsible for familial AD include the amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2), whereas the main genes responsible for familial FTLD are microtubule-associated protein tau gene (MAPT) and progranulin (GRN). Concerning sporadic AD, it is known that the presence of the ε4 allele of the apolipoprotein E gene is a susceptibility factor. A number of additional genetic factors contribute to susceptibility for AD and FTLD.
Mitochondrial Dysfunction and Oxidative Stress in Alzheimer's Disease
Authors: Moreira Paula I ,   Researcher, Faculty of Medicine and Centre for Neuroscience and Cell Biology, University of Coimbra
Published: June 2015

Oxidative stress and mitochondrial dysfunction are important issues in understanding the pathogenesis of Alzheimer's disease (AD). Mitochondria are pivotal in controlling cell life and death not only by producing adenosine triphosphate and sequestering calcium but also by generating reactive oxidative species and serving as repositories for proteins that regulate the intrinsic apoptotic pathway. Perturbations in the physiological function of mitochondria inevitably disturb cell function, sensitise cells to neurotoxic insults and may initiate cell death, all significant phenomena in the pathogenesis of AD. This article discusses evidence supporting the notion that mitochondrial dysfunction and oxidative stress are intimately involved in AD pathophysiology.
Continuous Dopaminergic Stimulation in Parkinson's Disease - What Have We Learned from Positron-emission Tomography?
Authors: Brooks David J , Pavese Nicola ,   Hartnett Professor of Neurology, and Head, Centre for Neuroscience, Department of Medicine, Imperial College London,   Senior Investigator Scientist, Medical Research Council – Neurology PET Group, and Honorary Senior Lecturer, Imperial College London
Published: June 2015

The hypothesis that pulsatile stimulation of striatal dopamine receptors in Parkinson's disease (PD) induces molecular and physiological changes in basal ganglia neurons and may contribute to the development of motor complications has led to the design of therapeutic strategies that provide more continuous dopaminergic stimulation. Newer agents and drug-delivery systems, such as slow-release preparations, catechol- O-methyltransferase and monoamine oxidase inhibitor agents, apomorphine and Duodopa™infusions, represent a significant step towards less pulsatile dopaminergic administration. However, their efficacy in providing steady brain levels of dopaminergic stimulation in the short and longer term has not yet been proved in patients. This article briefly reviews and discusses the findings of published positron-emission tomography (PET) studies that support or oppose the value of continuous dopaminergic stimulation in PD. The potential future value of PET for proof of mechanism in this area is also debated.
Olfactory Function in Parkinson's Disease
Authors: Haehner Antje , Hummel Thomas , Reichmann Heinz ,   Assistant Professor, Department of Otorhinolaryngology and Department of Neurology,   Professor, Department of Otorhinolaryngology,   Professor of Neurology, Department of Neurology, University of Dresden Medical School
Published: June 2015

Impairment of olfaction is a characteristic and early feature of Parkinson's disease (PD). Recent data indicate that >95% of patients with PD present with significant olfactory loss. Deficits in sense of smell may precede clinical motor symptoms by years and can be used to assess risk of developing PD in otherwise asymptomatic individuals. This article summarises the available literature on olfactory function in PD, which indicates that olfactory tests improve the diagnostic process in these patients; however, it is still unclear which lesion causes olfactory loss in 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: June 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), leucinerich 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.
‘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: June 2015

Chronic and acute infections have been implicated as risk factors that increase the risk of 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 empirical 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 destabilisation to negatively affect vascular risk; however, the evidence is preliminary.
Post-stroke Infections - Diagnosis, Prediction, Prevention and Treatment to Improve Patient Outcomes
Authors: Harms Hendrik , Halle Elke , Meisel Andreas ,   Clinical Scientist, Centre for Stroke Research Berlin, and Attending Neurologist, Department of Neurology, Charité Medical University Berlin,   Clinical Scientist, and Attending Microbiologist, Institute for Microbiology and Hygiene,   Professor of Neurology, NeuroCure Clinical Research Centre and Centre for Stroke Research Berlin, and Attending Physician, and Neurointensivist, Department of Neurology, Charité Medical University Berlin
Published: June 2015

Despite modern stroke treatment in dedicated stroke units and rehabilitation facilities, infection remains the most important medical complication after ischaemic stroke. Pneumonia and urinary tract infections are the most frequent post-stroke infections. Post-stroke infections not only prolong hospitalisation but also constitute a leading cause of early and long-term mortality and morbidity. They are commonly attributed to neurological sequelae such as immobilisation due to motor paralysis or dysphagia as a risk of aspiration. Recently, stroke-induced impairment of immunological competence has been described. This immunodepression syndrome promotes the development of post-stroke infection. Knowledge about risk factors for post-stroke infections, early and proper diagnosis and a deliberate decision for anti-infective treatment are of evident importance, but all of these are considered major challenges for stroke neurologists. In this article we will discuss new insights into diagnostic approaches and risk factors for post-stroke infections. Furthermore, we will focus on preventative approaches and the current treatment options.