bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Deep Hypothermic Cardiac Arrest in the Surgical Treatment of Complex Intracranial Aneurysms
Authors: Santiago Bruno M , Gradil Cátia , Sá Manuel Cunha e ,   Attending Neurosurgeon,   Resident Neurosurgeon,   Chairman, Department of Neurosurgery, Hospital Garcia de Orta, Almada
Published: October 2015

Giant and complex intracranial aneurysms can be formidable lesions to tackle from a surgical standpoint. Their treatment has witnessed an enormous improvement in recent decades with the development of several technical refinements, both surgical and endovascular. By combining optimal cerebral protection with extended periods of circulatory control, deep hypothermic cardiac arrest (DHCA) is a useful adjunct for appropriately dealing with very select cases. In this article we discuss the rationale behind the use of DHCA and review the results of the most relevant series recently published. DHCA remains an important though exceptional way of surgically treating giant and complex intracranial aneurysms.
Rapidly Progressive Dementia - Clinical Aspects and Management
Authors: Papageorgiou Sokratis G , Koros Christos ,   Assistant Professor of Neurology,   Resident in Neurology, Cognitive Neurology-Extrapyramidal Disorders Unit, 1st University Department of Neurology, Eginition Hospital, Medical School, University of Athens
Published: October 2015

Although no precise definition for rapidly progressive dementia (RPD) exists, this term is generally used to refer to cases with significant and progressive cognitive impairment that occurs over weeks or months. RPD represents an unusual but severe condition that causes distress not only for patients and their relatives but also for the clinicians involved, as multiple investigations and decisions about management must be made urgently to avoid misdiagnosing a treatable condition and to preserve as much of the neural tissue as possible from definite damage. While Creutzfeldt-Jacob disease (CJD) has for a long period of time been regarded as the prototype of RPD, this infrequent but severe condition can be produced by an extensive variety of causes such as various endocrine, metabolic or toxic disorders, central nervous system (CNS) infections, primary or secondary CNS neoplasms, various CNS vasculitides and various autoimmune conditions in which autoantibodies against neural tissue are produced, whether in the presence of a neoplasm or not. However, even in the more common and usually slowly progressive dementias such as Alzheimer’s disease, frontotemporal lobar degeneration, dementia with Lewy bodies and other degenerative dementias, as well as vascular dementia, establishment and progression of the disease is occasionally surprisingly accelerated, leading to a clinical presentation of RPD. The few published case series of RPD have shown that the relative frequency of underlying diseases depends mainly on the clinical setting. Thus, CJD has been found to be the most prevalent cause in referral centres for spongiform encephalopathies, while secondary causes are more prevalent in general referral centres for dementia diagnosis. In clinical practice, for the cases presenting with RPD, the diagnostic procedure must be exhaustive, starting with a detailed clinical evaluation and proceeding to a complete laboratory work-up and sophisticated neuroimaging studies. There has been recent enormous progress in imaging, with sensitive new sequences of magnetic resonance imaging and immunology; as a result, a plethora of antibodies against the CNS can now be detected in cases of autoimmune dementias, which has dramatically changed the diagnostic approach and early management of cases of RPD. The same favourable effect in clinical practice comes from the accumulated knowledge of the complex clinical picture of various causes of RPD, associated specific neurological features (pyramidal signs, ataxia, myoclonus) and systematic features (weight loss, hyponatraemia, hepatic disorders) and their mode of progression.
Transcutaneous Vagus Nerve Stimulation
Authors: Ellrich Jens ,   Professor of Medical Physiology, Department of Health Science and Technology, Medical Faculty, Aalborg University and Chief Medical Officer, Medical Department, cerbomed GmbH
Published: October 2015

Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides its recognised clinical efficacy, there are major drawbacks, such as invasiveness and a great many side effects. Therefore there is a medical demand for transcutaneous VNS (t-VNS®), which combines selective, non-invasive access to vagus nerve afferents with a low risk profile. Both treatments excite thick myelinated fibres of vagus nerve branches that project to the nucleus of the solitary tract in the brainstem. Preclinical data emphasise the equivalent anticonvulsive effects of both methods. Based upon the common mode of action and the first clinical data, the t-VNS device received Conformité Européenne (CE) approval. Besides the approved intended use for drug-resistant epilepsy and depression, a future clinical trial will address the efficacy of t-VNS in chronic pain.
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 colour-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 neurological disease, to have the abnormalities. The original Zamboni reports were widely publicised in the mainstream media, especially in Canada and sparked a raging controversy in the social media. Patients clamoured for trials of cerebral venoplasty and others demanded its availability or travelled 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 relation 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 emphasising the importance of proper scientific research.
Transthyretin-associated Familial Amyloid Polyneuropathy - Current and Emerging Therapies
Authors: Nuvolone Mario , Obici Laura , Merlini Giampaolo ,   Postgraduate Researcher, Amyloidosis Research and Treatment Centre, Foundation IRCCS San Matteo Hospital and Department of Molecular Medicine, University of Pavia, Institute for Advanced Studies, Pavia and Institute of Neuropathology, University Hospital of Zürich,   Attending Physician and Researcher, Amyloidosis Research and Treatment Centre, Foundation Scientific Institute Policlinico, San Matteo,   Professor, Amyloidosis Research and Treatment Centre, Foundation IRCCS San Matteo Hospital and Department of Molecular Medicine, University of Pavia
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-neurological 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, favouring 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.
Exercise Interventions to Improve Cognitive Performance in Older Adults - Potential Psychological Mediators to Explain Variation in Findings
Authors: Stock Jennifer , Clifford Angela , Hogervorst Eef ,   Graduate Researcher and Doctoral Candidate,   Graduate Researcher and Doctoral Candidate,   Professor of Biological Psychology, School of Sport, Exercise and Health Sciences, Loughborough University, UK
Published: October 2015

Evidence suggests that exercise interventions can improve cognitive performance in older adults and prevent dementia. However, there are inconsistent results across studies. Exercise interventions vary greatly in terms of their environment and specific features. As a consequence, the different types of social interaction, mental engagement and feedback alter the psychological impact of the exercise. In this article, mediating relationships are discussed in terms of the impact that psychological factors related to exercise can have on cognitive performance. The probable psychological mediators discussed here include self-efficacy, attitudes and self-perceptions of ageing, perceived control manifesting in a self-fulfilling prophecy, causal attributions of memory problems and mood. The mechanisms of these mediating relationships are unclear and further research is needed to investigate them. In addition, the magnitude of the effect of psychological mediators and their relative contribution compared with physiological mechanisms in this context should be further investigated.
Practical Electrophysiology for the Diagnosis of Multifocal Motor Neuropathy
Authors: Franssen Hessel , Berg Leonard H van den ,   Associate Professor,   Professor, Section of Neuromuscular Disorders, Department of Neurology, Rudolf Magnus Institute for Neuroscience, University Medical Centre Utrecht, The Netherlands
Published: October 2015

Nerve conduction studies (NCS) are necessary to distinguish multifocal motor neuropathy (MMN) from other disorders with a similar clinical picture. In MMN, NCS may show a unique combination of conduction block (CB) or conduction slowing consistent with demyelination, whereas sensory conduction in the same nerve is normal. This contribution discusses a relatively simple and practical electrophysiological approach for the diagnosis of MMN that can be used by any neurologist who has had training in NCS. When diagnosing MMN, the most important practical points are: careful stimulation technique, investigation according to a standardised protocol that includes at least five nerves per arm with stimulation up to Erb’s point, understanding of and adherence to criteria for conduction block and demyelinative slowing and exclusion of nerves with marked axon loss.
Role of Contrast-enhanced Magnetic Resonance Imaging in Multiple Sclerosis
Authors: Rovira Àlex , Auger Cristina ,   Head of Neuroradiology Section and Magnetic Resonance Unit, Department of Radiology and Associate Professor of Radiology, Universitat Autònoma de Barcelona, Vall d’Hebron University Hospital,   Neuroradiology Clinical Coordinator, MR Unit, Department of Radiology, Vall d’Hebron University Hospital, Barcelona, Spain
Published: October 2015

Magnetic resonance imaging (MRI) is an important diagnostic tool in different central nervous system (CNS) disorders including brain cancer and cerebrovascular, inflammatory and neurodegenerative diseases. The most commonly used MRI contrast agents are gadolinium-based compounds that have been successfully employed in combination with T1-weighted sequences to detect and monitor focal disease-related abnormalities. These gadolinium-based contrast agents facilitate the visualisation of areas of blood brain barrier disruption, show good performance in diagnostic procedures and present a favourable safety profile. In multiple sclerosis (MS), conventional MRI, including T2-weighted and gadolinium-enhanced T1-weighted sequences, is pivotal to diagnose and to monitor disease activity and progression. Advanced magnetic resonance (MR) techniques and new contrast agents are currently being developed to improve the ability to identify CNS structural and functional abnormalities in MS, which may better correlate with and predict the clinical course of the disease.
Neuroprotective Therapies for Multiple Sclerosis
Authors: Moreno Beatriz , Villoslada Pablo ,   Group Researcher,   Director, Neuroimmunology Group, Centre of Neuroimmunology, Institute of Biomedical Research August Pi Sunyer, Hospital Clinic of Barcelona, Spain
Published: October 2015

Multiple sclerosis (MS) is considered to be an autoimmune disease that is caused by the immune system attacking the central nervous system (CNS) leading to myelin loss and axonal damage, resulting in long-term disability. The pathophysiology of MS is complex with involvement of genetic and environmental factors that define the susceptibility to generate the autoimmune attack. In the last decade, several immunomodulatory drugs have been approved, including recombinant proteins such as interferon-beta, monoclonal antibodies such as natalizumab, or small chemicals including glatiramer acetate. In addition, there is a wide pipeline of new immunomodulators finishing Phase II or III trials. However, at present there are no approved treatments that directly reduce nervous system damage or enhance its repair. Novel neuroprotective agents have been identified in pre-clinical studies but their development is being prevented by the absence of appropriate understanding of the mechanisms of CNS damage by inflammation as well as by the lack of clinical platforms to test them. In this review, we describe the different mechanisms of axonal injury and discuss some of the principal therapeutic candidates that could provide neuroprotection in MS.
Peripheral Nerve Stimulation for Neuropathic Pain
Authors: Slavin Konstantin V ,   Professor, stereotactic and Functional Neurosurgery, Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, US
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 lower 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, summarises 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 practising 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.
Access Through Partnership  A Stakeholder Dialogue
Authors: Baker Mary , Isaacs Tom , Salonen Reijo , Bové Damien , Paterson Ken , Antonini Angelo ,   President, European Brain Council and Immediate Past President, European Federation of Neurological Associations, Brussels, Belgium,   Co-Founder, Cure Parkinsons Trust, London, UK,   Senior Vice President, Research and Development and Chief Medical Officer, Orion Corporation, Espoo, Finland,   Chief Regulatory Consultant, IDA Consultants Ltd, Doncaster, UK,   Chair, Scottish Medicines Consortium, Glasgow, UK,   Director, Parkinson Unit, IRCCS San Camillo, Venice and University of Padua, Padua, Italy
Published: October 2015

A major barrier to optimal care in Parkinson’s disease (PD) is the many years it takes for patients to gain access to new therapies and the best neurological services. A new treatment has to overcome many hurdles to become a clinically and cost-effective new therapy for patients, for example, gaining regulatory approval and reimbursement. Sharing opinions between the industry, neurologists, patients and other stakeholders about the benefits and risks of new treatments is important in influencing this process. The complex chain of events that currently characterises the development of new treatments for PD could be enhanced and accelerated by group discussions and collaborative care – right from the outset of the development process. Developing the process in this way would optimise patients’ receipt of the best treatments in a timely manner.
New Treatments for Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Mathey Emily K , Pollard John D ,   Research Fellow,   Emeritus Professor, Brain and Mind Research Institute, University of Sydney, Australia
Published: October 2015

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable chronic neuropathy in the western world. There are three treatment options currently available for CIDP: intravenous immunoglobulin, plasma exchange or corticosteroids. Despite the efficacy of these therapies CIDP patients are often left with permanent neurological deficits, have a poor clinical prognosis or in some cases do not respond to treatment. Furthermore, high cost and restricted availability make them unfeasible in some treatment centres, especially in the developing world. Recent advances in the understanding of the underlying pathogenic mechanisms in CIDP have brought a number of novel agents into consideration for use in CIDP. Many of these novel therapies have been used in similar autoimmune disorders and target immunopathogenic pathways common to CIDP. Here we review a number of these novel therapies and their applicability to CIDP.
Health Economics and Cost of Illness in Parkinson's Disease
Authors: Mateus Céu , Coloma Joana ,   Assistant Professor,   Researcher and Former MSc Student, National School of Public Health, Lisbon, Portugal
Published: October 2015

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. With a progressive course and no cure yet available, it is demanding for patients and their caregivers, but also for health and social support systems and ultimately for society as a whole. Everyday significant economic resources are spent due to PD, either directly on its treatment or in lost productivity. In this article, one tried to frame PD from an health economics' perspective and cost of illness studies conducted in 11 countries (Austria, Czech Republic, Finland, France, Germany, Italy, Portugal, Russia, Sweden, UK and US), published from 1998 to 2011, were reviewed. One main aspect subsists: costs associated with this disorder are high, disproportionately higher that its prevalence and PD poses a substantial economic burden on individuals and society.
Management of Motor Symptoms in Multiple Sclerosis
Authors: Barros Pedro , Sá Maria José ,   Neurology Resident, Neurology Department, Centro Hospitalar de Vila Nova de Gaia/Espinho, Portugal,   Neurology Resident; Senior Neurologist, Head of MS Clinic, MS Clinic, Centro Hospitalar de São João, Porto, Portugal,   Visiting Professor; Associate and Aggregate Professor of Neurology, Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal,   Neurology Resident; Senior Neurologist, Head of MS Clinic, MS Clinic, Centro Hospitalar de São João, Porto, Portugal,   Visiting Professor; Associate and Aggregate Professor of Neurology, Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal,   Senior Neurologist, Neurology Department, Centro Hospitalar de São João, Porto, Portugal
Published: October 2015

Although there has been a significant development, in recent years, regarding disease modifying treatments (DMT) in multiple sclerosis (MS), there is a continuous need to manage the wide range of symptoms associated with MS. Although surveys vary in their results, mobility is a major concern in MS patients. However, limited evidence exists for symptomatic drug treatment and so it is important to consider all therapeutic options in these patients. Here we review the current evidence in the management of three of the most common and disabling motor symptoms: spasticity, tremor and gait impairment.
An Algorithm of Migraine Treatment
Authors: Evers Stefan , Lisotto Carlo ,   Professor of Neurology, University of Münster and Director, Department of Neurology, Krankenhaus Lindenbrunn, Germany,   Neurologist, Headache Centre, Department of Neurosciences, University of Padua, Italy
Published: October 2015

A satellite symposium at the XXI World Congress of Neurology 2013 presented the third edition of the International Classification of Headache Disorders and summarised the main changes, which reflect the importance of diagnosis based on phenomenology rather than aetiology. For this reason, a treatment algorithm for migraines has been created to assess the correct pathway and to reinforce the fact that triptans are the most effective treatment option. The symposium also discussed new guidelines regarding efficacy parameters in clinical trials, emphasising the importance of sustained pain free without relapse, an outcome measure that is important to patients. Crossover patient preference trials represent a true intra-individual comparison and allow the assessment of multiple endpoints defined by the patient preference, rather than the investigator. In clinical studies, frovatriptan has shown favourable tolerability and sustained effect with a lower rate of relapse compared with other triptans. These findings were confirmed in a series of patients who participated in the preference trials.
Surgery and Neurointervention for Intracranial Atherosclerotic Steno-occlusive Disease
Authors: Amin-Hanjani Sepideh , Chun Ho Yu Simon , Charbel Fady , Inamasu Joji , Kato Yoko , Kwok-Chu Wong George ,   Professor, Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, US,   Professor, Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Hong Kong,   Professor, Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, US,   Professor, Department of Neurosurgery, Fujita Health University, Toyoake, Japan,   Professor, Department of Neurosurgery, Fujita Health University, Toyoake, Japan,   Professor, Division of Neurosurgery, Chinese University of Hong Kong, Hong Kong
Published: October 2015

Neurosurgeons and neurointerventionists interested in cerebral revascularisation to prevent stroke from intracranial atherosclerotic steno-occlusive disease were disappointed in 2011 with the closure of two important negative studies: the Carotid Occlusion Surgery Study (COSS) and Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study. Debates are centred on what causes these failures. While extracranial-intracranial (EC-IC) bypass and neurointervention (angioplasty and/ or stenting) cannot be considered a routine intervention for patients presenting with initial ischaemic event in the setting of atherosclerotic steno-occlusive disease, selected patients with severe haemodynamic impairment and/or recurrent symptoms despite maximal medical therapy may still benefit from surgery and neurointervention at high-volume centres, which can offer the procedure with low peri-operative morbidity.
New Magnetic Resonance Imaging Biomarkers Advance the Characterisation of Parkinson’s Disease
Authors: Ziegler David A , Corkin Suzanne ,   Post-doctoral Fellow, Department of Neurology and the Center for Integrative Neuroscience, University of California San Francisco, San Francisco, California, US,   Professor of Behavioral Neuroscience, Emerita, Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, US
Published: October 2015

The pathophysiology of idiopathic Parkinson’s disease (PD) is traditionally characterised as substantia nigra degeneration, but careful examination of the widespread neuropathological changes suggests individual differences in neuronal vulnerability. A major limitation to studies of disease progression in PD has been that conventional magnetic resonance imaging (MRI) techniques provide relatively poor contrast for the structures that are affected by the disease, and thus are not typically used in experimental or clinical studies. Here, we review the current state of structural MRI as applied to the analysis of the PD brain. We also describe a new multispectral MRI method that provides improved contrast for the substantia nigra and basal forebrain, which we recently used to show that these structures display different trajectories of volume loss early in the disease.
Paramètres cliniques, biochimiques et dimagerie prédictifs de I évolution de la sclérose en plaques
Authors: Svenningsson Anders , Hendin et Barry A ,   Maître de conferences, department de neurology, Umea University Hospital, Umea, Suede,   Professor Clinique de neurologie, faculté de médecine de IUniversity of Arizona, Phoenix, Arizona, États-Unis
Published: October 2015

Mieux prédire Iévolution de la maladie et la réponse aux traitements de fond de la sclérose en plaques (SEP) pourrait améliorer les résultats de traitement en proposant aux patients une approche thérapeutique spécifique. Plusieurs facteurs affectant Iévolution de la maladie ont été identifiés, parmi lesquels : Iorigine ethnique, Iâge dapparition de la maladie, lâge des premiers symptômes, Iévolution au début de la maladie et les résultats dimagerie. Malgré les résultats mitigés des études des facteurs pronostiques à IIRM (Imagerie par Résonance Magnétique), les avancées technologiques améliorent la capacité prédictive de IIRM, et de nouvelles techniques et mesures fournissent dautres moyens pour prédire Iévolution de la maladie et la réponse au traitement. La recherché dun biomarqueur prédictif est un domaine de recherche trés actif, mais les études restent peu concluantes. Les biomarqueurs potentiels incluent les protéines des neurofilaments, les microARN, Iexpression génique et les anticorps. Étant donné quil est peu probable quun seul facteur puisse prédire le cours de la maladie, plusieurs systémes de notation composite ont été proposés, mais aucun na encore été largement accepté. Cependant, il semble probable quà Iavenir, une combinaison dIRM et de biomarqueurs biochimiques servira de base pour la décision thérapeutique dans la SEP et permettra une approche individualisée.
Can Objective Measurements Improve Treatment Outcomes in Parkinson’s Disease?
Authors: Bergquist Filip , Horne Malcolm ,   Associate Professor, Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,   Professor, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria and Consultant Neurologist, Department of Medicine, University of Melbourne, St Vincent’s Hospital, Fitzroy, Victoria, Australia
Published: October 2015

Many examples in medicine show that therapies are most effective when measurement is used to guide their implementation, dose and effects. There are effective symptomatic therapies for the motor symptoms of Parkinson’s disease, which improve quality of life and have a health economic justification for their subsidisation. As measurement should lead to more effective deployment of these therapies, even in a percentage of cases, then costs of therapy would be reduced and by that percentage. We conclude that there is a clear need or continuous objective measures of dyskinesia and bradykinesia while patients go about their normal daily activities. The benefit of measurement would be greatest if these measures were directed at treating fluctuations.
Multiple Sclerosis and Falls—An Evolving Tale
Authors: Sosnoff Jacob J , Motl Robert W , Morrison Steven ,   Associate Professor, Department of Kinesiology and Community Health, College of Applied Health Sciences,University of Illinois at Urbana-Champaign, Illinois, US,   Associate Professor, Department of Kinesiology and Community Health, College of Applied Health Sciences,University of Illinois at Urbana-Champaign, Illinois, US,   Endowed Professor of Physical Therapy, Director of Research, School of Physical Therapy and Athletic Training, Old Dominion University, Norfolk, Virginia, US
Published: October 2015

Falls are a common health concern in the multiple sclerosis (MS) community with one out of two individuals with MS reporting a fall in the previous 6 months. Falls often lead to physical injury and have been found to be associated with reduced participation and quality of life. These adverse consequences underscore the importance of identifying risk factors for falls in MS so that appropriate interventions can be designed and tested. Ongoing research has suggested that clinical disability, balance and gait impairment are related to past and future falls. The data also suggest that cognitive impairment is related to falls. Fortunately, it appears that these fall risk factors and falls per se can be reduced with targeted interventions in persons with MS. However, the most effective fall-prevention strategy in persons with MS has yet to be elucidated. Ultimately, the reduction of falls in persons with MS has the potential to improve participation and quality of life.
Laboratory Diagnosis of von Willebrand Disease
Authors: Meiring Muriel , Badenhorst Philip N , Kelderman Mareli ,   Associate Professor and Specialist Scientist,   Professor and Chairman,   Medical Technologist, Department of Haematology and Cell Biology, University of the Free State
Published: October 2015

von Willebrand disease (VWD) is a bleeding disorder caused by either quantitative (type 1 and 3) or qualitative (type 2) defects of von Willebrand factor (VWF). No single available test provides appropriate information about the various functions of VWF, and the laboratory diagnosis of VWD is based on a panel of tests, including the measurement of factor VIII coagulant activity (FVIIIC), VWF antigen levels (VWF:Ag), VWF activity as measured by the ristocetin co-factor activity (VWF:RCo), the collagen-binding activity of VWF (VWF:CB), VWF multimer analysis, ristocetininduced platelet agglutination (RIPA), the factor-VIII-binding assay of plasma VWF and VWF propeptide levels. Due to the heterogeneity of VWF defects and the variables that interfere with VWF levels, a correct diagnosis of types and subtypes may sometimes be difficult, but is very important for therapy. Furthermore, the RCo assay and the RIPA test are based on platelet agglutination in reaction with the non-physiological antibiotic ristocetin. These tests also have low sensitivity and are difficult to standardise. Therefore, several analyses (tests) are required to diagnose VWD and it is important to be aware of the pitfalls to which these tests are subjected in terms of the diagnosis. In this article, the laboratory diagnosis of patients with type 1, 2A, 2B, 2M, 2N and 3 VWD will be explained by using a modified algorithm that was first proposed by the guidelines for diagnosis and treatment of VWD in Italy.
D-dimer Testing and Venous Thromboembolism
Authors: Prisco Domenico , Grifoni Elisa , Poli Daniela ,   Department of Medical and Surgical Critical Care, University of Florence,   Thrombosis Centre, Department of Heart and Vessels, Careggi University Hospital,   Department of Medical and Surgical Critical Care, University of Florence,   Thrombosis Centre, Department of Heart and Vessels, Careggi University Hospital,   Thrombosis Centre, Department of Heart and Vessels, Careggi University Hospital
Published: October 2015

With its high sensitivity and negative predictive value, D-dimer (DD) testing has gained a role in the diagnostic work-up of suspected venous thromboembolism (VTE) for the exclusion of the disease, potentially reducing the need for imaging tests. The diagnostic yield of DD testing is affected not only by the choice of the appropriate assay for its measurement, but also by patient characteristics. As a consequence, its clinical usefulness for the exclusion of suspected VTE should be carefully evaluated in special clinical settings. There is increasing evidence that DD testing after anticoagulation withdrawal for a first unprovoked VTE episode may be useful to identify patients at higher risk of recurrence, and may help clinicians with the decision of whether to continue or stop anticoagulant treatment. However, further studies are needed to establish the optimal timing of DD testing and the best DD cut-off level that predicts recurrence, and to develop a clinical prediction rule for recurrent VTE.
Sublingual Fentanyl (Abstral®) for Breakthrough Cancer Pain
Authors: Zeppetella Giovambattista ,   Medical Director, St Clare Hospice, Hastingwood
Published: October 2015

The sublingual fentanyl tablet is indicated for the management of breakthrough pain in patients with cancer who are already receiving opioid therapy for their background cancer pain. The pharmacokinetic, efficacy, tolerability and safety profile of the sublingual fentanyl tablet suggests that it has a valuable role to play in the symptomatic pharmacological management of breakthrough pain. The effective dose of the sublingual fentanyl tablet cannot be predicted from previous around-the-clock (ATC) or rescue medication; therefore, titration is required to determine the effective dose according to the needs of the individual patient.
Recent Advances in Oral Oncology
Authors: Rapidis Alexander D , Scully Crispian ,   Chairman, Department of Head and Neck/Maxillofacial Surgery, Greek Anticancer Institute, Saint Savvas Hospital, Athens, and Honorary Professor, University College London (UCL),   Director, Special Projects, UCL Eastman Dental Institute, and Professor, Special Care Dentistry, UCL
Published: October 2015

Oral cancer is becoming increasingly common and new risk factors have been recognised. Treatment remains largely surgical, but radiotherapy and, increasingly, chemotherapy and targeted therapy have roles to play.
Development of Oncogeriatry – A European Perspective from the French Experience
Authors: Terret Catherine , Droz Jean-Pierre ,   Associate Professor, Medical Oncology, University of Sherbrooke,   Emeritus Professor, University of Lyon–RTH Laënnec School of Medicine
Published: October 2015

Oncogeriatry is the clinical discipline concerned with the management of elderly cancer patients. It is based on a global oncological and geriatric approach to the health status of patients. Oncogeriatry has been widely adopted throughout the world, but the approaches used and the organisational solutions provided are complex and varied. Based on the French experience of a centralised health system, the different aspects are discussed: clinical management, organisation, clinical research and information. At a European level, the best approach seems to be a partnership between the International Society of Geriatric Oncology and the Elderly Task Force of the European Organisation on Research and Treatment of Cancer. This co-operation ensures comprehensive information on oncogeriatric programmes, clinical research and teaching programmes, thus enhancing the effectiveness of the oncogeriatric approach.
The Use of Rituximab in Immune-mediated Anaemia
Authors: Dierickx Daan , Verbeke Len ,   Haematologist, and Deputy Head, Department of Haematology,   Medical Intern, Department of Internal Medicine, University Hospitals Leuven
Published: October 2015

Immune-mediated anaemia is a collective term describing the occurrence of anaemia due to an immune dysfunction, leading directly or indirectly to the destruction of red blood cells. In recent years, as knowledge of the immune system has progressed, these disorders have also become better understood and their management improved. Monoclonal antibodies have emerged as a powerful tool in the treatment of many different disorders, including both haematological and non-haematological disorders. Most experience has been obtained with the use of rituximab, a chimeric mouse/human anti-CD20 monoclonal antibody, showing high overall response rates with a relatively safe toxicity profile. Here we describe the currently available evidence on the use of rituximab in immune-mediated anaemia. We will also reflect on potential side effects that might hamper the initial enthusiasm for its use in these disorders.
Recurrent Genomic Aberrations in Chronic Lymphocytic Leukaemia – Implications for Disease Pathogenesis and Prognosis
Authors: Mansouri Mahmoud , Rosenquist Richard ,   Scientist,   Professor of Molecular Haematology, Department of Genetics and Pathology, Uppsala University
Published: October 2015

Recurrent genomic aberrations in chronic lymphocytic leukaemia (CLL) are important predictors of clinical outcome. Deletion of 13q14 is the most frequent genomic aberration, found in >50% of patients, and is associated with a favourable prognosis. The deleted region harbours two microRNAs,mir-15aandmir-16-1, shown to regulateBCL2expression, an anti-apoptotic gene that is upregulated in CLL. Deletion of 11q, encompassing theATMgene, is present in 12–18% of patients and is associated with a poor prognosis. Deletion of 17p, which includes theTP53gene, defines the worst prognostic category and is detected in 5–10% of patients. Additionally, del(17p) is currently the only predictive marker of treatment in CLL. Trisomy 12 is present in 11–16% of patients and is associated with an intermediate outcome; however, the pathological relevance of this numerical alteration is still unknown. In recent years, the introduction of microarray technology has led to the discovery of several novel aberrations, although the incidence of these varies and their clinical significance remains unclear. Nevertheless, microarray analysis has further highlighted the presence of genomic complexity and its clinical relevance in CLL. Assessment of genomic aberrations is crucial for both the stratification of patients into risk groups and the implementation of treatment strategies.
Treatment of Chemotherapy-induced Nausea in Cancer Patients
Authors: Ryan Julie L ,   Assistant Professor, Departments of Dermatology and Radiation Oncology, James P Wilmot Cancer Center, University of Rochester Medical Center
Published: October 2015

For over 30 years, chemotherapy-induced nausea and vomiting have been the most severe and troublesome symptoms for cancer patients receiving chemotherapy. Unresolved chemotherapy-induced nausea and vomiting can lead to metabolic disorders, dehydration, nutritional depletion and oesophageal tears, and can reduce the daily functioning and quality of life of and interfere with treatment schedules. Despite the widespread use of antiemetics, chemotherapy-induced nausea continues to be problematic. Unlike vomiting, nausea is a subjective and unobservable phenomenon, making it extremely difficult to accurately assess and treat. Current research suggests that management of chemotherapy-induced nausea should focus on treating the symptoms before they occur rather than after they develop. This article highlights evidence-based interventions for the treatment of chemotherapy-related nausea.
Role of Epidermal Growth Factor Receptor Mutational Testing in Personalising the Treatment of Non-small-cell Lung Cancer
Authors: Ginsburg Philip J ,   Chief Medical Officer, AlliedPath, Inc.
Published: October 2015

Better methods of combating non-small-cell lung cancer (NSCLC) are constantly being sought. The recent movement towards the implementation of a personalised approach to treatment in oncology is a positive step in this direction. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) drugs such as gefitinib (Iressa®) and erlotinib (Tarceva®) are approved for the treatment of certain types and stages of non-small-cell lung cancer (NSCLC). It is now possible to determine the likelihood of response of a given patient’s tumour to treatment with this type of cancer drug using molecular diagnostic methods that detect the presence or absence of specific EGFR mutations. These diagnostic and therapeutic advances offer the potential to improve patient care and bring new hope to cancer patients.
The Use of Patient-reported Outcomes at an Individual Level – Benefits and Challenges
Authors: Czimbalmos Agnes , Bottomley Andrew ,   Research Fellow,   Assistant Director and Head, Quality of Life Department, European Organisation for Research and Treatment of Cancer
Published: October 2015

The aim of this article is to review the application of patient-reported outcomes (PROs) in clinical care and consider its benefits, challenges and potential improvements. Previous studies demonstrated that health-related quality of life (HRQoL) data provide information to clinicians on patient health status, QoL, symptoms and wellbeing, along with any changes in these, and helps clinicians judge the needs of patients and tailor treatments accordingly. In addition, the benefits of the application of HRQoL tools include the involvement of patients in informed decision-making in terms of their treatment or care, higher patient satisfaction with healthcare services, improved patient–clinician relationships and better communication. In many studies, health professionals have expressed their interest in using these measures but feel they need to better understand them. Despite the wide use of information-gathering questionnaires and their promising results, it is still a challenge to predict the full value of these measures in clinical care. This article addresses these major concerns.
The Emergence of Thrombopoietin Receptor Agonists as a Novel Treatment for Immune Thrombocytopenia
Authors: Stasi Roberto , Rhodes Elizabeth , Benjamin Reuben , Buyck Hubertus , Willis Fenella , Shannon Muriel S , Gordon-Smith Edward C ,   Department of Haematology, St George’s, University of London,   Department of Haematology, St Georges, University of London,   Department of Haematology, St Georges, University of London,   Department of Haematology, St Georges, University of London,   Department of Haematology, St Georges, University of London,   Department of Haematology, St Georges, University of London,   Department of Haematology, St Georges, University of London
Published: October 2015

Two thrombopoietin receptor agonists, romiplostim and eltrombopag, have completed phase III trials in patients with chronic immune thrombocytopenia and were shown to successfully improve platelet counts. Due to their proven efficacy and favourable side-effect profile, they have been granted marketing authorisation for use in this condition in the US, the EU and other countries. This article focuses on these two agents, their pre-clinical development and clinical trial results.
Evidence Supporting the Use of Recombinant Activated Factor VII in Congenital Bleeding Disorders
Authors: Johansson Pär I , Ostrowski Sisse R ,   Medical Director,   Consultant, Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen
Published: October 2015

Recombinant activated factor VII ([rFVIIa] NovoSeven) was introduced in 1996 for the treatment of haemophilia patients with inhibitors (HPIs) to factor VIII or IX. This article reviews the evidence for the use of rFVIIa in congenital bleeding disorders. English-language databases were searched in September 2009 for reports of randomised controlled trials (RCTs) evaluating the effect of rFVIIa on haemostasis in congenital bleeding disorders. Eight RCTs comprising 256 HPIs were identified. The evidence for the use of rFVIIa in HPIs in terms of dose, clinical setting, modes of administration, efficacy and adverse events was weak, given the limited number of patients included and the heterogeneity of the RCTs. Overall, the haemostatic efficacy of rFVIIa varied from 25 to 100% in the studies reviewed; <1% of the patients receiving rFVIIa developed a thromboembolic adverse event. The authors suggest that the addition FVIIa therapy to HPIs should be based on the patients ability to generate thrombin and form a clot, rather than being based on weight alone. Assays reflecting thrombin generation, such as whole-blood thrombelastography, have the potential to significantly improve the treatment of these patients.