bluuebunny/crossref_metadata_2025 huggingface dataset:
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 & Public Health, Leonard M Miller School of Medicine, University of 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, etiology, and clinical implications. Aging 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.
The Role of Fluoxetine and Selective Serotonin Re-uptake Inhibitors in Motor Recovery Following Acute Ischemic 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, Toulouse, France,   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 neurologic 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 neurologic functions was associated with a large intracerebral re-organization of the damaged human brain. The question of whether lesioned-brain plasticity can be modulated by external factors such as pharmacologic 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.
Mobility Concerns in Multiple Sclerosis—Studies and Surveys on US Patient Populations of Relevance to Nurses
Authors: Lee Jong-mi , Dunn Jeffrey ,   Nurse Practitioner,   Neurologist, Stanford Multiple Sclerosis Center, Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California, US
Published: October 2015

Despite significant advances in treatments and therapies for multiple sclerosis (MS) over the last two decades, there remains no effective treatment that can definitively halt the progression of functional impairments in MS. Impaired mobility, walking in particular, has been observed in early MS disease, and cross-sectional surveys according to MS clinical criteria have shown that approximately 50 % of existing patient populations with MS require mobility support, such as wheelchairs or walking aids, some or all of the time. Loss of mobility is one of the most disabling effects of MS, and adversely affects independence, employment, and quality of life. Additionally, as patients experience mobility loss, their ability to perform activities of daily living (ADL) decreases and dependence on the assistance of others increases. The stress and physical burden of caring for a friend or relative with MS may affect the health of caregivers and increase their own requirement for healthcare resources. The identification of therapeutic options for improving impaired mobility and coping with disability represents an important aspect of patient management. This review will discuss current published literature on mobility matters in MS, how they affect the patient, and how they are measured and treated, with inclusion of the perspective of a MS nurse specialist.
Multiple Sclerosis and Falls—An Evolving Tale
Authors: Sosnoff Jacob J , Motl Robert W , Morrison Steven ,   Associate Professor,   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, 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.
Cognitive Impairment in Lacunar Strokes
Authors: Appelros Peter ,   Associate Professor, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; and Research Fellow, Department of Neurobiology, Care Sciences and Health, Karolinska Institute, Stockholm, Sweden
Published: October 2015

Vascular cognitive impairment is closely related to stroke. Each condition is a risk factor for the other. Cognitive impairment is a symptom that makes it difficult for a stroke patient to live at home. In this review paper, different types of vascular cognitive impairment are discussed, with emphasis on cognitive impairment related to lacunar strokes (LACS). Symptoms, diagnostics, epidemiology, treatment, and prognosis are surveyed. LACS are often associated with leukoaraiosis, which is related to subcortical ischemic vascular dementia. Even if LACS often are mild, they may therefore be associated with cognitive impairment on longer term.
The Role of Neuromuscular Ultrasound when Diagnosing Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Kerasnoudis Antonios ,   Neurologist, Department of Neurology, St Josef-Hospital, Ruhr University, Germany
Published: October 2015

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired immune-mediated inflammatory disorder of the peripheral nervous system. The diagnosis is based in classic cases, on the distribution pattern of the neurologic semiology, and pathologic changes of nerve conduction studies (NCS). However, in cases with subtle clinical presentation, an extended diagnostic workup may be needed (cerebrospinal fluid examination, laboratory tests, nerve biopsy). NCS remain fundamental for the diagnosis, follow up, and measurement of response to immune-treatment in CIDP. However, new challenges arose on how best to acquire a static and dynamic imaging of the peripheral nerves, with the aim of providing a holistic approach to the nerve impairment. According to the literature, neuromuscular ultrasound is able to detect in cases of CIDP thickened or swollen roots, peripheral nerves, or brachial plexus, findings that are consistent with ongoing inflammation. This review provides a timely update on the nerve ultrasound findings of CIDP and future possibilities of neuromuscular ultrasound are also discussed.
Visual Dysfunction in Combat-related Mild Traumatic Brain Injury—A Review
Authors: Magone M Teresa , Cockerham Glenn C , Shin Soo Y ,   Staff Ophthalmologist, Department of Surgery/Eye Clinic, Ophthalmology Service, Veterans Affairs Medical Center, Washington, DC, US,   National Program Director, VA Ophthalmology Service, Palo Alto, California, US,   Chief, Ophthalmology Service, Department of Surgery, Veterans Affairs Medical Center, Washington, DC, US
Published: October 2015

Approximately half of all military personnel who have served in the conflicts in Iraq and Afghanistan are reported to have some degree of combat-related mild traumatic brain injury (TBI). Although in civilian concussion injuries symptoms typically resolve within several weeks, blast-induced mild TBI may be accompanied by prolonged symptoms and afferent and efferent visual dysfunction. Most commonly near vision problems and photophobia are the presenting symptoms. A complete eye exam including vision testing, oculomotor function, and near tasking, is highly recommended after blast-induced mild TBI to detect and improve symptoms in this young patient population. A review of the current literature is presented.
Identifying Pseudobulbar Affect in Alzheimer’s Disease and Dementia
Authors: Crumpacker David W , Engelman William A ,   Psychiatrist and Neurologist, Private Practice, Plano, Texas, US,   Clinical Scientist and Senior Research Associate, Evidera, Lexington, Massachusetts, US
Published: October 2015

Pseudobulbar affect (PBA) can be challenging to differentiate from the symptoms of various neurological diseases with which it is associated. In patients with Alzheimers disease (AD) and dementia such a diagnosis can be particularly difficult as illustrated by a case of an elderly male with sudden tearful outbursts, which is reported and discussed here. PBA attacks are often incorrectly attributed to emotion or distress in response to memory loss or a result of depression or dementia. PBA is common, affecting between 1040 % of people with AD but is frequently not detected or is misdiagnosed. Multiple authors have published clinical criteria for identifying PBA; in sum, it is described as a condition affecting the brain with episodes of laughing or crying that are sudden and unpredictable, occur without warning and are excessive, exaggerated, or not appropriate to the stimuli and are involuntary and difficult to control. Differentiating PBA from depression and other behavioral disturbances in AD and dementia is helpful to patients by identifying a specific cause of their symptoms and enabling appropriate management. Various different approaches have been taken in the treatment of PBA. A combination of dextromethorphan and quinidine has been shown in well-controlled trials and in clinical use to control the symptoms of PBA associated with several neurological diseases including AD and to reduce the burden on patients and their caregivers.
The Impact of Restless Legs Syndrome/Willis-Ekbom Disorder on Quality of Life
Authors: Kalloo Aadi , Gamaldo Charlene E , Kwan Anthony B , Salas Rachel E ,   BA Candidate, Department of Neuroscience, Johns Hopkins University,   Associate Professor, Department of Neurology, Sleep Division, Johns Hopkins University School of Medicine,   BA, Department of Neuroscience, Johns Hopkins University,   Assistant Professor, Department of Neurology, Sleep Division, Johns Hopkins University School of Medicine, Baltimore, Maryland, US
Published: October 2015

Restless legs syndrome (RLS), also known as WillisEkbom Disorder (WED), is a condition associated with nocturnal sensorimotor symptoms that can result in significant sleep disruption. RLS is a prevalent condition, affecting an estimated 3.914.3 % of the US population. Despite the most recently reported prevalence studies, many experts in the field still believe RLS is a generally underdiagnosed condition. RLS can negatively affect a patients quality of life (QoL) across several domains, such as daytime sleepiness, decreased general health, decreased immune function, stress, and mood. Of those patients with moderate-to-severe symptoms that require treatment, the currently available therapeutic options (e.g. iron supplements, dopamine agonists, benzodiazepines, opioids, and anticonvulsants) can also come with adverse side effects that can further impact QoL. The purpose of this article is to examine the QoL deficits experienced by RLS patients.
Extended-release Antiepilepsy Drugs—Review of the Effects of Once-daily Dosing on Tolerability, Effectiveness, Adherence, Quality of Life, and Patient Preference
Authors: Uthman Basim M ,   Professor and Vice Chair, Department of Neurology, Weill Cornell Medical College in Qatar, Qatar Foundation and Hamad Medical Corporation, Doha, Qatar
Published: October 2015

Long-term adherence to antiepilepsy drug (AED) regimens is frequently suboptimal. Poor adherence to therapy is associated with a number of negative consequences, including an increase in patient seizures and mortality. Nonadherence is related to a variety of factors, such as treatment-related adverse events, convenience of treatment, efficacy, and quality of life. There is therefore a need for treatment strategies in epilepsy that improve long-term adherence. One such strategy is the use of extended-release (ER) AED formulations. Advantages of ER AEDs over other AED formulations include the potential for once-daily dosing, a more stable mean drug concentration over time, improved tolerability profiles, maximal use of the therapeutic window, and the possibility to achieve better seizure control. Improvements in overall treatment effectiveness may therefore increase patient adherence. This review presents evidence related to patient adherence and preference patterns for ER AEDs and highlights the beneficial properties of ER AEDs.
The Diagnostic Path to Pompe Disease
Authors: Bodamer Olaf A , Hung Christina Y ,   Professor of Human Genetics, Biochemistry and Molecular Biology and Director,   Clinical Molecular Genetics Fellow (ABMG), Division of Clinical and Translational Genetics, Dr John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, US
Published: October 2015

Pompe disease (PD) is a lysosomal disease that primarily affects skeletal and smooth muscles due to a deficiency of acid alpha glucosidase. The resulting clinical phenotype reflects a continuum ranging from severe infantile to later onset forms of PD. Early diagnosis is essential to prevent long-term complications and/or disease progression through initiation of enzyme-replacement therapy. The diagnostic path to PD starts with the ascertainment of medical and family history as well as an in-depth clinical and neurologic evaluation. The involvement of proximal muscle groups including hip and thigh muscles as well as the diaphragm is characteristic for later onset PD. Once PD is considered creatine kinase (CK) should be measured, realizing that levels may be within normal limits in end stage disease. Ultimately, diagnostic confirmation is readily achieved by enzyme analysis in dried blood spots and/or leukocytes followed by molecular analysis. Muscle biopsy is not sensitive enough for diagnostic testing of PD but may be an important diagnostic test for the differential diagnosis of myopathies. Future diagnostic approaches include whole exome and genome sequencing, which may contribute to our understanding of genotypephenotype correlation and phenotype prediction.
Could Metabolic Therapy Become a Viable Alternative to the Standard of Care for Managing Glioblastoma?
Authors: Thomas N Thomas N , Marsh Jeremy , Mukherjee Purna , Zuccoli Giulio , DAgostino Dominic P ,   Professor of Biology,   Bachelor of Science,   Research Assistant Professor, Biology Department, Boston College, Chestnut Hill, Massachusetts, US,   Section Chief, Section of Neuroradiology, Childrens Hospital of Pittsburgh, and Associate Professor of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, US,   Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, US
Published: October 2015

Little progress has been made in the long-term management of glioblastoma multiforme (GBM) for more than 40 years. The current standard of care (SOC) for GBM involves radiotherapy with concomitant adjuvant temozolomide chemotherapy. Perioperative corticosteroids are also administered to the majority of GBM patients. The current standard treatment strategy for GBM increases availability of glucose (from steroids) and glutamine (from radio-necrosis) in the tumor microenvironment. Emerging evidence indicates that GBM, like most cancers, is a metabolic disease displaying a robust Warburg effect. It is well documented that glucose and glutamine are major metabolic fuels that drive tumor progression. Recent evidence suggests that neoplastic cells with macrophage/microglia properties can contribute to the most invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells as well as for the more rapidly proliferating cancer cells. Metabolic therapy exploits the biological differences between tumor cells and normal cells for the non-toxic targeting of the tumor cells. Studies in preclinical models show that calorie restricted ketogenic diets (KD-R), anti-glycolytic drugs, and hyperbaric oxygen therapy can reduce availability of glucose and glutamine in the tumor microenvironment while enhancing oxidative stress in tumor cells. The predominant ketone body (b-hydroxybutyrate) reduces oxidative stress in normal brain cells. The potential success of metabolic therapy was also seen in human glioma case studies suggesting that this therapeutic strategy could become a viable alternative to the SOC.
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 revascularization to prevent stroke from intracranial atherosclerotic stenoocclusive 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 centered 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 ischemic event in the setting of atherosclerotic steno-occlusive disease, selected patients with severe hemodynamic impairment and/or recurrent symptoms despite maximal medical therapy may still benefit from surgery and neurointervention at high-volume centers, which can offer the procedure with low peri-operative morbidity.
Should We Routinely Monitor Walking in Patients with Multiple Sclerosis?
Authors: Bethoux Francois ,   Associate Staff/Director, Rehabilitation Services, The Mellen Center for MS Treatment and Research, The Cleveland Clinic, Cleveland, Ohio, US
Published: October 2015

Walking is frequently affected by multiple sclerosis (MS), and mounting evidence demonstrates the impact of walking limitations on the lives of our patients, based on self-report measures and clinical assessments. While assessing the various aspects of walking can be complex and time-consuming, simple tools have been validated, which open the door to routine quantitative measurement of walking in the clinical management of our patients. The use of newer, widely available, and relatively affordable technologies, may improve the feasibility of such measurements, and potentially bring them into the patients own environment.
Migraine with Aura Phenomenology and Length
Authors: Viana Michele , Goadsby Peter J ,   Headache Science Center, C. Mondino National Neurological Institute, Pavia, Italy,   Headache Group, NIHR, Wellcome Trust Clinical Research Facility, Kings College London, UK
Published: October 2015

About 30 % of patients with migraine suffer from episodes of migraine with aura. Migraine with aura is characterized by transient focal neurologic symptoms, visual, sensory, or dysphasic, more rarely motor or brainstem, called aura that are usually followed by a full migraine. The symptoms of the aura phase develop usually progressively over minutes and generally last for 5 to 60 minutes, although in a significant proportion of patients can be longer. The presumed substrate of migraine with aura is cortical spreading depression (CSD), a primarily neuronal phenomenon that causes a progressive shutdown of the cerebral cortex, starting from the occipital area and spreading onward at a speed of 2 to 3 mm per minute. The susceptibility to generate a CSD seems to be an intrinsic property of the migrainous brain.
Update on Amifampridine as a Drug of Choice in Lambert-Eaton Myasthenic Syndrome
Authors: Oh Shin J , Sieb Jörn Peter ,   Distinguished Professor Emeritus, Department of Neurology, University of Alabama at Birmingham (UAB), Birmingham, Alabama, US,   Professor and Chief Physician, Department of Neurology, HELIOS Hanseklinkum Stralsund, Germany
Published: October 2015

Lambert-Eaton myasthenic syndrome (LEMS) is a disabling autoimmune disorder involving impairment of neuromuscular transmission and producing serious muscle weakness, for which few effective medications are currently available. 3,4-diaminopyridine (3,4-DAP, INN/USAN: amifampridine) is the leading treatment for LEMS and has been available for over 25 years as an unapproved drug under treatment and expanded access protocols filed with the US Food and Drug Administration (FDA) or from compounding pharmacies in the US. Administering the correct dose of 3,4-DAP is criticaloverdosing can increase the risk for seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies have shown a wide variation in the 3,4-DAP content of compounded preparations. A tablet formulation of 3,4-DAP phosphate salt (FIRDAPSETM) has been licenced in Europe with orphan medicinal product status since 2009 and appears to be as efficacious as the base in relieving the symptoms of LEMS. The product has also received orphan drug status in the US and is currently being evaluated in a multicenter, double-blind, placebo-controlled phase III trial to support New Drug Application (NDA) approval in the US. A recent safety trial in healthy volunteers using doses at and above normal levels has shown no effect on QT intervals, heart rate, or cardiac depolarization. Based on available clinical trial data, amifampridine phosphate was recently given Breakthrough Therapy designation by the FDA, which may enable fast-track NDA approval, thus increasing the potential for more patients with LEMS to receive an effective therapy.
Functional Electrical Stimulation for Foot Drop in Multiple Sclerosis
Authors: Dapul Geraldine P , Bethoux Francois ,   Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, US,   Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, US
Published: October 2015

Functional electrical stimulation is an effective treatment strategy for the management of foot drop in various neurologic conditions, as demonstrated in improvements in gait performance, mobility, physiologic cost, perceived walking ability, balance, fall frequency, and quality of life. In this article, we review the current literature on the effects of functional electrical stimulation for foot drop in persons with multiple sclerosis.
Patient-reported Outcomes—An Emerging Cornerstone of Effective Intravenous Immunoglobulin Therapy
Authors: Silvestri Nicholas , Ladha Shafeeq , Mozaffar Tahseen , Ayer Gretchen , Betts Lisa M ,   Assistant Professor of Neurology, University of Buffalo, New York, US,   Associate Professor of Clinical Neurology, Barrow Neurological Institute, Phoenix, Arizona, US,   Professor of Neurology, University of California, Irvine, US,   Director Business Development, Walgreen Co., Deerfield, Illinois, US,   Program Director, Walgreen Co., Deerfield, Illinois, US
Published: October 2015

Intravenous immunoglobulin (IVIG) therapy is increasingly important in the management of various immune-mediated neuromuscular disorders including chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), myasthenia gravis (MG), and other neuromuscular disorders. Administrative burden, quality of life (QoL) concerns, adverse event prevention, economic pressures, and logistical factors are driving greater IVIG use into the home setting where it is administered by nurses. Patient-reported outcome measures (PROMs) are selfassessment instruments designed to measure a patients disability, QoL, or their perceptions of health status in relation to specific diseases. PROMs may be a valuable means of monitoring disease status and treatment efficacy in patients receiving IVIG at home. Case reports and small clinical studies show that various specific and general purpose PROMs, such as the 15-item MG-specific QOL (MG-QOL15) and the Myasthenia Gravis Activities of Daily Living scale (MG-ADL), can provide valuable information for patient monitoring at home. PROMs may help to alert physicians that earlier follow-up or treatment regimen changes are needed. PROM data recording systems such as Walgreens PartnerPoint Clinical ManagementSMmaintain regular reporting to the physician and enable efficacy and adverse events to be tracked. Pilot studies of patients with neuromuscular disease receiving IVIG at home demonstrate a strong correlation in PROM scores between assessments administered by pharmacy clinical staff and those administered by physicians indicating the reliability and suitability of PROMs for remote patient management. Further work to validate additional commonly used PROMS for autoimmune disease is needed if they are to be useful when administered outside the physician clinic.
Chronic Inflammatory Demyelinating Polyneuropathy in Diabetes Patients
Authors: Abraham Alon , Alabdali Majed , Qrimli Mohammad , Barnett Carolina , Katzberg Hans D , Perkins Bruce A , Bril Vera ,   Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada,   Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada,   Department of Neurology, King Fahad University Hospital, University of Dammam, Saudi Arabia,   Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada,   Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada,   Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada,   Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai, Hospital and Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Canada,   Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada
Published: October 2015

Diabetes mellitus (DM) is pandemic, and is the leading global cause of polyneuropathy, most commonly, a distal symmetric sensorimotor polyneuropathy (DSP). By contrast, chronic inflammatory demyelinating polyneuropathy (CIDP) is rare, and characterized mainly by symmetrical proximal and distal muscles weakness. There are currently 15 sets of criteria using a variable combination of clinical, electrophysiologic, laboratory, and biopsy features to identify CIDP, but it is unclear if these criteria are the same in patients with and without DM. Slowed conduction velocity, a feature of demyelination, is observed in patients with type 1 DM with poor control, and the clinical characteristics of these patients differ from those who have CIDP and DM, suggesting a different pathophysiology. Treatment response rates in CIDP patients, with and without DM, are as high as 80 %, and it is recommended that treatment be started early to prevent secondary axonal loss. However, patients with type 1 DM with CIDP are far less likely to be treated than CIDP patients who do not have DM. In patients with type 1 DM with polyneuropathy who have prominent weakness or demyelination in electrophysiologic studies, a diagnosis of CIDP and a trial of therapy should be considered.
Brain Stimulation for Medically Refractory Epilepsy
Authors: Schomer Donald L ,   Professor, Neurology, Harvard University Medical School; Director, Laboratory of Clinical Neurophysiology; Chief, Comprehensive Epilepsy Program, Beth Israel Deaconess Medical Center, Boston, Massachusetts, US
Published: October 2015

Every physicians treatment goal for patients with epilepsy is to control or stop their clinical seizures with minimal to no short- or long-term complications. Medications are often effective in controlling seizures but have both short- and long-term consequences. Brain stimulation, with devices that include the vagal nerve stimulator, the responsive neural stimulator, and transcranial magnetic stimulation, offers additional potential for a therapeutic clinical response with significantly fewer short- and long-term side effects. These types of brain stimulators are discussed below.
Mobile Stroke Unit Hits the Road in Houston
Authors: Grotta James C ,   Director of Stroke Research, Clinical Innovation and Research Institute, Memorial Hermann-Texas Medical Center; Director, Mobile Stroke Unit Consortium, Houston, Texas, US
Published: October 2015

After 1 year of preparation, the nations first Mobile Stroke Unit (MSU) delivering acute stroke treatment with tissue plasminogen activator (tPA) in the prehospital setting was launched in mid 2014. The unit is being operated as part of a clinical trial comparing MSU management to standard management to determine how much faster patients can be treated, how much better patients do if treated in the first hour after symptom onset than if treated later, if the physician on board the MSU can be replaced by a remote physician via telemedicine, and the costs and quality-adjusted life years saved by the MSU approach. We are treating on average over two patients per week with intravenous tPA, with more than 30 % treated within the first hour of symptom onset.
Unmet Needs in Diabetic Macular Edema
Authors: Lim Jennifer I ,   Professor of Ophthalmology and Director of Retina Services, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago Eye and Ear Infirmary
Published: October 2015

Purpose:The purpose of this article was to review current therapies for diabetic macular edema (DME) and to discuss current unmet needs in the treatment of DME.Methods:The peer-reviewed literature was searched for information about the results of clinical trials on the treatment of DME. The Internet, Retina Society meeting abstracts, and publications (both peer-reviewed and non-peer-reviewed) were searched for information about ongoing clinical trials on the treatment of DME.Results:Laser photocoagulation until recently was the only treatment with proven efficacy in phase III randomized clinical trials for DME. Although visual acuity can be stabilized with laser treatment, visual improvement is uncommon. Recently, a phase III clinical trial showed that intravitreal ranibizumab with or without prompt laser resulted in superior visual acuity results at one year compared with eyes treated with triamcinolone or laser alone. Sustained drug delivery systems, preventive therapies, and novel drugs that prevent foveal lipid, reverse ischemia, and increase blood flow to the ischemic retina are needed.Conclusions:Current drug development is addressing the unmet needs of improving visual acuity in eyes with DME. Research is needed to develop novel therapies for sustained drug delivery, prevention of macular edema, and prevention of complications related to chronic macular edema.
Uveal Melanoma—Where are We Going?
Authors: Materin Miguel A , Damato Bertil ,   Assistant Professor, Director, Ocular Oncology Section, Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven,   Honorary Professor in Cancer Studies, Consultant Ophthalmologist, Ocular Oncology Service, Royal Liverpool University Hospital
Published: October 2015

Despite good local tumor control, about 50% of patients affected by uveal melanoma die of their disease. Poor prognosis has been related to increased patient age, larger tumor size, ciliary body involvement, epithelioid cell type, extraocular extension, lymphocytic infiltration and high mitotic rate. In recent years, cytogenetic analysis has shown a strong impact on the management of these patients. Since monosomy of chromosome 3 proved to be a high predictive factor for metastatic disease, more ocular oncologists perform tumor biopsy almost routinely. However, there are still controversies regarding these results, such as sampling errors, mainly of disomy 3 results; the impact on quality of life; and the presence of other chromosomal abnormalities that correlate with prognosis as recently described in the literature (e.g. chromosomes 6, 8, 15 and 18). New classification of uveal melanomas as class 1 or class 2 tumors, indicating low and high risk for metastasis, respectively, has also been proposed using gene expression profiles.
Toric Intraocular Lenses in Cataract Surgery
Authors: Mele Rosa Braga ,   Associate Professor, University of Toronto
Published: October 2015

Cylindrical deficits in patients with corneal astigmatism of 0.50 diopter (D) to 1.00D may influence visual acuity. Increasing age and cataract surgery are correlated with greater prevalence and extent of corneal astigmatism. Conventionally, spectacles and contact lenses have been used to improve or correct corneal astigmatism. However, increasing demand for freedom from spectacles for distance vision and high prevalence of pre-existing corneal astigmatism in cataract patients have forced cataract surgery for the correction of aphakia and pre-existing corneal astigmatism to become common practice. However, implantation of toric intraocular contact lenses (IOLs) into the eye during cataract surgery may be a more predictable, powerful, and stable way of correcting pre-operative corneal astigmatism and may provide an adjunct or alternative to spectacles or relaxing incisions. Early toric IOLs were associated with post-operative rotational stability, lens misalignment, and safety concerns. The use of the new AcrySof® IQ Toric IOL for the correction of aphakia and pre-existing corneal astigmatism has largely mitigated these concerns. In addition, the AcrySof® IQ Toric IOL may also replace other treatment options for correcting pre-existing corneal astigmatism in patients undergoing cataract surgery.
Loteprednol Etabonate in Ocular Inflammation
Authors: Sheppard John , Bartlett Jimmy ,   Professor of Ophthalmology, Microbiology, and Molecular Biology, Clinical Director, Thomas R Lee Ocular Pharmacology Center, Eastern Virginia Medical School, and President, Virginia Eye Consultants,   Professor and Chairman, Department of Optometry, School of Optometry, Professor of Pharmacology, Department of Pharmacology and Toxicology, School of Medicine, University of Alabama at Birmingham
Published: October 2015

Treatment of ocular inflammation imposes a major medical and economic burden. Topical corticosteroids are effective in reducing ocular inflammation but are limited by adverse events including elevation of intraocular pressure, development of cataracts, inhibition of wound healing, and increased risk for infection or viral reactivation. Loteprednol etabonate (LE) is a unique C-20 ester corticosteroid designed to produce a predictable therapeutic effect with a low incidence of side effects. Clinical trial data have demonstrated its efficacy in a variety of ocular inflammatory conditions including giant papillary conjunctivitis, seasonal allergic conjunctivitis, anterior uveitis, superficial punctate keratitis, and dry eye syndrome. These data have been corroborated by much clinical experience. Furthermore, LE may be used to reduce the inflammation associated with ocular surgery and thus improve surgical outcomes without the risks associated with traditional ketone corticosteroid use.
Evaluating Clinical Perceptions of a New Medication for Ocular Itch Associated with Allergic Conjunctivitis—Results of the Bepreve® 1.5% First Experience Field Survey
Authors: Parekh Jai G ,   Managing Partner, Brar-Parekh Eye Associates, Woodland Park, New Jersey, Chief of Cornea and External Diseases, St Joseph’s Regional Medical Center, Paterson, and Clinical Assistant Professor of Ophthalmology, The New York Eye and Ear Infirmary
Published: October 2015

Allergic conjunctivitis associated with seasonal or perennial allergy is an increasingly prevalent complaint. Patients seeking professional evaluation for symptoms of ocular allergy usually have exhausted over-the-counter options and expect rapid, effective relief from the treatment prescribed. With the introduction of Bepreve® (bepotastine besilate ophthalmic solution) 1.5%, a survey of US doctors was conducted to evaluate their opinions and impressions of the medication following the initial patient trial. Responses from 427 practitioners, representing a total of 7,340 patient experiences, suggest that Bepreve is a rapidly effective and comfortable treatment. Nearly all respondents reported being satisfied or very satisfied with the performance of Bepreve. These survey data from the office setting are consistent with clinical trial results demonstrating that Bepreve provides rapid, durable, and comfortable relief of ocular itch.
A Safe and Convenient Method of Inserting and Controlling Donor Tissue During Endothelial Keratoplasty
Authors: Walter Keith A , Griffin Neil B ,   Wake Forest University Eye Center, Winston-Salem, North Carolina,   Carolina Eye Associates, Pinehurst, North Carolina
Published: October 2015

Purpose:To describe the functional characteristics of a corneal endothelium delivery instrument, EndoSaver™, and report its clinical performance in more than 250 endothelial keratoplasty surgeries with a 4mm incision.Methods:Data were assessed from 144 patients with endothelial cell failure enrolled in a prospective, interventional, non-randomized, uncontrolled trial as per an institutional-review-board-approved protocol. Subjects underwent endothelial keratoplasty performed by two experienced surgeons using the EndoSaver. Donor tissue was loaded onto the device and inserted through a 4mm incision. The authors describe their experiences using the EndoSaver when performing endothelial keratoplasty and report six-month endothelial cell counts.Results:No primary graft failures occurred with either surgeon’'s group. The mean endothelial cell loss at six months was correlated to graft thickness. Donor tissue thickness that was between 52–120μm (n=107), and 122–158μm, had endothelial cell loss of 31 and 26%, respectively. Seventy-one patients (49%) had 20/40 or better vision at 6 months. Ninety-five (66%) patients had 20/60 or better visual acuity. Five patients (3%) had a visual acuity of 20/70 or worse.Conclusions:Our report indicates that the EndoSaver is a superior option when compared to the forceps insertion technique for endothelial keratoplasty. Data indicates that between two surgeons and centers there is little variability in final endothelial cell counts at six months. The EndoSaver is the only instrument capable of a single, small incision (4mm) clear cornea surgery that requires no additional instrumentation to perform endothelial keratoplasty.
Descemet-stripping Automated Endothelial Keratoplasty—A Review
Authors: Hwang Anita M , Lee Jimmy K ,   Clinical Instructor of Cornea, External Diseases, and Refractive Surgery at Doheny Eye Institute, University of Southern California Keck School of Medicine,   Director of Cornea and Refractive Surgery, and Assistant Professor of Ophthalmology, Yale University School of Medicine
Published: October 2015

Descemet-stripping automated endothelial keratoplasty (DSAEK) has become the procedure of choice to treat corneal endothelial dysfunction. The technique involves replacing the diseased host endothelium with a graft consisting of a thin layer of posterior stroma, Descemet membrane, and endothelium. In comparison to penetrating keratoplasty (PK), DSAEK confers quicker visual and structural recovery with absence of corneal surface incisions or sutures, and limits astigmatism. DSAEK has been proved to successfully achieve favorable visual acuity and graft clarity in bullous keratopathy, posterior polymorphous dystrophy, and failed PK grafts. This article discusses various DSAEK surgical techniques, short- and longterm post-surgical results, complications, and comparisons with other types of keratoplasty. With the advent of Descemet membrane endothelial keratoplasty (DMEK), in which only Descemet membrane is transplanted, visual rehabilitation may be attained sooner.
Insight and Advancement in Hereditary Retinal Degenerations
Authors: Sigler Eric J , Huang John J ,   Chief Resident, Department of Ophthalmology and Visual Science, Yale University School of Medicine,   Associate Professor, Department of Ophthalmology and Visual Sciences, Director of Ocular Immunology and Uveitis, and Director of Clinical Trials and Translational Research, Yale University
Published: October 2015

Hereditary retinal degenerations comprise a diverse group of inherited genetic defects in one or more retinal or retinal pigment epithelial cellular proteins. Traditionally, anatomic classification based on clinical and histopathologic phenotype has been used to organize these disorders. In the modern era of advanced molecular biological techniques and genetic screening the current classification system may soon become obsolete, due to the fact that significant overlap between different retinal degenerations has been observed, resulting from variation in gene expression, common genetic pathways, and variable inheritance patterns. In this article, we review the various clinical disease entities, emphasize a genetic classification system, and give special attention to recent advances in molecular biology and gene therapy.
Geometrical Optical Analysis of Defocused Retinal Images to Compute the Size of Retinal Blur Circles Relative to Object Size
Authors: Thibos Larry N , Thibos Cameron A ,   Professor of Optometry and Vision Science, School of Optometry, Indiana University,   Arabic Scholar and Celestial Photographer
Published: October 2015

Optical analysis of the blurred retinal image for single points of light reveals simple relationships between the amount of blur, the amount of defocus and/or astigmatism, and the pupil diameter. The same rules apply to extended objects that are treated as a collection of point sources. Although the angular size of blurred retinal images of extended objects is distorted slightly by ocular astigmatism, it is relatively unaffected by spherical ametropia.
Spectral-domain Optical Coherence Tomography Imaging of Age-related Macular Degeneration
Authors: Amorim Garcia Filho Carlos Alexandre de , Rosenfeld Philip J , Yehoshua Zohar , Gregori Giovanni ,   Postdoctoral Associate,   Professor of Ophthalmology,   Assistant Professor, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine,   Assistant Professor, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine
Published: October 2015

Spectral-domain optical coherence tomography (SD-OCT) high-speed, high-resolution imaging of the macula has become an essential tool for evaluating dry and wet age-related macular degeneration (AMD). This high-speed, high-resolution imaging strategy, combined with new innovative algorithms, permits reproducible measurements of the anatomic changes associated with AMD, which include drusen, geographic atrophy (GA), and choroidal neovascularization (CNV). To visualize drusen and larger retinal pigment epithelial detachments, an algorithm was developed for Cirrus HD-OCT (Carl Zeiss Meditec, Dublin CA) to detect elevations in the retinal pigment epithelium (RPE). To visualize GA, an algorithm was developed to provide en face visualization of the macula, which easily identifies and measures areas where the RPE has been lost. To visualize CNV and the associated macular fluid, an algorithm was developed to measure the retinal thickness between the internal limiting membrane and the RPE. No other imaging modality is capable of qualitatively and quantitatively following patients at all stages of AMD, which makes SD-OCT the ideal instrument for following disease progression and the effect of therapies.
Genetic Basis of Age-related Macular Degeneration
Authors: Othman Mohammad , Branham Kari , Heckenlively John R ,   Senior Research Associate,   Research Investigator,   Professor, Department of Ophthalmology and Visual Sciences, University of Michigan
Published: October 2015

Age-related macular degeneration (AMD) is the main cause of vision loss and impairment in the aging population in developed countries. It is clinically and genetically a complex disease with both environmental and genetic factors affecting the outcome of the disease. Other than the wet type of AMD, there is no treatment for the other forms of AMD. It is estimated that the number of AMD patients will double in the next decade, which will have a significant financial impact on the health system and will compete for health dollars. Understanding the role of genetics in the development of AMD is paramount to help with diagnosis and future treatment. Over the past few years, we have studied the genetics of AMD and reported modest to significant association between AMD and several genes including CFH, ARMS2, TLR4 and ApoE. Our recent genome-wide association studies confirmed these AMD susceptibility loci in addition to other genes in the complement system (C2, C3, CFB and CFI). Recent studies identified new loci near TIMP3 and HDL influencing susceptibility to AMD.