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.
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
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 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 workup 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
Algorithm for evaluation of ataxia. ADEM, acute disseminated
encephalomyelitis; AV, arteriovenous.
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, lactate, 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 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 workup can proceed at a slower pace. An overview
of an approach to the child with suspected seizures is presented
in Figure 547-2.
Algorithm for evaluation of seizure.
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
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 first-line medication. Squeezing atypical
cases into generally accepted syndromes defeats the purpose of this
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.13,14Although
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. Nonaccidental 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, bradycardia, 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
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.
Table 547-2. Early Developmental
Milestones in Children ||Download (.pdf)
Table 547-2. Early Developmental
Milestones in Children
|2 months||Head up in prone||Smiles, fixes and follows|
|3 months||Head/chest up in prone, grasps placed object||Coos|
|4 months||Rolls, reaches|
|6 months||Sits with support, transfers||Babbles, turns to sound||Mouthing objects|
|8 months||Sits without support, weight bears||Turns to name|
|10 months||Pincer grasp, starting to cruise, crawling||“Bye-bye” wave||Drinks from cup|
|12 months||Walks but falls easily||First words||Finger feeds, objects in and out of containers|
|15 months||Walks steadily, scribbling||Pointing, multiple single words||Spoon use, assists in dressing|
|18 months||Up/down stairs with assistance, climbing, throws
ball||Two-word phrases, pointing to body parts||Builds towers, plays with others|
|24 months||Up/down stairs one step at a time, kicks ball||Three-word phrases, pronouns|
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.
Algorithm for evaluation of developmental delay.
Algorithm for evaluation of developmental regression.
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 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.
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.
Algorithm for evaluation of ophthalmoplegia (restricted
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 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.
Algorithm for evaluation of abnormal movements. ASLO,
antistreptolysin O titer; CBC, complete blood count; ESR, erythrocyte sedimentation
rate; TSH, thyroid stimulating hormone.
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 hypoxia-ischemia, 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.
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
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 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 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.
Table 547-3. Helpful Questions
in the Evaluation of Headache ||Download (.pdf)
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?|
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.
Table 547-4. Indications
for Neuroimaging in Children with Headache ||Download (.pdf)
Table 547-4. Indications
for Neuroimaging in Children with Headache
|Worst headache of life|
|Steadily worsening over time|
|Focal neurological symptoms|
|Abnormal neurological examination|
|Abnormal eye movements|
|Presence of ventriculoperitoneal shunt|
|Presence of neurocutaneous syndrome (neurofibromatosis or
|Age younger than three years|
|Headaches or vomiting on awakening|
|Unvarying location of headache|
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.
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
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.
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.)
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.19 In
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).
(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.)
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.
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. Neuroimaging
is essential to help form a differential diagnosis.