bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenesis of Lewy Body Dementia
Authors: Pillai Jagan A. , Leverenz James B.
Published: March 2017

This chapter discusses the Pathogenesis of Lew Body Dementia. The Lewy body dementias (LBDs) are a spectrum of dementing neurodegenerative disorders underpinned by the pathological accumulation of α- synuclein protein in both intraneuronal inclusions, “Lewy bodies, ” and neuronal processes, “Lewy neurites”. The chapter concludes that, as with other forms of cognitive impairment in the aged, the pathophysiology of cognitive impairment in LBD is likely multifactorial. Although it appears that α- synuclein pathology, particularly in the limbic and neocortical regions are linked to cognitive changes, other pathologies such as AD likely also play a role. Emphasizing the complexity, a number of genetic factors have been implicated in the LBDs, some specifically with associations to the synucleinopathies and some with other pathophysiologic processes. This complexity will need to be considered as therapeutic interventions are evaluated for the LBD.
Types of Motor Neuron Diseases
Authors: Thakore Nimish , Pioro Erik P
Published: March 2017

Disorders of lower motor neurons (LMNs, or anterior horn cells) and upper motor neurons (UMNs), jointly termed motor neuron disorders (MNDs), are diverse and numerous. The prototypical MND, namely amyotrophic lateral sclerosis (ALS), a relentlessly progressive lethal disorder of adults, is the subject of another section and will not be discussed further here. Other MNDs include spinal muscular atrophy (SMA), of which there are four types: Kennedy’s disease, Brown-Violetto-Van Laere, and Fazio-Londe syndromes, lower motor neuron disorders as part of neurodegenerations and secondary motor neuron disease as part of malignancy, radiation and infection.
Upper Motor Neuron Disorders
Authors: Fink John K.
Published: March 2017

Symptomatic disturbance of corticospinal and corticobulbar tracts (collectively, the upper motor neuron UMN) occurs in innumerable acquired central nervous system disorders including the consequences of trauma, hypoxia-ischemia, inflammation (e.g. multiple sclerosis), toxins (e.g. thiocyanate1 and specific organophosphorus compound toxicity2) and deficiencies (e.g. hypocupremia3 and vitamin B12 deficiency). Variable degrees of UMN disturbance frequently accompany degenerative disorders in which disturbance of another neurologic system results in the primary clinical. Neuropathologic studies have shown prominent axon degeneration involving corticospinal tracts (HSP and PLS) and corticobulbar tracts (PLS); and mildly affecting dorsal columns (HSP and PLS to some degree). Myelin loss is considered secondary to axon degeneration. Loss of cortical motor neurons is observed in PLS. Anterior horn cells are typically spared in both HSP and PLS. Presently, treatment for HSP and PLS is symptomatic and includes physical therapy and spasticity reducing medications.
Temporal Lobe Epilepsy
Authors: Bertram Edward H.
Published: March 2017

Temporal lobe epilepsy, as discussed in this chapter, is a focal epilepsy that involves primarily the limbic structures of the medial temporal lobe (amygdala, hippocampus, and entorhinal cortex). In recent years animal models have been developed that mirror the pathology and pathophysiology of this disease. This chapter reviews the human condition, the structural and physiological changes that support the development of seizures. The neural circuitry of seizure initiation will be reviewed with a goal of creating a framework for developing more effective treatments for this disease.
Focal Cortical Dysplasias
Authors: Mahta Ali , Crino Peter B.
Published: March 2017

Focal cortical dysplasias (FCDs) are common malformations of cerebral cortical development that are highly associated with medically intractable epilepsy. FCDs have been classified according to neuropathological subtypes (type Ia, Ib, IIA, IIb, and III) based on the severity of cytoarchitectural disruption, and the presence of unique cell types (e.g., balloon cells). Most FCDs can be detected by neuroimaging studies and will require respective epilepsy surgery to cure refractory seizures. The pathogenesis of FCDs remains to be defined, although current belief is that these lesions result from sporadic somatic mutations occurring in brain development. A link to the mammalian target of rapamycin cascade has been defined for some FCD subtypes.
Epidemiology of Epilepsy
Authors: Hesdorffer Dale C
Published: March 2017

Epilepsy affects 1 out of every 26 people during their lifetime. Worldwide, the incidence of epilepsy ranges from 28.0/100,000 to 235.5/100,000, with the large variation attributable to differences in methodology across studies. The prevalence of active epilepsy provides important information about the burden of epilepsy in the population and spurs public health planner to assess the needs of the epilepsy population. The active prevalence of epilepsy ranges from 2.4/1,000 to 22.8/1,000 worldwide and more than 65 million people have active epilepsy. Risk factors for childhood-onset and adult-onset epilepsy are discussed, considering epilepsy etiologies (e.g., severe traumatic brain injury), newer risk factors without bidirectional relationships with epilepsy (e.g., low socioeconomic status), risk factors with bidirectional relationships (e.g., psychiatric disorders), and different types of acute symptomatic seizures (e.g., febrile seizures).
Medical Management of Epilepsy
Authors: Beal Jules C. , Perucca Emilio
Published: March 2017

Epilepsy affects approximately 65 million people worldwide, leading to significant morbidity and mortality including injuries, psychiatric comorbidities, social stress, and the risk of sudden death. The best indicator of quality of life in patients with epilepsy is seizure freedom. The chapter discusses the medical management of epilepsy, focusing on decision making, when to initiate treatment, how to choose an appropriate medication, and how to proceed when a medication fails. The treatment of epilepsy is a highly individualized process that must take into account an individual’s seizure type, risk of seizure recurrence, age, sex, medical comorbidities, and personal goals and preferences.
Neurobiology of Migraine
Authors: Rosenfeld Victor , Stern John
Published: March 2017

Migraine is a common and intermittently disabling condition with a myriad of clinical presentations. A detailed understanding of the neurovascular pathology of migraine has translated into effective strategies for both prevention as well as acute treatment; however, knowledge of the varied presentations is necessary for accurate diagnosis and optimal use of treatment. Treatment may include both acute and preventative interventions and options that span lifestyle modification, nonprescriptive supplements, prescription medications, and other interventions.
Overview of Autism and Intellectual Disabilities
Authors: Gipson Tanjala T. , Johnston Michael V.
Published: March 2017

Autism spectrum disorders (ASD) and intellectual disabilities (ID) are prevalent causes of brain dysfunction in childhood and they have a significant public health impact on quality of life and the ability to live independently. ID is defined by the presence of an intelligence quotient less than 70 on a standardized test combined with impaired adaptive skills of daily living, whereas autism is defined by a combination of impaired language and social skills as well as the presence of stereotyped movements or behaviors. The prevalence of ID is estimated to be 1/100 population, with higher numbers in low resource countries, whereas the prevalence of autism is estimated to be 1 in 68, 1/42 boys and 1/189 girls. Approximately 70% of individuals with autism also meet the criteria for ID, but ID is not necessary for the diagnosis of autism. Genetic disorders are an important cause of autism, and 80% of identical twins will share autism if it is present in one twin, whereas the rate of concurrence in fraternal twins is 30%. This overview describes some general features of the causation and neurobiology of ID and ASD that are discussed in more detail in the chapters on specific pediatric disorders later in this section.
Tuberous Sclerosis Complex
Authors: Gipson Tanjala T. , Poretti Andrea , McClellan Rebecca , Johnston Michael V.
Published: March 2017

Tuberous sclerosis complex (TSC) is a disease, commonly classified as a neurocutaneous disorder, which may result in benign tumors throughout the brain and body, skin lesions, epilepsy, and cognitive/behavioral difficulties. Scientific discovery in TSC has resulted in the availability of treatments designed to target the neurobiological core of TSC in children. However, research is needed to determine if these treatments are effective for multiple aspects of the TSC phenotype in children. Current pediatric research studies have focused on the effects of early treatment of epilepsy as well as identification of potential biomarkers. This chapter reviews the aspects of TSC unique to pediatric patients, the status of current research, and future directions.
Autism and Intellectual Disabilities
Authors: Menon Deepa U
Published: March 2017

PTEN (phosphatase and tensin homologue) on chromosome 10q23.3 is a tumor suppressor gene that encodes for a dual specificity phosphatase that regulates the phosphatidylinositol 3- kinase pathway and has an important role in brain development by affecting neuronal survival, neurite outgrowth, synaptic plasticity, and learning memory. Germline mutations of the PTEN gene have been implicated in a group of related tumor syndromes with autosomal dominant inheritance and variable expression and include the Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Juvenile Polyposis syndrome. These syndromes are collectively called the PTEN hamartoma tumor syndromes (PHTS) because they have a predisposition to tumors and hamartomas. PTEN germ line mutations have also been recently linked to autism and macrocephaly and the prevalence of PTEN mutation in children with autism spectrum disorder, and macrocephaly is reported to range from 1.1% to 16.7%.
Rett Syndrome
Authors: Smith-Hicks C. L. , Naidu S.
Published: March 2017

Rett Syndrome (RTT) is a neurodevelopmental disorder that predominantly affects females but males with RTT have been identified. RTT was first described by an Austrian pediatrician, Andreas Rett. Rett syndrome was mapped to chromosome Xq28 in 1998 and a year later it was determined to be due to mutations in the MeCP2 gene at this locus. Identification of the gene led to the broadening of the clinical phenotype and further characterization into classic and atypical forms of the disease that overlap with Autism spectrum disorders during the period of regression. More than 95% of individuals with classic RTT have mutations in the MeCP2 gene.
Angelman Syndrome
Authors: Barañano Kristin W.
Published: March 2017

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by maternal deficiency of the epigenetically imprinted gene UBE3A. It is characterized by severe developmental delay, an ataxic gait disorder, an apparent happy demeanor with frequent smiling or laughing, and severe expressive language impairments. Understanding the neurobiology of AS has focused on understanding how UBE3A is regulated by neuronal activity, as well as the targets of its ubiquitin E3 ligase activity. This has led to a model of the role of UBE3A in the regulation of experience-dependent sculpting of synaptic circuits. At this time, treatment is largely supportive, but efforts directed toward reversing the epigenetic silencing machinery may lead to improved synaptic function in AS patients.
Down Syndrome
Authors: Capone George T
Published: March 2017

People with Down syndrome (trisomy 21) are distinguished by having an extra copy of chromosome 21. Chromosome 21 contains an estimated 562 genes, including 161 known to code for functional proteins, and at least 396 considered novel. Gene dosage imbalance is the primary mechanism, which results in the molecular, cellular, histological, and anatomical features characteristic of the condition. Throughout brain development, major neurobiological events go awry, resulting in a differently organized brain and characteristic developmental delays noted during infancy and the preschool years. The consequences of gene dosage imbalance continue to have repercussions on neurobiological function throughout childhood and adult life.
Methylmalonic Acidemia
Authors: Srivastava Siddharth , Chinsky Jeffrey
Published: March 2017

Isolated methylmalonic acidemia (MMA) refers to a group of inborn errors of organic acid metabolism caused by impaired conversion of methylmalonyl-CoA to succinyl-CoA. Individuals with MMA experience both acute and chronic neurological complications. The pathophysiology likely reflects impaired energy metabolism in the mitochondria leading to neuronal toxicity in MMA. MMA presents with a spectrum of clinical phenotypes with onset of symptoms anytime from the neonatal period to adulthood. Once there is clinical suspicion for MMA, definitive diagnosis requires biochemical testing. The treatment of MMA centers on acute interventions when affected individuals are ill, as well as preventative measures when they are doing relatively well. Neuroimaging in MMA demonstrates a variety of findings.
Congenital Disorders of Glycosylation
Authors: Patterson Marc C.
Published: March 2017

Congenital disorders of glycosylation (CDG) comprise a family of multisystem diseases in which N- and O-linked glycosylation and glypiation of a variety of proteins and lipids is deficient. The hypoglycosylation of multiple glycoconjugates impairs normal development of the brain (and other organs), and is associated with both episodic and chronic organ dysfunction. Developmental disorders; seizures; strokelike episodes (and stroke); hearing and visual loss; peripheral neuropathy; coagulopathy; and immune, liver, endocrine, cardiac, and cutaneous manifestations may occur in varying combinations. Specific therapy is available for MPI-CDG and SLC35C2-CDG. Most forms of O-linked CDG affect muscle; these include congenital muscular dystrophies and limb girdle dystrophies.
Neonatal Brain Injuries
Authors: Goeral Katharina , Fatemi Ali , Johnston Michael V.
Published: March 2017

Neonatal brain injuries (NBIs) are important causes of motor and neurocognitive disabilities in children worldwide. This chapter discusses the most common types of NBIs in developed countries, namely neonatal encephalopathy associated with birth asphyxia in term infants, perinatal arterial ischemic stroke, perinatal white matter injury, and germinal matrix hemorrhage and neonatal hydrocephalus. Epidemiologic studies suggest that prenatal stressors, including intrauterine inflammation, maternal drug/toxin exposure, and placental pathologies are key players in the etiology of NBIs, whereas genetic contributors are yet to be identified. Hypothermia has become a standard neuroprotective strategy in neonatal encephalopathy, and novel therapeutics are currently being evaluated.
Epilepsy Syndromes in Childhood
Authors: Staedtke Verena , Kossoff Eric H.
Published: March 2017

Epilepsy syndromes of childhood are a heterogeneous group of disorders that occur at specific neurodevelopmental stages, with a variable prognosis ranging from benign to catastrophic. In clinical practice they are categorized based on seizure type, age of onset, clinical presentation, electroencephalographic (EEG) findings, as well as response to treatment. In addition, recent advancements in neuroimaging and genetic testing have become important diagnostic tools revealing underlying defects for some of these syndromes. This knowledge has consequences for clinical practice, as it opens new perspectives for early diagnosis, prognosis and treatment. Here, we provide an up-to-date overview of the most common pediatric epilepsy syndromes, their clinical findings, associated EEG findings, and clinical management.
Spina Bifida and Related Conditions
Authors: Kinsman Stephen L.
Published: March 2017

The term “spinal dysraphism” encompasses the broadest array of the conditions known as the neural tube defects. The open neural tube defects (spina bifida aperta and cystica) include both disorders of primary and/or secondary neuralation and are best defined as myelomeningocele complex (MMC) due to their protean nervous system manifestations beyond the spinal lesion. Closed spinal dysraphisms (so-called spina bifida occulta) include lipomatous lesions, forms of tethered spinal cord, sinus tracts, and forms of split spinal cord (diastematomyelia). Both genetic and environmental etiologies have been identified. Gene-environment and gene-gene interactions are also important in the pathobiology of these conditions.
Multiple Sclerosis: Pathology
Authors: Popescu Bogdan Florin Gh. , Guo Yong , Lucchinetti Claudia Francesca
Published: March 2017

The pathology of MS consists of areas of focal demyelination, known as plaques or lesions, characterized by inflammation, gliosis, and relative axonal preservation. Recent neuropathological studies have established that white matter lesions are heterogenous with respect to the targets of injury and mechanisms of demyelination, highlighting the need for the identification of surrogate clinical and/or paraclinical markers that would correlate with immunopatterns in the general MS population and for the design of novel therapeutic strategies specifically tailored to each immunopattern. Recent neuropathological studies have also shown the cortex is an early target of the MS disease process, and that inflammatory cortical demyelination may be driven by meningeal inflammation.
Neuromyelitis Optica
Authors: Schreiner Teri L. , Bennett Jeffrey L.
Published: March 2017

Neuromyelitis optica (NMO), or Devic’s disease is an inflammatory disorder of the central nervous system that preferentially affects the optic nerves and spinal cord. Initially considered a variant of multiple sclerosis (MS), NMO is now clearly recognized to have distinct clinical, radiographic, and pathologic characteristics. Historically, the diagnosis of NMO required bilateral optic neuritis and transverse myelitis; however, the identification of a specific biomarker, NMO-IgG, an autoantibody against the aquaporin-4 (AQP4) water channel, has broadened NMO spectrum disease to include patients with diverse clinical and radiographic presentations. This chapter addresses the diagnosis, pathophysiology, and management of the disease.
Other Proven and Putative Autoimmune Disorders of the CNS
Authors: Newsome Scott D.
Published: March 2017

Antiglutamic acid decarboxylase (GAD)-associated disorders are a group of rare neuroimmunological disorders that encompass an expanding spectrum of neurological syndromes. The pathophysiology of these disorders is not well understood, although the presence of very high levels of antibodies to GAD is indicative of immunological dysfunction. The most well-known disease within this class of disorders is stiff-person syndrome (SPS), which often manifests as painful spasms, stiffness/rigidity in axial and limb musculature, and increased lumbar lordosis. Other anti-GAD-associated disorders include isolated cerebellar ataxia, progressive encephalopathy with rigidity and myoclonus (PERM), and encephalitis. Treatment depends on the severity of disease, ranging from symptomatic to immunomodulating/immunosuppressant therapies.
Other Proven and Putative Autoimmune Disorders of the CNS
Authors: Flanagan Eoin P. , Caselli Richard J.
Published: March 2017

The historical term “Hashimoto’s encephalopathy” describes a serologically diverse spectrum of autoimmune encephalopathies that tend to be highly steroid responsive and unassociated with cancer. Patients typically present with subacute cognitive decline and serological evidence of autoimmunity that includes but is not limited to thyroid antibodies. An inflammatory spinal fluid and, in a subset of patients, MRI signal abnormalities are supportive. Patients often respond promptly to corticosteroids but relapses are typical. The continued discovery of novel neural-specific-autoantibodies such as voltage-gated-potassium-channel-autoantibodies associated with autoimmune encephalopathies highlights why the term “Hashimoto’s” is misleading. The authors advocate the more general term “autoimmune encephalopathy.”
Poststreptococcal Movement Disorders
Authors: Martino Davide , Giovannoni Gavin
Published: March 2017

The spectrum of “poststreptococcal” movement disorders and other behavioral abnormalities has expaanded and the array of neuropsychiatric features associated with rheumatic fever (RF) has been broadened. However, it is difficult to establish a causal link between Group A Streptococcus (GAS) and neuropsychiatric symptoms beyond RF, which has fuelled a long-lasting, and still unsolved, debate as to whether putative “poststreptococcal” disorders such as the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection) phenotype are distinct entities or not. This chapter provides an up-to-date overview of the conditions that are well established (Sydenham’s chorea) or proposed (poststreptococcal tic and obsessive-compulsive disorders) as secondary to an immune response toward GAS.
Other Proven and Putative Autoimmune Disorders of the Peripheral Nervous System
Authors: Leung Doris G.
Published: March 2017

Myasthenia gravis is in most cases an autoimmune disorder of the neuromuscular junction in which antibodies are directed at nicotinic acetylcholine receptors or other synaptic proteins, such as the MusK protein that is involved in the formation of the formation and maturation of the motor endplate. Less commonly, myasthenia gravis can result from antibodies directed to presynaptic calcium channels as a side effect of paraneoplastic antibodies (Lambert-Eaton syndrome) or from a developmental paucity of acetylcholine receptors in the neonatal form of the disease. Treatment is usually a combination of aceetylcoholinesterase inhibitors such as pyridostigmine to prolong the life of acetylcholine released at the neuromuscular junction and/or drugs such as corticosteroids aimed at reducing inflammation.
Stroke Epidemiology and Impact
Authors: Howard Virginia J
Published: March 2017

A cerebrovascular accident or stroke is an acute disease of blood vessels of the brain. Ischemic stroke is the most common type of stroke, estimated to be about 87% of all strokes. Ten percent are estimated to be intracerebral hemorrhagic stroke (ICH), and 3% subarachnoid hemorrhagic stroke (SAH). Stroke remains the fourth leading cause of death in the United States in 2012, only surpassed by diseases of the heart, cancer, and chronic lower respiratory diseases. Stroke is the 2nd leading cause of death worldwide. This chapter examines the epidemiology and impact of stroke in the United States and globally.
Acute Ischemic Stroke
Authors: Adams Harold P.
Published: March 2017

Ischemic stroke is a leading public health problem and the most common acute neurological disease. Advances in the understanding of the pathophysiology of stroke, in particular the importance of early restoration of adequate perfusion, have resulted in improvements in the management of patients with acute ischemic stroke. The interval from onset of stroke until the administration of interventions to restore blood flow is a crucial factor in success of treatment. Still, patients with stroke now are being treated successfully with neurological outcomes improving. These advances are reducing the likelihood of death or disability from this potentially devastating neurological disease.
Surgical and Radiologic Intervention for Prevention of Ischemic Stroke
Authors: Ringer Andrew
Published: March 2017

The etiology of ischemic strokes can be broadly categorized into several subtypes: cardioembolic, extracranial atherosclerotic, intracranial atherosclerotic, lacunar, traumatic (e.g., dissections), inflammatory (e.g., Moyamoya, vasculitis), and last cryptogenic. This chapter focuses on those etiologies that are treated or prevented by cerebrovascular specialist, including strokes due to extracranial athero-occlusive disease, intracranial athero-occlusive disease, arterial dissections, and Moyamoya disease. Both medical and surgical approaches are discussed.
Intracerebral Hemorrhage
Authors: Anderson Craig
Published: March 2017

Acute intracerebral hemorrhage is the most serious and least treatable form of stroke. The major risk factor is high blood pressure (BP). Management is largely supportive-to reduce brain injury, prevent complications, and promote recovery. Recent evidence suggests modest benefits from rapid control of elevated BP. Surgery remains controversial.
Genetic Disorders and Stroke
Authors: Poretti Andrea , Johnston Michael V.
Published: March 2017

A variety of monogenic and polygenic genetic disorders have been linked to stroke, making it important for the clinician to keep up with the new discoveries and the potential to provide new gene-based therapies. Hematologic disorders such as sickle cell disease and thrombophilia due to mutations in prothrombin, factor V Leiden, and homocysteine metabolism are fairly well known, but mutations in mitochondrial metabolism and matrix metalloproteinases are less recognized. In addition, results of genome-wide association studies (GWAS) in stroke populations are revealing mutations that could predispose to stroke in specific ethnic populations. These studies are also revealing some crossover in mutations between stroke and familial hemiplegic migraine as well as mutations in growth factors such as brain derived neurotrophic factor (BDNF) that appear to influence the recovery from stroke by altering cortical plasticity.
Targets for Neuroprotection in Ischemic Stroke
Authors: Felling Ryan J.
Published: March 2017

Cerebral ischemia or hypoxia-ischemia initiate a cascade of biochemical events including impaired reuptake of glutamate into perisynaptic glia causing glutamate flooding, calcium fluxing through NMDA glutamate channels, activation of neuronal nitric oxide synthetase, and impaired mitochondrial ATP production. In animal models it is possible to block these steps and protect the brain but the temporal window of protection after the insult lasts only a few hours. Recombinant TPA is clinically protective if given within 3 hours of stroke, but other agents have not been shown to protect brain tissue after stroke. However, total body cooling has also been shown to protect the brain of term infants if initiated within 6 hours of perinatal asphyxia, and a similar level of cooling may provide protection for the brain in adults who have been resuscitated after cardiac arrest.
Mechanisms Contributing to the Development and Progression of Diabetic Polyneuropathy
Authors: Hinder Lucy M. , Sullivan Kelli A. , Sakowski Stacey A. , Feldman Eva L.
Published: March 2017

Advances in our understanding of diabetes in human patients and experimental models indicate that a number of mechanisms may contribute to sensory nerve damage in diabetic polyneuropathy (DPN). In addition to oxidative stress, hyperglycemia and hyperlipidemia, recent research in pain, advanced glycation endproduct (AGE), and proteomics specify a contributory role for altered neuronal calcium homeostasis in DPN. Technology advances indicate neuronal energy balance and mitochondrial biogenesis, fission, and fusion are additional potential mechanisms. The effects of dysregulation or loss of insulin signaling and the effects of glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are also implicated.
Drug Discovery and Neuropathic Pain
Authors: Wainger Brian J.
Published: March 2017

Pain is one of the most common causes of physician visits and disability. Pain has been classified into specific subtypes. We refer to baseline or nociceptive pain as pain that results from an ongoing, high-threshold stimulus acting on an unenhanced somatosensory system. Inflammatory pain refers to pain in the setting of tissue damage and specifically the release of inflammatory molecules that activate and sensitize the nociceptive machinery. Hyperalgesia, or increased pain in response to a noxious stimulus, results from nociceptor sensitization whereas neuropathic pain results from a lesion or disease of the somatosensory system. Pain can have spontaneous, stimulus-independent components as well as evoked components such as hyperalgesia or allodynia, pain that is elicited by a normally innocuous stimulus. This chapter describes the research strategy for discovering new drugs to relieve these different kinds of pain.
Animal Models of Peripheral Neuropathy and Neuropathic Pain
Authors: Donaldson Katelyn , Höke Ahmet
Published: March 2017

There are numerous types of peripheral neuropathies and conditions that cause neuropathic pain with varying symptoms and different mechanisms of pathogenesis. Therefore, it is not surprising that many different animal models of peripheral neuropathies and neuropathic pain have been developed with varying degrees of fidelity to recapitulate the human disease. Nevertheless, these models are useful in a deconstructive manner to examine role of specific molecular pathways in pathogenesis of different types of peripheral neuropathies and test potential new drugs.
Diagnostic and Clinical Scales for Peripheral Neuropathy
Authors: Markman John D.
Published: March 2017

Due to the absence of a definitive pathological finding, objective biomarker, or imaging correlate, neuropathic pain syndromes may be graded as possible or probable depending on the results of neurological assessment. It is important to acknowledge the diagnostic uncertainty inherent in such a grading system based on probability in a condition for which there is no “gold standard” upon which to base validation studies. Neuropathic pain is a multidimensional entity, and specific syndromes may have distinct sensory profiles (i.e. different combinations of sensory signs and symptoms). Clinical suspicion for an underlying neuropathic mechanism increases when pain is characterized by features such as numbness, paresthesias, and allodynia and when the symptoms are generally resistant to standard over-the-counter and prescribed analgesics. In this chapter a variety pain scales are reviewed.
Entrapment Neuropathies
Authors: Teener James W.
Published: March 2017

Entrapment neuropathies are a subset of compression neuropathies caused by chronic impingement upon a nerve by nearby structures. The resulting pathology depends upon the duration and severity of entrapment, and ranges from demyelination if entrapment is mild or brief to axonal loss in more severe cases. Entrapment neuropathies typically cause symptoms referable to a single nerve distribution, but sensory symptoms may appear to extend beyond the typical dermatome of the entrapped nerve. Diagnosis is based upon clinical history and examination, and is supported by electrodiagnostic studies and imaging. A variety of supportive therapies may result in improvement of symptoms, but in cases of severe entrapment, surgical intervention to release the nerve is often necessary, and even then recovery is often incomplete.
Demyelinating Neuropathies
Authors: Goodfellow John A. , Davidson Amy I. , Willison Hugh J.
Published: March 2017

Many neuropathies have in common the basic pathophysiological mechanism of demyelination. Our understanding of the normal process of myelination and the molecular structure of myelin, nodes of Ranvier, and internodes has increased in recent years, yielding a greater understanding of the process of demyelination in disease. This chapter focuses on the inherited neuropathies as examples of non-inflammatory demyelinating neuropathies. For these conditions there are ongoing genotype-phenotype correlations and a greater appreciation of the importance of distal axonal degeneration as a consequence of demyelination.
Meningomas
Authors: Taylor Jennie , Wen Patrick Y.
Published: March 2017

Meningiomas are the most common primary brain tumor diagnosed in adults. Arising from the arachnoid (meningothelial) cells of the inner layer of the dura, they are often slow growing, but can lead to significant morbidity. They can invade through the outer layer of dura into overlying bone or skin, or into critical bordering structures such as the cavernous sinus or orbits, or encase cerebral blood vessels. These limitations can make surgical resection difficult if not impossible in some circumstance. However, they rarely metastasize outside the central nervous system (CNS), with the lungs being the most common site seen with higher-grade tumors.
Pituitary Tumors
Authors: Patel Toral R. , Tabar Viviane S.
Published: March 2017

Pituitary adenomas are among the most common intracranial tumors. The vast majority of these lesions are benign; however, many will require treatment due to local mass effect or hormone oversecretion. This chapter discusses the natural history, presentation, workup, and management of pituitary adenomas. Advances in surgical, medical, and radiation therapy are also reviewed. An improved understanding of this disease process will result in the adoption of less invasive and more efficacious treatments.
Primary Central Nervous System Lymphoma
Authors: DeAngelis Lisa M.
Published: March 2017

The lymphoid nature of PCNSL was established unequivocally by modern immunohistochemical techniques. PCNSL has been associated with a variety of congenital (Wiskott-Aldrich syndrome, ataxia-telangiectasia) and acquired (human immunodeficiency virus [HIV], renal transplant recipients) immunodeficiency states. PCNSL tends to be supratentorial, periventricular, and involve the deep structures such as the basal ganglia. The Epstein-Barr virus (EBV) plays an important role in initiating the development of PCNSL in immunocompromised patients includinig those with HIV infection. Leukoencephalopathy is a serious complication of effective PCNSL treatment, but apparent only when the patient is in a durable remission. Treatment utilizes chemotherapy with or without radiation, which can cause more cognitive disability than chemotherapy, and autologous stem cell therapy is under investigation in selected patients.
Familial CNS Tumor Syndromes
Authors: Krueger Darcy A. , Capal Jamie
Published: March 2017

Tuberous sclerosis complex is an autosomal dominant multi-system disease that involves the skin, brain, heart, lungs, and kidneys and is associated with seizures including infantile spasms, intellectual disability, autism and pulmonary and heart disease. Skin lesions can be particularly disfiguring and infantile spasms can be associated with marked cognitive decline. The outlook for patients has improved markedly with the recognition that TSC is caused by upregulation of the mammalian target of rapamycin (mTOR) enzyme, which connects energy needs and supply with cellular and neuronal growth. mTOR is upregulated in TSC because of mutations in hamartin or tuberin, which normally serve as a brake on mTOR. The drug rapamycin is commonly used as an immunosuppressive for patients undergoing kidney transplants; it has also found a new use in patients with TSC. Although the drug is immunosuppressive for non-TSC patients, careful titration of the drug in TSC patients corrects its upregulation but is not particulary immunosuppressive. Additional mTOR inhibitors such as everolimus have been developed and have been shown to be effective for pulmonary disease associated with TSC. Rapamycin in ointment form is dramatically effective in suppressing skin lesions of TSC and studies are underway to test the effect of mTOR inhibitors on seizures, brain tubers, intellect, and features of autism. Infantile spasms associated with TSC are very responsive to vigabatrin.
Medulloblastoma
Authors: De Braganca Kevin C , Packer Roger J
Published: March 2017

Medulloblastoma is the most common malignant brain tumor in pediatric patients. Patients are presently stratified to either standard or high-risk groups based on clinical and pathologic criteria. Approximately 80% of patients with standard risk disease are cured of their primary disease. High-risk and recurrent disease groups have a poorer outcome; 5-year progression-free survival is only 65% with high-risk disease. Disease control after recurrence is very poor. Treatment is multimodal and also aims to limit short- and long-term toxicities. Recent identification of four molecular subtypes of medulloblastoma may change risk assignment and therapy. Addressing the medical and psychosocial issues of survivors continues to improve the quality of life for these patients beyond the disease’s treatment.
Brain Metastases
Authors: Jo Jasmin , Schiff David
Published: March 2017

In the past, detection of brain metastases signaled the conclusion of aggressive systemic treatment and shifted the focus of care toward palliation. The median survival for patients with single brain metastasis without brain-directed treatment is about a month. Whole brain radiation therapy was the traditional palliative treatment utilized, offering an additional 2 to 5 months. More recently, in addition to whole brain irradiation, the roles of surgery, stereotactic radiosurgery, chemotherapy, and targeted therapies in the definitive management of brain metastases have been investigated in numerous studies. In selected patients, the use of aggressive local therapies can be associated with long survival and good quality of life. This chapter discusses the current state of the art therapeutic options for brain metastases.
Overview
Authors: Rosenfeld Myrna R. , Titulaer Maarten J. , Dalmau Josep
Published: March 2017

The chapter reviews a diversity of neurologic syndromes that are either proven or putatively autoimmune. The disorders affect all levels of the nervous system from neuromuscular junction, autonomic nervous system, spinal cord, brain, to retina. The pathologic substrates underlying the neurologic dysfunction are varied and include vasculitis (Behçets, Susac’s), encephalitis (NMDA receptor encephalitis), channelopathies (myasthenia, LEMS) and even an inflammatory granulomatous disease (neuro-sarcoid). The resulting syndromes cover myriad aspects of clinical neurology and neuropsychiatry. The understanding of and continued identification of autoimmune neurologic disorders is a very active area. With time some of these disorders may be moved to other sections while new disorders will join the autoimmune list. In this chapter we briefly review the emergence of the field of autoimmunity as it relates to the nervous system and make note of some of the open questions that remain.
History of Human Immunodeficiency Virus Infection and the Nervous System
Authors: Nath Avindra
Published: March 2017

It has been nearly three decades since the first descriptions of the neurological comploications of HIV infection. During this period of time there has been tremendous progress in defining the clinical syndromes, modes of diagnosis, detailed pathophysiology and modes of treatment. Many of the dreaded complications are now manageable particularly if diagnosed early. However, neurocognitive impairment associated with HIV infection still remains a significant cause of morbidity and much is needed to control; the effects of the virus on the brain and for the eventual eradication of the virus from the brain reservoir.
HIV-Associated Neurocognitive Disorders
Authors: Alexander Joshua , Croteau David J , Ellis Ronald J
Published: March 2017

Three subclassifications of HIV Associated Neurocognitive Disorders (HAND) can be delineated: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). HAND occurs in about half of patients infected with HIV. All forms, including ANI and MND, are associated with unemployment and reduced antiretroviral adherence, which can lead to loss of virologic suppression, further neurocognitive decline, and systemic illness. Fortunately, combined antiretroviral therapy can stabilize and even reverse cognitive impairment.
Congenital and Perinatal Viral Infections
Authors: Bale James F.
Published: March 2017

Despite remarkable advancements in the treatment and prevention of infectious diseases, congenital (also known as intrauterine) and perinatal (also known as neonatal) infections remain major causes of permanent neurodevelopmental disabilities worldwide. Fortunately, relatively few viral pathogens can infect the developing fetus or the newborn postnatally and induce neurological disease. These pathogens include cytomegalovirus, rubella virus, herpes simplex virus types 1 and 2, varicella zoster virus, lymphocytic choriomeningitis virus, the nonpolio enteroviruses, parechovirus, and human immunodeficiency virus. This chapter describes the clinical manifestations, diagnosis, treatment, and outcome of these congenital and perinatal viral infections.
Fungal Infections of the Central Nervous System
Authors: Singhi Pratibha , Nallasamy Karthi , Singhi Sunit
Published: March 2017

Fungal infections of the central nervous system are important because of their increasing incidence and the growing population of at-risk individuals. CNS spread is usually hematogenous but rarely can be due to direct invasion from adjacent structures. Morphology of the infecting fungus may predict the regions affected and the lesion phenotype. Meningitis and mass lesions are the most frequent. This chapter reviews the current understanding of the neuropathogenesis of fungal infections with mention of histopathological and imaging correlations. Important aspects of management are also discussed. Diagnosis requires strong clinical suspicion. Treatment is often multimodal with prolonged drug therapy, surgery, and supportive care.
Malaria
Authors: Thakur Kiran
Published: March 2017

Malaria persists despite efforts for global eradication and vaccine development, and continues to prove lethal in endemic regions. The neurological manifestations of malaria are often devastating, with a high mortality rate and significant morbidity in survivors. A major life threatening complication of malaria infection is cerebral malaria (CM), most commonly occurring in children in sub-Saharan Africa and adults in Southeast Asia. There should be a high suspicion for CM in patients who present in coma residing in or having recently traveled to malaria endemic regions. Other neurological manifestations posing significant morbidity include postmalaria neurological syndrome and side effects due to antimalarial medications. Discussions in this chapter are focused around the neurobiology of malaria infection, and the host- and pathogen-related factors that contribute to neurological manifestations of the mosquito-borne illness.
Prion Diseases
Authors: Mastrianni James A. , Gallardo Joshuae G.
Published: March 2017

Prion diseases are transmissible fatal neurodegenerative disorders resulting from the accumulation of misfolded prion protein. Although primarily sporadic diseases, 5% to 10% result from a mutation of the prion protein gene (PRNP), and less than 1% occur from exposure to prions. The current family of prion diseases includes Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), fatal insomnia (FI), variant CJD (vCJD), and variably protease-sensitive prionopathy (VPSPr). Kuru is a disease of historical interest that was transmitted through cannibalistic rituals. Iatrogenic CJD (iCJD) is the result of secondary transmission of prion disease from contaminated biologicals.
Neurological Complications of Infective Endocarditis
Authors: Grossman Jonah , Shams Tanzila , Sila Cathy
Published: March 2017

Infective endocarditis is the fourth leading cause of life-threatening infections, accounting for 40,000 annual U.S. hospital admissions. Due to decline in rheumatic heart disease, a shift in causative organisms from viridans streptococci to S. aureus, Group D Streptococcus, and multidrug-resistant species has been observed. The spectrum of neurological complications ranges widely from cerebrovascular pathologies-including septic embolization, mycotic aneurysms, and intracerebral hemorrhages-to seizures, meningitis, cerebritis, and abscess. Transthoracic echocardiogram remains the standard for initial investigation whereas CT scans, MRI with DWI sequence, and cerebral angiograms are useful for exploring neurological complications. Antibiotic regimens, tailored to culprit organisms, should be initiated early after obtaining blood cultures and continued for 4 to 6 weeks. Antithrombotic treatment may pose increased risk for intracerebral hemorrhage, even in the absence of mycotic aneurysms (MA). Unruptured MA must be treated according to risk of rupture and overall health of the patient. MAs either at risk or previously ruptured should be secured by neurosurgical or endovascular means. Early cardiac surgery is a viable option for prevention of septic embolization for high-risk cardiac diseases such as perivalvular abscess and infection with resistant organisms, but may increase mortality rates for those with decompensated heart failure.
Postinfectious Encephalitis
Authors: Miravalle Agusto A.
Published: March 2017

Postinfectious encephalomyelitis (PE) is an acute demyelinating monophasic disorder of the central nervous system (CNS). PE is thought to occur as an autoreactive response of the immune system as a consequence of an infectious agent or immunization. The treatment for this condition is usually high-dose systemic corticosteroids, IVIg, or plasma exchange. The overall prognosis for the disease is usually benign but severe cases have been reported.
Neurobiology of Circadian Rhythms Disorders
Authors: Jones Christopher R
Published: March 2017

Temporal organization of nervous system function includes daily rhythms driven by a molecular-genetic hypothalamic “clock” with an intrinsic period length of approximately (circa) one day (diem). The resulting circadian rhythm influences all aspects of brain function and internally synchronizes the circadian oscillations inherent in all other body tissues. Idiosyncratic circadian characteristics interact with perceived environmental stimuli to determine each individual’s entrainment pattern of external synchronization with the day-night cycle. Idiosyncratic entrainment patterns that may come to medical attention include delayed, free-running, advanced, or absent sleep rhythms. Prolonged jet travel and shift work are difficult entrainment challenges for most people.
Nutritional Deficiencies
Authors: Saylor Deanna , Probasco John C.
Published: March 2017

Nutritional deficiencies are estimated to affect at least one third of the world’s population. Although they are most common in developing countries, they are also found in the developed world where they often occur in the setting of alcoholism, eating disorders, post bariatric surgery, and malabsorptive disorders. Neurologic manifestations of vitamin deficiencies are varied, reflecting the diversity of biochemical activity of vitamins throughout the nervous system. Here the neurological manifestations of common vitamin deficiencies are examoned, beginning with a discussion of relevant biochemistry and pathophysiology of each respective vitamin. Several micronutrients are included in the tables within this chapter.
Cardiac Disease
Authors: Kelley Roger E.
Published: March 2017

Heart disease is a major contributor to stroke and other neurologic disorders in adults. Cardioembolic stroke accounts for roughly 15% of all stroke, and the most common mechanism is cardiac arrhythmia, with atrial fibrillation the leading contributor. Anticoagulation such as using aspirin or warfarin is chosen based on the presence of associated risk factors including congestive heart failure, hypertension, age, and diabetes mellitus. Heart failure ranks second in the incidence of stroke from cardioembolism, with other risk factors being endocarditis, severe cardiomyopathy, acute myocardial infarction, and patent foramen ovale. Recent clinical trials indicate that induction of total body hyopthermia after cardiac arrest to a target temperature of 32°C to 34°C, for 24 hours, had a more favorable neurological outcome compared with a normothermia group.
Review: Clinical Child Psychiatry
Authors: Winnicott Donald W.
Published: March 2017

In this review, Winnicott expresses his enthusiasm for Dr Soddy’s ninety-four descriptions of child guidance cases taken from the clinic at University College Hospital, London, where Soddy was for many years medical director.