Rudolph's Pediatrics, 22nd Ed.

CHAPTER 547. Clinical Approach to Neurologic Disease

Maitreyi Mazumdar

HOW TO USE THIS SECTION

This introductory section on pediatric neurology provides a clinically oriented guide to the evaluation of a child with suspected neurologic dysfunction. First we review a basic clinical approach and then we tackle specific neurologic presentations. We attempt to provide a broad framework that will help clinicians begin a thoughtful, focused workup of a child suspected of having a neurologic problem. After review of a basic approach, our discussions are organized around common neurologic presentations and physical findings. This section is not intended to be a comprehensive review of all neurologic disorders; instead, it should be used a starting point. The later sections of this chapter provide further detail about the pathophysiology, diagnoses, and management of these disorders. For reviews of the neurologic examination of infants and children, we refer the reader to Chapter 44 and the monographs and chapters by Dodge and Volpe referenced at the end of this chapter.1,2

THE CLINICAL APPROACH TO A CHILD WITH SUSPECTED NEUROLOGIC DYSFUNCTION

Diseases of the nervous system have a profound impact on the lives of infants, children, and their families. These disorders include epilepsy, cerebral palsy, mental retardation, learning disabilities, complex metabolic diseases, nerve and muscle diseases, and a host of other highly challenging conditions. The clinician approaching an infant or child suspected of having a neurologic disorder faces an imperative to provide an accurate diagnosis. The diagnosis will direct therapy and help the patient and family prepare for possible disability, as well as inform decision making regarding future children.

Medical students, residents, and experienced clinicians often find pediatric neurology inaccessible. Many are intimidated by the intricacy of neuroanatomy, the complexity of biochemical pathways, and the subtlety of a neurologic examination. This situation is compounded by the use of advanced diagnostic technologies such as electroencephalogram (EEG) and sophisticated brain imaging techniques that receive little emphasis in medical school training.

We believe clinicians can overcome many of the difficulties they experience in this area by adhering to the basic principles of clinical medicine and neurology.3 We will review these principles and the important contributions each makes to the diagnostic process.

1. Recognition of impaired neurologic function through careful history and physical examination

2. Identification of the specific part of the nervous system that has been affected (the section “Localization”)

3. Definition of the most likely etiologies, using mode and speed of onset, evolution of illness, and involvement of other organ systems, as well as relevant past and family histories (the section “Differential Diagnosis”)

4. Use of laboratory tests and other diagnostic technologies to determine which of the different possible etiologies is present

5. Assessment of the degree of disability

6. Initiation of therapy, if available, after weighing potential risks and benefits

HISTORY

Eliciting a careful history remains the cornerstone of the evaluation of children suspected of having neurologic disease. The purpose of the history is to define the nature and temporal profile of the neurologic complaint. The history should be obtained from the patient and parents; observations of teachers or others may also be important. The examiner should take the time to ask all questions needed to understand the details of the problem, including time of onset, exacerbating and alleviating factors, antecedent illnesses, and prenatal and perinatal conditions. If the complaints are paroxysmal and stereotyped, it is frequently useful to ask the child to describe the most recent episode in detail. The symptoms must be defined clearly, as terms have different meanings to different people. The word dizzy, for example, could mean light-headedness or vertigo. Light-headedness would be more suggestive of syncope, whereas vertigo might be caused by vertebrobasilar insufficiency.

Children presenting with headaches, abdominal pain, or reluctance to attend school may well have associated neurologic disturbances. Contributing factors may include previously unrecognized mental retardation, specific learning disabilities, and depression. Less frequently, such complaints may be the harbingers of more serious neurologic illness, such as hydrocephalus or encephalitis.

When evaluating a newborn, the history includes detailed questions about the pregnancy, including in vitro fertilization, maternal drug use, illness during pregnancy, and the presence and quality of fetal movements. The method of delivery and delivery complications should be ascertained as well as birth weight and head circumference. In the evaluation of children, the history includes a careful assessment of development because failure to reach developmental milestones or subtle developmental regression may be early signs of neurologic disease. For example, a young child with gradual loss of the ability to use and understand spoken language may be found to have Landau-Kleffner syndrome, a rare neurologic disorder associated with frequent seizures. Similarly, a young boy with X-linked adrenoleukodystrophy, a uniformly fatal disease characterized by progressive spasticity, obtundation, and adrenal insufficiency, will often present first with subtle behavioral change and developmental regression.

Recognition of similar complaints in other family members is relevant because many neurologic disorders are genetically determined. At minimum, a family history should include an explicit statement of the age and health status of all siblings, parents, parents’ siblings, and grandparents. Particular note should be made of any family members with mental retardation or deaths at an early age. Psychiatric histories of family members should not be neglected, as older family members classified as having schizophrenia or alcoholism may have had neurodegenerative disorders such as Huntington disease.

GENERAL MEDICAL EXAMINATION

The general medical examination is essential to a neurologic assessment and frequently provides clues to neurologic disease. The head circumference of all infants and young children should be recorded. Large or small head size often implies intracranial abnormalities. Inspection of the hair, nails, and skin may provide an immediate diagnosis (eg, a neurocutaneous syndrome such as neurofibromatosis-1). The Wood’s lamp is useful in bringing out hypopigmented skin lesions characteristic of tuberous sclerosis; this test should be performed on all infants presenting with infantile spasms. Examination of the lungs and the breathing pattern may uncover disturbances in respiration that reflect brainstem disease or neuromuscular abnormalities. Similarly, the presence of a mass in the abdomen or hepatosplenomegaly may indicate a diffuse process within the central nervous system, such as a storage disorder or cancer with metastasis. Asymmetries of the limbs may suggest atrophy or hemihypertrophy and provide clues to underlying disease.

NEUROLOGIC EXAMINATION

The neurologic examination itself should be as complete as possible and largely guided by historical data. The neurologic examination is traditionally compartmentalized: mental status, craniospinal examination, cranial nerve examination, motor and sensory examination, evaluation of coordination, and assessment of autonomic function. In infants and young children, the examination is best conducted without following a rigid format. Attempts at an “adult-type” examination may lead to crying and fussing and provide only limited information. Children should be watched in their spontaneous activity. Playing or otherwise interacting with the child is the best way to assess cognition, social adaptation, and language. By asking the child to jump, run, write, and use toys, the clinician can assess gross and fine motor function. With some imagination, sensitivity and patience, the experienced clinician can expect to complete the neurologic exam satisfactorily in all children.

Abnormal neurologic findings come in the form of abnormal behavior, developmental regression, impaired posture or gait, difficulty with movements of the face or extremities, and sensory disturbances, including pain.4Inexperience in examining a child often results in overlooking a neurologic deficit and therefore missing a diagnosis. For instance, mild chorea may appear as normal fidgetiness in a child with Sydenham chorea, a defining feature of acute rheumatic fever. A child with a peripheral neuropathy may come to medical attention because of ataxia; without a careful sensory examination including assessment of proprioception, the neuropathy may be missed. Repeated examinations may be necessary to establish the fundamental clinical findings and ascertain the course of the illness; there is a saying that in a difficult neurologic case, a second examination is the most helpful diagnostic test.3

LOCALIZATION

After neurologic dysfunction has been recognized through history and physical examination, the next step for the clinician is to identify what part of the nervous system is involved. This process, called localization, requires a basic understanding of neuroanatomy. The first distinction the general practitioner needs to make is whether the process (or “lesion”) involves the central nervous system (brain and spinal cord) or the peripheral nervous system (anterior horn cell, peripheral nerve, neuromuscular junction, and muscle). This distinction is very important as it directs further diagnostic workup. Localization constitutes the foundation of clinical neurology and can take years of diligent study to master. Despite its complexities, some basic principles of localization should be familiar to all physicians and are described below and summarized in Table 547-1. Much of the following is adapted from the classic textbook on localization by Brazis, Madseu, and Biller.5

Localization tends to be most precise when the lesion affects the peripheral nervous system. At the simplest level, injury to a muscle impairs the movement mediated by that muscle. Diseases that affect the neuromuscular junction cause diffuse, fluctuating weakness that often involves muscles of eye movement. Injury to a peripheral nerve causes weakness of the muscles innervated by that nerve and sensory loss in its cutaneous distribution. Lesions of the anterior horn cell present with weakness and later with fasciculations.

In the central nervous system, lesions in the spinal cord below the cervical level cause weakness of one or both legs and sensory loss often characterized by a horizontal level in the trunk. Lesions in the cervical cord or brainstem typically cause weakness or sensory loss on one or both sides of the body. Lesions of the lower pons give rise to gaze palsies and/or peripheral facial weakness. The localization of lesions in the cranial nerves is fairly straightforward, because these lesions cause deficits in the particular functions performed by cranial nerves, such as eye or facial movements.

As we ascend the neuroaxis, localization becomes less precise. Lesions in the cerebellum may cause ataxia. Lesions in the thalamus often cause sensory loss or memory loss. Lesions in the hemispheric white matter may give rise to weakness or visual field defects. Finally, lesions in the cortex manifest themselves by an array of motor, sensory, or behavioral findings that vary according to the area that has been injured. In young infants and children, lesions in the cortex may present as failure to reach developmental milestones or as developmental delay.

DIFFERENTIAL DIAGNOSIS

Because different disease processes affect the same parts of the nervous system, they may often present with similar signs and symptoms. For example, cerebellar ataxia may be the result of a genetic defect, a viral illness, or neo-plastic disease. Similarly, infantile spasms are found in infants with tuberous sclerosis and hypoxic-ischemic encephalopathy as well as variety of other disorders. To form a differential diagnosis, the clinician must be aware of the clinical detail of many disease entities, including their mode of onset, course, and natural history. Many of these details are well known; they will be reviewed later in this chapter and form the substance of following chapters.

Although pediatric neurology seems to many to be a collection of rare and unusual diseases with little relevance to a general pediatric practice, it is important to remember that even in here, unusual presentations of common diseases are more frequent than common presentations of rare diseases. For example, a previously healthy child with an abrupt onset of ataxia and abnormal eye movements is more likely to be suffering from drug ingestion or a viral infection than a rare neurodegenerative disease. In such a case, although the clinician should be aware of neurodegenerative disorders when forming a differential diagnosis, the search for a rare disease should not drive the diagnostic process.

Table 547-1. Distinguishing Features That Aid in Localization of Motor System Disorders

In children especially, every attempt should be made to look for a parsimonious diagnosis, or the simplest explanation of the patient’s signs and symptoms. For example, a child with ataxia, restricted eye movements (ophthalmoplegia), and areflexia is more likely to have the Miller-Fisher variant of Guillain-Barré syndrome than three separate, yet simultaneous, neurologic processes.

LABORATORY TESTING AND DIAGNOSTICS

Ancillary studies, such as laboratory testing, imaging, and neurophysiologic testing, may be planned intelligently only on the basis of clinical information. A “gun-shot” approach to testing, in which a broad array of tests is ordered at the outset, may expose the young child to unnecessary pain and risk and often derails the clinical process by uncovering incidental findings that require further investigation. The approach we suggest is to use ancillary testing initially to exclude items on the differential diagnosis that pose immediate harm to the patient. Once those items have been excluded, a thoughtful, directed workup may proceed at a slower pace, with emphasis placed on noninvasive procedures. We briefly describe some diagnostic tests commonly used in the evaluation of child with neurologic dysfunction.

Computed Tomography (CT)

Computed tomography (CT) scanning revolutionized the practice of neurology and neurosurgery by providing a noninvasive technique to show the intracranial and intraspinal structures. Conventional x-radiation is attenuated as it passes through the skull, cerebrospinal fluid, cerebral gray and white matter, and blood vessels. The intensity of the exiting radiation is measured and the data are integrated by computer. One can see hemorrhage, edematous brain, abscess, tumor tissue, calcifications, and the position of the ventricles and midline structures.

By its nature, CT involves larger radiation doses than the more common, conventional x-ray imaging procedures. Accumulating evidence from epidemiologic studies suggests that the organ doses corresponding to a common CT scan result in increased risk of cancer in children.6 For this reason, the use of CT scans should be considered carefully. The head CT is most appropriate in the evaluation of head trauma and the assessment of ventricular size in suspected cases of shunt malfunction and hydrocephalus. Even in the latter case, there are efforts to replace CT with limited magnetic resonance imaging (MRI) because of concerns about radiation exposure.

Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) produces detailed images using the body’s natural magnetic properties, specifically the hydrogen proton because of its abundance in water and fat. The basic elements of MRI scanning are discussed in detail in (see Chapter 552). Areas poorly seen on computed tomography (CT) scan (eg, posterior fossa and spinal cord) can be defined clearly by MR imaging. With the exception of detecting calcification/mineralization, MR imaging surpasses that possible by CT.

The clinical situation guides the radiologist’s choice of sequences, and thus clinical information should be communicated clearly when ordering an MRI. For example, a teenager with acute onset of arm and leg weakness after being tackled on the football field has a history that suggests acute stroke secondary to traumatic arterial dissection. The MRI should include specialized sequences such as diffusion-weighted-imaging (DWI), a sequence helpful in identifying acute ischemia. In addition, magnetic resonance angiography (MRA) provides visualization of the main intracranial arteries and can reliably detect vascular lesions and stenosis. A child with suspected infection or brain tumor might receive gadolinium contrast during the MRI, as this agent permits even sharper definition and highlights areas where the blood-brain barrier has been disrupted.

The degree of cooperation required to perform MR imaging limits its use in young children. Children often need to be sedated in order for the test to be properly performed. The main risks of MR imaging are dislodgement of metal clips and other ferromagnetic objects.

Cerebral Angiography

The use of conventional angiography has decreased remarkably due to the increased availability of CT and MRI. Its use is limited to diagnosis of aneurysms, vascular malformations, and arterial dissections. Following local anesthesia, a needle is placed in the femoral or brachial artery. A cannula is then threaded through the needle, along the aorta and the arterial branches to be visualized. In this way a contrast agent can be injected into the carotid and vertebral systems and to their extents in the neck and cranial cavity. Through the use of digital subtraction—a digital computer process to produce images—the vessels can be visualized with smaller catheters and smaller amounts of dye than was previously possible. Because of the risks of vascular spasm and of embolization of the artery from clot formation at the tip of the catheter, conventional angiography should not be undertaken unless it is absolutely necessary. The applications of cerebral angiography are discussed further in Chapter 552.

Electroencephalography (EEG)

Electroencephalography (EEG) continues to be an essential part of the study of children with seizures and those suspected of having seizures. EEG is also used in evaluation of the effects on the brain of many metabolic diseases, in the study of sleep, and in the operating room to monitor cerebral activity in anesthetized patients. EEG records spontaneous electrical activity generated in the brain. Metal electrodes are coated with conductive paste and placed on the scalp. Differences in voltage potential between electrodes are amplified and displayed on a screen. Digital systems permit reconstruction of the EEG with any desired derivation or format, and permit data manipulation for added analysis. Patients should be studied in the waking and sleeping states; activation procedures such as photic stimulation and hyperventilation are used to elicit epileptiform tendencies.7 The classification of epileptic seizures involves both clinical and electroencephalographic criteria, and is described further in Chapter 557.

Electromyography and Nerve Conduction Studies (EMG/NCV)

Electromyography (EMG) and nerve conduction studies (NCV) assess abnormalities in the peripheral nervous system. EMG is used to detect abnormal muscle electrical activity that can occur in many diseases, including muscular dystrophy and myositis. It is most helpful in distinguishing disorders of muscle from disorders of nerves. Nerve conduction studies involve stimulation of motor or sensory nerves and recording of the elicited responses. The test is used to identify nerve damage or destruction, such as that found in demyelinating diseases and hereditary neuropathies. EMG and nerve conduction studies are discussed in greater detail in Chapter 568.

EVALUATION OF DISABILITY

Once a diagnosis is established, the clinician’s next step is to determine the level of disability, if any, that is present. Two children may suffer from the same disease process, yet have very different levels of function. Chronic headache, for example, can lead one child to miss weeks of school and withdraw from social activities, whereas another child with the same disorder functions well with few limitations. The clinician must be sensitive to the individual child’s experience. The teenager who is missing weeks of school because of migraines is at high risk for developing comorbidities, such as a major depressive disorder. This patient requires more intensive intervention, including counseling and pain management specialists.

THERAPY

In the recent past, neurologic diseases in children were thought to be untreatable and the clinical method described above was considered to be little more than an intellectual exercise. Through advances in neuroscience, immunology, pharmacology, microbiology, and other fields, such is no longer the case. Specific therapies are now available for a growing number of diseases. The use of intravenous immunoglobulin (IVIG) for Guillain-Barre, for example, has completely changed the expected outcome for children with this disorder. Prior to the use of IVIG, many of these children died from respiratory failure; now these children regain full strength within weeks. Similarly, advances in surgery and chemotherapy have made childhood brain cancer a survivable disease for many children.

COMMON SIGNS AND SYMPTOMS OF NEUROLOGIC DISEASE

The goal of the following sections is to use the clinical method described above to frame the evaluation of common neurologic problems. In some of the examples, we focus mostly on history; in others, we focus on using the neurologic examination to guide localization; in others, we expand upon a differential diagnosis. We intend that these examples provide a starting point for the clinician. For a more comprehensive review, we reference the later chapters in this book that discuss these issues.

WEAKNESS

A systematic approach is necessary when evaluating a weak child, and the first question is whether the weakness is in fact due to a problem involving the nervous system. Many processes outside of the nervous system, such as febrile illness, chronic infections, electrolyte imbalances, and endocrinopathies are associated with weakness. These disorders most often lead to generalized symptoms and a lack of objective findings on neurologic examination.

The history should focus on the time course of the weakness, as this information provides clues to the etiology. Static weakness suggests a discrete injury, such as an infarction. Rapidly evolving weakness is most often caused by a Guillain-Barré syndrome, an acute demyelinating polyneuropathy. Episodic weakness suggests a paroxysmal cause, such as complicated migraine or epilepsy. Weakness that progresses in a slow and indolent fashion poses the greater difficulty in diagnosis, as it can suggest a neurodegenerative process or slowly growing tumor.

The primary purpose of the examination in these cases is to localize the anatomic site of the lesion causing weakness. Distinguishing features of the examination that aid in localization are described below and summarized in Table 547-1.2,8 Disorders related to central causes (ie, in brain or spinal cord) are characterized by weakness of the limbs, preserved or hyperactive deep tendon reflexes, and an absence of fasciculations. Other indications of cerebral disease include seizures and diffuse developmental delay. Central causes are as diverse as congenital malformation, hydrocephalus, transverse myelitis, disorders of neural tube development, and mass lesions such as tumors or empyemas. Brain or spinal imaging with magnetic resonance imaging (MRI) is likely to be helpful.

Diseases of the anterior horn cell are characterized by generalized weakness, absent reflexes, fasciculations, intact mental status, and normal sensation. Before the widespread use of vaccine, anterior horn cell disease in children was most often due to poliovirus infection. Acute paralytic poliomyelitis (Chapter 555) usually presents with asymmetric flaccid weakness and is usually preceded by nonspecific symptoms such as low-grade fever and diarrhea. Spinal muscular atrophy (Chapter 571) is an autosomal recessive disorder of the anterior horn cells. The most common form presents within the first years of life and is marked by progressive weakness with absent reflexes, tongue fasciculations, and eventually respiratory failure. Electromyography (EMG) and genetic tests confirm the diagnosis.

Diseases of the peripheral nerve cause generalized weakness and decreased reflexes sometimes accompanied by sensory disturbances. Guillain-Barre syndrome is an inflammatory disease that produces rapidly progressive symmetric ascending flaccid weakness with depressed reflexes and variable sensory findings (Chapter 570). Inherited neuropathies can also produce weakness, although the time course is usually much more gradual. Motor neuropathies such as Charcot-Marie-Tooth disease are reviewed in Chapter 570. Nerve conduction studies are commonly used to confirm the diagnosis of a motor neuropathy; an initial serum creatinine kinase may distinguish nerve-mediated weakness from muscle disease.

Diseases of the neuromuscular junction are characterized by weakness involving the face, eyelids, and extraocular muscles. Physical exam reveals normal deep tendon reflexes and sensory function. In infants, botulism is the prototypical disease of the neuromuscular junction. An infant affected by botulism will have a relatively acute onset of weakness preceded by difficulty feeding and constipation (Chapter 571). Myasthenia gravis, an autoimmune disorder most often caused by antibodies to the acetylcholine receptor in the motor end plate, causes fluctuating weakness that is more prominent with exercise and improves with rest (Chapter 571). EMG and antibody testing are used to confirm these diagnoses as well.

Muscle diseases are typified by weakness that is greater in the proximal limbs. A child with an acquired inflammatory myopathy, such as that seen in viral myositis, might initially have a low-grade fever and then report difficulty getting up from a chair. Duchenne muscular dystrophy is characterized by decreasing muscle mass and progressive loss of muscle function in male children. Early signs may include difficulties standing up and walking on stairs. The weakness progresses and the young boy eventually needs a wheelchair. Infants with congenital myopathies will present with generalized weakness, poor muscle bulk, and dysmorphic features that may be secondary to the weakness. Myopathies are often associated with other organ systems, such as the heart and skin. Initial evaluation usually includes serum creatinine kinase, an enzyme found primarily in muscle. Elevated levels of creatinine kinase suggest significant muscle injury such as that found in myopathy. Myopathies are reviewed in Chapter 572.

ATAXIA

Ataxia is defined as impaired coordination of movement and balance. The incoordination can be caused by processes as diverse as drug ingestion, varicella infection, brain tumors, and hereditary neurodegenerative disease. The pathology can be located at any level of the nervous system, from cerebral cortex to muscle. Ataxia is particularly frightening to children and parents, because it represents a loss of physical control and raises the possibility of some very debilitating diseases. As is usually true, a careful history and physical examination, followed by focused radiologic and laboratory assessments, can lead to proper diagnosis and timely intervention.

The time course of the symptoms usually provides the greatest information about ataxia.9-11 When taking the history, the clinician should determine whether the onset was acute (suggesting viral infection, drug ingestion, or the Miller-Fisher variant of Guillain-Barré syndrome), subacute over weeks (brain tumors, nutritional deficiencies, or paraneoplastic syndromes), or chronic over months to years (cerebellar degeneration or hereditary metabolic diseases). Other elements of the history should include whether the child has had a previous episode, whether there are medications in the house, and a full medical and family history, including that of migraines and epilepsy as these can also present with ataxia.

The general medical examination should include optic funduscopy to look for signs of increased intracranial pressure. The skin should be evaluated for viral exanthems and crusted lesions typical of varicella. Pharyngitis, cervical adenitis, and splenomegaly point toward other infectious etiologies such as mononucleosis. Cardiac assessment may reveal murmurs or arrhythmias that could lead to embolic stroke. Pes cavus and scoliosis may be apparent in a child with Friedreich ataxia, an autosomal recessive disorder. Oculocutaneous telangiectasias are often visible in a child with ataxia telangiectasia, also an autosomal recessive disorder characterized by progressive truncal ataxia and recurrent sinus infections.

The neurologic examination should attempt to provide information that aids localization, focusing on the cerebellum and its major input systems from the frontal lobe and posterior columns of the spinal cord. When an abnormality occurs in the vermis of the cerebellum, the child cannot sit still but constantly moves the body to and fro. In contrast, disturbances of the cerebellar hemispheres cause dysmetria and hypotonia. Bifrontal lobe disease may produce signs indistinguishable from those of cerebellar disease. Other features of cerebellar disease are a characteristic scanning speech and intention tremor. Loss of sensory input to the cerebellum because of peripheral nerve or posterior column disease causes a careful and hesitant gait that is worse when the eyes are closed. Children with weakness often stagger about, which can be mistaken for ataxia. Muscle strength must be specifically assessed.

The laboratory and radiologic workup for ataxia is outlined in Figure 547-1. The slow evolution of ataxia in a previously healthy child warrants rapid evaluation, as the most immediate concern is brain tumor; brain imaging should be performed without delay. The work-up for acute ataxia should include a complete blood count, measurement of electrolytes and glucose, toxicology screening of blood and urine, brain imaging, and lumbar puncture. If magnetic resonance imaging (MRI) or computed tomography (CT) demonstrates a mass lesion, hydrocephalus, or intracranial abnormality, cerebrospinal fluid (CSF) evaluation may be deferred. The presence of cells in the CSF may indicate infection, and elevated CSF protein levels are associated with Guillain-Barré syndrome and multiple sclerosis.

The workup for children with chronic or recurring ataxia is guided by the history and physical examination. Every child with chronic, progressive ataxia should undergo imaging, preferably MRI. Other structural abnormalities that could be found by MRI are cerebellar malformations, although these are most often found in children with other developmental abnormalities.

Special attention needs to be paid to a sensory examination in children with chronic ataxia. Children with sensory neuropathies such as those found in abetalipoproteinemia or vitamin E deficiency will present with difficulty walking and incoordination due to disrupted sensory input to the cerebellum. Children with Friedreich ataxia have degeneration of the posterior columns of the spinal cord in addition to degeneration of other parts of the brain and cerebellum.

Migraine, seizure, and some rare metabolic disorders may manifest with acute intermittent episodes of ataxia. Evaluation is again based on the history, but may include electroencephalogram (EEG) and electromyography (EMG). If metabolic disease is suspected, evaluation of amino acids, acid/base balance, lac-tate, pyruvate, ammonia, and ketones may be helpful. If the workup fails to disclose a diagnosis, referral for a detailed neurologic and genetic evaluation is warranted.

SEIZURES

Seizures are among the most common symptoms of disturbed brain function and a cardinal manifestation of neurologic disease. Physiologically, epileptic seizures are caused by an electrical discharge from a group of excitable neurons in any part of the cerebral cortex. This abnormal discharge can be the result of many different causes, ranging from a benign developmental predisposition to a fulminant central nervous system infection. History and physical examination will be able to differentiate the child needing immediate intervention from one whose work-up can proceed at a slower pace. An overview of an approach to the child with suspected seizures is presented in Figure 547-2.

FIGURE 547-1. Algorithm for evaluation of ataxia. ADEM, acute disseminated encephalomyelitis; AV, arteriovenous.

The clinician approaching an infant or child suspected of having seizures must first globally assess the child’s well-being. Status epilepticus is a medical emergency and needs to be treated quickly. It is not difficult to recognize the child who is in generalized convulsive status epilepticus; almost no other disorder is as dramatic. Nonconvulsive status epilepticus may be subtle. A child with slowing of ideation can soon progress to lethargy and obtundation due to continuous seizures. The recognition and management of status epilepticus is discussed further in Chapter 561.

A previously well child who has repeated seizures, depressed levels of consciousness, or appears otherwise unwell should be monitored very closely. If possible, the child should be placed in a hospital setting as the seizures could be the first sign of sepsis, meningitis, trauma, or a toxic or metabolic encephalopathy. The evaluation of a child with altered levels of consciousness is discussed later.

In a stable, nontoxic appearing child, careful history and physical examination will yield the most information. The goal of the history and examination is 2-fold: (1) to ascertain a clear account of the event in order to determine whether it was epileptic, and (2) to provide a global assessment of the child’s neurologic well-being, as seizures in children with underlying neurologic problems are less likely to be benign.12 Differentiation of epileptic seizures from attacks of other origin may be difficult. The only way to diagnose a seizure is a correct interpretation of the history; no laboratory or other study provides the diagnosis. In infants and very young children, breath-holding and gastroesophageal reflux are both often mistaken for epileptic seizure. In older children, syncope, sleep disorders, migraine, and conversion disorders need to be differentiated from epileptic seizures. In each instance, close attention should be paid to the setting, to precipitating factors, and to a detailed sequence of the events, including aura; motor, sensory, or psychological phenomena; automatisms; level of consciousness; incontinence; and postictal state.

FIGURE 547-2. Algorithm for evaluation of seizure.

Medical history should include questions about pregnancy and delivery, as well as previous episodes of head trauma, meningitis, and stroke. It is important to inquire specifically about the acquisition of developmental milestones, performance in school, and participation in social activities.

The physical examination should pay close attention to dysmorphic features, head size, and neurocutaneous skin findings, as these may point to an underlying disorder such as tuberous sclerosis or a chromosomal abnormality. The neurologic examination may uncover asymmetries or deficits that can aid in localizing an epileptic focus such as an area of cortical malformation.

The classification of epileptic seizures and epileptic syndromes is reviewed in Chapter 557.

These classification schemes are an attempt to place children with epilepsy into groups that have predictable natural histories and responses to particular classes of medications. For example, a child who is found to have rolandic epilepsy (also called benign focal epilepsy with central-midtemporal spikes) is expected to have infrequent, partial seizures during childhood with no neurologic sequelae in adulthood. Similarly, a child with complex partial seizures is expected to have his seizures well controlled with carbamazepine or one of its derivatives. A clinician knowledgeable about the major seizure types and seizure syndromes is better able not only to give parents a reasonable outlook of what to expect in the future, but also to choose the appropriate firstline medication. Squeezing atypical cases into generally accepted syndromes defeats the purpose of this classification system.

ALTERATION IN CONSCIOUSNESS

Consciousness is a state of awareness of both one’s self and the environment.13 Alteration in consciousness is a general term that describes disorders of mental activity including reduced awareness, diminished attention, and impaired cognition.14 Alteration in consciousness is always a symptomatic expression of an underlying problem. The clinician must be able to rapidly assess the level of consciousness and to identify the most likely causes for any disturbances. In Chapter 551, the major causes of acute deterioration of neurologic function including trauma, hydrocephalus, stroke, and infection are reviewed. Here we provide an overview that can guide the initial phase of an evaluation of a child with an altered level of consciousness. Management of the child with acute neurologic dysfunction is further discussed in Chapter 104.

Various terms that define changes in consciousness often are used interchangeably and incorrectly. A child who has a normal level of consciousness can be awakened and is aware of what is happening around him or her. The opposite of consciousness is coma, a state in which a person in unresponsive to stimuli, including pain.13,14 Although consciousness and coma represent the extremes of mental status, there are many abnormal states along that spectrum. Confusion occurs when there is a loss of clear thinking, usually manifested by impaired decision making. Disorientation often accompanies confusion. In general, disorientation to time occurs first, followed by disorientation to place, and then by deficiency in short-term memory. Delirium is characterized by acute mental status change, fluctuating course, and abnormal attention. Delirious children have extreme excitement and so become fearful, irritable, offensive, or agitated. Lethargy is a state resembling profound sleep, in which the child’s movement or speech is limited. A lethargic child can be aroused with moderate external stimulation but immediately relapses. Stupor is a condition of deep sleep or unresponsiveness from which the child can be aroused only with repeated vigorous stimuli.

In a typical day, the body cycles from a state of wakefulness to drowsiness and then sleep. This cycling is modulated by the reticular activating system, a core brainstem structure. For any disease to cause altered consciousness, it must do one of the following: (1) produce bilateral dysfunction of the cerebral hemispheres, (2) damage or depress the reticular activating system, or (3) damage or depress both the cerebral hemispheres and the reticular activating system.13 Diffuse cerebral hemisphere dysfunction is usually due to metabolic or infectious causes; dysfunction of the reticular activating system is usually due to compressive or destructive causes.

The initial physical survey of a child with altered consciousness includes assessment of the child’s airway, breathing and circulation, checking for bleeding, and stabilization of the cervical spine. Lifesaving interventions such as tracheal intubation and administration of fluids, pressor agents, or glucose should always take precedence over diagnostic procedures. From an initial survey, many of the common causes of altered consciousness, such as head injury, ingestion, and hemorrhage, are recognized.

Once the child is stabilized, the history and physical examination should focus on identifying both the cause and progression of the altered level of consciousness. Information about the onset of neurologic symptoms is particularly important. Time of day, location, and duration of initial symptoms may offer clues to the underlying cause. Clearly, a history of trauma will direct the workup to identify the extent and location of injury. Early morning headaches and somnolence are seen with increased intracranial pressure. Lethargy in an older child following an outing with friends should raise suspicion for a toxic ingestion or drug use.14 An abrupt change in mentation often results from an acute event such as a hemorrhage or obstructive hydrocephalus. A gradual onset of symptoms over hours or days suggests a metabolic, infectious, or toxic cause. Continued clinical deterioration may signal increasing intracranial pressure, systemic infection, or progressive metabolic derangement. Drug use or availability should be ascertained. Family members may identify psychiatric causes of unresponsiveness. The family may describe previous similar episodes from which the patient recovered, or current social stresses. Nonacci-dental trauma always should be considered in any infant presenting with an altered level of consciousness.

Vital signs—temperature, pulse, respiratory rate, and blood pressure—are crucially important. If a child is febrile, an infectious cause is likely. The respiratory rate and pattern may be helpful in localizing the cause for neurologic dysfunction. Slow breathing points to opiate or barbiturate intoxication whereas deep, rapid breathing suggests acidosis or pulmonary disease. Diseases that elevate intracranial pressure cause cyclic Cheyne-Stokes respiration. The pulse or blood pressure often is abnormal in cases of impending cerebral herniation. In particular, the Cushing triad (systemic hypertension, brady-cardia, abnormal respiration) is a late sign of increased intracranial pressure.14 The general physical examination should investigate any signs of systemic illness, meningismus, trauma, drug ingestion, and increased intracranial pressure.

Although limited in many ways, the neurologic examination is crucially important in order to localize the cause of the disturbance, and in doing so to help differentiate between structural and metabolic causes. A detailed description of the state of consciousness is essential. The exact stimulus and the patient’s specific response should be recorded. The pupillary reflex is a balance between parasympathetic and sympathetic innervation. Because pathways that control this reflex lie adjacent to the reticular activating system, lesions that impinge or affect the brainstem alter pupillary size or the ability of the pupil to react to light. On the other hand, the pupillary reflex is relatively resistant to metabolic insult; although small, the pupils maintain the ability to react to light. Therefore, a child with unequal, sluggishly reactive, or unreactive pupils should be presumed to have brainstem dysfunction in the area of the reticular activating system and likely a structural cause for the abnormal level of consciousness, as opposed to a medical cause that would spare the pupillary reflex.14

Dysfunction of extraocular movements also may accompany structural causes of altered consciousness. In particular, the oculocephalic reflexes are helpful in assessing low brainstem function. In a child with a functioning brainstem, when the head is turned to one side, the eyes move in conjugate fashion (one eye adducts and the other abducts), regardless of the level of consciousness. If there is a brainstem lesion at the level of the medial longitudinal fasciculus, the eyes move dysconjugately when the head it turned. If there is a low brainstem lesion, the eyes do not move at all relative to the head; in this “doll eyes” phenomenon, the eyes appear as if they were painted on the head.

Motor response to a painful stimulus can help localize the level of brainstem dysfunction. Lesions at or above the diencephalic level are associated with decorticate posturing, so the legs stiffen and the arms are rigidly flexed at the elbow and wrist. As the lesion moves rostrally to the level of the midbrain or upper pons, the arms and legs extend and pronate in response to pain, in what is called decerebrate posturing. If the lesion extends to the medulla, the child’s muscles are flaccid, and there is no response to painful stimuli.13

A child who has any acute alteration in level of consciousness should be transferred immediately to an acute care facility for additional evaluation and management. If the neurologic examination suggests a structural cause, early imaging of the brain with a computed tomography (CT) scan or magnetic resonance imaging (MRI) is indicated and can provide a rapid and accurate diagnosis. MRI is preferred because of the lack of radiation; however, CT scanning typically is used in the acute setting because of availability and logistic considerations.

DEVELOPMENTAL DELAY AND REGRESSION

Developmental delay is one of the most common problems encountered in a pediatric practice. The approach to the evaluation and management of developmental delay is discussed further in Chapters 91 and 185. Slow progress in the attainment of developmental milestones may be caused by a broad range of entities, from a normal variant of development to static encephalopathies to neuromuscular disease. In contrast, developmental regression (the loss of previously attained developmental milestones) is almost always caused by progressive neurologic disease.4,15 Distinguishing delay from regression is critical. If the parents report developmental regression, they should be pressed for specifics. A child with a static encephalopathy will often experience increased difficulty when reaching school age as new challenges reveal previously silent areas of brain injury. This increased difficulty in learning new tasks should not be interpreted as developmental regression.

A thorough history is essential for evaluation of a child with developmental delay. A three-generation pedigree should be obtained, explicitly stating the health and developmental status of individual family members as well as the occurrence of specific neurologic conditions, such as mental retardation, neuromuscular disorders, and epilepsies. Maternal pregnancy losses, the possibility of parental consanguinity, and precise ethnic heritage are relevant questions that, although uncomfortable to probe for, have to be asked.16 Attention should be paid to the details of the pregnancy and delivery of the child, including maternal medications or drug use, as well as complications such as pregnancy-induced hypertension, intercurrent infection, and gestational diabetes. If the mother has had previous children, the relative quantity of fetal movements compared with other pregnancies may be useful information. Birthweight, need for resuscitation and admission to a neonatal intensive care unit, feeding difficulties, or neonatal seizures are good markers of a possibly compromised newborn nervous system. The medical history should include ascertaining any chronic medical conditions, hospital admissions, surgical procedures, or medication use. Additionally, it is important to understand the child’s social and family context, socioeconomic status, and childcare arrangements.

Once this background is established, the next step is to obtain a detailed developmental history, focusing first on the domain (ie, motor, language, or social) of parental concern. A guide to early developmental milestones is presented in Table 547-2. Parents usually recall key milestones well, such as independent walking and first meaningful words. Milestones for older children include attainment of skills required to perform activities of daily living such as feeding, toileting, dressing, and self-hygiene. Asking the parent to compare a child with their peers or siblings or recall a child’s developmental performance at a specific milestone (ie, first or second birthday) may provide a snapshot of delay. It is essential to establish whether the child’s delay is global or domain specific (ie, motor and language), or has autistic features.16 The latter is ascertained through specifically asking about eye contact, emotional awareness, desire for sameness, and presence of repetitive behaviors or obsessive preoccupations.

The physical examination is essential because it may confirm a suspicion suggested originally by history or suggest a novel etiology that was previously unsuspected. Height, weight, and head circumference are essential. A skin exam may reveal stigmata of a neurocutaneous disorder or myelodysplasia. Dysmorphic features need to be specifically looked for. Hepatosplenomegaly and coarsening of the facies may be a tip-off to an underlying storage disorder.

Formal neurologic assessment aims to identify abnormalities that may aid in localizing the cause for delayed development. A cranial nerve examination may reveal retinal abnormalities, nystagmus, dysphagia, or dysarthria. The delayed child commonly experiences, and should be screened for, primary sensory impairments affecting vision or hearing. The motor examination focuses on discovering lateralizing features and abnormal movements in order to postulate central or peripheral nervous system pathology. Cerebellar function can be assessed by the observation of gait and the smoothness and accuracy of reaching for objects.

A formal developmental assessment fills in the information obtained through initial observation. Children can demonstrate fine motor skills through manipulation of blocks and pen and paper tasks. Gross motor skills are revealed through ball playing, running, and going up and down stairs. Spontaneous speech and story telling provides insight into vocabulary, grammatical capabilities, and comprehension. Although a number of formal developmental instruments have been developed for use in the office by physicians, many of these are too time intensive for regular use. Allied health professionals such as occupational therapists and speech pathologists are helpful in this context and often have more expertise in applying such standardized measures.

Frameworks for laboratory and radiologic evaluation of a child with developmental delay and regression are presented in Figures 547-3 and 547-4. In general, laboratory testing needs to be selective and rationally based, because extensive testing is neither justified nor feasible on the basis of yield, invasiveness, or costs.16,17 For a child with global developmental delay, a specific etiology can be identified in 50% to 60% of cases, and the etiology is most often intrapartum asphyxia, cerebral malformations, chromosomal abnormalities, or prenatal exposures such as drug or alcohol use.16 If a specific diagnosis is strongly suspected, laboratory investigations should selectively target this possibility. In the absence of any suspected diagnosis, a karyotype, testing for fragile X syndrome, and neuroimaging (MRI if available) are suggested on a screening basis. Metabolic testing (including capillary blood gas, lactate, ammonia, liver function studies, serum amino urine organic acids, and very long chain fatty acids) are appropriate only in certain clinical situations such as developmental regression, episodic decompensation, family history of a similarly affected child, parental consanguinity, suggestion of white matter involvement, or the absence of newborn screening.

Ongoing management of a child with developmental delay requires input from many different disciplines. Allied health professionals from the fields of occupational therapy, physical therapy, speech-language pathology, and psychology should provide assessments as well as goal-directed therapeutic interventions.16 These health professionals often become crucial resources for information and counseling as families adapt to their child’s developmental concerns and limitations.

ABNORMAL EYE MOVEMENTS

Abnormal eye movements in children may result from abnormal visual development in infancy or may be a sign of underlying neurologic disease.15 Binocular vision is maintained by a highly complex system involving multiple levels of the nervous system. Because of this complexity, abnormal eye movements may indicate a problem in the brain, brainstem, cranial nerves, neuromuscular junction, or muscle, or even a disease process primarily located outside of the nervous system.

Table 547-2. Early Developmental Milestones in Children

FIGURE 547-3. Algorithm for evaluation of developmental delay.

When a child is brought to medical attention because of abnormal eye movements, the history should establish the time course of symptoms, including onset and any fluctuations. Congenital conditions are usually recognized shortly after birth but sometimes are not detected until several months of age or even later. Detailed questions should explore exposure to medications, recent or concurrent illnesses, changes in weight, and the presence of other neurologic symptoms such as ataxia or myoclonus. In addition, the history should include an overall assessment of development.

Full eye movements require the proper functioning of cranial nerves III, IV, and VI. The physical examination first should establish full movements of the eyes. An infant’s eye movements can be evaluated by various maneuvers, including the use of a rotating drum, spinning the infant through 360 degrees of arc, and tilting an infant who is held vertically into a semiprone position. An older child may be asked to follow an object with his or her eyes.

Restricted eye movements, also called ophthalmoplegia, may be due to a large number of causes. Cranial nerve VI palsy limits abduction of the eye (lateral rectus muscle) and often accompanies increased intracranial pressure. Tilting of the head to one side may be a sign of contralateral superior oblique muscle weakness (cranial nerve IV). Cranial nerve III palsies may be partial or complete. A complete third nerve lesion, as may be seen in uncal herniation syndrome, produces ptosis, a dilated pupil, and a “down-and-out” position of the eye. Partial lesions may produce only ptosis or involve some of the innervated ocular muscles (medial rectus, inferior rectus, superior rectus, and inferior oblique muscles). The evaluation of ophthalmoplegia is outlined in Figure 547-5. As a general rule, children with a new-onset sixth nerve palsy should undergo neuroimaging, with magnetic resonance imaging (MRI) if available.

FIGURE 547-4. Algorithm for evaluation of developmental regression.

Nystagmus is a rhythmic oscillating movement of the eyes. Nystagmus may be either congenital or acquired. Congenital nystagmus will present shortly after birth and is horizontal, even in upgaze and downgaze. Convergence and eye closure dampen congenital nystagmus. Spasmus nutans is a congenital nystagmus that typically presents between 4 and 14 months of age and disappears by age 5. It is associated with a clinical triad of head nodding, head tilt, and monocular nystagmus. Although spasmus nutans is typically a benign condition, it is important to exclude a chiasmal glioma.15

Of the several types of acquired nystagmus, most can be well localized within the central nervous system. Seesaw nystagmus may be seen in lesions involving the midbrain and parasellar region (pituitary tumor or craniopharyngioma). Downbeat nystagmus is seen in disorders of the cervicomedullary junction, such as Arnold-Chiari malformations, skull base tumors, spinocerebellar degenerations, and toxic metabolic conditions such as medication toxicity (specifically, phenytoin, and lithium). Conversion retraction nystagmus is usually associated with a dorsal midbrain lesion. Nystagmus of the abducting eye is characteristic of internuclear ophthalmoplegia, a manifestation of a lesion within the medial longitudinal fasciculus seen most often in children with multiple sclerosis (Chapter 556).

Opsoclonus refers to rapid, chaotic, but conjugate eye movements. Opsoclonus-myoclonus syndrome is characterized by acute or subacute onset of abnormal eye movements, myoclonic jerks, ataxia, dysarthria, and behavior change. One of the major triggers of opsoclonus-myoclonus syndrome in children is neuroblastoma. See Chapter 556 for discussion of paraneoplastic disorders.

ABNORMAL MOVEMENTS

Abnormal movements need to be seen to be fully understood. If abnormal movements are not present at the time of the examination, the parents should be instructed to attempt to obtain a videotape of the movements at home. Even when seen, abnormal movements can be difficult to define. Chorea may resemble myoclonus; dystonia may resemble spasticity; and paroxysmal movement disorders such as dystonia and tics may resemble other paroxysmal neurologic problems, such as seizures.18 It is important to keep an open mind and to reevaluate a child with abnormal movements if symptoms worsen or initial therapy is not effective.

In the case of a child with abnormal movements, the history should provide a description of the movements and a trajectory of their onset and time course, as well as a list of any exacerbating factors. In children, excessive movements are more common than diminished movements. Paroxysmal movements are more characteristic of tics and dystonia, whereas continuous movements are more often seen in chorea. Medications are a relatively common cause of movement disorders in children; access to medications, especially anticonvulsants, antipsychotics, and illicit drugs needs to be assessed. Environmental or emotional states can modulate a movement disorder, especially in a child with a tic disorder. A history of recent systemic disease, such as rash, fever, sore throat, or palpitations may provide clues to an underlying infection or medical disease as the cause of abnormal movements.18 A framework for the evaluation of abnormal movements is presented in Figure 547-6.

FIGURE 547-5. Algorithm for evaluation of ophthalmoplegia (restricted eye movements).

Tics commonly are defined as stereotyped, intermittent, sudden repetitive movements. Movements that involve skeletal muscle are called “motor” tics; those that involve the diaphragm or laryngeal-pharyngeal muscles are termed “phonic” or “vocal” tics. Tics are frequently preceded by a premonitory sensation or urge, and a sense of relief usually follows performance of the tic. Some older children and adolescents are able to suppress tics for limited periods of time. The ability to suppress tics sets tic disorders apart from most other movement disorders.15, 18, 19 Tic severity seems to be modulated by environmental stimuli, stress, intercurrent infection and poor sleep. In addition to tics, patients who have tic disorders may have a number of comorbid behavioral symptoms, including attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. Tic disorders are discussed in more detail in Chapter 566.

Chorea is characterized by frequent, unpredictable, purposeless movements that tend to flow chaotically from body part to part. In children, chorea may cause the appearance of fidgeting, but when they are of large amplitude, chorea can involve dramatic, flinging limb movements (ballismus).18 Chorea can be classified by cause into primary and secondary disorders. Primary chorea, uncommon in childhood, can be caused by benign familial chorea and Huntington disease. Huntington disease rarely presents in childhood with chorea but is usually characterized by parkinsonism and dystonia. Most chorea in childhood is secondary. The most important cause of chorea in childhood is acute rheumatic fever (see Sydenham chorea, Chapter 566). Other important causes include systemic lupus erythematosus, drug ingestion, hyperthyroidism, infection and cardiac surgery, perinatal hypoxiaischemia, and degenerative disorders such as Wilson disease (Chapter 566).

Dystonia is a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. In primary dystonias, dystonia is the only or primary feature and usually has a specific causative genetic mutation or unknown cause. The two most important types of primary dystonia in children are dopa-responsive dystonia and idiopathic torsion dystonia (formerly known as dystonia musculorum deformans). Secondary dystonias are those disorders in which the dystonia is due to another cause, such as a medication or an underlying neurodegenerative disease. For a more detailed discussion of dystonia, see Chapter 566.

FIGURE 547-6. Algorithm for evaluation of abnormal movements. ASLO, antistreptolysin O titer; CBC, complete blood count; ESR, erythrocyte sedimentation rate; TSH, thyroid stimulating hormone.

Myoclonic movements are very brief, abrupt, involuntary, nonsuppressible contractions involving a single muscle or muscle group. Myoclonus may be present in normal situations (most notably sleep) and in numerous pathologic situations, both epileptic and nonepileptic.18 Diffuse central nervous system injury from virtually any cause can result in myoclonus, but the location and quality of myoclonic movements may be helpful in determining the cause. Myoclonus of the palatal muscles, for example suggests a brainstem lesion. Myoclonus in the setting of opsoclonus or ataxia suggests a paraneoplastic syndrome (eg, neuroblastoma) or a peri-infectious autoimmune process. Myoclonus can be the manifestation of epileptic neurodegenerative disease, such as progressive myoclonic epilepsy, Lafora body disease, neuronal ceroid lipofuscinosis, and mitochondrial disorders. Myoclonus can also be a manifestation of other neurodegenerative processes, including lysosomal storage diseases (Chapter 574), Wilson disease, and Huntington disease.

Stereotypies are intermittent, involuntary, repetitive, purposeless movements that are usually rhythmic. Examples of stereotypies in children are arm flapping, rocking, licking, mouth opening, and hand waving. Stereotypies, unlike tics, tend not to change over time.18 Stereotypies typically do not bother the child but can be distressing to the parents. Stereotypies commonly are associated with mental retardation, autism, Rett syndrome, and blindness, but they also occur in otherwise normal children.

Tremor is an involuntary oscillating movement with a fixed frequency. Tremor is classified by when it occurs: at rest, with intention, or at action. Rest tremor is defined as tremor involving a body part that is inactive and support against gravity. The most common cause of rest tremor in children is antipsychotic medications.18 Intention tremor occurs as a moving body part approaches a target and is a sign of cerebellar dysfunction. Action tremor occurs during maintained posture or voluntary movement. All people have a low-amplitude physiological (action) tremor inherent in movement that is not ordinarily noticed. Hyperthyroidism is routinely associated with an enhanced physiological tremor. Essential tremor is another type of action tremor and usually appears in the hands; it is rhythmic and not dysmetric (does not get worse at endpoint), which is helpful in distinguishing it from cerebellar dysfunction. Medication, such as propranolol, is reserved for cases of essential tremor in which tremor impairs function.

HEADACHES

Headaches are common during childhood and become more frequent during adolescence. Headache is so frequently benign from the point of view of serious organic illness that the clinician risks being lulled into a false sense of security. On the other hand, overreaction to headache also occurs, communicating undue concern to the parents and child as well as leading to excessive laboratory examinations and neuroimaging tests.20 Fortunately, headache is particularly well suited to a systematic clinical assessment. A focused history and physical examination, as well as judicious use of laboratory and neuroimaging, can lead to the correct diagnosis and management in all cases.

Table 547-3. Helpful Questions in the Evaluation of Headache

When did the headache begin?

How did the headache begin?

What is the temporal pattern of the headaches?

What is the headache frequency?

How long does the headache typically last?

Do the headaches happen at any particular time or circumstance?

Is there an aura or prodrome?

Where is the pain?

What is the pain like?

Are there associated symptoms?

What do you do during the headache?

Would I know you had a headache if I saw you?

What makes the headache better and worse?

Are there symptoms between headaches?

Are there any other health problems?

Are you taking medications?

Is there a family history of headaches?

What do you think is causing the headaches?

Data from Newman LC, Lipton RB, Solomon S: Headache history and neurological examination. IN Tollison and Kunkel (eds): Headache, Diagnosis and Treatment, 1993; Lance J: Pattern recognition from the history, in mechanism and management of headache, 4th edition. London, England, Butterworth Scientific 1982; Rothner AD: Headaches in children: A review. Headache 18:169-175, 1978.

Table 547-3 presents a patient “database” useful in delineating the features of pediatric headache.21 Headaches that have been present for years are unlikely to be due to significant intracranial pathology. In contrast, new-onset frequent headaches that have been associated with worsening severity over days to weeks are worrisome and will require neuroimaging. Headaches that occur at night or in the early morning are more likely to reflect increased intracranial pressure, and therefore deserve further investigation.

Intermittent headaches separated by intervals of complete well-being are frequently migraine. Children with migraine may be aware of an aura and may be able to describe or draw their symptoms. If the aura is persistently unilateral, on the same side, a structural lesion should be excluded. Migraine is typically throbbing, although many younger children may describe it as heavy or pressing. Migraine is usually accompanied by nausea, vomiting, photophobia, phonophobia, or anorexia. Migraineurs will often describe benefit from sleep or simple analgesics taken early in the headache course. Aggravating factors in migraine include activity, light, noise, and smells.22 For a detailed discussion of migraines, see Chapter 565.

A detailed account of all medications may help identify drugs that have headaches as an adverse effect. More commonly, medications are used to treat the headaches. Quantifying the child’s use of nonprescription analgesics will identify those at risk for rebound headaches. A medication history may also reveal exposure to medications that are associated with pseudotumor cerebri. These medications include vitamin A, tetracycline, corticosteroids, atypical antipsychotics, and oral contraceptives.

It is important to ask the child what he or she thinks is causing the headaches.21 Some children will identify a particular stressor, of which the parents are often unaware. Parents also then get a chance to discuss their fears of underlying pathology. A family history should be obtained; many children with migraine have first-degree family members with similar headaches.

The general and neurologic examinations focus on identifying a secondary cause of headache. The most important findings of a child with headaches include hypertension, presence or absence of nuchal rigidity, ophthalmic disc abnormalities, exanthems, fever, purulent rhinorrhea, cephalic bruits, sensory deficits, abnormal reflexes, or mental confusion. It is important to check for dental abscesses, neck muscle spasm or tenderness, temporomandibular joint mobility and cutaneous lesions such as café au lait spots.22,23 Signs of trauma to the head would suggest a possible concussion. Some children with concussion may have very mild ataxia. Postconcussive syndromes are discussed further in Chapter 565.

Children whose headaches are secondary to increased intracranial pressure may have evidence of papilledema or optic nerve pallor, especially those who have longstanding increased pressure from idiopathic intracranial hypertension. Diagnostic studies are seldom required unless risk factors are identified. Magnetic resonance imaging (MRI) or computed tomography (CT) is indicated in patients with a chronic-progressive headache pattern and those who have abnormal findings on neurologic examination (Table 547-4). Children younger than three years infrequently have primary headache syndromes, and the complete neurologic examination, including visualization of the optic fundus, can be difficult. These younger patients should be evaluated more urgently. An electroencephalogram (EEG) is of limited use in the routine evaluation of headache in children. If headache is associated with alteration of consciousness or abnormal involuntary movement, the differential diagnosis will include complex partial seizure disorders and an EEG may be required.

Lumbar puncture to identify bacterial or viral meningitis is mandatory in a febrile patient with headache with nuchal rigidity and without alteration of consciousness, signs of increased intracranial pressure, or lateralizing features. A measurement of opening pressure at the time of lumbar puncture is helpful in suspected cases of pseudotumor cerebri or chronic meningitis. If the patient’s mental status is altered or focal findings are evident, neuroimaging is warranted before lumbar puncture, although blood cultures should be drawn and antibiotic therapy empirically started before the patient is transported for neuroimaging.

Table 547-4. Indications for Neuroimaging in Children with Headache

Acute headache

Worst headache of life

Thunderclap headache

Steadily worsening over time

Focal neurological symptoms

Abnormal neurological examination

Papilledema

Abnormal eye movements

Hemiparesis

Ataxia

Abnormal reflexes

Presence of ventriculoperitoneal shunt

Presence of neurocutaneous syndrome (neurofibromatosis or tuberous sclerosis)

Age younger than three years

Headaches or vomiting on awakening

Unvarying location of headache

Meningeal signs

Data from Lewis D. Headaches in children and adolescents. American Family Physician. 2002;65:625-632.

FIGURE 547-7. Pupillary reflex pathway. (Source: Reprinted with permission from Dale Purves. Fig 12.3, The circuitry responsible for the pupillary light reflex. Neuroscience, 2nd edition. p 826, 2001.)

VISION LOSS

A remarkably complicated system is required for vision to be experienced, starting with the eye itself and continuing all the way to the occipital cortex. As such, many different disease processes can affect a child’s vision, from disorders of the eye itself to those affecting the retina, optic nerve, optic chiasm, optic radiations, and occipital lobe. In the following discussion, we will focus on an approach to identifying neurologic conditions that lead to abnormal vision; ophthalmological conditions are considered elsewhere.

A term infant with normal vision should be able to fix and follow, and show a visual preference for patterns, particular those with more and larger details.19 Preference for novel patterns becomes apparent at 3 to 5 months. A ball of red yarn is commonly used as a target for testing of visual fixation and following in newborns and young infants.2 Failure to detect a response raises concern for vision loss in the infant; often, infants with visual loss also exhibit aimless horizontal and vertical roving eye movements.

Older children very rarely complain about vision loss and instead will compensate or try to adapt to the deficit. Some children with vision loss may present with rubbing the eyes, becoming irritable when doing close work, or having eyes that are not aligned. Children with visual field deficits often display frequent head turning. Children with cortical vision impairment will often stare at bright lights or have a preferential gaze directed at colorful objects.

The neurologic examination of a child with suspected vision loss includes assessment of visual acuity, pupillary responses, visual fields, and examination of the anterior segment and fundus with a direct ophthalmoscope. Visual acuity is usually measured through the use of Snellen chart (Allen cards for younger children). For children who are uncooperative, preverbal, or simply unable to provide objective information, visual acuity is assessed from observation of behavioral responses or through the use of neurophysiologic tests such as visual evoked potentials.

To understand pupillary responses, the clinician must have a basic understanding of the neuroanatomy of the pupillary light reflex (Fig. 547-7). Afferent (incoming) signals from the retina are transferred through the optic nerve to the lateral geniculate body and then to both Edinger-Westphal nuclei. Efferent (outgoing) signals then pass from the Edinger-Westphal nuclei to the ciliary ganglia and to the constrictor muscles of the irises. In normal circumstances, when the clinician shines a light in one eye, the pupil constricts (direct response) and the contralateral pupil also constricts at the same time. This consensual response occurs because the efferent innervation is bilateral. In a case of unilateral optic neuritis (inflammation of the optic nerve), shining a light in the affected eye causes a sluggish reaction in that eye, or an impaired direct response. As the efferent system is still intact, a consensual response can still be seen with constriction of the contralateral pupil. This finding is termed an afferent pupillary defect. Causes of optic neuritis include multiple sclerosis, other autoimmune disorders, such as lupus, viral infections, such as herpes-zoster, and some medications, most notably ethambutol. Optic neuritis is discussed in further detail in Chapter 556.

Visual field defects occur in children and are difficult to diagnose. Sometimes a visual field loss results in no particular symptoms. A dense hemianopia will cause head turn but a quadrantanopia might not.19In order to perform confrontational visual field testing, the clinician must capture the child’s attention and wave objects of interest in each of the four quadrants in turn. The child should make a fairly accurate eye movement to the object of interest. In older children, automated perimetry tests are often used to detect visual field defects (Fig. 547-8).

A direct ophthalmoscope is used to examine the anterior segment and optic fundus. Examination is often difficult in young children. Nevertheless, the clinician should make every effort to identify media opacities and abnormal retinal findings that could indicate neurologic disease. The anterior segment and fundus examinations are reviewed in the chapters in this book on ophthalmology.

The clinician considering neurologic causes for vision loss should determine first whether the vision loss is congenital or acquired, static or progressive. Most congenital causes of low vision are static as well. Periventricular leukomalacia may cause damage to the optic radiations and, thus cortical visual impairment. Congenital optic atrophy is often the result of perinatal hypoxic-ischemic events. Intrauterine infections such as rubella, toxoplasma, and cytomegalovirus can cause retinitis and vision loss; hearing is often also impaired. Progressive vision loss may be the result of many different processes and often heralds neurodegenerative disease. If a history of progressive vision loss is established, it is necessary to ask about seizures, developmental regression, and other signs of neurologic deterioration.

FIGURE 547-8. Visual fields. (Source: Reprinted with permission from Dale Purves. Fig 12.8, Visual field deficits resulting from damage at different points along the primary visual pathway. Neuroscience, 2nd edition, p 834, 2001.)

Once the time course is established, the next step is to localize the cause of vision loss using an understanding of the visual pathways (Fig. 547-7). Retinal disease has a large differential diagnosis and is discussed at length elsewhere in this book. When retinal disease is accompanied by neurologic deterioration, it is important to consider mitochondrial diseases, Refsum disease, neuronal ceroid lipofuscinosis, and neurodegeneration with brain iron accumulation (see Chapter 566).

The most common cause of optic nerve atrophy is tumor compression of the optic nerve or optic chiasm. Many children with craniopharyngioma will not report vision loss until vision in the second eye is significantly involved. Children with neurofibromatosis (Chapter 578) often present with visual loss due to chiasmal glioma. Optic nerve atrophy may result from mitochondrial disease such as Leber hereditary optic neuropathy or Leigh syndrome. Optic neuritis in children is mainly due to demyelination, as seen in neuromyelitis optica and multiple sclerosis (Chapter 556), but may also be caused by viral or fungal infections, other autoimmune diseases, and toxins such as methanol and lead, as well as by ischemic disease.

Visual loss that localizes to the optic radiations or occipital cortex can be caused by many different entities including tumors, abscesses, and white matter disease such as that found in leukodystrophies. A young boy with X-linked adrenoleukodystrophy will often first come to medical attention after failing a visual screen at school. Leukodystrophies are discussed further in Chapter 576. Neuroim-aging is essential to help form a differential diagnosis.