bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Imaging Findings of Radiation-induced Changes After Treatment of Malignant Gliomas and Metastases with a Particular Emphasis on Radiation Necrosis
Authors: Alonso Raquel Cano , Peña Mar Jimenez de la , Rodriguez Manuel Recio , Arranz Javier Carrascoso , Fernandez Vicente Martinez de Vega , Moreno Javier Pardo ,   General Radiologist,   Deputy Chief,   Deputy Chief,   Deputy Chief,   Chief of Service, Department of Diagnostic Imaging,   Deputy Chief, Department of Neurology, Hospital Universitario Quirón Madrid
Published: October 2015

New contrast-enhancing lesions discovered on routine follow-up brain imaging at or near the site of previously treated primary or metastatic brain tumours represent a clinical and radiological challenge, as radiation necrosis and tumoral recurrence often present at standard magnetic resonance imaging (MRI) with overlapping imaging features. Since the advent of combined therapy, including surgery and/or radiotherapy and chemotherapy, the post-treatment radiological assessment has been made earlier, with a subsequent higher incidence of early radionecrosis and a potential risk of mistaking it for disease progression. Therefore, both clinical and imaging follow-up are essential. This article briefly describes and illustrates the temporal patterns and spectrum of MR findings of radiation-induced brain injury and considers practical aspects of conventional and advanced MR sequences (diffusion-weighted imaging, perfusion MR and MR spectroscopy), with a particular emphasis on the distinction between tumoral recurrence and radiation necrosis.
Constructive Interference in Steady State Imaging in the Central Nervous System
Authors: Gonçalves Fabrício Guimarães , Amaral Lázaro Luis Faria do ,   Neuroradiology Fellow, Montreal General Hospital, McGill University Health Center,   Neuroradiologist, and Chief, Neuroradiology Department, Hospital da Real Beneficiência Portuguesa de São Paulo
Published: October 2015

Constructive interference in steady state (CISS) is a fully refocused fast-gradient echo sequence that is mainly used in the assessment of the central nervous system. The most important advantages of steady-state imaging are short acquisition times, high signal-to-noise ratio, and better contrast-to-noise ratio. Owing to its cisternographic effect, CISS is useful in the assessment of the cranial nerves, and can also be used when studying cysts, cystic masses, and neurocysticercosis and in hydrocephalus cases. CISS has been shown to be useful in spinal imaging, epecially in cases of arteriovenous malformation and when it is helpful to better characterise intra- and extramedullary cystic abnormalities.
Neuroinflammatory Cytokines - The Common Thread in Alzheimer Pathogenesis
Authors: Griffin W Sue T , Barger Steven W ,   Dillard Professor and Vice Chairman,   Professor of Geriatrics, Neurobiology and Developmental Sciences and Internal Medicine, Donald W Reynolds Department of Geriatrics and the Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences and Geriatric Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System,   Professor of Geriatrics, Neurobiology and Developmental Sciences and Internal Medicine, Donald W Reynolds Department of Geriatrics and the Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences and Geriatric Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System
Published: October 2015

This article discusses the potential role of the cytokine cycle and its corollary as drivers of the relentless progression of Alzheimer’s neuropathologies, whether they are the result of gene mutations, gene polymorphisms and/or environmental and comorbid conditions. Based on the discovery of cytokine overexpression as an accompaniment to the dementia-related glial activation, the cytokine hypothesis was proposed. This states that in response to the negative impact on neurons of known and unknown risk factors – which include genetic inheritance, comorbid and environmental factors – microglia and astrocytes become activated and produce excess amounts of the immune-modulating cytokine interleukin-1 (IL-1) and the neuritogenic cytokine S100B, respectively. Finding that these glial events occur in foetuses and neonates with Down’s syndrome provided the first evidence that productive immune responses by activated glia precede rather than follow overt AD-related pathology. This finding can be added to the demonstration of IL-1 induction of amyloid-β(Aβ) precursor protein and astrocyte activation with excess production of neuritogenic factor S100B. This combination suggests that IL-1 and S100B overexpression would favour the Aβ production and dystrophic neurite growth necessary for laying down neuritic Aβ plaques. This, together with demonstration of IL-1 induction of excessive production of the precursors of other features common in AD prompted a corollary to the cytokine hypothesis. The corollary states that regardless of the primary cause of the neuronal insult, the result will be chronic glial activation, which in turn will result in further neuronal injury, still more glial activation with excess cytokine expression and so on. This article discusses known causes, genetic and environmental risk factors, and comorbid conditions and the potential contribution of glial activation with excessive cytokine expression to each.
Stimulation of Plasticity and Functional Recovery After Stroke - Cell-based and Pharmacological Therapy
Authors: Chopp Michael , Li Yi ,   Scientific Director, Neuroscience Research, Department of Neurology, Henry Ford Hospital and Department of Physics, Oakland University,   Neurologist, Department of Neurology, Henry Ford Hospital
Published: October 2015

Stroke is a major cause of mortality and morbidity worldwide. There are two approaches to treat stroke, a neuroprotective approach that focuses on reducing the lesion and a neurorestorative one, designed to promote neurological recovery by treating the entire central nervous system (CNS). To date, clinical trials of neuroprotective agents for stroke have failed. Recently, cell-based and pharmacological neurorestorative therapies have shown enormous promise in reducing neurological deficits caused by stroke. This article will briefly describe preclinical studies on how the injured CNS can be stimulated by cell-based and pharmacological therapies to amplify its intrinsic restorative processes and thereby lead to improvement in neurological function post-stroke.
Long-term Efficacy and Safety with Continuous Dopaminergic Stimulation Pump Treatments in Parkinson’s Disease
Authors: Busk Kar in , Johansson Anders , Nyholm Dag ,   Biomedical Student,   Post-doctoral Researcher and Consultant Physician,   Associate Professor, Department of Neuroscience, Neurology, Uppsala University
Published: October 2015

Continuous dopaminergic stimulation (CDS) is important for symptom control in advanced stages of Parkinson’s disease (PD). The most efficacious approaches are pump treatments with dopaminergic drugs: subcutaneous infusion of the dopamine receptor agonist apomorphine and intestinal infusion of levodopa/carbidopa gel. Both methods decrease motor fluctuations in long-term follow-ups, including parkinsonian and dyskinetic states, when compared to conventional optimised oral therapy. Also non-motor symptoms may be improved. Adverse drug reactions are usually less pronounced although high levodopa doses, which are common with levodopa/carbidopa infusion, may cause hyperhomocysteinaemia and cobalamin deficiency. Technical complications are specific for each infusion strategy. Formation of subcutaneous nodules is the most common problem with apomorphine infusion. Dislocation of the intestinal tube is the most common problem with levodopa/carbidopa infusion. Both pump treatments may be used for 24-hour infusion in selected patients. The long-term experience is reviewed. To conclude, CDS pump treatments may be successfully used for several years in advanced PD.
Nicardipine Prolonged-release Implants - A Potential Tool for the Prevention of Cerebral Vasospasm?
Authors: Schubert Gerrit Alexander , Seiz Marcel , Thomé Claudius ,   Senior Physician,   Senior Physician,   Professor and Chairman, Department of Neurosurgery, Medical University Innsbruck
Published: October 2015

Despite considerable effort, no effective prophylactic treatment for cerebral vasospasm after subarachnoid haemorrhage (SAH) has been identified thus far. Treatment approaches have included the application of intravenous and therefore systemic vasodilatory drugs, which in turn have been found to be associated with significant side effects while at the same time exerting only limited efficacy. Consequently, a more local application, namely the intrathecal delivery of nicardipine prolonged-release implants (NPRI) has been developed. After surgical clipping of the causative aneurysm, these implants may be positioned adjacent to the proximal vasculature most at risk for developing delayed vasospasm. Several studies were able to show a dramatic reduction in both the incidence and severity of angiographic vasospasm, which in turn reduces the development of cerebral infarction and delayed ischaemic neurological deficits. While efficacy appears to be dose dependent, a reduction of angiographic vasospasm incidence from 70 % to less than 10 % has been observed, paralleled by an improvement of functional outcome. However, when applied intraventricularly after coiling of the offending aneurysm, effects were less pronounced. At this time, NPRIs seem to represent a very promising treatment option for the prevention of cerebral vasospasm after SAH, and larger studies will be needed to further supplement previous findings.
Primary Angiitis of the Central Nervous System - Clinical Approaches, Challenges and Controversies
Authors: Gioia Laura , Poppe Alexandre Y , Lanthier Sylvain ,   Senior Neurology Resident,   Clinical Assistant Professor,   Associate Professor, Cerebrovascular Disease Centre, Department of Medicine, Research Centre, University of Montreal Hospital Centre and University of Montreal
Published: October 2015

Primary angiitis of the central nervous system (PACNS) is a rare and life-threatening form of vasculitis confined to the CNS. A timely diagnosis is a real challenge because clinical manifestations of PACNS are diverse and nonspecific. Headaches, cerebrospinal fluid inflammation and abnormal brain magnetic resonance imaging are prevalent. When PACNS is suspected, a thorough investigation is mandatory to rule out several potential simulators and confirm the diagnosis. Treatment of PACNS is also a challenge involving competing forces, which include the threat of serious adverse effects of potent immunosuppressive agents and the risk of neurological deteriorations due to insufficient immunosuppressant therapy. Efforts are ongoing to delineate subtypes requiring different therapeutic approaches and having distinct prognoses. Despite recent progress, PACNS is still fatal in as much as one-sixth of cases. Long-term follow-up is mandatory in patients with PACNS.
Beautiful Eyes Guiding Powerful Hands - The Role of Intraoperative Imaging Techniques in the Surgical Management of Gliomas
Authors: Riva Marco , i Giuseppe Casacel , Castellano Antonel la , Fava Enrica , Falini Andrea , Bello Lorenzo ,   Resident, Division of Neurosurgery, Department of Neurological Sciences, University of Milan,   Resident, Division of Neurosurgery, Department of Neurological Sciences, University of Milan,   Research Fellow, CERMAC, Vita-Salute San Raffaele University,   Senior Researcher, Division of Neurosurgery, Department of Neurological Sciences, University of Milan and Istituto Clinico Humanitas, Rozzano,   Associate Professor, CERMAC, Vita-Salute San Raffaele University,   Senior Associate Professor, Division of Neurosurgery, Department of Neurological Sciences, University of Milan and Istituto Clinico Humanitas, Rozzano
Published: October 2015

The aims of the surgical management of cerebral gliomas are to achieve the widest feasible resection and preserve the patient’s functional integrity. This results in an improved survival rate and a favourable quality of life. When treating this disease, current neuroradiological techniques are important for preoperative depiction and planning, and intraoperative image-guided resection, especially when the tumour involves eloquent cortical and subcortical structures. Knowledge of these techniques and their limitations, and appropriate expertise are therefore necessary to gain the complete benefit of their diagnostic and therapeutic power.
Combination Therapy in Moderate to Severe Alzheimer’s Disease - Overview and Discussion Points for the Future
Authors: Molinuevo José L ,   Consultant Neurologist, Alzheimer’s Disease and Other Cognitive Disorders Unit, Institut Clinic of Neuroscience, Neurology Service, Hospital Clinic, Barcelona
Published: October 2015

Two effective symptomatic therapies are available for Alzheimer’s disease: the cholinesterase inhibitors (ChEIs) and memantine, an N-methyl-D-aspartate receptor antagonist. Current data demonstrate that combination therapy with memantine and a ChEI produces symptomatic benefits in all domains of AD. The benefits of combination therapy are greater than those of ChEI monotherapy, are sustained long term and appear to increase with time.
New Diagnostic Criteria for the Behavioural Variant of Frontotemporal Dementia
Authors: Pijnenburg Yolande AL ,   Neurologist, Department of Neurology and Alzheimer Centre, VU University Medical Centre
Published: October 2015

In September 2011, the International Behavioural Variant Frontotemporal Dementia Criteria Consortium established a new set of clinical diagnostic criteria for the behavioural variant of frontotemporal dementia (bvFTD). Following the 1998 criteria by Neary et al., where five core items had to be present to make a diagnosis of bvFTD, the new criteria incorporate six clinical hallmarks and demand that at least three of these are present. Moreover, a degree of probability and a role for neuroimaging findings are introduced within the criteria. The new diagnostic criteria have a sensitivity of 76 % for probable bvFTD and a sensitivity of 86 % for possible bvFTD. They provide a good starting point for a more accurate diagnosis of bvFTD.
Neurogenesis in Stroke Treatment
Authors: Zhang Rui Lan , Chopp Michael ,   Health Services Researcher, Department of Neurology, Henry Ford Hospital,   Scientific Director, Neuroscience Research, Department of Neurology, Henry Ford Hospital and Department of Physics, Oakland University
Published: October 2015

Findings of stroke-induced neurogenesis in the adult brain have raised hopes that amplification of endogenous neurogenesis contributes to improvement of neurological outcomes. This article briefly reviews stroke-induced neurogenesis and emerging potential therapies aimed at amplification of endogenous neurogenesis during stroke recovery.
The Role of Fluoxetine and Selective Serotonin Re-uptake Inhibitors in Motor Recovery Following Acute Ischaemic Stroke
Authors: Chollet François , Tardy Jean , Pariente Jérémie , Loubinoux Isabelle , Albucher Jean-François ,   Professor,   Physician Neurologist,   Assistant Professor,   Researcher in Neuroscience, Department of Neurology, Purpan University Hospital, INSERM U825, Paul Sabatier University Toulouse III,   Physician Neurologist
Published: October 2015

Until now, recombinant tissue plasminogen activator thrombolysis within the first hours after a stroke has been recognised as the only validated treatment able to improve the spontaneous – and most of the time incomplete – recovery of neurological functions after stroke. However, we have learnt from research over the last decade, in part based on the considerable improvement in neuroimaging techniques, that spontaneous recovery of neurological functions was associated with a large intracerebral re-organisation of the damaged human brain. The question of whether lesioned-brain plasticity can be modulated by external factors such as pharmacological agents is now addressed, with the aim of improving recovery and reducing the final disability of patients. We review the preclinical and clinical arguments for a direct action of selective serotonin re-uptake inhibitors in promoting recovery after stroke in humans.
An Overview of the Treatment Options for Acute Migraine
Authors: Antonaci Fabio , Ghiotto Natascia , Evangelista Maurizio ,   Professor, University Consortium for Adaptive Disorders and Head Pain, Pavia,   Neurologist, Headache Science Centre, Casimiro Mondino National Institute of Neurology Foundation, Pavia,   Professor, Catholic University of the Sacred Heart and Institute of Anaesthesiology, Resuscitation and Pain Therapy, Rome
Published: October 2015

Migraine is a primary headache disorder associated with a high socioeconomic burden. The first step in effective migraine management, following confirmation of the diagnosis, is patient education: the condition is carefully explained, to ensure that it is properly understood, and realistic expectations are set. The choice of acute treatment has changed over time as the available therapeutic options have increased. Abortive migraine therapy can be either specific (ergot derivatives and triptans) or non-specific (analgesics and non-steroidal anti-inflammatory drugs). Even though acute symptomatic therapy can be optimised, migraine remains a chronic and potentially progressive condition.
Update on Amyloid-associated Intracerebral Haemorrhage
Authors: Grysiewicz Rebbeca , Gorelick Philip B ,   Assistant Professor of Neurology, Section of Cerebrovascular Disease and Neurological Critical Care, University of Illinois College of Medicine at Chicago,   Medical Director, Hauenstein Neuroscience Center, Saint Mary’s Health Care and Clinical Professor, Translational Science and Molecular Medicine, Michigan State University
Published: October 2015

Cerebral congophilic or amyloid angiopathy (CAA) is a clinicopathological entity that is considered a common cause of primary non-traumatic brain haemorrhage in the elderly. CAA is frequently associated with Alzheimer’s disease (AD) and has become a primary focus of scientific inquiry. The spectrum of intracerebral haemorrhage (ICH) that may occur in CAA includes: cerebral lobar haemorrhages, deep haemorrhages, purely subarachnoid and subdural haemorrhages and cerebral microbleeds. CAA is also associated with microinfarcts, leukoencephalopathy and superficial siderosis. This brief article will provide an update on the advances in our understanding of CAA-associated ICH with a focus on the following topics: neuropathology and mechanism of CAA-related haemorrhage; epidemiology, including genetic and other possible risk factors; clinical presentation; diagnosis, including newer imaging modalities; and prospects for prevention and treatment.
Deep Brain Stimulation for Parkinson’s Disease - A Review
Authors: Honey Christopher R , Ranjan Manish ,   Associate Professor of Neurosurgery, Surgical Centre for Movement Disorders, University of British Columbia, Vancouver,   Associate Professor of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore
Published: October 2015

The majority of patients with Parkinson’s disease (PD) can be treated with medications. As the disease progresses, however, certain symptoms may evolve that are refractory to medical therapy but ideally suited to surgical intervention. Tremor, dyskinesia and motor fluctuation can be effectively treated with deep brain stimulation (DBS). This article highlights which PD patients can benefit from DBS and summarises how the operations are performed and what are the expected outcomes (and potential complications). The relevant literature is reviewed for experienced clinicians and our personal bias is highlighted for those new to the field (and hoping to avoid our early mistakes).
Non-motor Symptoms in Parkinson’s Disease
Authors: Uc Ergun Y , Tippin Jon , Chou Kelvin L , Erickson Bradley A , Doerschug Kevin C , Jimmeh Fletcher Decontee M ,   Associate Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City,   Associate Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City,   Clinical Associate Professor, Departments of Neurology and Neurosurgery, University of Michigan,   Assistant Professor, Department of Urology, University of Iowa,   Associate Professor, Department of Internal Medicine, University of Iowa,   Assistant Professor, Department of Neurology, University of Iowa, and Neurology Service, Veterans Affairs Medical Center, Iowa City
Published: October 2015

In addition to typical motor dysfunction (parkinsonism), diverse non-motor symptoms (NMS) are frequently observed in patients with Parkinson’s disease (PD). Some NMS may antedate the diagnosis of PD. Examples of NMS include cognitive impairment, autonomic dysfunction, visual dysfunction, sleep abnormalities and psychiatric disorders. NMS are associated with wide-ranging abnormalities in extranigral dopaminergic systems and non-dopaminergic (e.g. cholinergic, noradrenergic, serotoninergic) systems. The type and severity of NMS vary based on age, disease severity and predominant motor symptoms. NMS can be disabling and reduce quality of life. Treatment of NMS can be challenging. Some NMS are helped by dopaminergic treatment, whereas others can be induced or exacerbated by treatments that help the motor dysfunction. Physicians should probe their PD patients about their NMS and address them for better care. Clinical trials should incorporate NMS as outcomes for more meaningful conclusions on the effect of treatments under investigation.
Childhood Absence Epilepsy - A Review of Treatment Strategies and Perspectives for the Future
Authors: Rheims Sylvain , Ryvlin Philippe ,   Neurologist,   Professor, Department of Functional Neurology and Epileptology and Institute for Children and Adolescents with Epilepsy, Hospices Civils de Lyon, and INSERM U1028, CNRS UMR5292, Translational and Integrative Group in Epilepsy Research, Lyon Neuroscience Research Center
Published: October 2015

Childhood absence epilepsy (CAE) is one of the most common forms of paediatric epilepsy. However, there is still a gap between the prevalence of CAE in paediatric epilepsies and the paucity of available data regarding its therapeutic management. Only nine randomised controlled trials have been published in the field over the past four decades, with many suffering from major methodological limitations. A recent large randomised double-blind controlled trial reported that ethosuximide and sodium valproate are the most effective anti-epileptic dugs in CAE and that cognitive performance appears to be better with ethosuximide than with sodium valproate. Although lamotrigine also demonstrated anti-absence properties in the same trial, it proved to be significantly less efficacious than ethosuximide or sodium valproate. Despite these recent advances, several questions, including long-term outcomes, management of refractory CAE and treatment duration, remain unanswered and further studies are required to refine therapeutic decisions.
Sudden Unexpected Death in Epilepsy - An Overview of Current Understanding and Future Perspectives
Authors: Friedman Daniel , Hirsch Lawrence J ,   Assistant Professor and Epileptologist, Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Medical Center,   Professor of Neurology and Co-Director, Comprehensive Epilepsy Center, Department of Neurology, Yale University
Published: October 2015

Sudden unexpected death in epilepsy (SUDEP) is likely to be the most common cause of disease-related mortality in people with epilepsy. The most commonly encountered scenario is that a previously healthy person is found dead in bed by family. Patients with frequent generalised tonic-clonic seizures are at highest risk but SUDEP can occur in patients who have never had convulsions. The mechanisms of SUDEP are poorly understood but seem to be related to seizure-related cardiac, respiratory or cerebral dysfunction. Seizure control is the only clear strategy to prevent SUDEP but that is not possible in the 30 % of patients with treatment-resistant epilepsy. Understanding the pathophysiology of SUDEP may lead to prevention strategies for patients who continue to have seizures despite maximal therapy.
Cognitive and Behavioural Predictors of Alzheimer’s Disease Progression
Authors: Starr John M , Russ Tom C , McGrory Sarah ,   Professor,   Clinical Research Fellow, Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Scottish Dementia Clinical Research Network, NHS Scotland, and Centre for Cognitive Ageing & Cognitive Epidemiology, University of Edinburgh, UK,   PhD Studentship in Dementia Research, Alzheimer Scotland Dementia Research Centre, University of Edinburgh, UK
Published: October 2015

Alzheimer’s disease (AD) can be thought of as divided into pre- and post-diagnostic phases. There is evidence that cognitive and behavioural traits influence the risk of AD diagnosis. Following diagnosis, it may be difficult to tangle the causal direction between cognitive and behavioural measures as predictors or manifestations of AD progress, though people with higher lifetime cognitive trait scores appear to be protected somewhat against worsening cognitive scores and behavioural changes. The pre-diagnostic phase can be considered as a state where AD neuropathology is progressing without manifestations of this and a prodromal phase where, typically, episodic memory is impaired. Far fewer data exist that inform about the effects of cognitive or behavioural predictors during this phase, though those from large brain tissue bank collaborations indicate that education, a correlate of cognitive function, does not influence the extent of neuropathology.
Social and Economic Benefits of Early Optimised Treatment for Parkinson’s Disease Patients - Improved Quality of Life and Greater Productivity
Authors: Lökk Johan , Persson Ulf , Wainwright Michael ,   Professor and Head Physician, Geriatric Department, Institute of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm,   Professor of Health Economics, The Swedish Institute for Health Economics, Lund,   Uppsala Science Park, Uppsala, Sweden
Published: October 2015

From a broad societal perspective, the economic burden of Parkinson’s disease ranges from direct medication expenses to costs associated with home help and lost production. The last two generally arise in the more advanced stages of the disease. Savings are nevertheless possible and the two main ways of attaining this are by slowing down disease progression and reducing the time patients spend in off-periods. Earlier onset of optimised treatment, both in the initial and later disease stages, has the potential to achieve both. We highlight examples of advanced therapies that alleviate severe motor symptoms and thereby prolong the time patients can remain in their own homes and at their places of work. Health economic calculations for two forms of advanced therapy, continuous dopaminergic stimulation via pumps and deep brain stimulation, are also shown.
Clinical Differential Diagnosis of Multifocal Motor Neuropathy
Authors: Léger Jean-Marc , Gavriliuc Eugen ,   Professor,   Fellow, Centre National de Réference Maladies Neuromusculaires Rares, CHU Pitié-Salpêtrière and University Pierre et Marie Curie (Paris VI), Paris, France
Published: October 2015

Multifocal motor neuropathy (MMN) is a rare, clinically well-defined condition within the spectrum of chronic, immune-mediated neuropathies. A typical patient history involves slowly or stepwise progressive, predominantly distal, asymmetrical limb weakness and muscle wasting, most frequently in the arm, that may have developed over a period of years. As a rare condition, MMN may present a diagnostic challenge for non-specialists and some patients may wait years for a correct diagnosis. Timely and accurate diagnosis is essential for patients with MMN. Unlike some motor neuropathies, MMN is treatable with intravenous immunoglobulin and untreated patients are likely to experience progressive muscle weakness that may result in serious functional impairment and impaired quality of life. The aim of this article is therefore to provide a guide for non-specialist neurologists to the clinical recognition and differential diagnosis of MMN.
The Long-term Treatment of Multifocal Motor Neuropathy with Intravenous Immunoglobulin
Authors: Berg Leonard H van den ,   Professor of Neurology, Rudolf Magnus Institute of Neuroscience, Department of Neurology, University Medical Centre Utrecht, The Netherlands
Published: October 2015

Multifocal motor neuropathy (MMN) is a rare, purely motor neuropathy. It is a progressive disorder, most patients eventually developing severe fatigue and weakness in the arm muscles that severely impair daily functioning and quality of life. Unlike other motor neuropathies such as motor neurone disease, MMN is treatable with regular infusions of intravenous immunoglobulin (IVIg). Four double-blind, randomised, placebo-controlled studies have shown that in the short term, IVIg significantly improves muscle strength and disability in more than 70 % of patients. The 11 observational studies reviewed in this article confirm that long-term maintenance treatment with IVIg maintains clinical improvement compared to pre-treatment baseline in most patients. Infusions are generally well tolerated, but regular monitoring and re-evaluation of the IVIg maintenance regimen is essential, as most patients need progressive increases in dosage or reduced intervals between infusions to maintain their response to treatment. In the absence of accepted predictive markers, maintenance IVIg should be individualised, based on each patient’s initial response, disability and the interval between the first infusion and decline in muscle strength.
Advances in our Understanding of the Pathophysiology, Detection and Management of Cerebral Amyloid Angiopathy
Authors: Pontes-Neto Octavio M , Auriel Eitan , Greenberg Steven M ,   Postdoctoral Research Fellow, J Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, US and Associate Professor of Neurology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil,   Stroke Research Fellow, J Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, US,   Director, Hemorrhagic Stroke Research, J Philip Kistler Stroke Research Center, Massachusetts General Hospital and Professor of Neurology, Harvard Medical School, Boston, Massachusetts, US
Published: October 2015

Cerebral amyloid angiopathy (CAA) is pathologically defined as the deposition of amyloid protein, most commonly the amyloid β peptide (Aβ), primarily within the media and adventitia of small and medium-sized arteries of the leptomeninges, cerebral and cerebellar cortex. This deposition likely reflects an imbalance between Aβ production and clearance within the brain and leads to weakening of the overall structure of brain small vessels, predisposing patients tolobar intracerebral haemorrhage (ICH), brain ischaemia and cognitive decline. CAA is associated with markers of small vessel disease, like lobar microbleeds and white matter hyperintensities on magnetic resonance imaging. Therefore, it can be now be diagnosed during life with reasonable accuracy by clinical and neuroimaging criteria. Despite the lack of a specific treatment for this condition, the detection of CAA may help in the management of patients, regarding the prevention of major haemorrhagic complications and genetic counselling. This review discusses recent advances in our understanding of the pathophysiology, detection and management of CAA.
Advances in Surgical Options for Medically Refractory Epilepsy
Authors: Gigante Paul R , Goodman Robert R ,   Resident, Department of Neurological Surgery, Columbia University Medical Center,   Chairman, Department of Neurosurgery, St Luke’s-Roosevelt Hospital Center and Associate Professor of Clinical Neurological Surgery, Department of Neurological Surgery, The Neurological Institute of New York, Columbia University Medical Center, New York, US
Published: October 2015

The evolution of surgical treatment for medically refractory epilepsy (MRE) has been influenced over the last decade by substantial advancements in imaging- and device-related technology, as well as an expanding assemblage of prospective data that support the utilisation of surgery for MRE. These data, which have grown to include randomised trials and long-term follow up for established surgery, as well as large series for investigational procedures, have demonstrated safe, efficacious results with proper patient selection. Prospective randomised trials of three surgically implanted neuromodulatory devices, vagus nerve stimulators, deep brain stimulators and responsive neurostimulators have demonstrated safety and significant seizure frequency reduction. Numerous studies have provided strong evidence for the efficacy and safety of temporal lobe resective surgery and recent studies have focused on applying alternative approaches to open resective surgery for patients presumed to have a medial temporal seizure focus. These alternatives include stereotactic radiosurgery, radiofrequency ablation and a magnetic resonance imaging (MRI)-guided laser technique for thermal ablation. Current evidence for these new surgical options for the treatment of medically refractory epilepsy will be presented and discussed.
Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease
Authors: Bohnen Nicolaas I , Albin Roger L , Müller Martijn LTM , Chou Kelvin L ,   Professor, Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan and Veterans Administration, Ann Arbor, Michigan, US,   Professor, Department of Neurology, University of Michigan, and Veterans Administration, Ann Arbor, Michigan, US,   Research Investigator, Department of Radiology, University of Michigan, Ann Arbor, Michigan, US,   Clinical Associate Professor, Departments of Neurology and Neurosurgery, University of Michigan, Ann Arbor, Michigan, US
Published: October 2015

There is a need to explore non-dopaminergic approaches to treating balance and gait problems in Parkinson's disease (PD). There is emerging evidence on the role of cholinergic denervation of the pedunculopontine nucleus (PPN) thalamus system and falls in PD. Preliminary clinical trial data suggest that the subgroup of PD patients with frequent falls may be suitable candidates for future cholinergic augmentation clinical trials. Recent controlled clinical trials using methylphenidate have been unable to confirm earlier reports of improved gait in PD. Although progressive deterioration of axial motor symptoms occur with deep brain stimulation of the subthalamic nucleus or globus pallidus interna, new preliminary research suggests that other surgical stimulation sites, such as the PPN, may have a potential benefit on gait and balance impairments in PD. Continuing vigorous exercise and physical fitness should be highly encouraged to patients with PD who are at risk of physical deconditioning and fear of falling, but effective antifall physical therapy interventions remain an unmet clinical need.
Blood Pressure and White Matter Hyperintensity Volume - A Review of the Relationship and Implications for Stroke Prediction and Prevention
Authors: Modir Royya , Gardener Hannah , Wright Clinton B ,   Neurology Resident, Department of Neurology,   Assistant Scientist, Department of Neurology,   Scientific Director, Evelyn F McKnight Brain Institute and Associate Professor, Department of Neurology and Department of Epidemiology and Public Health, Leonard M Miller School of Medicine, University of Miami, Miami, Florida, US
Published: October 2015

A heavy burden of white matter hyperintensities (WMH) is a risk factor for stroke and vascular cognitive impairment making it important to understand their pathophysiology, aetiology and clinical implications. Ageing studies suggest a linear relationship between blood pressure (BP) and both WMH and microstructural integrity in normal-appearing white matter and, after age, hypertension is the strongest risk factor for WMH. Numerous large population-based observational studies have reported significant associations between elevated BP and WMH burden, however, the relative importance of systolic versus diastolic BP remains controversial. Limitations of prior studies include the use of only a single measurement of BP and oversimplifying hypertension as a dichotomous variable. Race/ethnic differences in the association between BP and WMH have been suggested, but most studies only included older Caucasians. Antihypertensive treatment has been demonstrated to slow WMH progression, but lowering BP in the elderly may also reduce brain perfusion in those with poor autoregulation. Ongoing trials aim to clarify the effects of BP treatment on WMH progression in multi-ethnic populations and the implications of these findings for stroke prevention require further study.
Treatment of Aggressive Pituitary Adenomas and Carcinomas – An Overview
Authors: Syro Luis V , Ortiz Leon D , Rotondo Fabio , Uribe Humberto , Penagos Luis C , Horvath Eva , Kovacs Kalman ,   Neurosurgeon, Department of Neurosurgery, Pablo Tobón Uribe Hospital and Medellin Clinic, Medellin, Colombia,   Neuro-oncologist, Division of Neuro-oncology, Cancerology Institute, Las Americas Clinic, Medellin, Colombia,   Research Associate, Department of Laboratory Medicine, Division of Pathology, St Michael's Hospital, University of Toronto, Ontario, Canada;,   Professor, Department of Neurosurgery, SOMA Clinic, Medellin, Colombia,   Professor, Division of Otolaryngology, Medellin Clinic, Medellin, Colombia,   Senior Scientist, Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, University of Toronto, Ontario, Canada,   Emeritus Professor, Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, University of Toronto, Ontario, Canada
Published: October 2015

Most pituitary tumours are non-invasive, benign adenomas that remain confined to the sella turcica. Some of them recur, have a rapid growth rate, and invade surrounding tissues. These adenomas, considered aggressive pituitary tumours, are difficult to manage and present problems due to incomplete resection. A pituitary carcinoma is diagnosed when craniospinal and/or systemic metastases are documented. Treatment options for pituitary adenomas are surgery, radiation and drugs. Recent publications report the efficacy of temozolomide in the treatment of aggressive pituitary adenomas and carcinomas. Indications for, results with, and side effects of temozolomide therapy in aggressive pituitary tumours and pituitary carcinomas are reviewed here. Alternative treatment options for resistant or recurrent pituitary tumours are also discussed.
Gamma Knife Radiosurgery for Trigeminal Neuralgia – A Review
Authors: Monaco Edward A , Kano Hideyuki , Kooshkabadi Ali , Lunsford L Dade ,   Resident,   Research Assistant Professor,   Resident,   Professor, Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, US
Published: October 2015

Gamma knife radiosurgery (GKRS) evolved from the vision of Lars Leksell as a method of bloodless surgery for treating a wide variety of intracranial pathologies. Since the first GKRS procedure for trigeminal neuralgia (TN) in the early 1970s, thousands of medically refractory patients have been treated, with good results. GKRS has become a first-line treatment for medically refractory TN along with microvascular decompression and percutaneous rhizotomy. GKRS offers the advantages of minimal invasiveness and extremely low risk. When recommending a surgical treatment modality for medically refractory TN, one must consider patient preferences, procedural risks, medical co-morbidities and the success rates of the various approaches. In this context, we review the role of GKRS in the treatment of medically refractory TN.
Temozolomide in the Treatment of Aggressive Pituitary Tumours - An Overview of Existing Knowledge and Future Perspectives
Authors: McCormack Ann ,   Staff Specialist Endocrinology, St Vincent’s Hospital and Ganan Institute of Medical Research, Sydney, Australia
Published: October 2015

The management of aggressive pituitary tumours remains a challenge, however, the recent identification of temozolomide as a chemotherapeutic agent with significant efficacy against these tumours has heralded a new therapeutic era. There has been an exponential growth in the international experience with temozolomide over the past five years, now totalling 50 published cases. Overall, 67 % of cases demonstrated a response to temozolomide. Prolactin- and adrenocorticotrophic hormone (ACTH)-secreting tumours respond more frequently than non-functioning tumours. Response is typically evident in the first three months of treatment. Adverse effects occur in almost half of patients, although the majority are mild. The expression of a DNA repair enzyme, 06-methylguanine-DNA methyltransferase (MGMT), as determined by immunohistochemistry, appears to be the primary determinant of response to temozolomide in pituitary tumours. There is suggestion that MGMT may also play a role in pituitary tumorigenesis. Over the next few years we will see temozolomide used earlier in the treatment algorithm of aggressive pituitary tumours, making it imperative to collect global long-term data on its use.
The Timing of Continuous Dopaminergic Stimulation for Optimal Clinical Outcomes
Authors: Winkler Christian ,   Consultant Neurologist, Head of Movement Disorders Section, Department of Neurology, University Hospital Freiburg, Freiburg, Germany
Published: October 2015

The timing of continuous dopaminergic stimulation (CDS) treatment is an important consideration for achieving optimal motor functioning in Parkinson’s disease patients. Delaying treatment with levodopa/carbidopa intestinal gel (LCIG) infusion in patients with severe ‘on-off’ fluctuations may result in a poorer and slower response, while early initiation of CDS therapy increases the chance of achieving continuous ‘on’ without dyskinesia. Furthermore, overnight LCIG infusion is indicated when there is severe akinesia overnight, but daytime-only LCIG infusion treatment can lead to a reduction in overnight motor fluctuations after several months.
Deep Brain Stimulation in Parkinson’s Disease – Impact on Quality of Life
Authors: Toft Mathias ,   Physician and Researcher, Department of Neurology, Oslo University Hospital, Oslo, Norway
Published: October 2015

Health-related quality of life (HRQoL) is reduced in Parkinson’s disease patients. Deep brain stimulation (DBS) is an established treatment for motor problems and motor fluctuations in advanced Parkinson’s disease. Three randomised trials were recently conducted to assess the effects of DBS on HRQoL. All studies found improvements in HRQoL after surgery. DBS of the subthalamic nucleus and the globus pallidus interna improved HRQoL to a similar degree. However, in the long-term, such improvements may not be maintained, perhaps because HRQoL is a subjective measure and subjective perceptions of disability may change over time. DBS has proven long-term efficacy on motor symptoms, and the decline in benefit over time may also be explained by progression in the non-motor symptoms of the disease. Several predictors of HRQoL improvements after DBS have been identified, including good levodopa response, young age and good cognitive function.
Subcutaneous Apomorphine Infusion – An Update
Authors: Katzenschlager Regina ,   Consultant Neurologist, Department of Neurology, Danube Hospital, Vienna, Austria
Published: October 2015

Continuous delivery of dopaminergic drugs is an important treatment strategy to delay or reverse motor complications in Parkinson’s disease (PD). Subcutaneous apomorphine (APO) infusion has been shown (in uncontrolled studies) to significantly reduce ‘off’ time and dyskinesia duration and severity, and long-term data show the beneficial effects persist for several years. There is some evidence that the maximum antidyskinetic effect of APO infusion may be attained when oral medications are reduced or discontinued, making monotherapy an important clinical goal. Recent studies demonstrate possible positive effects of APO infusion on the non-motor symptoms of PD. However, more trials are needed to assess the neuropsychiatric effects of this treatment. Moreover, randomised controlled trials are needed to compare APO infusion with best medical treatment and with other invasive treatments such as levodopa/carbidopa intestinal gel infusion and deep brain stimulation.
Sleep Disordered Breathings in Patients with Stabilised Stroke – A Case Control Study
Authors: Sacchetti Maria Luisa , Mascio Maria Teresa Di , Marca Giacomo Della , Losurdo Anna , Minni Antonio , Tinelli Emanuele , Ottaviani Silvia , Toni Danilo , Caramia Francesca , Fiorelli Marco ,   Assistant Professor of Neurology,   Neurologist, Department of Neurology and Psychiatry Sapienza University, Rome, Italy,   Assistant Professor of Neurology,   Resident of Neurology, Catholic University, A Gemelli, Rome, Italy,   Otorhinolaryngologist, Department of Sensory Organs,   Radiologist,   Neurologist,   Associate Professor of Neurology,   Associate Professor of Neuroradiology,   Assistant Professor of Neurology, Department of Neurology and Psychiatry, Sapienza University, Rome, Italy
Published: October 2015

Aim of the study: In order to characterise sleep disordered breathing (SDB) in patients with stable stroke, a prospective observational study is ongoing in Rome. We report the results of the first 55 cases studied.Methods: A consecutive series of patients with acute stroke, admitted to the stroke unit of two different Roman University Hospitals, were screened. Participants were submitted to both clinical and instrumental evaluations at stroke onset and then at 4 months. The diagnostic tests included polisomnographyc (PSG) study and brain MRI. SDB, either central or obstructive, was diagnosed in presence of an apnoea/hypopnoea index (AHI) value ≥5. Statistical analysis was performed with SPSS version 18.0 for Windows. Comparisons were done by ϰ2 tests or via Fisher’s exact test depending on which was more appropriate. Correlations were done with non-parametric tests (Spearman’s rho). Statistical significance was set at p<0.05.Results: Fifty-five PSG studies were performed. Forty-two cases (76.4 %) had a SDB. Twenty-eight out of the 42 (67 %) cases with an AHI ≥5 had an obstructive sleep apnoea-hypopnoea (OSAH) and 12 (29 %) cases had a central sleep apnoea-hypopnoea (CSAH). Patients affected by CSAH were significantly older than those affected by OSAH (p=0.052). In the group of patients affected by predominantly OSAH, the longer the time interval from stroke to PSG, the shorter both the total sleep period and the total sleep time. Patients with predominantly CSAH were more frequently arrhythmic and more frequently affected by increase in pharyngeal tissue and referred significantly more frequently inattention or unrefreshing sleep.Discussion and Conclusions: The hypothesis we postulate is that, in a subgroup of patients with stroke, stroke moves to worsen patients’ pre-existing breathing condition, causing ventilatory instability. In these cases, central apnoea may take precedence over the obstructive one, in a loop gain circuit over than one, that gives rise to alternating obstructive and central events (possible complex-sleep apnoeas). Multicentre studies, capable of enrolling larger cohorts, are needed to confirm this hypothesis.