All physicians, regardless of their medical specialty or the setting in which they treat patients, must be able to perform a neurologic examination. In the outpatient office, up to 9 to 10% of all symptoms suggest the possibility of neurologic disease and up to 5% of emergency department visits are due to primary neurologic disease. The neurologic examination is critical in triaging these patients, selecting diagnostic tests, and indicating management. This review covers how to think about the neurologic examination, the screening examination, and diagnosis-focused neurologic examinations with an emphasis on stroke, epilepsy, encephalopathy and coma, neurodegenerative diseases, neuromuscular disease, and functional disorders. The figure shows a conceptual approach to the neurologic examination. The tables list components of the screening neurologic examination, neurologic examination focus points for suspected stroke and suspected epilepsy, lateralization and localization of common seizure semiologies, and neurologic examination focus points for encephalopathy/coma, suspected neurodegenerative disease, suspected neuromuscular disease, and suspected functional neurologic disorders.

This review contains 1 figure, 13 tables, and 14 references

Keywords: Neurologic examination, neurodegenerative disease, neuromuscular disease, neurologic screening

Modern neuroimaging has revolutionized the practice of neurology by allowing visualization and monitoring of evolving pathophysiologic processes. High-resolution magnetic resonance imaging (MRI) can now resolve structural abnormalities on a near-cellular level. Advances in functional imaging can assess the in vivo metabolic, vascular, and functional states of neuronal and glial populations in real time. Given the high density of data obtained from neuroimaging studies, it is essential for the clinician to take an active role in understanding the nature and significance of imaging abnormalities. This chapter reviews computed tomography and MRI techniques (including angiography and advanced sequences), specialized protocols for investigating specific diagnoses, risks associated with imaging, disease-specific imaging findings with general strategies for interpretation, and incidental findings and artifacts. Figures include computed tomography, T1- and T2-weighted signal intensity, diffusion-weighted magnetic resonance imaging, magnetic resonance spectroscopy, imaging in epilepsy and dementia, extra-axial versus intra-axial lesions, typical lesions of multiple sclerosis, spinal imaging, spinal pathology, vascular pathology, intracranial hemorrhage, and common imaging artifacts. Tables list Hounsfield units, patterns of enhancement from imaging, advanced techniques in imaging, magnetic resonance imaging sequences, and the evolution of cerebral infarction and intraparenchymal hemorrhage on magnetic resonance imaging.

This chapter contains 12 figures, 13 tables and 216 references

Keywords: computed tomography, magnetic resonance imaging, angiography, intracranial hemorrhage, embolism, neuroimaging, multiple sclerosis, spinal imaging

The term movement disorders encompasses a wide range of conditions that cause abnormal movements. This review discusses hypokinetic movement disorders, including bradykinesia, akinesia, akinetic rigid syndrome, and Parkinsonism, an akinetic rigid syndrome that is one of the most common of all the movement disorders which is most often a manifestation of Parkinson disease (PD). The review looks at the epidemiology, etiology, pathology, diagnosis, treatment, and management of PD. Other parkinsonian syndromes include progressive supranuclear palsy, corticobasal syndrome, multiple system atrophy, vascular parkinsonism, normal pressure hydrocephalus, drug-induced parkinsonism, and dementia associated with Parkinson disease. Hyperkinetic movement disorders include tremor, dystonia, tics, myoclonus, and chorea. They include Huntington disease, Wilson disease, tardive dyskinesia, Tourette syndrome, and essential tremor. Figures in this review include examples of generalized dystonia, moderate parkinson disease, affected handwriting, Kayser-Fleischer ring, cervical dystonia, head deviation, and writer's cramp. Tables provide clinical definitions, clues to drug-induced parkinsonism, and a list of drugs that can cause parkinsonism.

This review contains 129 references.

Pain is experienced within a complex biologic, emotional, psychological, and social context that may defy physical examination, diagnostic procedures, and laboratory tests. This chapter aims to empower internists to improve their medical practices in pain management. It provides a scientific background that covers nociception and how sensory processing occurs at multiple levels in the body. Clinical assessment is detailed, as well as diagnostic categories that include mixed or uncertain chronic pain syndromes (back pain, fibromyalgia, postamputation pain, pain from cancer and bone) and neuropathic pain syndromes (polyneuropathy, mononeuropathy multiplex, ganglionopathy, genetic disorders, focal and regional syndromes). Treatment of chronic pain can be surgical or interventional. Pharmacologic treatment for acute and chronic nociceptive pain includes special considerations for geriatric and terminal patients. For treatment of neuropathic pain, medications are the major component. One tables lists iatrogenic nerve injuries that can cause posttraumatic neuralgia and complex regional pain syndrome. Other tables detail stepwise pharmacologic management of neuropathic pain and cite recommendations on opioid use from the Centers for Disease Control and Prevention. One figure illustrates how pain transducers monitor and influence tissue conditions. Other figures show sensory processing in the spinal cord dorsal horn, physical findings in the feet of patients with bilateral foot pain from small-fiber polyneuropathy, illustrate how examination can identify specific nerve injuries causing chronic pain, and provide classification of chronic pain syndromes. This chapter contains 82 references.

Dizziness is the quintessential symptom presentation in all of clinical medicine. It is a common reason that patients present to a physician. This chapter provides background information about the vestibular system, then reviews key aspects of history-taking and examination of the patient, then discusses specific disorders and common presentation types. Throughout the chapter the focus is on neurologic and vestibular disorders. Normal vestibular anatomy and physiology are discussed, followed by recommendations for history-taking and the physical examination. Specific disorders that cause dizziness are explored, along with common causes of non-specific dizziness. Common presentations are discussed, including acute severe dizziness, recurrent attacks, and recurrent positional vertigo. Finally, the chapter looks at laboratory investigations in diagnosis and management. Figures include population prevalence of dizziness symptoms, the anatomy of inner structures, primary afferent vestibular nerve activity, the head thrust test, the Dix-Hallpike maneuver, the supine positional test, the canalith repositioning procedure, and the barbecue roll maneuver. Tables list physiologic properties and clinical features of the components of the peripheral vestibular system, information to be acquired from history of the present illness, common symptoms patients report as dizziness, examination components, distinguishing among common peripheral and central vertigo syndromes, common causes of nonspecific dizziness, types of dizziness presentations, relevant imaging abnormalities on neuroimaging studies, vestibular testing components, and medical therapy for symptomatic dizziness.

This review contains 8 highly rendered figures, 10 tables, and 68 references.

Stroke is a leading cause of neurologic morbidity and mortality, and rapid treatment is key for a good outcome. This review addresses the epidemiology, common presenting symptoms, causes, and treatment of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Current recommendations for the emergent evaluation and treatment of an acute ischemic stroke are highlighted, including recently updated indications and contraindications for intravenous recombinant tissue plasminogen activator administration and recent guidelines for the expanded role of endovascular mechanical embolectomy for stroke due to acute large vessel occlusion. An algorithm of diagnostic evaluations to assist with identification of the cause of ischemic stroke is offered. Evidence-based primary and secondary stroke prevention is discussed, including the ideal choice of antithrombotic based on identified stroke mechanism and optimal risk factor management. Best practice supportive measures for the post-stroke patient are highlighted, including recent guidelines for the management of elevated intracranial pressure. Management of uncommon causes of ischemic stroke is also addressed. 

This review contains 7 figures, 9 tables, and 84 references.

Key Words:Intracerebral hemorrhage, ischemic stroke, recombinant tissue plasminogen activator, subarachnoid hemorrhage, antiplatelet therapy, endovascular therapy

In 2013, the International Encephalitis Consortium proposed clinical criteria for acute encephalitis consisting of 24 hours of altered level of consciousness, lethargy, or personality change and at least three additional supportive features. Although viruses are the most common cause of acute encephalitis, not all encephalitides are acute, viral, or even infectious. Chronic encephalitis can be pathologically similar to acute encephalitis, but the causative agents and clinical manifestations vary. Management of encephalitis is largely supportive; however, for many common encephalitides primary preventive approaches exist. This module reviews the epidemiology, manifestations, diagnosis, management, and prevention of various encephalitides, including herpes family encephalitis (herpes simplex virus, varicella-zoster virus, cytomegalovirus, human herpesvirus 6), arbovirus encephalitis (West Nile virus, eastern equine encephalitis virus, tick-borne encephalitis virus, Japanese encephalitis virus), other encephalitides associated with viruses (influenza virus, human immunodeficiency virus, John Cunningham virus, rabies virus), encephalitides associated with bacteria (Mycoplasma pneumonia, Listeria monocytogenes), and autoimmune encephalitis (acute disseminated encephalomyelitis, paraneoplastic and other autoimmune encephalitides, immune reconstitution inflammatory syndrome). Tables include the International Encephalitis Consortium’s supportive feature of encephalitis, differential diagnosis for magnetic resonance imaging (MRI) findings in the patient with suspected encephalitis, diagnostic considerations for triaging workup of infection-associated encephalitis, differential diagnosis of arboviral infections by location of travel or residence, and preventive strategies for select infectious encephalitis. Figures include MRIs showing patients with herpes simplex encephalitis, varicella-zoster virus, eastern equine encephalitis, HIV, Listeria monocytogenes, acute disseminated encephalomyelitis, acute hemorrhagic leukoencephalitis, and immune reconstitution inflammatory syndrome.

This module contains 8 highly rendered figures, 5 tables, 78 references, and 5 MCQs.

Ataxia is a disorder of balance and coordination. The most common forms are cerebellar ataxia and afferent/sensory ataxia. Ataxias can be classified as primary or secondary, as well as hereditary, nonhereditary degenerative, and sporadic. This review covers the primary (congenital, hereditary, and nonhereditary degenerative ataxias) and secondary cerebellar ataxias and afferent/sensory ataxias. Hereditary ataxias are classified as autosomal recessive cerebellar ataxias (such as Friedreich ataxia and ataxia-telangiectasia), autosomal dominant cerebellar ataxias (currently known as spinocerebellar ataxias, such as spinocerebellar ataxia type 3 or Machado-Joseph disease), episodic ataxias, X-linked cerebellar ataxias, and mitochondrial ataxias. Idiopathic degenerative cerebellar ataxias include the cerebellar form of multiple system atrophy (MSA-C) and idiopathic late-onset cerebellar ataxias. Secondary cerebellar ataxias or acquired ataxias include ataxias due to exogenous or endogenous nongenetic causes, such as toxic, paraneoplastic, immune mediated, nutritional, infectious, and secondary to focal injury to the cerebellum. Afferent/sensory ataxia represents a special group of ataxias with many possible causes and is associated with peripheral neuropathies, dorsal root ganglionopathies, sensory nerve root involvement, and posterior spinal column involvement. Figures show several clinical and radiologic (magnetic resonance imaging) signs of autosomal recessive, autosomal dominant ataxias, and multiple system atrophy (type C). Tables list the most common neurologic signs of cerebellar and afferent/sensory ataxias, the main forms of autosomal recessive and autosomal dominant cerebellar ataxias, and the most common causes of secondary cerebellar and afferent/sensory ataxias.

This review contains 5 figures, 11 tables, and 98 references.

Key words: afferent/sensory ataxias, ataxias, autosomal recessive cerebellar ataxias, congenital ataxias, nonhereditary degenerative ataxias, secondary cerebellar ataxias, spinocerebellar ataxias

Headaches are a near-universal experience, with a 1-year prevalence of 90% and a lifetime prevalence of 99%. Headaches and pain to the head account for roughly 3% of visits to US emergency departments annually, making them the fourth most common reason for seeking emergency care. There are numerous types of headaches, and although the majority are benign, types exist that may result from serious and potentially life-threatening causes. As such, it is important for the physician to consider a broad differential diagnosis for every headache patient. This review discusses the classification of headaches, identifies pain-sensitive structures in the head, discusses the history and examination in patients with headache, and describes many of the primary and secondary headaches. Figures show the areas of the brain sensitive to pain; 1-year prevalence of migraine in men, women, and children; frequency of attacks in migraineurs; prevalence of headaches by age group and in patients with cerebrovascular disorders; and symptoms of idiopathic intracranial hypertension. Tables list the major categories of headache disorders, key elements of the headache history, helpful questions to ask, features of selected primary and secondary headaches, reasons to consider neuroimaging, efficacy of selected over-the-counter medications, triptans available in the United States, medication options for urgent or emergency treatment of migraine, selected preventive medications for migraine, generally accepted indications for preventive treatment, general principles for the use of preventive medications, titration schedules for preventive medication, interval or short-term preventive treatment of menstrual migraine, strategies for managing increase in migraines in patients starting estrogen replacement therapy, transition medications for rapid, temporary suppression of headaches, medications possibly effective for cluster and hypnic headaches, differential diagnosis of the acute, severe, new-onset headache, and etiologies of papilledema and headache.

This review contains 6 figures, 23 tables, and 115 references.

Tension-type headache (TTH) is a significant but underappreciated condition that is much more frequent than migraine, 42% versus 11%, and produces significant socioeconomic burden. Why then do research advances in this condition seem to lag?

One reason is that precise epidemiologic data are lacking, with lifetime prevalence estimates varying from about 13 to 78%. Also, classification is confounded by whether or not to include the occasional but universal headache as TTH. Furthermore, TTH pathophysiology is debated, with some feeling that the pathophysiology of TTH is similar to and on a spectrum with migraine, and some feeling that it is entirely separate and related to peripheral and muscular mechanisms. More recently, central pain mechanisms have also been implicated in the pathophysiology. In addition, a large body of information connects stress and TTH.

Although TTH varies widely in frequency and severity among and within patients, TTH pain, compared with pain in other headache types, could be characterized generally as more mild in severity and more generalized in location. This review discusses the current epidemiologic data and diagnostic challenges in TTH and the current pathophysiologic mechanisms.

As of 2012, over one in eight Americans is over the age of 65, and this number is rising, particularly in the 85+ age group. This segment of the population has a rate of hospitalization three times higher than that for persons of all ages. General internists and family medicine physicians provide a large portion of care for this age group and should therefore be comfortable using a comprehensive approach to geriatric assessment. This review describes general considerations regarding geriatric care, including the process of taking a functional history and clinical implications of geriatric care. The geriatric assessment process is discussed in terms of physical, cognitive, social, and medical domains. The benefits of geriatric assessment in primary care, specialty care, and hospitalized patients are described. Tables outline activities of daily living, sensory changes with aging, major causes of visual impairment in the geriatric population, major neurocognitive disorder diagnostic criteria, medications to avoid or use with caution based on Beers criteria and Screening Tool of Older individuals’ Potentially inappropriate Prescriptions criteria, U.S. Preventive Services Task Force–recommended services relevant to older adults, and vaccinations in older adults. Figures illustrate the key vulnerabilities of older adults; outcomes linked to functional dependence; common disorders associated with cognitive concerns; domains of cognition and examples of impairment in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition; the social and medical domains of geriatric assessment; barriers to medication adherence in older patients; and resources for medication appropriateness in older adults.

This review contains 8 highly rendered figures, 8 tables, 110 references, and 5 MCQs.

Traumatic brain injury remains a leading cause of death and disability worldwide. Patients with severe traumatic brain injury are best treated with a multidisciplinary, evidence-based, protocol-directed approach, which has been shown to decrease mortality and improve functional outcomes. Therapy is directed at the prevention of secondary brain injury through optimizing cerebral blood flow and the delivery of metabolic fuel (ie, oxygen and glucose). This is accomplished through the measurement and treatment of elevated intracranial pressure (ICP), the strict avoidance of hypotension and hypoxemia, and in some instances, surgical management. The treatment of elevated ICP is approached in a protocolized, tiered manner, with escalation of care occurring in the setting of refractory intracranial hypertension, culminating in either decompressive surgery or barbiturate coma. With such an approach, the rates of mortality secondary to traumatic brain injury are declining despite an increasing incidence of traumatic brain injury.

This review contains 3 figures, 5 tables and 69 reference

Key Words: blast traumatic brain injury, brain oxygenation, cerebral perfusion pressure, decompressive craniectomy, hyperosmolar therapy, intracranial pressure, neurocritical care, penetrating traumatic brain injury, severe traumatic brain injury

Major neurocognitive disorder is the most common neurodegenerative condition in the world and the leading cause of dependence and disability among older adults worldwide. There are numerous etiologies for major neurocognitive disorder, of which Alzheimer disease (AD) is the most common. Available evidence indicates that the risk factors for major neurocognitive disorder include older age, female sex, lower educational attainment, obesity, and vascular risk factors, including smoking, hypertension, diabetes mellitus, and hyperlipidemia. Certain etiologies for major neurocognitive disorder are heritable, especially those due to AD and frontotemporal lobar degeneration. The pathophysiologic changes associated with the various etiologies of major neurocognitive disorder include neuronal loss, senile plaques, neurofibrillary tangles, vascular pathology, and α-synuclein neuronal inclusions. Major neurocognitive disorder remains a clinical diagnosis with a thorough history, appropriate laboratory tests, and standardized rating scales assisting in determining the etiology and severity of the condition. In older adults, major neurocognitive disorder must be differentiated from depression and delirium as these three conditions may have similar clinical presentations or may coexist. Current data indicate that approximately a third of the cases of major neurocognitive disorder, especially those due to AD, may be prevented by controlling potentially modifiable risk factors, including diabetes, depression, smoking, physical inactivity, midlife hypertension, midlife obesity, and low educational attainment. Currently, the only Food and Drug Administration–approved medications are acetylcholinesterase inhibitors and memantine for use in major neurocognitive disorder due to AD and rivastigmine (an acetylcholinesterase inhibitor) for major neurocognitive disorder due to Parkinson disease.

This review contains 5 figures, 13 tables, and 63 references. 

Key words: acetylcholinesterase inhibitors, Alzheimer disease, amyloid precursor protein, frontotemporal lobar degeneration, Lewy body disease, major neurocognitive disorder, memantine, Parkinson disease, tau proteins, vascular disease

About 13,000 deaths each year in the United States are attributed to primary central nervous system (CNS) malignancies. An estimated 20% of patients with cancer eventually develop clinically apparent CNS metastases, and an estimated 170,000 cases of brain metastases are diagnosed in the United States yearly. Autopsy studies suggest that as many as 50% of patients dying from advanced cancer may have metastasis to the CNS. This chapter provides an overview of primary and metastatic CNS malignancies with in-depth discussion of gliomas, primary CNS lymphoma, meningioma, brain metastases, leptomeningeal metastases, and metastatic epidural spinal cord compression. Discussions cover epidemiology, etiology, diagnosis, and treatment of gliomas, including surgery, radiotherapy, and chemotherapy for both newly diagnosed gliomas and recurrent gliomas. The epidemiology, diagnosis, treatment and prognosis for primary CNS lymphomas are reviewed, as well as the epidemiology, etiology, diagnosis, treatment, and prognosis for meningiomas. Epidemiology, diagnosis, and prognosis for brain metastases are briefly discussed, and the section on treatment includes surgery, stereotactic radiosurgery, and whole-brain radiotherapy for patients with three or fewer brain metastases. The sections on leptomeningeal metastases and metastatic epidural spinal cord compression cover diagnosis, treatment, and prognosis. This chapter contains 126 references.

The word fatigue implies a sense of exhaustion, lassitude, or inability to generate drive or energy. In taking a medical history of a patient with fatigue, the examiner should pursue questions of timing and circumstance. A medical or psychiatric diagnosis can be established in two thirds of patients who complain of fatigue, and in many cases, they are remediable. This chapter reviews the history of fatigue, including outbreaks. The clinical picture, diagnostic criteria, special considerations in diagnosis, general medical disorders, prescription drugs, postural orthostatic tachycardia syndrome, neutrally mediated hypotension, Chiari malformation, neurologic causes of fatigue, psychiatric investigation, laboratory investigations, magnetic resonance imaging (MRI) studies, pathophysiology, prognosis, and treatment are detailed. Asthenia is discussed in relation to clinical data, the central nervous system, muscle, and electromyography (EMG). Tables include terms and phrases used for indicating fatigue; definitions, features, and medical causes of chronic fatigue syndrome (CFS); blood tests to evaluate chronic fatigue; symptoms of CFS determined from laboratory studies; MRI studies for detecting CFS; outcomes of MRI studies of CFS; summary of CFS facts; summary of drugs used for fighting fatigue in multiple sclerosis patients; clinical testing for signs of asthenia; considerations when measuring creatine kinase; EMG testing in search of abnormalities; and decisive EMG findings. Figures show maps of sensory loss, an MRI of a relapsing-remitting multiple sclerosis patient, white matter hyperintensities, a diagram of EMG testing, and repetitive stimulation testing for neuromuscular transmission disorder.

This chapter contains 5 highly rendered figures, 14 tables, 74 references, and 5 MCQs.

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN,and C9ORF72).

Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

The aim of this review is to provide an overview of Huntington disease (HD) and other genetic choreas with an emphasis on clinical presentation, diagnosis, treatment, and expected outcome. Chorea is a syndrome characterized by brief, abrupt, involuntary movements resulting from a continuous flow of random muscle contractions. The first step in approaching a subject with chorea is to define the underlying etiology because the natural history and management vary accordingly. Age at onset, body distribution, other neurologic features, and family history are important in establishing the cause of chorea. HD is the most common etiology of genetic choreas worldwide. It is a progressive neurodegenerative disorder transmitted as an autosomal dominant trait characterized by a combination of movement disorders, cognitive decline, and behavioral abnormalities that causes progressive disability and death. When an HD phenotype test is negative for this condition, other causes, such as neuroacanthocytosis; spinocerebellar ataxia 17; Huntington disease–like syndrome 2, 3, or 4; benign hereditary chorea; and dentatorubral-pallidoluysian atrophy, as well as others, should be investigated. 

This review contains 2 figures, 5 tables, and 112 references.

Key words: Huntington, movement disorders, genetic choreas, neurodegenerative disorder

This comprehensive review addresses the many challenges in treating refractory migraine. Issues relating to pathophysiology are covered. A unique “refractory scale for migraine patients” is introduced. The definition and role of medication overuse headache are presented with a much different perspective than is usually found. Issues outside of medication that are covered include active coping, acceptance, resilience, and catastrophizing. A number of outpatient treatments are thoroughly discussed. These include the role of onabotulinum toxin, the application of polypharmacy, when to employ sphenopalatine ganglion  blocks, the role of occipital and trigger-point injections, the implementation of long-acting opioids, the advantages of stimulants, and the possible use of monoamine oxidase inhibitors. Miscellaneous approaches include muscle relaxants, nasal or intravenous ketamine, transcranial magnetic stimulation, memantine, and ergonovine. Finally, many cutting-edge “refractory clinical pearls” are listed. 

This review contains 8 highly rendered figures, 4 tables, and 25 references.

Key Words: Headache, migraine, chronic, refractory, medication overuse, alternative, treatments

Psychiatric disorders often co-occur with migraine, and these comorbid conditions compound disability and are risk factors for medication overuse and migraine progression. For these reasons, attention to psychiatric comorbidities in clinical practice is of paramount importance. Assessment of depression, anxiety, and sleep disorders is recommended, focusing on the core cognitive and emotional symptoms of the comorbidities and using measures validated among medical patients. Pharmacologic treatment of migraine and comorbid psychiatric conditions is challenging owing to a lack of agents with proven efficacy for both conditions, side effect profiles that may exacerbate one condition, and potential drug interactions. Existing data suggest that migraineurs with psychiatric symptomatology can obtain positive outcomes with appropriate preventive medications, behavioral interventions for headache or the comorbid condition, or a combination thereof.

Keywords: anxiety, comorbidity, depression, insomnia, migraine, pharmacotherapy, relaxation, stress management

Behavior change is an essential component of any migraine management plan. Behavioral migraine treatments are interventions designed to change a patient’s behavior with the result of a reduction in migraine symptoms and migraine-related disability. Behavioral treatments commonly target medication adherence, behavioral and psychosocial factors known to precipitate migraine (including stress, sleep, and skipping meals), maladaptive cognitive patterns, and comorbid psychiatric symptoms (most commonly depression and anxiety). Guidelines and evidence from randomized clinical trials indicate that biofeedback, relaxation treatments, and cognitive-behavioral therapy are effective preventive migraine treatments. Patient education and self-monitoring are foundational components to any behavioral intervention for migraine. Portable personal technology is increasingly becoming an essential part of migraine patient care and provides another avenue for supporting adherence to medication and behavioral migraine management.  

This review contains 6 figures, 10 tables, and 52 references.

Key words: Anxiety; behavior; biofeedback; cognitive-behavioral therapy; depression; migraine; psychology; relaxation; sleep; stress; breathing exercises

Peripheral nerve and sphenopalatine ganglion blocks are a safe, effective treatment option for headache disorders, although, despite a wealth of anecdotal experience, the evidence is conflicting for efficacy in chronic migraine prophylaxis. Neurostimulation has emerged as an effective treatment modality for migraine with both noninvasive and minimally invasive options available. Such options include transcutaneous supraorbital nerve stimulation for prophylaxis and single-pulse transcranial magnetic stimulation for the acute treatment of migraine with aura. Although occipital nerve stimulation may be effective for some patients with intractable chronic migraine, the evidence is mixed and procedure-related complications are common. Emerging treatment modalities for acute and preventive treatment of migraine include noninvasive vagus nerve stimulation and implanted sphenopalatine ganglion stimulation.

This review contains 5 figures, 7 tables, and 108 references

Keywords: headache, migraine, neurostimulation, nerve block, pain

Higher cognitive functions, such as abstract reasoning, complex decision making, and language, are the mental faculties that separate our species from other animals. When these faculties become impaired as a result of neurologic disease, striking and devastating behavioral changes result. Many neurologic diseases are associated with impaired cognition and behavior, and their etiologies are as varied as their clinical presentations. In this review, the focus is on dementia with Lewy bodies (DLB), the frontotemporal dementias (FTDs), and vascular cognitive impairment (VCI). The review covers the epidemiology and diagnosis of  DBB, FTDs, and VCIs, as well as the etiology and genetics. Figures show neuroimaging in DLB, management of DLB, FTLD clinical syndromes, FTLD clinicopathologic correlations: approximate distribution of pathotypes for behavioral-variant FTD and primary progressive aphasia (PPA) variants, PPA-semantic subtype, PPA-logopenic subtype, post-stroke VCI, and subcortical ischemic vascular disease subtype of VCI. Tables list diagnostic criteria for DLB, FTD genetics: gene/protein relationship, clinical syndrome, salient geatures, VCI: clinical and pathologic features of the main subtypes, summary guidance based on VCI prevention studies, and summary guidance based on VCI treatment studies.

This review contains 8 highly rendered figures, 5 tables, and 254 references.

Migraine is a common and often disabling neurologic disorder. No longer thought of as neurovascular in etiology, migraine is now known to be a complex disorder of the brain with strong genetic underpinnings. The impact of migraine may extend beyond the affected individual to also impact partners and children. Although many patients search to identify “triggers” of migraine, teasing out such relationships can be remarkably complex. The premonitory phase of a migraine attacks can include symptoms such as food cravings, photophobia, and increased yawning—symptoms that could, for example, lead a person to mistakenly conclude that the migraine attacks are “triggered” by eating chocolate, bright lights, or being tired. We review current evidence on the epidemiology, impact, and pathophysiology of migraine. 

This review contains 9 tables, and 94 references.

Key words: Epidemiology, impact, migraine, pathophysiology, socioeconomic status, gender

As of 2016, treatment of Alzheimer disease (AD) dementia and the principal non-AD dementias is entirely palliative. Although there are several drugs approved for the treatment of mild to moderate AD dementia, these drugs—the cholinesterase inhibitors and memantine—have rather modest benefits. In general, nonpharmacologic approaches to the management of patients with dementia emphasize support for the caregiver, attention to safety, and providing a supportive and socially enriched environment for the patient. Depression is common in dementias of diverse etiology; lower doses of later-generation antidepressants are effective in controlling depressive symptoms in patients with dementia. Agitation is not a ubiquitous occurrence in patients with dementia, but physically aggressive behavior, hallucinations, and delusions affect a sizable fraction of patients with dementia. There is much controversy regarding the appropriate medication classes to use in cases of agitation, but the antipsychotic agent quetiapine is often effective and unique among its class in not causing parkinsonism or tardive dyskinesia.

Key words: antidepressants, antipsychotic agents, caregiver support, cholinesterase inhibitors

The motor neuron diseases (MNDs) are a family of diseases commonly categorized by their propensity to affect upper or lower motor neurons and by their mode of inheritance. The chapter provides some content on infectious MNDs caused by viral infections affecting the motor neurons in the anterior horn of the spinal cord. However, the chapter devotes most of its attention to the inherited and sporadically occurring MNDs. The majority of research into adult MND focuses on amyotrophic lateral sclerosis (ALS) due to its high prevalence, rapid progression, and phenotypical similarities between its inherited form and its sporadic form. As our knowledge of genetic mechanisms underlying ALS pathology has grown, common themes have emerged. These include abnormalities in RNA biology, axonal transport, protein folding, and inflammatory responses. These themes currently drive much of the direction in ALS experimental therapy development. It is clear that MND is complex and involves several different molecular pathways. Given this complexity, ALS might not be a single disease entity, and if this is the case, treatment approaches may need to be targeted to specific pathologies rather than all ALS patients on a broad scale. Chapter content is enhanced by tables outlining the types of MNDs, criteria for supporting a diagnosis, first-line workup, the genes associated with ALS, ALS efficacy outcome measures, symptom management of ALS, and spinal muscular atrophy classification. Mechanisms of ALS are illustrated, and clinical photographs demonstrate symptoms.

This review contains 5 figures, 14 tables and 253 references

Keywords: motor neuron disease, amyotrophic lateral sclerosis, electromyography, Guillain-Barré syndrome

Multiple sclerosis (MS) is a relatively common cause of neurologic symptoms and disability in young adults. The distinguishing pathologic features of MS are loss of myelin and inflammation in the central nervous system (CNS). The myelin sheath is essential for rapid conduction of nerve signals along large-diameter axons. Oligodendrocytes produce and maintain myelin in the CNS, and Schwann cells produce and maintain myelin in the peripheral nerves. In addition to MS, there are a number of related disorders causing demyelination, inflammation, or both in the CNS. This chapter discusses MS and related disorders, including neuromyelitis optica, optic neuritis, acute disseminated encephalomyelitis, transverse myelitis, Behçet syndrome, neurosarcoidosis, inherited demyelinating diseases (leukodystrophies, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]), and virus-induced demyelination (progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis). The section on MS covers epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, and prognosis. Figures include organization of the microenvironment of larger-diameter axons, typical magnetic resonance imaging findings in MS and neuromyelitis optica, postgadolinium images of the cervical spine in MS, and an approach to treatment of relapsing-remitting MS. Tables list MS and related disorders, distribution of neurologic deficits at the onset of MS, differential diagnosis of MS, disease-modifying therapies for relapsing-remitting MS, and selected leukodystrophies, as well as diagnostic criteria and selected symptomatic therapies for MS.

This chapter contains 3 highly rendered figures, 7 tables, 82 references, 1 teaching slide set, and 5 MCQs.

The trajectories of serious illness and dying have changed in the last century; in the past, patients lived shorter lives and often died quickly of infectious disease, whereas patients in the 21st century live longer and often with prolonged debility in the advanced stages of illness. As a result, patients with serious illness can suffer undertreated symptoms and often feel poorly prepared for the final stages of disease. With more options for advanced life support and other aggressive interventions at the end of life, patients and families face increasingly complex medical decisions in the terminal phase of illness, and the treatments they receive do not always align with their goals and values. Emerging evidence suggests that integrating palliative care into the treatment of advanced illness can improve outcomes, decrease costs, and improve both patient and family satisfaction. Consequently, patient access to high-quality specialty-level palliative care is becoming standard of care at most academic cancer centers and more available in the community. This chapter describes the practice and principles of specialty-level palliative care and outlines specific "generalist" palliative care competencies essential for all physicians caring for patients with serious illness, including prognostication, patient-centered communication, and the navigation of ethical dilemmas in the field of palliative care. Tables outline the philosophy of palliative care, domains of suffering, location of death of hospice patients, the palliative performance scale, median survival times for cancer syndromes, indicators associated with a poorer prognosis in congestive heart failure, the NURSE mnemonic for accepting and responding to emotion, palliative care communication competencies in the intensive care unit, and the SPIKES mnemonic for breaking bad news. Figures depict causes of death in 1900 versus 2010, palliative care through the trajectory of serious illness, theoretical trajectories of disease, life expectancies for women and men, mortality at 1 year post discharge, and a model for patient-centered communication. 

This chapter contains 6 highly rendered figures, 9 tables, 169 references, 1 teaching slide set, and 5 MCQs.

Pediatric movement disorders encompass a heterogeneous array of neurologic symptoms and syndromes and may be acquired or inherited. Movement phenomenology and age at symptom onset provide important clues in identifying the underlying etiology and establishing a diagnosis. Movement disorders are classified as hyperkinetic (increased movement) or hypokinetic (reduced amplitude and/or rate of movement). In children, hyperkinetic movement disorders are substantially more common than hypokinetic disorders; in adults, a mix of hyper- and hypokinetic disorders is the norm. We present a framework for evaluating a child with abnormal movements and describe a broad range of pediatric movement disorders: chorea, neurotransmitter-associated syndromes, tic disorders, stereotypies, primary dystonias, and dystonic cerebral palsy. Recently described genes associated with pediatric movement disorders, such as ADCY5-related dyskinesia, NKX2.1-associated chorea and dystonia, and the primary dystonias (DYT2 and DYT26), are highlighted. The developmental regulation of neurotransmitter metabolism, a dynamic process that leads to dramatic shifts in neurotransmitter availability in childhood and adolescence, is also reviewed. The myelination and maturation of long-range neuronal networks are described, and the timing of these changes is related to the timing of childhood movement disorders. Incorporating age and timing into a framework for assessing abnormal movements in children has the potential to improve both clinical and research approaches to these disorders. Understanding the genetic and pathophysiologic bases of abnormal movements may aid clinicians in rapidly recognizing and distinguishing these disorders. Recognizing the clinical specificity and age dependency of abnormal movements in children may guide researchers in identifying the molecular underpinnings of these disorders. 

Key words: Movement disorders, gene expression, childhood development, childhood hyperkinetic disorders

Muscle disease (myopathy) can be acquired or hereditary. Symptoms include skeletal muscle weakness, atrophy, muscle cramps or myalgias, and impaired function of respiratory, pharyngeal, facial, or ocular muscles. Clinicians must identify treatable myopathies and initiate therapy before permanent weakness occurs. For patients with untreatable disorders, proper supportive care, rehabilitation, genetic counseling, and psychological support are critical. This chapter covers common myopathies, including muscular dystrophies; malignant hyperthermia; metabolic myopathies; mitochondrial myopathies and encephalopathies; ion channelopathies, periodic paralyses, and nondystrophic myotonias; and drug-induced myopathies. Clinical presentation, diagnosis, pathogenesis, and therapy are emphasized. Tables describe genetic classification of the limb-girdle and distal muscular dystrophies; proteins involved in myofibrillar myopathy; other distal myopathies; and antirheumatic, antiinflammatory, and immunosuppressive drug-induced myopathy. Figures show the sarcolemmal membrane and enzymatic proteins associated with muscular dystrophies, sarcomeric and nuclear proteins associated with muscular dystrophies, and major metabolic pathways used by muscle.

This chapter contains 3 highly rendered figures, 4 tables, 107 references, and 5 MCQs.

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. PD predominantly affects elderly people, and most countries are now facing a marked demographic change, with a progressively larger proportion of the population reaching old age. Thus, PD is expected to cause an increasing social and economic burden on society in the near future. The causes of PD are still mostly unknown. There has been a substantial progress in our understanding of the genetic basis of PD in the past 15 years; however, these mutations explain only a small fraction of all PD cases and other non-genetic factors may play a role. This review covers the epidemiology, pathology, and clinical diagnosis of PD. Figures show age-specific incidence of PD, age-specific prevalence of PD, PD risks for exposures reported in high-quality studies, PD and atypical parkinsonism clinical features, and neuroimaging alterations in PD and atypical parkinsonism. Tables list factors associated with increased or decreased risk of PD, Braak staging scheme of α-synuclein pathology in PD, United Kingdom Parkinson’s Disease Society Brain Bank clinical diagnostic for PD, National Institute of Neurological Disorders and Stroke diagnostic criteria for PD, differential diagnosis of parkinsonian syndromes, and “atypical” atypical parkinsonism.

This review contains 5 figures, 12 tables, and 109 references

Keywords: Parkinson disease, parkinsonism, geriatrics, neuroimaging, α-synuclein, neurology

Traumatic brain and spinal cord injuries are significant causes of permanent disability and death. In 2010, 823,000 traumatic brain injuries were reported in the United States alone; in fact, the actual number is likely considerably higher because mild traumatic brain injuries and concussions are underreported. The number of new traumatic spinal cord injuries has been estimated at 12,000 annually. Survival from these injuries has increased due to improvements in medical care. This review covers mild traumatic brain injury and concussion, moderate to severe traumatic brain injury, and traumatic spinal cord injury. Figures include computed tomography scans showing a frontal contusion, diffuse cerebral edema and intracranial air from a gunshot wound, a subdural hematoma, an epidural hematoma, a skull fracture with epidural hematoma, and a spinal fracture from a gunshot wound. Tables list requirements for players with concussion, key guidelines for prehospital management of moderate to severe traumatic brain injury, key guidelines for management of moderate to severe traumatic brain injury, brain herniation brain code, key clinical practice guidelines for managing cervical spine and spinal cord injury, and the American Spinal Injury Association’s neurologic classification of spinal cord injury.

This review contains 6 highly rendered figures, 12 tables, and 55 references.

Brain and spinal abscesses are focal infections of the central nervous system that are often associated with significant morbidity and mortality if not recognized early and managed in a timely manner. In patients with brain abscess, the clinical manifestations run the gamut from indolent to fulminant; most are related to the size and location of the space-occupying lesion within the brain and the virulence of the infecting organism. Untreated spinal epidural abscess usually progresses through four stages: backache and focal vertebral pain, nerve root pain, spinal cord dysfunction, and complete paralysis. Magnetic resonance imaging is the diagnostic neuroimaging procedure of choice in patients with brain and spinal abscesses; on diffusion-weighted images, restricted diffusion may be seen and may help distinguish abscesses from necrotic neoplasms. Aspiration of the abscess is important to facilitate microbiologic diagnosis; after aspiration and submission of specimens for special stains, histopathologic examination, and culture, empirical antimicrobial therapy should be initiated based on stains of the aspirated specimen and the probable pathogenesis of infection. Once the infecting pathogen is isolated, antimicrobial therapy can be modified for optimal treatment. Surgical therapy is often required for the optimal approach to patients with brain and spinal abscesses.

This review contains 6 figures, 5 tables, and 72 references.

Key words: antimicrobial therapy for central nervous system infections, brain abscess, epidural abscess, focal intracranial infections, head trauma, infections in immunocompromised hosts, spine infections, subdural empyema, toxoplasmosis 

Chorea is a common hyperkinetic movement disorder that can have a large differential diagnosis. Causes can include genetic and sporadic etiologies, including metabolic abnormalities, autoimmune, structural, paraneoplastic, psychogenic, and iatrogenic causes. The workup can be challenging due to this large number of possible causes, and can include basic metabolic and specialized blood analysis such as genetic testing, in addition to imaging studies and cerebrospinal fluid analysis. Treatment of symptoms outside the realm of reversible causes can be challenging, and is a major focus of current research. This review covers sporadic causes, genetic causes, and management. Figures show a flowchart for evaluation of patients with chorea, a computed tomography scan of a Huntington disease patient showing caudate head atrophy, brain computed tomography scan showing calcification, and acanthocytosis. Videos show mild and moderate Huntington disease, Huntington disease-like 2,  and chorea-acanthocytosis. Tables list metabolic abnormalities that can manifest as chorea, paraneoplastic and nonparaneoplastic syndromes associated with chorea, and reported successful therapies for chorea.

Tension-type headache (TTH) is an incredibly common condition. The clinician should be careful to distinguish TTH from migraine and from causes of secondary headache. The importance of regular sleep, nutrition, hydration, and appropriate management of life stressors cannot be overemphasized. The mainstays of abortive pharmacologic therapy for TTH are the nonsteroidal antiinflammatory drugs. Most of these drugs are thought to have roughly equivalent efficacies based on many older clinical trials and more recent meta-analyses. The side effects of this drug class can be severe and include renal toxicity and gastrointestinal bleeding; these drugs may also increase cardiovascular risk. Tricyclic antidepressants are thought to be the most effective preventive therapy for TTH, particularly amitriptyline. Other antidepressant medications as well as muscle relaxants may also be beneficial in some patients. A number of other nonpharmacologic and procedural therapies exist, although the evidence supporting the use of these treatments is variable. However, in many patients, these other modalities can be helpful therapeutic adjuncts. In this review, we also discuss the evidence base for physical therapy, acupuncture, trigger-point injections, massage therapy, and psychological therapy. 

Tremor is the most common movement disorder and denotes a rhythmic and involuntary movement of one or several regions of the body. This review covers disease definition, essential tremor, enhanced physiologic tremor, parkinsonian tremor, dystonic tremor, orthostatic tremor, cerebellar tremor, Holmes tremor, neuropathic tremor, palatal tremor, drug-induced and toxic tremors, functional tremor, rare tremor syndromes, tremorlike conditions, and treatment of tremor. Figures show action tremor assessment, the central nervous system circuits of tremor, magnetic resonance imaging findings in specific tremor conditions, general management of tremor patients, an algorithm for the treatment of parkinsonian tremor, and an algorithm for the treatment of dystonic tremor and primary writing tremor. Tables list types of tremor according to the condition of activation, tremor conditions in newborns and during childhood, clinical features of the most common tremor syndromes, motor signs other than tremor and nonmotor features of essential tremor patients, Movement Disorder Society consensus criteria for the diagnosis of essential tremor, genetic and environmental causes of essential tremor, causes of enhanced physiologic tremor, drugs and toxins known to cause tremor, paroxysmal tremors, pseudorhythmic myoclonus in the differential diagnosis of tremor, and pharmacologic management of essential tremor.

This review contains 6 figures, 7 videos, 15 tables, and 167 references.

Key words: essential tremor, movement disorder, pathologic tremor, physiologic tremor, tremor

A seizure is a sudden change in behavior that is accompanied by electrical discharges in the brain. Many patients presenting with a first-ever seizure are surprised to find that it is a very common event in both children and adults. Epilepsy, a chronic disorder of the brain characterized by recurrent unprovoked seizures, is far less common. Patients who present to the emergency department with seizures vary considerably in underlying etiology, symptoms, and prognosis. Optimal care of the seizure patient in the emergency department requires differentiating those who need little intervention from those requiring intensive resuscitation. This review presents the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of seizure. Figures show the progression of selected neuronal pathophysiologic mechanisms involved over time during and after status epilepticus, tongue bite from seizure, a general emergency department management strategy for patients with seizure presentations, an electroencephalogram of a patient who experienced convulsive syncope after placement of an intravenous line, and staged treatment of status epilepticus. 

This review contains 5 figures, 8 tables, and 55 references. 

Key words: Acute seizure, convulsion, epilepsy, seizure, status epilepticus, antiepileptic drug, neuroimaging

Delirium, an acute confusional state characterized by disturbances in attention, cognition, and arousal, is present in 7 to 10% of older emergency department (ED) patients, underdiagnosed in the ED setting, and associated with increased short-term mortality. Delirium is typically precipitated by a physiologic stressor, such as an acute medical illness, a new medication, or a change in environment. The keys to the care and management of delirious patients are timely diagnosis of delirium and identification and treatment of the precipitating cause. The medical evaluation should include a formal delirium assessment that includes tests of attention and targeted diagnostic tests to identify the underlying etiology, such as infection, metabolic derangement, neurologic emergencies, new medications, and/or toxidromes. Pharmacologic treatment of delirium should be limited to patients who are severely agitated and at risk for substantial harm to self and/or others and patients with delirium secondary to alcohol withdrawal. Typical and atypical psychotics at low doses are first line for use in severely agitated patients. Benzodiazepines may worsen delirium and should be reserved for treatment of patients with delirium secondary to alcohol withdrawal or if sedation is required for critical imaging and/or procedures. ED physicians should also be conscious of and strive to minimize iatrogenic precipitants of delirium.

This review contains 2 figures, 10 tables and 53 references

Key words: aged, agitation, arousal attention, confusion, delirium, delirium/diagnosis, delirium/etiology, delirium/therapy, dementia complications, geriatrics, risk factors

Traumatic spinal cord injury currently affects approximately 285,000 persons in the United States and carries with it significant morbidity and cost. Early management focuses on adequate ventilation and hemodynamic resuscitation of the patient and limiting motion of the spine to prevent a second injury. Medical management targets maintenance of adequate blood flow to the spinal cord, whereas surgical management focuses on decompression, realignment, and stabilization of the vertebral column. In this chapter, we discuss the approach to the patient with traumatic spinal cord injury, injury types, and medical and surgical management.

This review contains 9 figures, 4 tables and 30 references

Key Words: American Spinal Injury Association score, burst fracture, Chance fracture, compression fracture, hangman, mean arterial pressure therapy, odontoid fracture, spinal cord injury, traction