bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition and Gastrointestinal Emergencies
Authors: Orellana Renán A. , Coss-Bu Jorge A.
Published: March 2017

Appropriate nutrition must be tailored to the specific needs of individual patients. Needs depend on the child’s baseline nutritional status, the severity of disease, and specific organ dysfunction. Enteral nutrition is preferable whenever possible. Parenteral nutrition may be necessary when efforts to supply adequate nutrition enterally are contraindicated or unsuccessful. Patients with symptoms of acute abdomen require prompt recognition of surgical and nonsurgical disorders. Upper gastrointestinal hemorrhage may require transfusion of blood products, vasoactive drug infusion to minimize ongoing losses, and endoscopy following stabilization. Pancreatitis typically requires an orogastric/nasogastric tube for decompression, aggressive pain management, and radiological evaluations. Abdominal compartment syndrome needs to be recognized promptly to avoid further injury. Acute liver failure commonly leads to multiorgan system dysfunction and death. Specific therapy is available only in a minority of cases, and outcome depends on excellent supportive care, prompt evaluation by a pediatric gastroenterologist, and referral to a transplant center.
Toxicological Emergencies
Authors: Buttram Sandra D. W. , Ruha Anne-Michelle
Published: March 2017

This chapter includes essential information about common toxic exposures requiring pediatric intensive care unit care. Specific agents, grouped into categories, are reviewed, including analgesics (acetaminophen and aspirin), opiates, carbon monoxide, cardiovascular medications (calcium channel antagonists and β‎ blockers), tricyclic antidepressants, sulfonylureas, and toxic alcohols. An overview of each agent followed by clinical presentation, and appropriate diagnostic evaluation and management are provided, including alkalinization with administration of sodium bicarbonate, need for hemodialysis, and use of specific antidotes (e.g., naloxone, n-acetyl cysteine, glucagon, fomepizole).
Neurobiology of Disease
Authors: Johnston, MD Michael , Adams Jr., MD Harold , Fatemi, MD, MBA Ali
Published: March 2017

Neurobiology of Disease includes nearly 200 brief but substantial survey chapters on all the major disorders of the nervous system in both adults and children from the perspective of cutting edge neurobiology that is relevant to diagnosis and treatment. The chapters are written mostly by clinicians who are experts and thought leaders in their fields, and who are also active participants in clinical and/or basic research. Readers can find information about recent discoveries that are having a clinical impact, as well as reliable information about the new genetic discoveries that are driving diagnosis as well as being targets for therapeutic research. The book’s editors, Michael Johnston at Johns Hopkins and the Kennedy Krieger Institute, and Harold Adams at the University of Iowa, are respected international authorities in pediatric neurology and adult neurology, respectively, with substantial records of teaching and scholarship. Ali Fatemi, who trained in pediatric neurology and neurogenetics at Massachusetts General and is head of the Moser Center for Leukodystrophies, brings expertise in clinical and research neurogenetics to the editorial team.
History of Parkinsonism
Authors: Silver Michael , Factor Stewart A.
Published: March 2017

This chapter explores the history of Parkinson’s disease and similar conditions. Dr James Parkinson’s initial description of this syndrome is covered along with all of the major developments in the understanding of the disease since then up to the modern era. Therapies are detailed, from early herbal remedies up to current treatment, including dopamine and levodopa, non-levodopa therapy, and surgery, and glimpses are given of potential future therapies. The conditions that are similar, the so-called “parkinsonian conditions,” are discussed as well. Synonyms: idiopathic Parkinson disease; Parkinson syndrome, Parkinson’s disease, Parkinson plus.
Essential Tremor
Authors: Dalvi Arif , Lyons Kelly E. , Pahwa Rajesh
Published: March 2017

Essential tremor (ET) is the most common cause of tremor. Most studies suggest that the cerebellum is involved in the pathophysiology of ET and that it is an autosomal dominant disorder; however, the actual cause and a gene responsible for the majority of cases have not been identified. The diagnosis of ET is based on evaluation of clinical signs and symptoms. Pharmacological treatment is effective in 30% to 50% of casesm, with primidone and propranolol being first line therapies. Some benefit has also been reported with gabapentin, topiramate, and benzodiazepines. Deep brain stimulation effectively reduces medication-resistant ET in appropriate cases.
The Expanded Polyglutamine Tract Spinocerebellar Ataxias
Authors: Storey Elsdon
Published: March 2017

The spinocerebellar ataxias are dominantly-inherited neurodegenerative disorders whose major clinical feature is incoordination. Although 32 have been described to date, those characterized by (CAG)n repeat expansions resulting in elongated polyglutamine tracts in their respective host proteins (SCAs 1, 2, 3, 6, 7, 17, and in part 8) are the most common and have been subject to the most detailed investigation of their pathogenic mechanisms. All are characterized by polyglutamine tract aggregates, toxicity of which was initially thought to be their pathogenic mechanism. However, recent research has emphasised the importance of host protein context, and the disease-specific mechanisms that this implies.
Ataxias
Authors: Shakkottai Vikram G.
Published: March 2017

Autosomal recessive cerebellar ataxias are a group of inherited neurological disorders with progressive balance and gait difficulties. In these disorders, cerebellar ataxia is often accompanied by eye movement abnormalities and peripheral nervous system involvement. A unifying mechanism for disease pathogenesis that is common to all the recessive ataxias likely does not exist. Nevertheless, some pathophysiological pathways are common to several autosomal recessive cerebellar ataxias. Specific gene defects in each disorder are summarized in the chapter. The most common recessively inherited ataxias are Friedreich ataxia and Ataxia telangiectasia. A recessive ataxia must be considered for any individual with progressive cerebellar ataxia with onset less than 30 years. The treatment is primarily supportive, but some recessive ataxias have specific treatment.
Alzheimer’s Disease
Authors: Rafii Michael S.
Published: March 2017

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and is characterized by a protracted asymptomatic phase estimated to begin approximately 15 to 20 years. Clinically, AD initially manifests itself by progressive memory impairment, specifically, a loss of episodic memory function characterized by impaired free recall that does not improve with cueing. This is followed by a gradual decline in other cognitive domains leading to functional dependency, which essentially defines the dementia phase of the illness and has been the cornerstone of diagnostic criteria. About 50% of all MCI patients progress to Alzheimer’s dementia, and therefore MCI is thought to represent prodromal AD when they harbor the pathological changes associated with AD, including hippocampal atrophy, elevated CSF amyloid and Tau, as well as the presence of amyloid on PET scan.
Diagnosis and Therapy for Lewy Body Dementia
Authors: Turk Bela R. , Fatemi Ali
Published: March 2017

Almost undistinguished some 30 years ago, dementia with Lewy bodies is now shown to be the second most common neurodegenerative cause of dementia in the elderly. A host of neuroinflammatory mechanisms are attributed to Lewy bodies and their component alpha synuclein, a common pathology shared by Parkinson disease and Parkinson disease with dementia. Accurate diagnosis of patients is essential, as they show unique impairment patterns, which differ from other forms of dementia and show severe adverse reaction to neuroleptic medication, a common treatment in other degenerative diseases.
Clinical Presentations, Diagnostic Criteria, and Lab Testing
Authors: Thakore Nimish J , Pioro Erik P
Published: March 2017

Amyotrophic lateral sclerosis (ALS) is the protypical motor neuron disease, which is characterized by the simultaneous presence of upper motor neuron (UMN) and lower motor neuron (LMN) signs in the same extremity or in the cranial-bulbar region. UMN signs at spinal levels include spasticity, slowness of motor activation, hyperactive deep tendon reflexes and extensor plantar responses, whereas UMN signs at the cranial level include spastic dysarthia (slow, labored, nasal); slowness of tongue movements, and hyperactive jaw, gag, and facial reflexes. LMN signs at the spinal level include muscle atrophy, fasciculations, and weakness and LMN signs at the cranial level include tongue atrophy and weakness, facial weakness, tongue and facial fasciculations, palatal weakness, weak cough, and dysphonia. ALA is fatal in 2 to 4 years, and the only medication known to prolong tracheostomy-free survival
Biological Basis of Primary Generalized Epilepsies—Genetics
Authors: Marini Carla , Guerrini Renzo
Published: March 2017

Primary generalized epilepsies account for 30% of all epilepsies. These age-related epilepsies without structural brain lesions and normal development have a high heritability. Based on the main seizure type and their age of onset, four main subsyndromes are recognized. Rare autosomal dominant families carry mutations in a few genes involved in ion channel functions, whereas common genes are yet to be discovered. The complex inheritance involving multiple genes is the major limiting factor preventing to uncover their genetic architecture. Understanding genetic determinants is the key to unraveling the neurobiology and to improve therapies for these disorders.
Biological Bases of Symptomatic Generalized Epilepsies in Children
Authors: Nita Dragos A. , Cortez Miguel A. , Perez Velazquez Jose Luis , Carter Snead O.
Published: March 2017

Symptomatic generalized epilepsies represent a group of challenging epilepsy syndromes, most often seen in children, which share the hallmark of a triad encompassing multiple seizure types, electroencephalographical (EEG) evidence of diffuse brain involvement, and dysfunction in the intellectual domain (global developmental delay or mental retardation). SGEs include the early myoclonic encephalopathy, early infantile epileptic encephalopathy (Ohtahara syndrome), West syndrome, epilepsy with myoclonic-astatic seizures, epilepsy with myoclonic absence, Lennox-Gastaut syndrome, and the progressive myoclonic epilepsies. SGEs may arise from various genetic, developmental, or acquired brain pathologies and also can be associated with other cerebral or systemic defects and thus being part of a broader epilepsy syndrome phenotype. SGEs are associated with significant mortality and morbidity and most patients with SGE grow up to have intractable epilepsy, mental retardation, and depend on parents and institutions for the activities of the daily living. The mechanisms of SGE are numerous and heterogeneous and the EEG findings usually reflect the age-related changes as the brain matures.
Neuroimaging of Epilepsy
Authors: Gomes William A.
Published: March 2017

Neuroimaging is essential for clinical care and basic research in epilepsy. MRI is the primary tool, but adjunctive techniques are commonly employed including MRS, PET, SPECT, and MEG. These techniques facilitate localization and characterization of seizure foci prior to epilepsy surgery, and also allow preoperative assessment of risk to eloquent brain regions. Evaluation of patients with MRI-negative epilepsy remains a major clinical challenge and motivation for contemporary research.
Alternative Therapies for Epilepsy
Authors: Stafstrom Carl E.
Published: March 2017

Up to one third of patients with epilepsy suffer from seizures that are refractory to medications. For these patients, many of whom are not surgical candidates, dietary therapies provide a promising alternative. The best known dietary therapy is the ketogenic diet, which was developed in the 1920s; newer variants of the ketogenic diet, such as the medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment, afford excellent seizure control with fewer dietary restrictions. Together, dietary approaches offer drug-resistant patients hope for seizure reduction and an improved quality of life.
Neurofibromatosis Type 1
Authors: Wolf David S.
Published: March 2017

Neurofibromatosis type 1 is a common, autosomal dominant, monogenetic neurocutaneous disorder. It is characterized by café au lait spots, axillary and inguinal freckling, Lisch nodules, optic pathway gliomas, neurofibromas, and distinctive bony abnormalities. Also associated with this condition are other central nervous system tumors, scoliosis, hypertension, vascular abnormalities, and cognitive issues such as learning disabilities and attention deficit-hyperactivity disorder.
Coffin-Lowry Syndrome
Authors: Johnston Michael V.
Published: March 2017

Coffin-Lowry syndrome (CLS) is a relatively rare (1:50,000-100,000 incidence) sex-linked neurodevelopmental disorder that includes severe intellectual disability, dysmorphic features including facial and digital abnormalities, growth retardation, and skeletal changes. Most cases are sporadic with only 20% to 30% of cases having an additional family member. CLS is caused by variable loss of function mutations in the RPS6KA3 gene that maps to Xp22.2 and codes for the hRSK2 S6 kinase that phosphorylates the transcription factor CREB (cAMP response element binding protein) as well as other nuclear transcription factors. Phosphorylated CREB (pCREB) plays a major role in memory formation in fruit flies and mammals by activating specific genes through epigenetic histone acetylation.
Congenital Hypothyroidism
Authors: Gregory Mary Lee
Published: March 2017

Congenital hypothyroidism (CH) results from the effects of insufficient thyroid hormone on the developing fetus and infant, and is characterized by severe intellectual disability and growth inhibition. CH can result from maternal iodine deficiency, which can be abolished by appropriate dietary iodine supplementation. Alternately, CH may be caused by congenital defects of the thyroid gland and thyroid hormone biosynthesis abnormalities (primary congenital hypothyroidism), or by “central hypothyroidism,” in which the brain produces insufficient thyroid stimulating hormone. Treatment of these latter etiologies requires administration of thyroid hormone.
Pediatric Neurotransmitter Disorders
Authors: Pearl Phillip L. , Welch William P.
Published: March 2017

The pediatric neurotransmitter disorders represent an enlarging group of neurological syndromes characterized by inherited abnormalities of neurotransmitter synthesis, metabolism, and transport. Disorders involving monoamine synthesis include guanosine triphosphate cyclohydrolase deficiency (Segawa disease or classical Dopa-responsive dystonia as the heterozygous form), aromatic amino acid decarboxylase deficiency, tyrosine hydrolase deficiency, sepiapterin reductase deficiency, and disorders of tetrahydrobiopterin synthesis. These disorders can be classified according to whether they feature elevated serum levels of phenylalanine. Disorders of γ-amino butyric acid (GABA) metabolism include succinic semialdehyde dehydrogenase deficiency and GABA-transaminase deficiency. Glycine encephalopathy is typically manifested by refractory neonatal seizures due to a defect in the glycine degradative pathway. Pyridoxine-responsive seizures have now been associated with deficiency of α-aminoadipic semialdehyde dehydrogenase as well as a variants requiring therapy with pyridoxal-5-phosphate and folinic acid.
Attention Deficit-Hyperactivity Disorder
Authors: Bay Mihee J. , Shapiro Bruce K.
Published: March 2017

Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children and is characterized by developmentally inappropriate levels of attention and/or activity level. The current diagnostic criteria are summarized in the recently updated DSM-5. Although the neurobiology of ADHD is not completely understood, dysfunction in the fronto-striatal network and catecholaminergic system is likely implicated in pathophysiology of ADHD although recent studies suggest involvement of other neural substrates as well. Stimulants have been the mainstay of pharmacotherapy for ADHD due to its role in increasing available catecholamines in the synapse. However, treatment approach should be multimodal.
Diseases of Mitochondrial Energy Metabolism
Authors: Weissman Jacqueline , Emrick Lisa
Published: March 2017

Mitochondrial disorders are a group of inherited diseases of energy metabolism caused by impairment of mitochondrial function-primarily disorders of the oxidative phosphorylation system but also the more recently described disorders of mitochondrial transport and fission. This review will focus on primary disorders of mitochondrial oxidative phosphorylation. The neurologic system is one of the most profoundly affected by mitochondrial dysfunction and the effects can be varied and widespread. This has led to these diseases being commonly called mitochondrial encephalomyopathies. The heterogeneity of clinical presentation, laboratory findings, neuroimaging findings, pathologic findings, and genetic findings in these diseases make diagnosis extremely difficult. Treatment for mitochondrial disorders is currently lacking a solid evidence base but this is a rapidly expanding area of research.
Cerebral Creatine Deficiency Disorders
Authors: Schutz Peter W. , Stockler Sylvia
Published: March 2017

Cerebral creatine deficiency disorders that result in very low levels of creatine in the brain, can cause in intellectual disability, seizures, expressive speech disorder and behavior disorders if not treated in early childhood. CCDDs comprise disorders of creatine synthesis (arginine:glycine [AGAT; MIM 602360]; guanidinoacetate methyltransferase deficiency [GAMT; MIM 601240]) and of creatine transport (SLC6A8 deficiency [SLC6A8; MIM 300036]). Inborn errors of creatine synthesis-but not, as yet, of transport-can be treated by creatine substitution and are thus treatable causes of intellectual disability.
Glutaric Aciduria Type I
Authors: Vernon Hilary
Published: March 2017

Glutaric Aciduria type I is a recessive inborn error of metabolism caused by deficiency of glutaryl-CoA dehydrogenase. This enzyme is responsible for catabolism of L-lysine, L-hydroxylysine, and L-tryptophan. Deficiency of this enzyme leads to abnormal accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine. Untreated individuals are at extremely high risk for encephalopathic crisis, usually triggered by an intercurrent illness or other stressor, and typically occurring between 3 and 36 months of age. This crisis classically results in bilateral striatal injury. Treatment, which can help to prevent encephalopathic crises, includes dietary lysine restriction, carnitine supplementation, and careful metabolic management during intercurrent illness.
Cerebral Palsy
Authors: Jasien Joan M. , Shapiro Bruce K. , Hoon Alexander H.
Published: March 2017

Cerebral palsy (CP) describes a group of disorders of movement/posture causing activity limitation that are attributed to nonprogressive disturbances in the immature brain that can change over time. The immature human brain undergoes organizational changes during intrauterine and postnatal life creating potential temporal periods of selective vulnerability to damage. Understanding the compensatory plasticity process after the brain injury may provide new insights into the pathogenesis of CP.
The Neurobiology of Encephalopathy of Prematurity
Authors: Gerner Gwendolyn J. , Burton Vera Joanna
Published: March 2017

The risk of brain injury following premature birth increases with birth at earlier gestational ages and lower birthweights. The presentation of brain injury and subsequent neurodevelopmental sequelae in this population are extremely heterogeneous, as the injury is due to multifactorial causes; however, increasing amounts of research are elucidating the underlying mechanisms and pathways. This chapter broadly reviews the neurobiology of encephalopathy of prematurity, as well as clinical considerations, associated neurodevelopmental outcomes, and future directions in clinical care and research.
Migraine and Headache in Children
Authors: Klein Jessica , Oakley Christopher
Published: March 2017

Headache is the number one reason for referral to a pediatric neurologist, and these children report a quality of life similar to children with cancer and arthritis; therefore this concern warrants particular attention to accurately diagnose, evaluate, and treat. Of the primary headache disorders, tension is the most common, whereas migraine is often the most disabling. Other examples of childhood headaches include migraine precursors, cluster, trigeminal autonomic cephalalgias, and neuralgias. The aim of this chapter is to define migraine and other primary headache disorders of childhood, discuss the neurobiology of headache, and review clinical presentation, diagnostic workup, and treatment.
Congenital Hydrocephalus
Authors: Joanna Burton Vera , Ahn Edward
Published: March 2017

Congenital hydrocephalus is defined as the abnormal accumulation of cerebrospinal fluid resulting in the enlargement of the ventricular system in which the intracranial pressure is known or suspected to be elevated and present since before birth. Congenital hydrocephalus can occur in isolation but is often associated with other conditions such as aqueductal stenosis and spina bifida. Surgery, generally the placement of a ventriculopritoneal shunt, is the mainstay of treatment. Cognitive outcomes are variable and most predicted by associated disability.
Multiple Sclerosis: MRI and Other Imaging Approaches in MS
Authors: Absinta Martina , Reich Daniel S.
Published: March 2017

Aside from its paramount diagnostic role, imaging techniques, particularly magnetic resonance imaging (MRI), provide unparalleled insights into multiple sclerosis (MS) by assessing the spatiotemporal dynamics of the associated inflammation and neurodegeneration. This dynamical view, predicated on interrogation of individuals with MS at multiple time points, is impossible with pathology. The chapter approaches MRI in MS from this perspective, describing features related to lesion development and location, as well as assessment of global and regional damage. It summarizes current knowledge, addresses the limitations of that knowledge, and suggests ways in which imaging can advance future research.
Multiple Sclerosis: Monitoring Disease Activity and Progression
Authors: Bhargava Pavan , Saidha Shiv
Published: March 2017

Multiple sclerosis is a chronic inflammatory and degenerative disorder of the central nervous system. Measuring disease activity and progression are an integral part of the management of the disorder. A number of different approaches, including clinical measures, imaging metrics, and blood/cerebrospinal fluid biomarkers have been investigated for their utility in monitoring disease activity and progression. Each of these different approaches has certain advantages, as well as limitations, and this chapter provides an overview of these different assessment strategies.
Symptoms of Multiple Sclerosis
Authors: Costello Kathleen , Newsome Scott D.
Published: March 2017

Symptoms of MS can be categorized as primary, secondary, or tertiary. Primary symptoms are those that are a direct result of CNS damage, such as fatigue, bladder dysfunction, visual disturbances, incoordination or imbalance, etc. Secondary symptoms are complications arising from these symptoms such as falls due to imbalance, spasticity or weakness, or UTI due to bladder retention. Tertiary symptoms are the social and vocational consequences of primary and secondary symptoms and can include divorce, job loss, financial hardship, and social isolation. Careful evaluation of these symptoms along with appropriate treatment and long-term follow-up can contribute to the quality of life for patients with MS.
Exercise and Multiple Sclerosis
Authors: Hebert Jeffrey R
Published: March 2017

The Centers for Disease Control and Prevention has stated that significant health benefits are obtainable for persons with disability who engage in physical activity, recommending 30 to 40 minutes of daily, moderately intense activity. However, persons with MS are frequently physically inactive, with findings of a 6-month activity reduction rate of 6%. This progressive lessoning of physical activity over time is a major contributor to worsening of symptoms and ancillary medical complications such as cardiovascular disease, obesity, and impaired bone health, underpinning the importance of exercise and physical activity by persons with MS. In addition to its effect on endurance and body composition, exercise may also reduce disease activity in MS. A regular exercise program combining exercise and physical activity that is tailored to the patient’s individual condition should be an important part of the plan of care for patients with MS.
Paraneoplastic Neurological Disorders
Authors: Probasco John C.
Published: March 2017

Paraneoplastic neurological disorders (PNDs) are estimated to affect approximately 0.01% of all patients with cancer. The majority of PNDs are thought to be the byproduct of immune-mediated processes directed against tumor-related antigens, processes which are sometimes effective against a systemic cancer. The inciting cancer is often asymptomatic or occult, with patients presenting to the neurologist with a variety of neurological symptoms and signs depending on the area(s) of the central, peripheral, and autonomic nervous system involved. The diagnosis of a PND is reserved for patients with histologically proven cancer; however, clinical presentation and diagnostic test results may make the diagnosis of a PND highly probable in the absence of the diagnosis of a cancer.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Authors: Wells Elizabeth M.
Published: March 2017

Anti- N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe but treatable recently identified form of immune-mediated encephalitis associated with antibodies in serum and cerebrospinal fluid (CSF) against the GluN1 subunit of the NMDAR. Research has rapidly expanded the understanding of disease mechanisms and how the condition manifests in different populations (e.g., pediatrics vs. adult, cancer vs. noncancer, male vs. female). Immunocytochemical, physiological, and molecular studies of the effects of human CSF on the rodent and murine brain in vitro and in vivo indicate a noncytotoxic antibody-mediated mechanism of disease pathogenesis. Finding positive antibodies prompts a search for occult neoplasm, most likely ovarian teratoma in young women; other age groups and male patients are less likely to have tumor but need to be screened. Fifty percent of patients respond to first line steroids, IVIG, plasma exchange or a combination, and many others improve with addition of rituximab or cyclophosphamide. Cured patients may have cognitive or motor sequelae, and refractory disease and death may occur despite treatment. Knowledge about etiology and biomarkers of refractory disease are lacking. Additional work is needed to further elucidate the origin of the immune-mediated response, to determine optimal clinical management and develop effective therapies for refractory patients.
Other Proven and Putative Autoimmune Disorders of the CNS
Authors: Haghighi Afshin Borhani , Kalman Bernadette
Published: March 2017

Behcet’s Disease (BD) is a multiorgan disorder characterized by oral and genital ulceration, uveitis, and dermatological symptoms. BD is most prevalent in the Mediterranean countries and East Asia, but also occurs in Europe and North America. The etiology remains unknown. Evidence suggests that BD is an autoimmune disorder with complex traits. Neuro-Behcet’s Syndome (NBS) develops in about 5% to 30% of patients with BD and presents with parenchymal or nonparenchymal pathology. The course of NBS is highly variable. Treatment strategies include modulations of the immune response and tissue degeneration, along with symptomatic medications. Main directions of current research include genomic studies, biomarker discovery, and inventive drug- development strategies.
Autoimmune Encephalitis
Authors: McKeon Andrew
Published: March 2017

Autoimmune encephalitis clinically encapsulates a spectrum of disorders including limbic encephalitis, and other autoimmune CNS disorders, which often have a paraneoplastic cause. Unlike multiple sclerosis, autoimmune encephalitides are unified by well-characterized neural-specific IgG biomarkers detectable in serum or CSF. Diagnostic laboratory, in vitro and neuropathological studies have demonstrated two broad groups. The first, characterizable by the detection of neuronal nuclear, cytoplasmic, or nucleolar antibodies (such as ANNA-1, aka anti-Hu), likely have a cytotoxic T cell mediated pathogenesis. The second, characterizable by the detection of antibodies targeting plasma membrane antigens, such as NMDA receptor, are likely mediated (at least in part) by pathogenic antibody.
Vasculitis of the Central Nervous System
Authors: Pagnoux Christian , Swartz Richard H.
Published: March 2017

Central nervous system (CNS) vasculitis is an extremely challenging diagnostic and therapeutic disease. Multiple conditions, including reversible cerebral vasoconstrictive syndrome and intracranial atherosclerosis, can mimic it. Infections, systemic diseases, particularly systemic vasculitides, drug abuse, neoplasms, and some other disorders can cause secondary CNS vasculitis. Primary CNS vasculitis is extremely rare. A definite diagnosis requires a brain biopsy, which may show granulomatous inflammation, lymphocytic inflammation, and/or acute necrotizing vasculitis. The pathogeny remains unknown. The treatment of secondary CNS vasculitis relies on that of its cause, whereas treatment for primary CNS vasculitis is not codified but usually relies on high-dose glucocorticoids, combined, at least for the most severe forms, with an immunosuppressant, mainly cyclophosphamide.
Common Risk factors for Stroke and Medical Prevention Therapies
Authors: Khouri George , Ozark Shelly , Ovbiagele Bruce
Published: March 2017

Stroke from thrombosis or emboli in cerebral vessels or hemorrhage is one of the most commonly encountered and most devastating neurological diseases. Rapid loss of function occurs due to an interruption of blood supply to the brain, leading to tissue ischemia and cell death. The risk of both ischemic and hemorrhagic stroke doubles for each successive decade after age 55, which is likely independent of other risk factors such as diabetes, hypertension, and hyperlipidemia. Lifestyle modifications, antiplatelet therapy and control of hyperlipidemia and hypertension are the mainstays of prevention.
Vascular Biology of Cerebral Ischemia
Authors: Ellis Jason A. , Connolly E. Sander
Published: March 2017

Carotid stenosis may be treated by carotid endarterectomy (CEA) or carotid artery stenting (CAS). Moderate asymptomatic carotid stenosis (50%-70%) is associated with a low risk of ischemic stroke and does not warrant treatment. The severe stenosis (>70%) population sees a marginal benefit in seen with CEA. In the Asymptomatic Carotid Atherosclerosis Study, authors concluded that for patients with less than 60% stenosis, a 5.9% absolute risk reduction was obtained over 5 years with CEA compared with maximum medical management (11 vs. 5.1%).
Sturge-Weber Syndrome and Related Cerebrovascular Malformation Syndromes
Authors: Quain Angela , Comi Anne M.
Published: March 2017

Sturge-Weber syndrome is a rare disorder presenting with a capillary malformation, better known as a port-wine birthmark, on the upper face, glaucoma, and a leptomeningeal angioma. Most children develop seizures and strokes, with variable degrees of neurodevelopmental impairments including hemiparesis, visual field deficits, cognitive deficits, epilepsy, and migraines. In 2013, a somatic activating mutation in GNAQ was identified in the capillary malformations and leptomeningeal angiomas of Sturge-Weber patients. In the diagnosis of Sturge-Weber syndrome, contrast-enhanced imaging is essential to the diagnosis of brain involvement. Functional imaging has demonstrated impaired venous drainage and a role for seizures in exacerbating perfusion deficits. Aggressive seizure management is fundamental to treatment. Some data supports the use of low-dose aspirin to reduce the occurrence of strokelike episodes and seizures.
Neuropathies Associated with Infection or Toxic Exposure
Authors: Leung Doris G.
Published: March 2017

Among the many causes of peripheral neuropathy are those mediated by environmental exposure to infectious and toxic agents. The most common neuropathy associated with HIV is HIV-associated distal sensory polyneuropathy (HIV-DSP). The clinical presentation of HIV-DSP is one of a distal, symmetric, often painful, small-fiber sensory axonal polyneuropathy. Other infectious causes of neuropathy include hepatitis C, leprosy, Lyme disease, rabies, and diphtheria, and antibiotic drugs such as isoniazid can also cause neuropathy. Heavy metals and a variety of other toxins including chemotherapeutic agents such as platinum, vincristine, and thalidomide disrupt peripheral nerve function. High doses of pyridoxine can cause damage to the dorsal root ganglia and foodbourne toxins such as saxitoxins found in shellfish.
Diabetic and Prediabetic Neuropathy
Authors: Zilliox Lindsay , Russell James W.
Published: March 2017

Impaired glucose regulation (IGR) constitutes a spectrum of impaired glucose and metabolic regulation that can result in neuropathy. Several different pathways of injury in the diabetic peripheral nervous system that include metabolic dysregulation induced by metabolic syndrome induce oxidative stress, failure of nitric oxide regulation, and dysfunction of certain key signaling pathways. Oxidative stress can directly injure both dorsal route ganglion neurons and axons. Modulation of the nitric oxide system may have detrimental effects on endothelial function and neuronal survival. Reactive oxidative species can alter mitochondrial function, protein and DNA structure, interfere with signaling pathways, and deplete antioxidant defenses. Advanced glycelation end (AGE) products and formation of ROS are activated by and in turn regulate key signal transduction pathways.
Anatomy, Localization, and Pattern Recognition of Peripheral Neuropathy
Authors: Kolb Noah , Smith A. Gordon
Published: March 2017

Peripheral neuropathy is one of the most common causes of presentation to a neurologist. A clear understanding of the involved anatomy, appropriate historical questions, and important exam findings is fundamental in making the correct diagnosis. This chapter delineates a practical localization-based approach to neuropathy pattern recognition and diagnosis.
Immune-Mediated Neuropathies
Authors: Davidson Amy I. , Goodfellow John A. , Willison Hugh J.
Published: March 2017

Immune-mediated neuropathies are a spectrum of diverse conditions with a commonality springing from dysregulation of the immune system. Clinical phenotypes can vary, along with onset and evolution of the condition, though paresis, paraesthesia, and pain are all common hallmarks. These conditions, although relatively rare, can be potentially life threatening, and functionally debilitating. The mainstay of treatment is immunomodulation, which continues to be an area of research interest, and with our improving understanding of the neurobiology of these conditions, novel targets are arising. This chapter looks to define these clinical syndromes, shedding light on their underpinning mechanisms and how to manage them.
Infiltrative Astrocytomas
Authors: Mammoser Aaron
Published: March 2017

Diffuse astrocytomas are WHO grade II astrocytomas that are distinguished from other WHO grade I and II astrocytomas because they are infiltrative, incurable, and have an intrinsic tendency to undergo malignant transformation to an anaplastic astrocytoma or a secondary glioblastoma. They are most often diagnosed in young adults in their 30s and 40s, and have a genetic profile that is different than primary glioblastoma. Anaplastic astrocytomas frequently arise from diffuse astroctyomas and share many of the same molecular abnormalities but tend to acquire more as they inevitably progress to glioblastoma. Recent studies identified mutations associated with WHO grade II and III tumors that predict a progression to a secondary glioblastoma with a better overall prognosis than primary glioblastoma. WHO grade II and III tumors that do not exhibit this typical mutation pattern often behave more aggressively than their counterparts, with a worse prognosis than higher grade tumors with a more favorable genotype.
Primary Central Nervous System Tumors
Authors: Theeler Brett J. , Gilbert Mark R.
Published: March 2017

Ependymomas are rare primary central nervous system (CNS) tumors that are thought to arise from ependymal cells lining the ventricular system located throughout the CNS. Ependymomas occur in all age groups but are more common in the pediatric population. Ependymomas typically present as mass lesions within the ventricular system, brain or spinal cord parenchyma. As with most central nervous system tumors, pathologic evaluation is required for definitive diagnosis. Ependymomas are typically treated with a combination of surgery and radiotherapy although this varies depending on tumor location, tumor grade, patient age, extent of tumor resection, and other pretreatment factors. Recent molecular studies demonstrate molecularly defined tumor heterogeneity that appears to have a region-specific pattern. Translating the emerging molecular profiles of ependymomas into improved treatment strategies is the primary goal of ongoing research efforts.
Pineal Region Neoplasms
Authors: Haranhalli Neil , Graber Jerome J.
Published: March 2017

Pineal region tumors include a diverse array of neoplasms arising from various components of the pineal gland, including germ cell tumors, germinomas, teratomas, pineocytomas, pineoblastomas, and tumors derived from glial tissues including gliomas, astrocytomas, oligodendrogliomas, and ependymomas. Benign lesions of the pineal gland can include pineal cysts, calcifications and meningiomas. Metastatic tumors can also be found in the pineal region. Numerous infectious and inflammatory conditions can mimic pineal tumors. Most patients present with symptoms of hydrocephalus or Parinaud’s syndrome. Diagnosis often requires biopsy, though some germinomas may be diagnosed based solely on serum and cerebrospinal fluid biomarkers.
Familial CNS Tumor Syndromes
Authors: Hussain Ibrahim , Gutmann David H.
Published: March 2017

Neurofibromatosis type 1 (NF1) is an inherited cancer predisposition syndrome affecting 1 in 2,500 to 3,000 individuals worldwide. Key clinical features of NF1 include pigmentary abnormalities, learning disabilities, and orthopedic problems. Individuals with NF1 are prone to the development of benign peripheral nerve sheath tumors, and 15% to 20% of affected children harbor low-grade gliomas of the optic pathway. Since the discovery of the NF1 gene and its protein neurofibromin, advances in understanding the molecular mechanisms of NF1 have resulted in the discovery of new treatments. In addition, genetically-engineered animal models of NF1-associated tumorigenesis have served as platforms for validating molecular targets for future medical therapies.
Familial CNS Tumor Syndromes
Authors: Taylor Jennie W , Plotkin Scott R
Published: March 2017

Neurofibromatosis type 2 (NF2) is a genetic disorder caused by constitutional mutations in the NF2 tumor-suppressor gene. Bilateral vestibular schwannomas are the hallmark of the syndrome, though meningiomas, ependymomas, and other peripheral schwannomas are common. Inheritance is autosomal dominant and de novo mutations are found in about 50% of patients. Standard treatment for symptomatic tumors is surgery. Radiation therapy may be considered for progressive tumors that are not surgically accessible, but secondary cancers after radiation have been reported. Retrospective studies suggest that bevacizumab may be active for progressive vestibular schwannomas and trials of chemotherapy for NF2-related tumors are in progress. This chapter reviews the epidemiology, genetic features, clinical characteristics, and current treatments for patients with NF2.
Familial CNS Tumor Syndromes: Von Hippel-Lindau Disease
Authors: Kaur Gurvinder , Ampie Leonel , Weiner Joseph , Ganju Aruna
Published: March 2017

Von Hippel-Lindau disease can be inherited or may be caused by a spontaneous mutation. Individuals diagnosed with this disease are prone to developing multiple benign tumors termed hemangioblastomas. This chapter addresses the epidemiology, clinical picture, and treatment of these tumors; specifically within those patients with this genetic disorder.
Pontine Gliomas
Authors: Schroeder Kristin , Becher Oren
Published: March 2017

Pontine gliomas-also known as diffuse intrinsic pontine gliomas (DIPG)-primarily occur in children and typically present subacutely with a combination of cranial nerve palsies associated with long track signs including hyper-reflexia in the legs, positive Babinski responses, and cerebellar signs. On imaging they typically appear as intrinsic mass lesions within the pons. Treatment with radiation can prolong the course of from months to years but the tumors are rarely curable. Chemotherapy combined with radiation therapy targeted at specific signaling pathways has shown only modest impact on survival.
Acute Bacterial Meningitis
Authors: Singhi Pratibha , Sankhyan Naveen , Singhi Sunit
Published: March 2017

Bacterial meningitis is one of the severest infections in childhood. Neuronal damage in meningitis is largely due to the extensive inflammatory cascade induced by pathogenic bacteria. This chapter discusses the current understanding of the interaction of multitude of factors in the pathogenesis of bacterial meningitis. This includes the mechanisms involved in transcellular traversal of the bacteria, and induction and release of several inflammatory cytokines and chemokines. The management of a child with bacterial meningitis requires meticulous supportive care and timely, appropriate, and adequate antibiotic therapy. The chapter also reviews the current understanding of some important clinical aspects of care of a child with bacterial meningitis.
Cerebrospinal Fluid
Authors: Greenlee John E.
Published: March 2017

Evaluation of cerebrospinal fluid is of essential importance in the diagnosis of central nervous system infections, with a major role in the diagnosis of meningitis and encephalitis. In bacterial and viral meningitis, CSF evaluation is usually straightforward, and well-defined serological and molecular techniques are available for CSF examination in many of the more common viral encephalitides. This is in contrast to CSF evaluation in cases of tuberculous and chronic meningitis, in which organisms may be difficult to detect by culture or polymerase chain methods or antigen detection. This chapter first discusses the anatomy and physiology of CSF production, reviews concepts of CSF analysis, and then reviews CSF changes in the major categories of central nervous system infections.
Varicella Zoster Virus Infection of the Nervous System
Authors: Gilden Don , Cohrs Randall J. , Mahalingam Ravi , Nagel Maria A.
Published: March 2017

Varicella zoster virus (VZV) is a human herpesvirus that causes varicella (chickenpox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. Reactivation of VZV due to a decline in the cell-mediated immune response to VZV in elderly or immunocompromised individuals causes zoster (shingles), frequently complicated by chronic pain (postherpetic neuralgia) and serious neurological disease (meningoencephalitis, myelitis and VZV vasculopathy due to retrograde spread of virus after zoster. Here, we describe clinical, laboratory and pathological features of neurological complications of VZV reactivation, including diagnostic testing to verify VZV infection of the nervous system, since all neurological complications of zoster may occur without rash. We also discuss VZV latency, primate models to study varicella pathogenesis and immunity, and immunization of elderly individuals to prevent VZV reactivation.
Brain Abscess
Authors: Turk Bela R. , Fatemi Ali , Johnston Michael V.
Published: March 2017

Brain abscess provides a challenging clinical problem and a medical emergency. Multiple mechanisms of pathogen dissemination and a wide spectrum of etiologic agents source the varying intracranial locations of infection. Due to this, the disease presents in a divergent and nonspecific manner. Timely diagnosis and imaging studies are crucial to improve outcomes as well as individual neurological and neurosurgical case management.
Spinal and Intracranial Epidural Abscess, and Subdural Empyema
Authors: West Tyler R. , Baldwin Kelly J
Published: March 2017

A spinal epidural abscess is an infection that resides in the epidural space of the spinal canal, and most commonly occurs from hematogenous seeding or direct extension from adjacent structures. Normal skin flora such as Staphylococcus and Streptococcus spp are the most common organisms to cause an epidural abscess, typically when host immunity is compromised or due to barrier disruption. The clinical presentation is heterogeneous, but often will progress over time to spinal cord compression. Intracranial epidural abscess and subdural empyema occur within the skull and are frequently spread via direct extension of infections from contiguous structures or as complications from neurosurgical procedures. Prompt diagnosis and treatment is essential for improving morbidity and mortality.
Babesiosis
Authors: Feldman Kristyn E. , Biddle Joshua
Published: March 2017

Babesiosis is a zoonotic, tick-transmitted infection caused by intraerythrocytic protozoa of the genus Babesia. Although over 100 Babesia spp. may infect a broad range of both domesticated and wild animals worldwide, only a handful have been observed to infect man. Human illness can range from an asymptomatic, subclinical infection to severe, fulminant disease resulting in death. Definitive laboratory diagnosis can be made by blood smears or serological evaluation by immunologic or molecular methods. The longstanding treatment regimen of choice for most Babesia spp. infections is oral quinine plus intravenous clindamycin.
Amoebic Infections of the Central Nervous System
Authors: Singhi Pratibha , Saini Arushi G.
Published: March 2017

Free-living amoebae are ubiquitous and can cause severe infections of the nervous system. The pathogenesis involves neuronal damage due to the activation of inflammatory cascade induced by the pathogenic amoebae, including both acute fulminant and chronic granulomatous inflammation. The diagnosis requires high clinical suspicion; eliciting history of contact with water or soil habitats of free-living amoebae is important. The chapter provides an overview of the different types of nervous system infections caused by the four genera of free-living amoebae, including their pathogenesis, rapid diagnostic tools, clinical features, and treatment strategies. Management includes timely, appropriate, and adequate antimicrobial therapy and supportive care.