bluuebunny/crossref_metadata_2025 huggingface dataset:
Focal Cognitive Syndromes
Authors: Caselli Richard J.
Published: November 2021

The neurologic results of cortical lesions reflect the structural properties of the affected region. Lesions affecting primary sensorimotor cortices result in primary sensorimotor deficits that are qualitatively all-or-nothing, such as blindness (hemianopia) and paralysis (hemiparesis). Quantitatively, though, the severity of the deficit depends on the extent of the lesion (so that a hemiparetic patient may not be completely paralyzed but simply weak). Lesions affecting modality-specific association regions result in conceptually more complex disorders that are confined to a single modality, such as nonfluent aphasia (a form of motor speech disorder reflecting the language-dominant hemisphere) or prosopagnosia (a visual disorder impairing the ability to disambiguate visually similar entities, specifically faces, reflecting the “what” visual pathway in inferotemporal cortices).
Cellular Signaling
Authors: Staff Nathan P. , Madigan Nicolas N.
Published: November 2021

Cell communication in the nervous system is finely tuned to respond rapidly to external stimuli, to modify itself according to those stimuli, and to produce more effective responses in the future. The physical basis for this cell communication is the manipulation of ion gradients with ion pumps and channels, chemical neurotransmission, and synaptic plasticity, all of which are discussed in this chapter.
Cellular Injury and Death
Authors: Madigan Nicolas N. , Staff Nathan P.
Published: November 2021

Cell death occurs after an irreversible insult or stress overwhelms the cell’s compensatory mechanisms of homeostasis and repair. Cellular necrosis, apoptosis, and autophagy are increasingly understood to be interconnected biochemical processes that may coexist in vascular, inflammatory, and neurodegenerative conditions. Traditional classifications of cell death pathways are 1) necrosis; 2) programmed nuclear cell death, including apoptosis; and 3) autophagy. These processes occur in the context of variable cause and severity of injury, variable cellular metabolic and energy states, and variable fitness to compensate.
Chromosomal Syndromes
Authors: Gavrilova Ralitza H.
Published: November 2021

Electroencephalography (EEG) provides useful information for diagnosis, evaluation, and prognosis when patients have cerebral disease or related conditions. It is particularly helpful for evaluation of patients with transient neurologic disorders and altered states of consciousness. EEG electrodes are placed according to the International 10-20 System, which uses the inion and nasion and the ear or mastoid as landmarks to facilitate uniform placement.
Electroencephalography: Basic Concepts
Authors: Burkholder David B. , Britton Jeffrey W.
Published: November 2021

Electroencephalography (EEG) is a useful diagnostic and prognostic tool for evaluation of patients with epilepsy, encephalopathy, focal lesions, coma, or brain death. The 3 main types of epileptiform discharges are spikes, sharp waves, and spike-and-wave discharges. Spikes have a steep ascent and descent and are brief (duration ≤70 milliseconds). Sharp waves, in contrast, are longer (70-200 milliseconds). Spike-and-wave discharges consist of a spike followed by an after-coming slow wave. All the discharges may occur singly or in trains, and any may be present in either focal epilepsy or generalized epilepsy.
Electroencephalography: Evaluation of Neurologic Disorders
Authors: Burkholder David B. , Britton Jeffrey W.
Published: November 2021

Electroencephalography (EEG) is a useful diagnostic and prognostic tool for evaluation of patients with epilepsy, encephalopathy, focal lesions, coma, or brain death. The 3 main types of epileptiform discharges are spikes, sharp waves, and spike-and-wave discharges. Spikes have a steep ascent and descent and are brief (duration ≤70 milliseconds). Sharp waves, in contrast, are longer (70-200 milliseconds). Spike-and-wave discharges consist of a spike followed by an after-coming slow wave. All the discharges may occur singly or in trains, and any may be present in either focal epilepsy or generalized epilepsy.
Nerve Conduction Studies and Needle Electromyography
Authors: Crum Brian A.
Published: November 2021

Nerve conduction studies (NCSs) and needle electromyography (EMG) should be considered extensions of the neurologic history and examination of the peripheral sensory and motor systems. NCSs assess large, myelinated sensory and motor nerve fibers. EMG assesses primarily type 1 muscle fibers. Because of the limitations of NCSs and EMG, small-fiber function (ie, small-fiber neuropathies) and, to an extent, type 2 muscle-fiber diseases (ie, steroid myopathy) cannot be excluded with these studies. The main goal of NCSs and EMG is to obtain objective evidence of disease within the peripheral nervous system and to assist with localization of the problem.
Cerebrospinal Fluid
Authors: Laughlin Ruple S.
Published: November 2021

The total volume of cerebrospinal fluid (CSF) within the ventricles and subarachnoid space is about 150 mL. The absorption of CSF is directly linked to intracranial pressure. In steady states, the rate of CSF absorption equals CSF formation, and the normal resting pressure of CSF is typically between 150 and 180 mm H2O (reference range, 65-200 mm H2O [5-15 mm Hg]). The most common cause of error in measurement of CSF pressure is failure to position the patient properly (the correct position is lateral decubitus; the right atrial pressure serves as the reference [0 mm H2O]).
Neuroimaging
Authors: Kim Dong Kun , Black David F.
Published: November 2021

Neuroimaging is commonly used in the clinical setting to aid in determining a diagnosis and prognosis and in making therapeutic decisions. This chapter reviews indications, pitfalls, underlying physics, safety issues, and examples of select neuroimaging methods. Computed tomography (CT) is the most frequently used cross-sectional technique for the initial evaluation of a patient with acute neurologic symptoms because of its availability, speed, and reliability. CT is also invaluable for patients with acute trauma because of its high spatial resolution and bone–soft tissue contrast.
Principles of Psychiatry and Psychology
Authors: Polsinelli Angelina J. , Machulda Mary M.
Published: November 2021

Cognition, psychiatric and psychological constructs, and an approach to the evaluation of cognition and psychological disorders are discussed in this chapter. Cognitive evaluations may include simple office-based procedures, but formal neuropsychological testing and functional imaging have aided practitioners in further understanding and treatment of disorders, as well as understanding of normal function. Cognition is a general term used to describe processing information, such as attention, language, memory, decision-making, and problem solving. Cognitive psychology is the specialty of psychology that examines mental processes and studies how individuals perceive, think, learn, and remember.
Psychological Development Through the Life Cycle
Authors: Lapid Maria I. , Olsen Mark W.
Published: November 2021

Human development from conception to death can be viewed from a number of perspectives, including biologic, cognitive, emotional, social, and moral. This chapter reviews the major features of various facets of development from infancy through toddlerhood, preschool, school-aged, preadolescence, adolescence, the transition into early adulthood, adulthood, and late adulthood. It includes consideration of developmental tasks and challenges, as well as the importance of the environmental influence of family, peers, school, and the broader social milieu. Psychological aspects and specific stages of elderly persons are also described.
Personality and Illness
Authors: Palmer Brian A.
Published: November 2021

A personality disorder (PD) is defined in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) as “an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture, is pervasive and inflexible, has an onset in adolescence or early adulthood, is stable over time, and leads to distress or impairment.” DSM-5 has revised the PDs to individual disorders. They no longer are reported in Axis II; DSM-5, unlike previous editions, does not use the axis system.
Miscellaneous Psychiatric Disorders
Authors: Martin Kari A.
Published: November 2021

In a number of psychiatric disorders, patients present with medical and psychological symptoms that are not well explained by a medical condition or substance use. The prevalence of somatic symptom disorder in the general US adult population may be about 5% to 7%. Associated demographic characteristics include female sex, older age, fewer years of education, lower socioeconomic status, unemployment, and a history of childhood adversity, comorbid psychiatric illness, social stress, and reinforcing illness benefits. A high level of medical care utilization rarely alleviates the patient’s concerns.
Psychiatric Disorders Associated With Infancy, Childhood, and Adolescence
Authors: Bhagia Jyoti
Published: November 2021

This chapter covers key psychiatric disorders of infancy, childhood, and adolescence. In some instances, the disorders are mentioned briefly herein and covered in more detail in other chapters, as indicated. Attention-deficit/hyperactivity disorder (ADHD) is a neurobiologic disorder present in 11% of US children between the ages of 4 and 17 years and is 3 times more common in boys than in girls. Some symptoms must be present before age 12 years, although the average age at diagnosis is 7 years. The causes of ADHD are unknown. However, several factors have been suggested that likely mediate expression of ADHD, including prematurity, prenatal toxin exposure, mechanical insults to the nervous system, and natal stress.
Pharmacologic Treatment of Psychiatric Disorders
Authors: Miller Keith A. , Morgan Robert J.
Published: November 2021

Human behaviors such as thinking, feeling, and action can be viewed as products of the interactions between brain circuits, neurotransmitters, and oscillations that are influenced to a certain extent by inherited genes, acquired values, and social norms. A psychiatric disorder reflects a dysfunctional brain, and 1 way to treat such a condition is through the use of pharmacologic compounds that can help restore order in a disorderly brain.
Nonpharmacologic Treatment of Psychiatric Disorders
Authors: Leffler Jarrod M.
Published: November 2021

Pharmacologic therapies often complement nonpharmacologic therapies in the treatment of psychiatric disease. An overview of the theory and practice of psychotherapy and interventions is provided in this chapter. Psychodynamic or psychoanalytic psychotherapy, developed by Sigmund Freud, has influenced many forms of psychotherapy. The underlying framework of psychoanalytic theory holds that a majority of a person’s psychological experiences are unconscious.
Ischemic Stroke: Uncommon and Special Situations
Authors: Arnold Fiebelkorn Catherine E. , Klaas James P.
Published: November 2021

Most ischemic stroke is caused by atherosclerosis (large- and small-vessel disease) and cardioembolic sources (eg, atrial fibrillation). However, it is important to recognize the clinical, laboratory, and radiologic manifestations of rarer causes of stroke since the treatment may differ from the treatment of more typical causes. This chapter reviews the less common causes of stroke in addition to stroke in special situations: stroke in children, stroke in pregnant women, spinal cord infarction, and cerebral venous sinus thrombosis.
Acute Ischemic Stroke Evaluation and Treatment
Authors: Scharf Eugene L.
Published: November 2021

Acute ischemic stroke is a neurologic emergency where an estimated 2 million neurons a minute are lost secondary to ischemia. Treatments of acute stroke are directed at early revascularization of the occluded vessel and to preserve neuronal death and improve collateral flow. Treatments are time sensitive, an aspect that places great importance on early symptom recognition, correct diagnosis, and clinical management. In acute ischemic stroke, in short, “time is brain.”
Secondary Prevention of Ischemic Stroke
Authors: Williams Lindsy N.
Published: November 2021

After an ischemic stroke is diagnosed, a diagnostic evaluation ensues to determine the mechanism of the stroke and contributing risk factors. The appropriate antithrombotic is selected in accordance with the mechanism of the stroke, and the contributing risk factors are treated with pharmacologic agents and lifestyle changes. This chapter discusses the selection of antithrombotic medication, medical treatment, and lifestyle changes for contributing risk factors.
Intraparenchymal Cerebral Hemorrhage
Authors: Aguilar Maria I.
Published: November 2021

Intraparenchymal cerebral hemorrhage (ICH) is the presence of blood in the brain parenchyma. It is a neurologic emergency and may carry severe morbidity and death. This chapter focuses mainly on spontaneous, nontraumatic ICH (ie, hemorrhage not related to trauma, arteriovenous malformation, cerebral aneurysm, or tumor). ICH accounts for 15% to 20% of all new strokes annually. Among the US general population, the incidence is 15 cases per 100,000 person-years.
Unruptured Intracranial Aneurysms and Vascular Malformations
Authors: Brown Robert D.
Published: November 2021

Knowledge of the natural history of unruptured intracranial aneurysms and vascular malformations of the brain is important because this information can be weighed against the morbidity and death rates of intervention to decide on the most appropriate treatment of an individual patient. This chapter reviews the epidemiologic factors and natural history of common intracranial vascular abnormalities.
Principles and Management of Increased Intracranial Pressure
Authors: Kumar Shivram , Wijdicks Eelco F. M.
Published: November 2021

Intracranial pressure (ICP) is a reflection of the total volume inside the skull. Normal ICP is 5 to 15 mm Hg. Intracranial hypertension is defined as sustained ICP of more than 20 mm Hg. Increased ICP may lead to a reduction of cerebral perfusion pressure, a shift of brain tissue, and, as a result, secondary brainstem injury. Early recognition and treatment of elevated ICP are needed to prevent irreversible damage.
Nontraumatic Subarachnoid Hemorrhage
Authors: Chakraborty Tia , Fugate Jennifer E.
Published: November 2021

Subarachnoid hemorrhage (SAH) is defined as blood in the subarachnoid space. Nontraumatic SAH is most commonly caused by rupture of an aneurysm located at the circle of Willis. Patients often present with acute thunderclap headache but also may lose consciousness or have focal neurologic deficits. Detection of an aneurysm, if present, and its treatment are needed urgently to prevent recurrent bleeding. Patients with nontraumatic SAH are prone to numerous complications that require preventative measures, early recognition, and treatment.
Acute Hyperthermia Syndromes
Authors: Hawkes Maximiliano A. , Wijdicks Eelco F. M.
Published: November 2021

A high core body temperature is a medical emergency. Neuronal mitochondria and plasma membranes are thought to undergo protein changes at temperatures higher than 40°C, which lead to brain damage or dysfunction. In addition, the effects of hyperthermia on an already injured brain cause further injury. Control of fever is one of the important additional interventions necessary to control increased intracranial pressure and status epilepticus and to treat hypertensive surges in patients with sympathetic system overdrive.
Treatment of Multiple Sclerosis
Authors: Kantarci Orhun H.
Published: November 2021

A comprehensive and ideal approach to treatment of multiple sclerosis (MS) has 5 levels of intervention. They are 1) prevention of active disease (clinical or subclinical relapses) in the first place, to prevent cumulative relapse-associated disability burden; 2) shortening the duration of active inflammatory demyelination associated with relapses, to limit the extent of irreversible central nervous system injury; 3) induction of more complete recovery after a relapse, to prevent or delay an ensuing chronic progressive neurodegeneration; 4) slowing the progressive phase of MS after progression ensues; and 5) treatment of symptoms and complications. The ultimate combined goal of these intervention levels is to alter the natural history of MS and prevent progression responsible for the main quantity of disability in MS, thereby improving the quality of life for patients with MS. Currently, treating physicians can accomplish levels 1, 2, and 5. Level 3 and level 4 interventions are yet to be developed sufficiently to affect the disease course meaningfully.
Non–Multiple Sclerosis Central Nervous System Inflammatory Disease
Authors: Zalewski Nicholas L. , Pittock Sean J.
Published: November 2021

Multiple sclerosis (MS) is the most common inflammatory central nervous system (CNS) disease. Yet, clinicians should be cognizant of other demyelinating and nondemyelinating CNS inflammatory diseases, some of which mimic MS. This chapter reviews the spectrum of non-MS CNS inflammatory diseases and MS mimics.
Classification and Approach to Movement Disorders
Authors: Youssef Paul E. , Mack Kenneth J. , Flemming Kelly D.
Published: November 2021

Movement disorders are conventionally divided into 2 major categories. Hyperkinetic movement disorders (also called dyskinesias) are excessive, often repetitive, involuntary movements that intrude into the normal flow of motor activity. This category includes chorea, dystonia, myoclonus, stereotypies, tics, and tremor. Hypokinetic movement disorders are akinesia (lack of movement), hypokinesia (reduced amplitude of movement), bradykinesia (slow movement), and rigidity. Parkinsonism is the most common hypokinetic movement disorder. In childhood, hyperkinetic disorders are common, whereas hypokinetic movement disorders are relatively uncommon.
Hypokinetic Movement Disorders: Parkinson Disease
Authors: Tisel Sarah M. , Klassen Bryan T.
Published: November 2021

Parkinson disease (PD) is the classic hypokinetic movement disorder and one of the most common and widely recognized neurodegenerative conditions. PD is distinct from parkinsonism, a term that refers to a syndrome of rest tremor, bradykinesia, rigidity, and postural instability. The mechanism behind the progressive degeneration and cell death that result in PD is not precisely understood. Substantia nigra depigmentation occurs on a macroscopic level and loss of dopaminergic neurons and gliosis on a microscopic level.
Cerebellar Disorders and Ataxias: Acquired Disorders
Authors: Hassan Anhar
Published: November 2021

Disorders of the cerebellum or its connections can result in ataxia characterized by imbalance and incoordination of gait, limbs, speech, and eye movements. The pathologic changes may be confined to the cerebellum or simultaneously affect other parts of the central nervous system or peripheral nervous system. Ataxias are generally classified as acquired, inherited, or sporadic. The differential diagnosis is broad and daunting. However, a detailed history and examination can rapidly narrow the list. Key information includes age at onset; rate of disease progression; family history; presence of pure cerebellar syndrome or other neurologic signs; other systemic features; and imaging findings.
Cerebellar Disorders and Ataxias: Inherited Disorders
Authors: Hassan Anhar
Published: November 2021

Disorders of the cerebellum or its circuitry can result in ataxia. These disorders may be acquired or inherited. Inherited ataxias may be autosomal recessive (eg. Friedrich ataxia), autosomal dominant (eg, spinal cerebellar atrophy) or X linked (eg, fragile X–associated ataxia syndrome). Chapter 73 (“Cerebellar Disorders and Ataxias: Acquired Disorders”) reviews the clinical approach to patients with ataxia and discusses acquired forms of ataxia. This chapter reviews clinical approaches, diagnostic details, and treatment of inherited ataxias.
Syndromes of Cognitive Dysfunction
Authors: Kumar Shivram , Flemming Kelly D.
Published: November 2021

Cognitive function refers to the mental process of knowing things. It includes high-level cortical functions such as memory, language, perception, and executive function (planning, initiating, and reasoning) that generally depend on the alert state and focused attention. Dysfunction of cognition without a change in consciousness may result in various disorders, including aphasia, apraxia, agnosia, executive dysfunction, and memory disorders such as dementia and amnesia. Transient dysfunction of cognition associated with a change in level of consciousness or attention may be due to delirium or confusional states. This chapter broadly introduces the specific definitions of cognitive dysfunction and the overall differential diagnoses.
Nondegenerative Dementias and Encephalopathies
Authors: Flanagan Eoin P.
Published: November 2021

Nondegenerative dementias are a diverse but important group of cognitive disorders because they may be reversible with treatment. Thus, evaluation is important when a nondegenerative dementia is suspected. Many causes of nondegenerative dementia result in what is known as subcortical dementia, which is thought to be primarily due to damage to the frontal subcortical connections. Typical clinical features include inattention, bradyphrenia (slowed thought process), executive dysfunction (difficulties planning and sequencing tasks), apathy, psychomotor slowing, and mood disorders. Gait apraxia and urinary difficulties may coexist. Cortical features such as agnosia, seizures, aphasia, and ideomotor apraxia are typically absent.
Epidemiology and Pathophysiology of Epilepsy
Authors: Burkholder David B.
Published: November 2021

About 10% of people in the United States have 1 seizure in their lifetime; less than 4% have recurrent seizures or epilepsy. Currently, more than 3.4 million people in the United States have active epilepsy, making it one of the most common neurologic disorders. Seizures can develop at any age, but the most common times are during childhood and after age 60 years. The greatest incidence is in elderly patients. Acute symptomatic seizures (also called provoked seizures or reactive seizures) result from new and active insults to the central nervous system.
Treatment of Epilepsy
Authors: Hoerth Matthew T.
Published: November 2021

A systematic approach can simplify the process of epilepsy treatment, and knowledge of the antiseizure drugs is essential. This chapter summarizes the approach to treatment, presents a summary of medications and alternative therapies, and discusses treatment in special situations. A rational approach should be taken when selecting medications for the treatment of seizures associated with epilepsy. The choices for drug selection are ever expanding, which can make the selection process difficult for even experienced epileptologists, let alone trainees and patients. On the other hand, the diverse choices available allow medications to be tailored to each patient’s specific situation.
Peripheral Nerve Disorders
Authors: Berini Sarah E. , Staff Nathan P.
Published: November 2021

Disorders of the peripheral nerves are some of the most common conditions that neurologists face in clinical practice. The wide differential diagnosis that often accompanies peripheral nerve disorders may be narrowed by careful attention to the history (time course, severity, preexisting disease, and family history); peripheral neuroanatomy; patient symptomatology (sensory loss, paresthesia, pain, and weakness); and neurologic examination (sensory loss, weakness, atrophy, and reduced muscle stretch reflexes). Electromyography is used to assess large-diameter myelinated axons (touch, pressure, vibration, proprioception, and motor) and aid in localization by helping to narrow the differential diagnosis and predict axonal or demyelinating pathophysiology.
Neuromuscular Junction Disorders
Authors: Goodman Brent P.
Published: November 2021

The neuromuscular junction (NMJ) is a critical component of the motor unit that is made up of the distal, unmyelinated nerve terminal, synaptic space, and end-plate region of the muscle fiber. Contraction of muscle fiber involves a coordinated series of steps that ultimately generates an action potential at the muscle end plate (also known as an end-plate potential). Normally the end-plate potential substantially exceeds the threshold necessary to trigger an action potential in the muscle fiber, and this difference is termed the safety factor of neuromuscular transmission. Disorders that affect the NMJ reduce this safety factor, a change that results in fatigable weakness.
Autonomic Disorders
Authors: Singer Wolfgang
Published: November 2021

A practical but arbitrary classification of autonomic disorders is used at Mayo Clinic. Presented in a modified and abbreviated form in this chapter, that classification serves to organize and provide an overview of autonomic disorders. It is organized by anatomical systems and levels, although some syndromes and disorders do not fit neatly into this organization and therefore are assigned their own category. This classification quickly shows how abundant and interspersed autonomic dysfunction is among various categories of neurologic disease. Therefore, the role of this chapter is not to describe every disorder that can be associated with autonomic dysfunction. Rather, the chapter focuses on disorders with autonomic dysfunction as a predominant or important feature and thereby covers what are generally referred to as autonomic disorders.
Clinical Neurotology
Authors: Eggers Scott D.
Published: November 2021

Normal balance is the consequence of continuous interaction between visual, vestibular, and proprioceptive mechanisms. The vestibular system is a system in which head movements and positions cause mechanical forces to be transduced into electrochemical signals that are relayed to the central nervous system for the purpose of maintaining clear stable vision and equilibrium. With a basic understanding of physiology, common disease processes, and examination techniques, a correct diagnosis can generally be made at the bedside.
Primary Headache Disorders: Migraine, Tension-Type, and Chronic Daily Headaches
Authors: Whealy Mark A. , Cutrer F. Michael
Published: November 2021

Primary headache disorders are those in which the headache is the primary feature of the disorder and is not otherwise explained by a structural, genetic, or metabolic cause. This chapter reviews the clinical features, diagnosis, and treatment of common primary headache disorders, including migraine, tension-type, and chronic daily headaches. Migraine usually starts during adolescence, and 90% of patients with migraine have their first attack by age 40 years. In childhood, there is a slight male predominance, but after puberty, a 3:1 female predominance is established. The highest reported prevalence of migraine is in patients who are 30 to 39 years old.
Primary Headache Disorders: Trigeminal Autonomic Cephalalgias, Headaches With Specific Triggers, and Other Primary Headache Disorders
Authors: VanderPluym Juliana H. , Halker Singh Rashmi B.
Published: November 2021

Primary headache disorders are those in which the predominant clinical feature is headache that is not caused by or attributed to another disorder. This chapter reviews the common primary headache disorders of migraine, tension-type headache, and chronic daily headache. The present chapter reviews less common primary headache disorders, such as trigeminal autonomic cephalalgias and headaches with certain triggers. A careful history, physical examination, and additional testing are often necessary to rule out a secondary cause.
Secondary Headache Disorders
Authors: Starling Amaal J. , Dodick David W.
Published: November 2021

In the evaluation of a patient with headache, the first task is to differentiate between a secondary headache and a primary headache. This step is essential because secondary causes of headache may require vastly different evaluation and treatment than primary headache disorders. Thunderclap headache (TCH) is an acute, severe headache with an abrupt onset, reaching maximum intensity in less than 1 minute. TCH is a neurologic emergency and should immediately prompt an urgent evaluation for a secondary headache.
Neuropathic Pain Syndromes
Authors: Watson James C.
Published: November 2021

The International Association for the Study of Pain defines neuropathic pain as pain that is initiated or caused by a lesion or disease affecting the somatosensory system in either the peripheral nervous system or the central nervous system. Several well-recognized descriptors for neuropathic pain suggest a neuropathic rather than nociceptive pathophysiology (hot, burning, painful cold, freezing, prickling or tingling, pins and needles, electrical, shooting, stabbing, lancinating, and itching). However, whether the pain descriptors are used alone or incorporated into questionnaires to identify neuropathic pain, their sensitivity and specificity are limited (generally 70%-85%); therefore, verbal pain descriptors are insufficient for making the diagnosis of neuropathic pain.
Introduction to Neoplastic Disease
Authors: Porter Alyx B.
Published: November 2021

The advanced imaging readily available at most medical centers allows easier identification of neoplastic disease of the nervous system. Despite earlier detection, nervous system neoplasms continue to be an important cause of neurologic morbidity and death. This chapter broadly reviews the clinical manifestations and general approach to diagnosis and management of nervous system tumors. Subsequent chapters review individual types of tumors, complications of therapy for tumors, and paraneoplastic diseases.
Glial Tumors
Authors: Sharma Akanksha , Johnson Derek R.
Published: November 2021

Glial tumors are primary brain and spinal cord tumors arising from supporting cells of the central nervous system, including oligodendrocytes, astrocytes, microglia, and ependymal cells. Collectively, glial tumors are the most common category of primary brain tumors. They may be infiltrative or well circumscribed. Prognosis ranges from surgical cure to survival of less than 2 years, depending on tumor type. Age is the strongest risk factor for glioma in adults, with incidence rates increasing from a low of 3.2 per 100,000 person-years among persons age 20 to 34 years to a high of 19.3 per 100,000 person-years among those age 75 to 84 years.
Peripheral Nerve Sheath Tumors
Authors: Kumar Shivram , Ruff Michael W.
Published: November 2021

Nerve sheath tumors involve the connective tissue surrounding a peripheral nerve. They may be found incidentally or may be symptomatic. In most cases, nerve sheath tumors are benign. A detailed personal and family history and careful physical examination should be performed to assess for association with neurofibromatosis 1 or 2 or schwannomatosis. This chapter reviews the genetics, clinical features, diagnosis, and management of the common types of peripheral nerve sheath tumors.
Metastatic Disease
Authors: Sharma Akanksha , Porter Alyx B.
Published: November 2021

Intracranial metastases are the most common brain tumors in adults and outnumber primary brain tumors by 10 to 1. Nearly 200,000 patients are affected every year in the United States, and these metastases have become the most common neurologic complication of cancer. Intracranial metastases are occurring with increased frequency as a result of improved therapies for systemic cancers that extend survival. Most patients with brain metastases have lung cancer as the primary malignancy, followed in frequency by breast, melanoma, renal cell, and thyroid cancers. The prognosis when brain metastases are detected differs on the basis of the underlying cancer type.
Paraneoplastic and Other Autoimmune Neurologic Disorders
Authors: Lopez Chiriboga A. Sebastian , McKeon Andrew
Published: November 2021

A paraneoplastic disorder arises from remote effects of malignancy, rather than direct tumor invasion. Paraneoplastic neurologic disorders occur because of the vigorous immune responses directed against antigens expressed in tumors. The vigor of the immune response usually ensures that neoplasm is confined to the primary organ and regional lymph nodes. However, in the clinical setting of paraneoplastic disease, the immune response may attack any part of the nervous system (brain, spinal cord, nerve, neuromuscular junction, or muscle), and antibodies are either directed at intracellular neuronal proteins or against neuronal cell surface or synaptic proteins. Treatment is often aimed at the cancer and suppression of the abnormal immune response.
Syndromic Approach to Neuroinfectious Diseases
Authors: Kumar Shivram , Flemming Kelly D.
Published: November 2021

A general approach to clinical syndromes associated with infection of the nervous system can be useful when an infectious agent is suspected. This chapter provides a general overview of clinical syndromes of neurologic infectious disease. Subsequent chapters review bacterial, viral, fungal, and protozoan infections and prion disorders. Meningitis refers to inflammation of the leptomeninges caused by either infectious or noninfectious processes. It is associated with an increased white blood cell count in the cerebrospinal fluid. Infectious agents may be bacteria, viruses, or fungi. Noninfectious causes include autoimmune conditions, malignancies, and medications.
Bacterial Infections of the Nervous System
Authors: Toledano Michel
Published: November 2021

Bacterial infections of the nervous system manifest themselves in several ways, most of which are neurologic emergencies. This chapter reviews the classic syndromes of meningoencephalitis and focal infection (cerebritis or abscess) and the syndromes of neurosyphilis, tuberculosis, botulism, leprosy, Lyme disease, Whipple disease, rickettsiosis, diphtheria, and ventricular shunt infections.
Neurocutaneous Disorders
Authors: Keating Gesina F.
Published: November 2021

Neurocutaneous disorders, formerly called phakomatoses, are characterized by cutaneous and neurologic findings. Many are genetic, but some are sporadic. Often these disorders affect other organ systems as well and require lifetime surveillance for complications. Neurofibromatosis type 1 is the most common neurocutaneous disorder. With a prevalence of approximately 1 in 3,000 persons, it is more than 10 times more common than neurofibromatosis type 2.
Lysosomal Storage Disorders
Authors: Dhamija Radhika , Conboy Erin , Wong-Kisiel Lily C.
Published: November 2021

Lysosomes are membrane-bound organelles that degrade various macromolecules. Lysosomal storage diseases are a clinically, enzymatically, and genetically heterogeneous group of disorders resulting from intracellular accumulation of substrates. Mechanisms of lysosomal storage disorders include 1) primary deficiency of specific hydrolases; 2) defects in activator proteins required for enzyme-substrate interactions in posttranslational modification of enzymes or in transport of the substrate from lysosomes; and 3) abnormalities of fusion between autophagic vacuoles and lysosomes. Substrate accumulation is slowly progressive, leading to considerable morbidity and mortality.
Mitochondrial Disease
Authors: Dhamija Radhika , Conboy Erin , Gavrilova Ralitza H.
Published: November 2021

Primary mitochondrial diseases are a heterogeneous group of disorders that result from defects of the oxidative phosphorylation system of the mitochondria. Often underrecognized, mitochondrial diseases are uncommon (estimated incidence, 1 in 10,000 live births). Mitochondria are double-membrane–bound cytoplasmic organelles whose primary function is to provide energy (ie, adenosine triphosphate [ATP]) from the breakdown of carbohydrates, protein, and lipids by means of the electron transport chain and the oxidative phosphorylation system. The respiratory chain of mitochondria, located in the inner mitochondrial membrane, consists of 5 multimeric protein complexes (complexes I-IV and ATP synthase [complex V]). The structural proteins of these complexes are encoded by both mitochondrial and nuclear genes. Therefore, primary mitochondrial disorders can follow a maternal or mendelian inheritance pattern.
Neurologic Complications of Nutritional Disorders
Authors: Goodman Brent P.
Published: November 2021

A number of medical and neurologic conditions may result from inadequate ingestion, absorption, transport, or storage of critical vitamins and micronutrients. Individuals at risk for inadequate dietary intake include those who are receiving prolonged parenteral nutrition for various chronic medical conditions, those who have eating disorders or chronic alcoholism, and those who are part of a resource-limited population. Malabsorption may result from several conditions, including chronic gastrointestinal disorders and gastrointestinal surgeries. Excessive intake of vitamins such as vitamin B6 may directly cause neurotoxicity, and copper deficiency myeloneuropathy may result from excessive ingestion of zinc (often in the form of denture cream aggressively used for loose-fitting dentures), which competes with copper for absorption within the gastrointestinal tract.
Neurologic Associations With Cardiac, Pulmonary, Renal, Hepatobiliary, and Hematologic Disease
Authors: Kumar Shivram , Flemming Kelly D.
Published: November 2021

The brain has a higher demand for cardiac output than any other organ, and it strictly relies on oxygen and glucose metabolism. Consequently, the brain is exquisitely sensitive to homeostatic disturbances and extraneural organ dysfunction leading to cardiac, pulmonary, renal, hepatobiliary, and hematologic diseases. The primary neurologic manifestation of extraneural organic dysfunction is diffuse bihemispheric dysfunction or encephalopathy, which often lacks lateralizing or localizing signs. Common clinical findings are lethargy, difficulty with attention and orientation, sleep-wake disturbance, and psychomotor slowing. As organic dysfunction progresses, a moderate encephalopathy ensues, with worsening cognitive function, gross disorientation, hypoactive or hyperactive psychomotor state, frontal release signs, asterixis, and myoclonus. If organ failure (eg, hepatic or renal) progresses further, stupor and coma may result unless organ function improves. Patients with underlying organic brain disease from degenerative dementia can decompensate out of proportion to neurologically normal counterparts, resulting in encephalopathy even from minor organ dysfunction or infection.
Neuropharmacology of Sleep
Authors: Castillo Pablo R.
Published: November 2021

Sleep disorders often respond to both pharmacologic agents and nonpharmacologic therapies. This chapter reviews the pharmacology of and indications for specific sleep agents. Most of the agents approved by the US Food and Drug Administration for insomnia, with the exception of antidepressants and ramelteon, modulate the function of the γ-aminobutyric acid (GABA)-A receptor complex. The ventrolateral preoptic nucleus (VLPO) has a critical role in sleep initiation and maintenance. GABA is the primary inhibitory neurotransmitter of the VLPO. Medications used for sleep promotion include benzodiazepines, chronobiotics, sedating antidepressants, histamine blockers, and γ-hydroxybutyric acid.
Clinical Sleep-Related Breathing Disorders
Authors: Arunthari Vichaya , Dredla Brynn K.
Published: November 2021

Sleep-related breathing disorders are categorized into obstructive sleep apnea syndromes, central sleep apnea syndrome, and sleep-related hypoventilation or hypoxic syndromes. These disorders can occur in adults and children. Clinical characteristics, diagnosis, and treatment are discussed in this chapter. Sleep apnea occurs when recurrent complete (apnea) or nearly complete (hypopnea) cessation of airflow develops, accompanied by preservation of the respiratory drive manifested as persistent respiratory muscle effort. Apnea is defined as the cessation of airflow for more than 10 seconds, using a valid measure of airflow. Hypopnea is an airflow reduction of at least 30% from baseline that lasts at least 10 seconds and is accompanied by an oxygen desaturation of 4% or more.
Hypersomnias and Sleep-Related Movement Disorders
Authors: Arunthari Vichaya , Dredla Brynn K.
Published: November 2021

Hypersomnias are disorders associated with excessive daytime sleepiness not related to sleep deprivation, disturbed nocturnal sleep, circadian rhythm disturbances, sleep-related breathing disorders, or a medical condition. This chapter reviews the primary hypersomnias of narcolepsy and idiopathic hypersomnia. Sleep-related movement disorders, including restless legs syndrome and periodic limb movements of sleep, are also commonly encountered in clinical practice. These common syndromes are reviewed in this chapter.
Lesions Found by Chance
Authors: Wingerchuk Dean M.
Published: November 2021

A healthy 26-year-old woman with a history of episodic migraine without aura since age 12 years had a first-ever event of transient visual impairment. She reported to her neurologist that she “lost vision” for 15 minutes and described a “black blob” with a bright jagged border that moved across her binocular visual field and resolved without sequelae. Minutes later, one of her typical migraine headaches developed. Given the patient’s history of typical episodic migraine, the new visual event’s clinical characteristics were highly consistent with a migraine aura. Because of the new transient visual symptoms, the neurologist ordered brain magnetic resonance imaging, which showed several periventricular white matter lesions, including some that involved the corpus callosum and were oriented perpendicular to the septocallosal surface.

The patient was counseled about the magnetic resonance imaging findings and expressed the desire to fully evaluate her risk of multiple sclerosis.

The patient was diagnosed with radiologically isolated syndrome.

The patient was counseled regarding the relevance of the magnetic resonance imaging findings and risk of future development of multiple sclerosis. She was not prescribed a disease-modifying therapy for multiple sclerosis.

This patient has radiologically isolated syndrome —incidentally found magnetic resonance imaging lesions consistent with demyelination in a patient with no symptoms or signs suggestive of multiple sclerosis.
Severe Monocular Vision Loss Followed by Gait Difficulty
Authors: Weinshenker Brian G.
Published: November 2021

A 56-year-old woman sought care for painless vision loss over 24 hours in the superior field of her right eye, which progressed to total vision loss. Intravenous corticosteroids were administered over 5 days, and she recovered well. Approximately 6 months later, paresthesias and sensory loss of her legs developed, which was sufficiently severe that she was unable to walk. She had severe impairment of vibration sense and lesser impairment of position sense, as well as proximal weakness of both legs. She recovered but had persistent burning dysesthesias of the legs.

Magnetic resonance imaging of the orbits at the onset of symptoms showed gadolinium enhancement extending from the middle of the orbit posteriorly, almost to the level of the optic chiasm. Magnetic resonance imaging of the spine at the time of acute myelitis revealed a long spinal cord lesion extending from the lower cervical cord to the conus which was central and homogeneous on T2 images and exhibited patchy gadolinium enhancement. Cerebrospinal fluid analysis showed 37 leukocytes/µL with lymphocyte predominance and negative tests for oligoclonal bands. On serologic analysis, she was positive for aquaporin-4-immunoglobulin G antibodies by enzyme-linked immunosorbent assay.

The patient was diagnosed with neuromyelitis optica spectrum disorder, aquaporin-4-immunoglobulin G seropositive.

The patient was started on rituximab treatment. After 2 years, she decided to discontinue treatment because she was concerned about potential adverse effects. Six months after discontinuing rituximab, severe weakness of her right leg developed, which improved with intravenous corticosteroids. Rituximab therapy was restarted, 2 doses of 1 g each, but she had 1 further episode of myelitis 2 weeks after receiving rituximab. Six months later, her visual acuity in the right eye was only counting fingers, and she had a flaccid paraplegia with areflexia of the lower extremities and total loss of sensory function below T4.
Progressive Cerebellar Ataxia After Natalizumab Treatment
Authors: Toledano Michel
Published: November 2021

A 47-year-old woman with a history of relapsing-remitting multiple sclerosis (MS) receiving natalizumab therapy sought a second opinion regarding a recent diagnosis of secondary progressive disease.

She was first diagnosed with multiple sclerosis 8 years earlier. While taking natalizumab, she was monitored for the development of antibodies to JC polyoma virus. Nine months before our evaluation, anti-JC polyoma virus antibodies became positive, with an increased index of 1.1. Given sustained remission, she was continued on natalizumab with increased surveillance and a plan to switch to a different disease-modifying therapy after 24 months.

Five months later she noted subacute onset of slurred speech and right upper extremity incoordination. Over the next 4 months she continued to have clinical decline.

On examination she had moderate ataxic dysarthria and right greater than left appendicular ataxia. She relied on a wheelchair for transportation and required 1-person assist to stand. Reflexes were brisk with bilateral Babinski sign.

This patient with relapsing-remitting multiple sclerosis on natalizumab had a new subacute progressive cerebellar syndrome without radiographic evidence of disease activity.

Repeated magnetic resonance imaging showed worsening cerebellar atrophy, right sided greater than left sided, and evolving T2 hyperintensity in the brainstem without enhancement or mass effect. JC polyoma virus polymerase chain reaction was positive.

The patient was diagnosed with JC polyoma virus granule cell neuronopathy.

Natalizumab was discontinued, and she was treated with 4 of 5 planned cycles of plasma exchange. After her 4th cycle, worsening symptoms developed. Magnetic resonance imaging showed gadolinium enhancement in the brainstem supportive of immune reconstitution inflammatory syndrome. She received high-dose intravenous methylprednisolone followed by a prednisone taper. Her disability progression stabilized.

JC polyoma virus central nervous system infection, 1 of several infections reported among treated patients with multiple sclerosis, occurs almost exclusively in immunosuppressed patients, including those receiving disease-modifying therapy for multiple sclerosis.