bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies for Studying the Epilepsy Genome
Authors: Ferraro Thomas N. , Dlugos Dennis J. , Hakonarson Hakon , Buono Russell J.
Published: May 2013

Current leading theories on the etiology of the group of diseases called epilepsy implicate both genes and factors in the environment. Genetic research has the potential to identify molecular and cellular mechanisms that can be targeted directly for therapeutic intervention. Although nearly two decades have passed since the discovery of the first epilepsy-causing gene mutation1 and mutations in about a dozen other human genes are now well characterized,2,3 the vast majority of genetic variation that contributes to the development of epilepsy is undiscovered. Thus, there is a critical need to continue to elucidate the epilepsy genome. This chapter will review the comprehensive genome-wide approaches that are being used to achieve this goal.
Sodium Channel Mutations and Epilepsy
Authors: Catterall William A.
Published: May 2013

While many pathophysiological changes contribute to seizure susceptibility, recent work suggests that genetic factors are especially important. Polygenic inheritance patterns have been associated with febrile seizures and idiopathic epilepsy and may be important in determining susceptibility to acquired epilepsy following brain injury. Monogenic inheritance patterns are seen in a number of epilepsies associated with mutations in ligand-gated or voltage-gated ion channels. The genes most frequently associated with epilepsy encode brain sodium channels.
The GABAAγ2(R43Q) Mouse Model of Human Genetic Epilepsy
Authors: Petrou Steven , Reid Christopher A.
Published: May 2013

Epilepsy is a complex disease of neuronal networks; therefore, an understanding of the consequences of genetic dysfunction at clinically relevant temporal and spatial scales requires in vivo models. Although in vitro models have and will continue to shed light on aspects of molecular pathogenesis, gaining knowledge of the effects of mutations on the emergent properties of brain networks is critical if we are to fully understand disease genesis. Genetically modified animal models provide an avenue to investigate disease mechanisms of human mutations at this level of organization. Genetically engineered knockin models, in which the human epilepsy mutation is integrated into the mouse genome and replaces the endogenous allele, are potentially one of the most useful in vivo models for understanding epileptogenesis in genetic epilepsy. These mouse models most closely replicate the human genetic disorder and are becoming the gold standard for investigating the mechanisms underlying specific human epilepsy syndromes.
Gene Interactions and Modifiers in Epilepsy
Authors: Meisler Miriam H. , O'Brien Janelle E.
Published: May 2013

The genetic basis for most cases of human epilepsy remains unknown, in spite of recent successes in identifying the roles of SCN1A and related ion channels. This situation is likely to change dramatically in the near future with the introduction of individual genome sequencing. Using inexpensive, high-throughput next-generation sequencing technology, 〉90% of the 180,000 exons in the human genome can be sequenced from individual samples. The first few exomes published in 2009 and 2010 revealed that every human carries approximately 500 rare amino acid sequence variants not previously described. A spectrum of variation extends from benign variants without functional consequences to mutations causing significant loss of function. By revealing all of their genetic variants, genome sequencing of epilepsy patients will accelerate the discovery of primary disease genes as well as genetic modifiers. The urgent challenge will then be to recognize the subset of amino acid substitutions that change the function of the encoded protein. Functional assays to distinguish between benign and pathogenic variants will be an increasingly important component of epilepsy research in order to interpret the abundant genetic information. Identification of additional epilepsy genes and their genetic modifiers will provide new targets for intervention and should lead to more effective treatments for seizure disorders.
Genes in Infantile Epileptic Encephalopathies
Authors: Depienne Christel , Gourfinkel-An Isabelle , Baulac Stéphanie , LeGuern Eric
Published: May 2013

In this chapter, we will focus on the genes responsible for infantile EEs as the main component of the clinical picture and not on those included in complex phenotypes encountered in metabolic diseases or in contiguity syndromes due to large chromosomal abnormalities. Indeed, the association of EE with a dysmorphy or extraneurological symptoms should lead to specific metabolic or cytogenetic investigations. In the first part of this chapter, we will review the genes involved in early infantile epileptic encephalopathies (EIEEs). Although the mutations in these genes are rare, their screening has to be integrated into a rational diagnostic strategy. It is particularly important to rule out genetic etiologies since there is a risk of the disease recurring in the family. In this review, we will focus on DS as an example of a genetically determined infantile EE to emphasize the difficulties and pitfalls that might be encountered in such diseases.
Developing Models of Aristaless-Related Homeobox Mutations
Authors: Marsh Eric D. , Golden Jeffrey A.
Published: May 2013

Mutations in the Aristaless-related homeobox gene (ARX) have been causally linked to a variety of neurological conditions, particularly infantile spasms syndrome. ARX is a developmentally regulated homeobox transcription factor with expression both in the ganglionic eminence and in the cortical ventricular zone early in development.1 Postnatally, the expression pattern is restricted to GABAergic (gamma-aminobutyric acid) neurons in the cortex and basal ganglia. During development, ARX functions primarily as a transcriptional repressor2: modulating migration and fate specification of interneurons and controlling ventricular zone proliferation. How loss of function of ARX leads to an epilepsy phenotype is poorly understood. Three genetically modified mice lines have been generated3–5 to address this issue. These models each develop epilepsy, and all have changes in interneuron subtype patterns strongly implicating alterations of interneuron development as a cause of epilepsy. Analysis of these models will both further the molecular understanding of the function of ARX and allow dissection of the pathophysiological properties of the ARX-related epilepsies. This chapter will review the current knowledge of the function of Arx, the Arx mouse models, and discuss how these models can lead to a better understanding of the role of interneuron loss in the development of epilepsy during early childhood.
Major Susceptibility Genes for Common Idiopathic Epilepsies
Authors: Pal Deb K. , Greenberg David A.
Published: May 2013

Clinical observations confirm that the idiopathic epilepsies are neurodevelopmental disorders strongly influenced by genetic factors. Genetic epidemiological studies prove major genetic influences on two common forms of idiopathic epilepsy to be discussed here: rolandic epilepsy (RE) and juvenile myoclonic epilepsy (JME). The common forms of these idiopathic syndromes have a complex genetic inheritance, and this fact complicates the task of finding and elucidating the susceptibility genes as well as proving their pathogenic role. Genetic heterogeneity and phenotype definition are much more serious factors in studying common complex epilepsies than they are in the study of densely affected epilepsy pedigrees showing Mendelian inheritance. In complex disorders, several genes and sometimes environmental factors are believed to contribute to disease etiology; as a result, proving a causative role for any one gene, in a genetic model involving multiple genes, can present a challenge.
Myoclonin1/EFHC1 in Cell Division, Neuroblast Migration, and Synapse/Dendrite Formation in Juvenile Myoclonic Epilepsy
Authors: Grisar Thierry , Lakaye Bernard , de Nijs Laurence , LoTurco Joseph J. , Daga Andrea , Delgado-Escueta Antonio V.
Published: May 2013

In this chapter , we review these putative roles of Myoclonin 1/EFHC1 during brain development and during adulthood. We posit the hypothesis that JME is a developmental disease involving neuronal migration and synaptic bouton and dendritic morphogenesis.
Progressive Myoclonus Epilepsy
Authors: Lehesjoki Anna-Elina , Gardiner Mark
Published: May 2013

Loss-of-function mutations in CSTB are the primary defect in EPM1. In CSTB mutation-negative patients, PRICKLE1 and SCARB2 should be considered for testing. Lost lysosomal association of CSTB is an important contributing factor to EPM1. CSTB has an endogenous neuroprotective role, with different neuronal populations having different sensitivity to CSTB deficiency. The function of CSTB and the molecular mechanisms of EPM1 remain to be elucidated. Eight genes underlying human NCLs have now been identified: PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, and CSTD. However, the biological function of the proteins encoded by NCL genes remains elusive, and it is still uncertain whether a common pathway at the molecular level underlies the accumulation of ceroid-lipofuscin. Diagnosis by enzymatic testing or DNA analysis is now available for several subtypes, and new treatment approaches are being developed.
Cognitive and Behavioral Comorbidities of Epilepsy
Authors: Kleen Jonathan K. , Scott Rod C. , Lenck-Santini Pierre-Pascal , Holmes Gregory L.
Published: May 2013

In this chapter, the mechanisms of both permanent and dynamic impairments in cognition and behavior associated with epilepsy will be reviewed. As will be discussed, there is now considerable evidence that the final common pathway for the cognitive and behavioral disturbances is likely through epilepsy-induced altered neuronal signaling resulting in malfunctioning network activity.
Migraine and Epilepsy—Shared Mechanisms within the Family of Episodic Disorders
Authors: Rogawski Michael A.
Published: May 2013

In 1906, the British neurologist Sir William R. Gowers delivered a clinical lecture at the National Hospital for the Paralysed and Epileptic, Queen Square, London, in which he pointed out the resemblance between migraine and epilepsy.1 He argued that migraine is a borderland disease to epilepsy: “near it but not of it.” Gowers recognized that migraine and epilepsy often occur together in the same patient and that the two conditions are similar in their “character and nature.” In recent years, the association between migraine and epilepsy as comorbid conditions has been confirmed. Moreover, migraine and epilepsy are now recognized to be key members of a large family of episodic disorders that also includes periodic paralyses, cardiac arrhythmias, and episodic movement disorders. Studies of the pathophysiological mechanisms underlying the generation of migraine aura and focal seizures indicate remarkable similarities. The identification of genes responsible for both conditions is perhaps the strongest evidence for shared underlying mechanisms.
Calcium Channel α2δ Subunits in Epilepsy and as Targets for Antiepileptic Drugs
Authors: Dolphin Annette C.
Published: May 2013

Voltage-gated calcium (CaV) channels are involved in numerous physiological processes, the most important being muscle contraction, hormone secretion, and synaptic transmission. The pore-forming subunit of CaV channels is the α1 subunit, and this determines the main biophysical and pharmacological properties of the channels (Fig. 75–1). There are three main subgroups of CaV channels, CaV1–3. The low-voltage-activated calcium channels (CaV3 or T-type channels) appear to be able to function well as monomers. However, the high-voltage activated (HVA) CaV1 and CaV2 subfamilies are normally heteromeric, with the α1 subunit being associated with a CaVβ subunit and an α2δ subunit (for reviews see refs. 1–3; Fig. 75–1). Ten mammalian α1 subunits (Fig. 75–1), four β subunits, and four α2δ subunits have been cloned. These are described in more detail below.
Neurosteroids—Endogenous Regulators of Seizure Susceptibility and Role in the Treatment of Epilepsy
Authors: Reddy Doodipala Samba , Rogawski Michael A.
Published: May 2013

Neurosteroids are endogenous modulators of neural excitability that are believed to have a role in the regulation of seizure susceptibility in the setting of preexisting epilepsy. Menstrual and stress-related fluctuations in seizures may in part be related to changes in brain neurosteroid levels. In addition, men with TLE who have suppression of the hypothalamic-pituitary-gonadal axis may have a reduction in testosterone-derived neurosteroids that could worsen seizures. Treatment with exogenously administered natural neurosteroids or synthetic analogs such as ganaxolone may be beneficial to treat partial seizures. Further studies are required to determine if neurosteroid replacement is a useful therapeutic approach for seizure exacerbations related to endogenous neurosteroid fluctuations, such as in catamenial epilepsy and stress. In the future, agents that influence the endogenous synthesis of neurosteroids, such as TSPO ligands, may find utility as an alternative to neurosteroids themselves in the treatment of epilepsy.24,131
Neonatal Seizures and Neuronal Transmembrane Ion Transport
Authors: Kahle Kristopher T. , Staley Kevin J.
Published: May 2013

This book chapter will discuss recent work that has provided insight into the role of NKCC1 in fostering excitatory GABAergic neurotransmission in the immature brain and how the pharmacological inhibition of NKCC1 might hold promise for the treatment of neonatal seizures.
Clinical Problems in Brain Death
Authors: Wijdicks Eelco F.M.
Published: May 2013

Chapter 6 discusses the clinical problems faced in the assessment and determination of brain death, and the subsequent discussion about organ donation.
Epidemiology of Late-Life Mood Disorders
Authors: Marino Patricia , Sirey Jo Anne
Published: May 2013

The reported rates of late life mood disorders vary across studies with a number of factors that contribute to the identification and documentation of late life mood disorders. Factors include variability in the definition of mood disorders, measures used to evaluate depression and settings from which data is collected. In this chapter we review the rates of reported later life mood disorders with particular attention paid to the assessment methods used and the populations sampled. This focus represents the increasing move out into the ‘community’ and the increased efforts to detect the prevalence of later life mood disorders in settings that support older persons.
Depression in Dementia
Authors: Marano Christopher M. , Rosenberg Paul B. , Lyketsos Constantine G.
Published: May 2013

Depression is among the most common and troubling neuropsychiatric symptoms of dementia. It is important to diagnose and treat depression in dementia given its substantial adverse effects on patient and caregiver quality of life. The symptoms of depression in dementia often differ from those of a typical major depressive episode seen in younger adults. As the most common cause of dementia and the subject of the vast majority of dementia research, the chapter focuses on depression in Alzheimer’s dementia (AD) as a prototype for the evaluation and management of depression in dementia. We briefly review the epidemiology and non-cognitive manifestations of AD and then discuss current evidence regarding the presentation, etiology, diagnosis, and treatment of depression in AD.
Current Issues in Informal Caregiving Research
Authors: Schulz Richard
Published: May 2013

The goal of this chapter is to provide an up-to-date overview of the current status of informal caregiving with a focus on key unresolved issues in this literature. We begin with a discussion of prevalence of caregiving in the U.S. and show how rates can vary by several orders of magnitude depending on definitions used and populations sampled. Relying on national surveys of caregivers, we next characterize who they are, whom they care for, and the types of tasks carried out by caregivers. This is followed by detailed discussion of both the detrimental and potentially beneficial health effects of caregiving, their causes, and methodological challenges associated with this research area. Mental health effects, particularly depression, figure prominently in the caregiving health effects literature. Caregiver interventions with a focus on emerging innovative treatment strategies are briefly described next. We conclude with five recommendations for future research and policy in this arena.
Post-Stroke Depression and Vascular Depression
Authors: Volk Sarah , Steffens David C.
Published: May 2013

Both acute stroke and silent cerebrovascular disease have been associated with depression. The corresponding diagnostic entities—post-stroke and vascular depression— have each been linked to cognitive impairment, disability, and mortality. Though the underlying mechanisms are not fully understood and may be similar, the literature to date supports two distinct constructs based on differences in clinical features, risk factors, prognosis, and treatment. Post-stroke depression more closely resembles endogenous depression, while vascular depression is associated with specific features of executive dysfunction, anhedonia with limited depressive ideation, psychomotor retardation, disability, absent family history of mood disorder, and poorer response to antidepressant treatment.
Depression and Medical Illness in Late Life
Authors: Mezuk Briana , Gallo Joseph J.
Published: May 2013

In this chapter we set the stage for understanding the dynamic relationship between depression and medical conditions in later life by discussing the growing diversity of the aging population and the wide racial disparities in the burden of medical illness over the life course. We provide and discuss a conceptual framework that emphasizes the potential psychological, behavioral, social, and biological mechanisms through which depression and medical illness interact to cause disability and death. The intersection of stress, resources, depression, health behaviors, medical morbidity, and mortality across the life course provides an opportunity to synthesize our understanding of the sources of health disparities. This model has implications for development of new service delivery models that integrate the care of depression into the care of chronic medical conditions.
Bidirectional Relationships Between Sleep, Insomnia, and Depression
Authors: Chiara Baglioni Mathias Berger, , Riemann Dieter
Published: May 2013

The close relationship between sleep disturbances and depression has been known for a long time. The existing database shows that a combination of disturbances in sleep continuity, sleep architecture and REM sleep occurs more frequently in patients with depression compared to other psychopathological conditions. Theories about sleep abnormalities in depression focussed on neurochemical background or on chrono-biological sleep regulatory models. However, in the last 10 years the research focus has shifted from searching for specific alterations in sleep to a different strategy investigating the predictive value of insomniac symptoms for the development of depression. These data offer interesting perspectives for treatment of depression, with respect to: the predictive role of sleep disturbances for treatment response; the specific effect of antidepressant treatments on sleep; the role of sleep-wake manipulation; the necessity to add treatment for insomnia or to consider its potential preventive effect for future development of depression.
Psychotherapy
Authors: Areán Patricia A.
Published: May 2013

The focus of this chapter is on psychotherapy for late life mood disorders. The reader will be introduced to the evidence-base for psychotherapy in late life depression (LLD), and the methods for making psychotherapy accessible to all older adults, including people who are home-bound/disabled, are seen in primary care medicine, and who suffer from mild to moderate cognitive impairments. In particular, this chapter will provide and introduction to three evidence-based psychotherapies for late life mood disorders, Cognitive Behavioral Therapy (CBT), Problem Solving Therapy (PST) and Interpersonal Therapy (IPT). This chapter concludes with recommendations for future research.
Late-Life Mood Disorders and Home-Based Services and Interventions
Authors: Bazelais Kisha N. , Pickett Yolonda R. , Bruce Martha L.
Published: May 2013

Compared to ambulatory older adults, homebound seniors have exceptionally high rate of depression but poorer access to mental health care. In well defined homebound populations, the prevalence of major depression is generally estimates as 9%-13% with approximately 1/3 having significant depressives symptoms. Many depressed homebound seniors are prescribed antidepressants but symptoms persist more often than not. In-home psychotherapy, delivered face-to-face or by tele-technology, can be effective by addressing psychosocial problems such as disability, social isolation, and limited finances, that are common in the homebound. Successful service delivery models for depression include identification, treatment, and care management. The most feasible approach for implementing these models for homebound older adults is to integrate them into existing home-based care offered by the home health or aging services sectors.
Neuropathological Markers in Late-Life Depression
Authors: Miguel-Hidalgo José Javier , Rajkowska Grazyna
Published: May 2013

Neuroimaging and clinical studies of late-life depression point to neuropathological changes in the prefrontal cortex of subjects with late-life mood disorders. Research on the cellular basis of that neuropathology reveals an age-related increase in neuronal vulnerability in the orbitofrontal and dorsolateral prefrontal cortices, but less so in subcortical regions. Unlike depression earlier in life, late-life depression likely involves activation in the expression of glial markers and possibly enhancement of glial proliferation. The relationship of glial and neuronal changes to neuroimmune disturbances that occur both in depression and during normal aging remains to be fully characterized, although it may be related to inflammatory disruption in the deep white matter of the prefrontal cortex.
Pharmacokinetics and Pharmacodynamics in Late Life
Authors: Bigos Kristin L. , Bies Robert R. , Pollock Bruce G.
Published: May 2013

Older patients are the major recipients of drugs, however most research during drug development is conducted in healthy younger adults. Adverse drug events are common in older adults, but are often preventable. Safe and effective drug therapy requires an understanding of both drug disposition and response in older individuals. Geriatric patients are a heterogeneous population, which is evident in the highly variable drug concentrations and differences in dose-concentration-response relationships. While there is a paucity of data regarding the age-related changes in pharmacokinetic differences in antidepressants, there is increasing evidence that the clearance of some drugs decreases with aging and therefore older patients may experience greater concentrations than younger patients at the same dose. Combined with the fact that older adults seem to be more sensitive than younger patients to adverse effects of antidepressants at lower concentrations, it is critical to control for differences in drug exposure. This chapter reviews the current data on the pharmacokinetics and pharmacodynamics of antidepressants, as well as benzodiazepines, mood stabilizers, and antipsychotics, focusing on differences in age-related changes in drug clearance and drug response, as well as side effects and drug interactions that are more prevalent in older adults.
Functional Brain Imaging in Bipolar Disorder
Authors: Altshuler Lori L. , Townsend Jennifer D.
Published: May 2013

The prefrontal cortex (PFC) integrates and regulates emotional responses. Diminished subcortical and limbic modulation and frontolimbic abnormities may represent substrates for the acute mood episode characteristic of bipolar disorder (BP).

This chapter will review fMRI studies performed in subjects with bipolar disorder during manic, depressive or euthymic states. Paradigms using tasks that probe emotion processing, emotion regulation, executive function, working memory and response inhibition have been used to assess activation in specific brain regions. Some abnormalities appear to be state related while others may represent enduring trait deficits.
Neurocritical Care
Authors: Wijdicks Eelco F.M. , Rabinstein Alejandro A.
Published: May 2013

This resource provides the clinician with specific focus and insight on interventions in acute neurologic disorders. Neurocritical care in daily practice pertains to managing deteriorating patients, treatment of complications but also end-of-life care assisting families with difficult decisions.
Surgery for Cerebral Hemorrhage
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Cerebral hemorrhage sometimes requires neurosurgical evacuation. Surgery becomes an option when a patient has deteriorated. The indications for intervention, and particularly the timing of intervention, are discussed. This chapter also reviews the available evidence from clinical trials.
Fulminant Bacterial Meningitis
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Outcome in acute bacterial meningitis is dependent on early initiation of antibiotic treatment. This chapter discusses the pros and cons of corticosteroids, choice of antibiotics, how to rapidly assess the severity of the illness, and how to find the source of the infection.
Respiratory Support in Acute Neuromuscular Respiratory Failure
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Assessing the need for respiratory support in acute neuromuscular disease is difficult. This chapter discusses indications of triage to the intensive care unit, the benefits and risks of noninvasive mechanical ventilation and indications of intubation in acute neuromuscular disorders, such as Guillain-Barré syndrome and myasthenia gravis.
Endovascular Recanalization in Acute Stroke
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Major hemispheric stroke from large intracranial vessel occlusion may not respond to intravenous thrombolysis and may require a more aggressive endovascular approach. How to make that determination using CT angiogram and CT perfusion is discussed. This chapter mentions currently used mechanical clot disruption devices and what they can achieve.
Decompressive Craniectomy in Acute Stroke
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Large hemispheric ischemic strokes may swell, and decompressive craniectomy is sometimes the only way to salvage the patient from certain neurologic death. Not everyone is persuaded by this last-resort measure. Who benefits and how much is discussed.
Hypothermia After Cardiopulmonary Resuscitation
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Hypothermia protocols are increasingly used to treat comatose patients after CPR. The indications, management, and implications for neurologic prognostication are discussed.
Acute Delirium
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Perhaps one of the most difficult disease states to handle well. Acute agitation may lead to complications and prolongation of ICU stay. Inadequate use of medication may only lead to further complications.
Early Hypotension and Fever
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

The sudden appearance or fever and hypotension in any patient with an acute brain injury requires a quick evaluation and intervention. How to successfully approach this problem is illustrated in a typical case scenario.
Acute Hypertension After Stroke
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Blood pressure goals after acute ischemic and hemorrhagic stroke are commonly established early on. The rationale for treatment but also the uncertainties of when to treat are discussed in detail.
Weaning of the Ventilator in Myasthenia Gravis
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Weaning from the ventilator after intubation after treatment for myasthenic crisis is difficult with a high probability of reintubation. Stategies for successful weaning and extubation are discussed.
Hyponatremia After Subarachnoid Hemorrhage
Authors: Wijdicks Eelco F. M , Rabinstein Alejandro A
Published: May 2013

Hyponatremia is a very common electrolyte abnormality in the NICU and in particular after subarachnoid hemorrhage. Evaluation and treatment are discussed. How to calculate rate of infusion of fluids is highlighted.
Evidence-Based Medicine and Statistics in Cardiology
Authors: Rihal Charanjit S.
Published: May 2013

Evidence-based medicine is the conscientious and explicit use of the current best evidence from systematic research to guide medical decision making in the care of individual patients. Its practice takes into consideration 3 elements: clinical setting, scientific evidence, and physician-patient factors. Cardiology examinations test an understanding of the basic principles of biostatistics and their use in medical decision making with statistical questions about the probability of disease or therapeutic outcomes and the evaluation of diagnostic test results. Medical decision making requires the appropriate understanding and application of diagnostic test results, which include historical information, physical examination findings, and laboratory evaluations. The performance of a diagnostic test is assessed by comparing the results of the diagnostic test with the results of a criterion standard in a study population.
Restrictions on Drivers and Aircraft Pilots With Cardiac Disease
Authors: Kopecky Stephen L.
Published: May 2013

This chapter reviews three basic topics: restrictions for those operating a private motor vehicle, restrictions for those operating a commercial motor vehicle, and restrictions for those operating an aircraft. Restrictions for those operating a private motor vehicle are from the National Highway Traffic Safety Administration. There are no clear cut statutory rules for who can or cannot drive. The recommendations are designed to aid the physician when performing a medical evaluation and making recommendations. Drivers of commercial vehicles must be certified as fit-to-drive by a medical practitioner, although there are no statutory rules to follow. The FAA requires all pilots to obtain an airman medical certificate. The ultimate decision to grant a license to an individual pilot is made by the FAA.
Stress Echocardiography
Authors: Pellikka Patricia A.
Published: May 2013

Stress echocardiography is used for detection of coronary artery disease. The technique has evolved into a widely used, versatile technique not only for diagnosis of ischemic heart disease but also for determination of prognosis. The rationale for stress echocardiography is that stress results in wall motion abnormalities in regions subtended by a stenosed coronary artery; these wall motion abnormalities can be detected with echocardiography. Imaging methods, interpretation of findings, and prognostic value are reviewed.
Transesophageal Echocardiography
Authors: Puwanant Sarinya , Sinak Lawrence J. , Chandrasekaran Krishnaswamy
Published: May 2013

Multiplane transesophageal echocardiography allows excellent visualization of all cardiac structures and great vessels. The common clinical indications for transesophageal echocardiography are assessment of complications of myocardial infarction, detection of aortic dissection, diagnosis of infective endocarditis and its complications in native and prosthetic valves, determination of embolic source, visualization of cardiac tumors, evaluation of congenital heart diseases, and assessment of critically ill patients. Transesophageal echocardiography is also a valuable adjunctive imaging method during cardiovascular surgery and percutaneous cardiac interventions.
Cardiovascular Computed Tomography and Magnetic Resonance Imaging
Authors: Gerber Thomas C. , Walser Eric M.
Published: May 2013

Image formation in clinical CT relies on the mathematical conversion of projection data that have been obtained by measuring the attenuation of a fan-shaped x-ray beam from many angles around the patient. Image formation in clinical MRI relies on the alignment of hydrogen nuclei or protons along an external magnetic field. CT examinations are faster and easier to perform than MRI examinations and, therefore, are more widely offered. CT scans result in a 3-dimensional dataset that can be reformatted in any arbitrary plane after the examination is complete. Most cardiovascular MRI examinations consist of many image acquisitions, and experience is needed to obtain the desired views. Recent technical developments in CT and MRI have facilitated vascular imaging because an entire scan can now be completed during the transit time of one intravenous bolus administration of contrast material. The newer, 64-slice CT scanners and the newer pulse sequences for MRI have essentially replaced diagnostic angiography for large and medium-sized vessels.
Atlas of Congenital Heart Defects
Authors: Phillips Sabrina D. , Cetta Frank
Published: May 2013

This chapter presents images and descriptions of various types of congenital heart defects. Scimitar syndrome, atrial septal defect, Ebstein anomaly, Eisenmenger syndrome, coarctation of the aorta, transposition of the great arteries, tetralogy of Fallot, patent ductus arteriosus, and fistulas are reviewed.
Electrocardiographic Diagnoses: Criteria and Definitions of Abnormalities
Authors: Hammill Stephen C.
Published: May 2013

This chapter is a diagnostic guide for all physicians who evaluate ECGs, and the criteria are of specific value to persons taking professional examinations in cardiology and internal medicine. The criteria are those used in clinical practice at Mayo Clinic, and thus they may differ in minor ways from those used on examinations. Check the specific diagnoses available on the answer sheet. These criteria are not endorsed by any professional examination body or organization.
Cardiac Cellular Electrophysiology
Authors: Lee Hon-Chi
Published: May 2013

Ion channels are integral membrane proteins that regulate the traffic of ions in heart cells. They are determinants of the cardiac action potential, which in turn underlies cardiac impulse conduction, excitation-contraction coupling, automaticity, and arrhythmogenesis. Conceptually, the configuration of the cardiac action potential is determined by the sum of ionic current activity at any given time point during the cardiac cycle. Specific cardiac ion channels are discussed along with their clinical relevance according to their participation in the different phases of the cardiac action potential. Various types of cardiac tissues have different ion channel compositions and thus, different configurations of action potentials. Proper cardiac function relies on the coordinated regulation of cardiac rhythm generation and conduction.
Heritable Cardiomyopathies and Channelopathies: Clinical Presentations, Genetics, and Implications of Genetic Testing
Authors: Bos J. Martijn , Ackerman Michael J.
Published: May 2013

The field of genetic cardiac diseases has evolved and discoveries along the continuum of research have been translated into clinical practice. Genetic insights have increased our understanding of the heritable cardiomyopathies and channelopathies, enabled identification of preclinical and potentially at-risk family members, and opened the door for considering new therapeutic options. The genomic revolution, however, has also brought with it the need to acquire a new vocabulary to understand the role of genetics and genetic testing in the evaluation and care of patients with these heritable heart diseases. This chapter discusses the clinical presentations, the most important genotype-phenotype relationships, and the implications of genetic testing for clinical practice for some of the most common heritable cardiovascular diseases: hypertrophic cardiomyopathy, Arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.
Pediatric Arrhythmias
Authors: Cannon Bryan C.
Published: May 2013

Although the mechanisms of dysrhythmias in pediatric and adult patients are usually the same, the clinical presentations and management plans may vary considerably. Many aspects of the pediatric ECG such as QRS axis, PR interval, and ventricular hypertrophy voltages are age dependent; therefore, a table of normal values based on age is necessary when evaluating ECGs from pediatric patients. In addition, heart rates are much faster in children, with resting heart rates up to 160 beats per minute being common in children younger than 1 year. The maximum sinus heart rate is also faster in younger patients, with the maximum rate typically being 220 beats per minute minus the age. This is an important fact to note when distinguishing sinus tachycardia from pathologic arrhythmias in this age group. This chapter reviews the salient features of most pediatric dysrhythmias, including their management.
Supraventricular Tachycardia
Authors: Gard Joseph J. , Habib Ammar , Asirvatham Samuel J.
Published: May 2013

Supraventricular tachycardia is a generic term encompassing various arrhythmias, including atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. This chapter focuses on paroxysmal supraventricular tachycardia. This arrhythmia is among the most commonly encountered in general cardiology practice, and the 3 most common forms are atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and atrial tachycardia. Clinical features, electrocardiographic recognition, and treatment options are reviewed.
Ventricular Tachycardia and Ectopy
Authors: Munger Thomas M.
Published: May 2013

A relatively common arrhythmia, ventricular tachycardia (VT) is present in 1% to 2% of patients during the first year after MI. This is the largest subgroup of patients with VT who require treatment. Surgical and catheter ablative techniques—using direct current and, later, radiofrequency energy—have been used in an attempt to eradicate reentrant foci that are responsible for VT in patients who have coronary artery disease. In addition to these patients, there are subsets of patients who have VT that occurs in the absence of coronary artery disease (ie, with dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, infiltrative diseases of the heart, and congenital heart disease). Additionally, VT can emerge in patients with structurally normal hearts; these patients may or may not have associated repolarization syndromes. VT is an arrhythmogenic cause of sudden death, although in patients with normal repolarization and structurally normal hearts, sudden death is rarely a complication.
Syncope: Diagnosis and Treatment
Authors: Shen Win-Kuang
Published: May 2013

Diagnosis and prognosis are 2 key objectives in syncope evaluation. The diagnosis of the cause of syncope determines the appropriate therapy to prevent recurrent syncope. The prognosis of a patient with syncope has broader implications, including the risk of recurrent syncope, sudden cardiac death, and overall survival. Prevention of recurrent syncope is determined by the effectiveness of therapy for a given condition. A clear understanding of the interrelationships between diagnosis and prognosis during syncope evaluation allows physicians to deduce an effective management approach. This chapter summarizes key areas for patient evaluation and management, including definition and differential diagnosis of syncope, pertinent history and physical examination findings, appropriate use of diagnostic testing, and treatment of various conditions causing syncope.
Pacemakers
Authors: Cha Yong-Mei , Hayes David L.
Published: May 2013

Indications for permanent pacing are divided into 3 classes: class I (necessary), class II (may be necessary; cost-benefit analysis needed), class III (unlikely to be of benefit). Common conditions for which pacing may be indicated are classified according to current guidelines. Pacing modes and nomenclature, lead type and implantation, and troubleshooting are also covered.
Implantable Cardioverter-Defibrillator Trials and Prevention of Sudden Cardiac Death
Authors: Gersh Bernard J.
Published: May 2013

Since the early 1980s, the development of implantable cardioverter-defibrillators (ICDs) has revolutionized the approach to prevention of sudden cardiac death. Multiple clinical trials have defined the indications for ICD therapy in the prevention of primary and secondary sudden cardiac death. The current understanding of risk stratification is a victory for evidence-based medicine; perhaps no other area of cardiology has been so rigorously evaluated. As such, these fact-driven clinical trials are rich fodder for the cardiology board examination.
Intracardiac Electrophysiology Tracings
Authors: Madhavan Malini , McLeod Christopher J. , Packer Douglas L. , Asirvatham Samuel J.
Published: May 2013

The field of analysis and interpretation of intracardiac electrograms is fascinating but complex and often intimidates the general cardiovascular trainee. For the cardiovascular board examination, however, a very limited and fundamental knowledge of intracardiac electrograms is expected. In this chapter, the normal intracardiac electrogram sequence is introduced and briefly explained; tracings illustrate the main concepts that may be tested on the cardiovascular board examination.
Rheumatic Heart Disease
Authors: Moore Andrew G.
Published: May 2013

Rheumatic heart disease is the most serious manifestation of acute rheumatic fever and is the most common cause of death in acute rheumatic fever. Rheumatic heart disease is the end result of carditis, which affects 30% to 80% of patients who have acute rheumatic fever. Damage to the cardiac valves, which is the hallmark of rheumatic heart disease, may be chronic and progressive; in conjunction with left ventricular dysfunction, it can lead to congestive heart failure and death. Clinical features, subclinical disease, left ventricular dysfunction, treatment, and management are discussed in this chapter. The special consideration of rheumatic fever in pregnancy is also reviewed.
Epidemiology of Valvular Heart Diseases
Authors: Nkomo Vuyisile T.
Published: May 2013

Valvular heart diseases are an important public health problem worldwide. They are classically related to rheumatic fever and rheumatic heart disease. Rheumatic fever and rheumatic heart disease are thought to result from an autoimmune reaction to group A streptococcal pharyngeal infection, which leads initially to valve regurgitation (mitral regurgitation more often than aortic regurgitation) and later to valve stenosis (mitral stenosis more often than aortic stenosis). Although the incidence of rheumatic heart disease has decreased markedly in economically developed countries owing to the dramatic decrease in the incidence of rheumatic fever, rheumatic heart disease persists in economically developing countries owing to the persistently high incidence of rheumatic fever.
Cerebrovascular Disease and Carotid Artery Stenting
Authors: Spittell Peter C. , Holmes David R.
Published: May 2013

Carotid artery disease is common in patients with atherosclerosis in other vascular beds (ie, coronary and peripheral arteries) and has a wide spectrum of clinical presentations (asymptomatic carotid bruit, TIA, or stroke). Given the dire consequences of stroke and the fact that stroke may not be preceded by warning symptoms or signs such as TIA, there has been great interest in predicting and identifying patients at risk. Identification of carotid artery stenosis has been an important component of this process. Carotid endarterectomy is superior to medical therapy for patients with symptomatic carotid artery disease and a high-grade stenosis, including carotid territory or retinal TIAs or nondisabling stroke with an ipsilateral high-grade carotid artery stenosis. The increased morbidity and mortality associated with carotid endarterectomy in high-risk patients formed the rationale for the application of carotid artery stenting. Pertinent clinical trials are also reviewed.
Vasculitis
Authors: Wennberg Paul W.
Published: May 2013

By definition, vasculitis is inflammation of a vessel. Practically, vasculitis is a diverse group of diseases that are as difficult to classify as they are to diagnose and treat. Large, medium, and small arteries, capillaries, and venules may be involved. The presenting symptoms vary by the organ system or systems affected. Both primary and secondary causes of vasculitis exist, and several conditions can mimic vasculitis. This chapter discusses types of vasculitis grouped by vessel size, with cardiovascular pathology emphasized whenever appropriate.
Heart Disease in Women
Authors: Best Patricia J. M. , Hayes Sharonne N.
Published: May 2013

Cardiovascular disease is the leading cause of death in women, outnumbering deaths from all other causes combined. Each year, more than 500,000 women experience a myocardial infarction and more than 250,000 die of coronary artery disease. Furthermore, the prevalence of cardiovascular disease in women, including coronary artery disease, congestive heart failure, stroke, and hypertension, exceeds that in men in the population older than 55 years. Because of the higher proportion of women in the aging population, each year more women die of cardiovascular disease than men. Diagnostic testing, disease manifestions, and treatment options for women with cardiovascular disease are reviewed in this chapter.
Heart Disease in the Elderly
Authors: Syed Imran S. , Murphy Joseph G. , Wright R. Scott
Published: May 2013

Older patients have more heart disease than younger patients; they also benefit more from aggressive medical therapy but at the cost of a higher incidence of adverse side effects. Heart weight increases about 1 g per year between ages 30 and 90 years, probably owing to left ventricular hypertrophy secondary to an age-related increase in systolic blood pressure. Ventricular hypertrophy leads to significant changes in cardiac function with age, including an increase in left ventricular stiffness, reduced filling during early diastole, and a prolonged diastolic isometric relaxation phase. The conduction system undergoes marked changes with age, including the loss of 50% to 75% of the pacemaker cells of the sinoatrial node and fibrosis of the specialized conduction tissue of the bundle of His. The result of these physiologic changes in relation to diagnosis and treatment of heart disease in the elderly are reviewed in this chapter.
Acute Coronary Syndromes
Authors: Wright R. Scott , Kopecky Stephen L. , Murphy Joseph G.
Published: May 2013

The leading cause of death in western societies is an acute coronary syndrome. Acute coronary syndrome occurs when there is acute destabilization of a previously stable atherosclerotic plaque within the coronary circulation, usually due to plaque rupture or plaque erosion that results in acute myocardial ischemia. Acute coronary syndrome classification includes four frequently overlapping conditions (unstable angina, ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and sudden cardiac death), each of which are reviewed in this chapter.