Courtney J. Wusthoff, MD and Robert Ryan Clancy, MD

Neurologic Examination of the Newborn Infant

The ideal state for a neurologic examination, state 3, is usually achieved 1 to 2 hours after feeding or, conversely, 1 to 2 hours before the next feed. ¹

Acute neonatal encephalopathy (ANE) refers to the clinical syndrome of global brain dysfunction in the newborn, diagnosed through the history and examination. Babies with ANE have depression at birth, impaired mental status (lethargy or coma), hypotonia, inactivity, disordered sucking and swallowing, diminished primitive and postural reflexes, and reduced or absent deep tendon reflexes. Many, but not all, have clinical or subclinical seizures. ANE has numerous potential etiologies, such as acquired brain injury (e.g., hypoxic-ischemic encephalopathy, trauma, stroke, hemorrhage); infection; metabolic disease; or even severe, catastrophic types of neonatal epilepsy, which will be discussed later. Neonatal encephalopathy must always be distinguished from the term hypoxic-ischemic encephalopathy (HIE), which specifically refers to the clinical syndrome of acute encephalopathy in a newborn owing to hypoxic ischemia. The majority of neonates with ANE do not have HIE.

Developmental reflexes include both primitive and postural reflexes. Primitive reflexes are patterns of behavioral responses to stimulation that arise and extinguish at predictable ages in healthy newborns and infants. The familiar Moro reflex is elicited by sudden extension of the head in relation to the body, as with a light drop of the head ( Fig. 14-1). A newborn will respond by opening the hands and abducting and extending the arms and legs, followed by flexion. The Moro reflex is abnormal if asymmetric or depressed. Other examples of primitive reflexes include the palmar grasp, plantar grasp, glabellar, root, and suck reflexes. Postural reflexes determine the distribution of flexion or extension tone in the trunk and limb muscles depending on the orientation of the head and neck in space. The familiar “fencing posture” arises from the asymmetric tonic neck reflex, which is elicited by turning and holding the supine baby’s head to the left or right side for several seconds. The newborn reflexively responds by extending the arm and leg (by way of increased extension tone) on the side to which the face is pointing, while the other arm and leg flexes (by way of increased flexion tone) ( Table 14-1).

The maneuver is performed by grasping the baby’s hand and trying to bring the baby’s elbow across the midline. In a healthy term infant the elbow can be brought no further than the midclavicular line on the same side. In the case of prematurity, hypotonia, or brachial plexus injury, the elbow is easily brought past the midline, like a scarf. ²

The plantar response is extensor (upward response of the hallux) in most neonates for at least the first month up through the first year of life. A flexor response (toes turning down and inward, with foot everting) is also normal and not of concern. A definite and reproducible assymetry could be abnormal.

The term newborn should be able to follow an object both horizontally and vertically with the eyes. This may be assessed using a picture with contrasting black and white lines (e.g., Teller acuity targets); an object of a single bright color; or the examiner’s face, at about 10 inches from the baby. The examiner can move the object slowly across the field of vision to assess if eye movements are full and conjugate. Another method is to use a striped cloth or drum to elicit opticokinetic response and determine that eye movements are symmetric. Pupillary constriction responses to light develop between 30 and 32 weeks. ³

The glabellar tap is performed by tapping between the eyes to elicit bilateral blinking. It is a “poor man’s” corneal reflex that tests the afferent loop (cranial nerve V) and the efferent loop (cranial nerve VII). The same goal may be accomplished by stroking the eyelashes to elicit a blink. Facial nerve function is evident with good bilateral eye closure and symmetry of the face during crying. Auditory function is tested by behavioral responses to sound. A coordinated sucking and swallowing reflex should develop at approximately 35 weeks’ gestation, and poor sucking in a term newborn is of concern. Observe the tongue for fasciculations. Listen to the cry. An encephalopathic neonate may have a characteristic cry that is shorter and higher pitched. An infant who has been intubated may be hoarse; however, one with laryngeal palsy can be stridorous or hoarse. An infant with neuromuscular weakness may make the facial grimace of a cry, but be unable to generate sound.

A central facial paralysis (or “central seventh”) is caused by a lesion in the brain somewhere in the pathway from the primary motor cortex down to the nucleus of the seventh cranial nerve. A central facial palsy (i.e., central seven palsy) produces a gradation of weakness, which affects the lower face and mouth much more severely than the forehead muscles, which are less weak. Central facial paralysis may also have an associated hemiplegia. A peripheral facial palsy is caused by a lesion in the facial nerve nucleus or anywhere along the nerve’s track. A peripheral facial palsy affects the upper and lower face equally. For example, a “10%” injury of the peripheral 7th nerve will cause an equal 10% weakness of the forehead muscles, nasolabial fold, and lower mouth muscles.

Sometimes confused for a true facial palsy is an absence or hypoplasia of the left or right “depressor anguli oris” muscles. These muscles insert on the angle of the mouth and pull down or depress the corners of the mouth when an infant is crying. If the muscle from one side is missing or underdeveloped, that side of the mouth does not pull down as far during crying. To those not aware of this condition, this may be misinterpreted as “facial drooping” or weakness on the good side. Of course, without crying, the two sides of the mouth appear even. This condition is occasionally associated with congenital heart disease.

First, observe the position of the baby and the spontaneous movements. Observe the quantity and quality of the movements. Examine the tone by gentle flexion and extension of the limbs. Is there an associated paucity of movement of an arm or leg? Observe the rebound of the extremity; the rate at which a limb returns to its original position is helpful in gauging tone ( Fig. 14-3). Measuring the popliteal angle (which may be as great as 180 degrees at 28 weeks’ gestation but decreases to 110 degrees at term) allows for objective interobserver comparison of lower extremity tone. Head control can be gauged by either sitting the infant in the neutral position with good shoulder girdle support or pulling the baby off the surface of a bed (traction maneuver). ⁴⁵

The deep tendon reflexes develop, as does tone, several weeks earlier in the legs than in the arms, and the patellar and Achilles responses are attainable by 33 weeks’ gestation in most neonates. Note that when a knee-jerk response is obtained, a crossed adductor response may also occur as a normal variant up through 6 months of age.

Bilateral ankle clonus of 3 to 5 beats may be a normal finding, especially in infants who are crying, hungry, or jittery. Sustained ankle clonus is abnormal.

Myoclonus is a brief, involuntary twitch or jerk of a muscle or group of muscles. It is frequently seen in healthy newborns, particularly when they are drowsy or sleeping. Benign neonatal myoclonus is very common, may persist for several weeks, and does not indicate a brain abnormality. Much less common are myoclonic seizures in newborns; these are myoclonic jerks that are shown on electroencephalography (EEG) to have an ictal correlate, meaning they are true epileptic seizures. Many babies with myoclonic seizures will have other abnormalities on exam to suggest their myoclonus is not benign; in some cases EEG is necessary to make the distinction. ⁶

Jitteriness describes a pattern of rapid, high frequency, vibratory, shaking movements that may fluctuate in amplitude and frequency. These movements may be spontaneous or may be triggered by touch or startle. Jitteriness is more common in babies with hypoglycemia or other metabolic disturbance, drug withdrawal, or mild encephalopathy. Jitteriness differs from myoclonus because myoclonus is a very brief, twitching contraction of muscles, whereas jitteriness is more often a sustained pattern of tremulous movements lasting seconds or longer. Jitteriness may be distinguished from seizures in that jitteriness tends to resolve by holding the baby or changing position of the baby or limb. Furthermore, jitteriness does not involve altered consciousness or autonomic changes. Myoclonus and jitteriness are but two examples of conditions that could be confused for genuine epileptic seizures in the neonate. ⁷⁸

The Skull, Spine, and Brachial Plexus

The 50th percentile is 35 cm. Normal head circumference involves approximately 2 cm growth per month for 3 months, 1 cm growth per month for 3 more months, and then roughly 0.5 cm growth per month for the next 6 months, for a total of 12 cm in the first 12 months after birth. Premature infants should attain the head circumference of a healthy term infant, but illness and nutritional factors may slow the rate of growth. Relative to term infants, the head circumference of an otherwise healthy preterm infant may even be greater for the first 5 postnatal months, after which differences are less pronounced ( Table 14-2).

Asymmetric IUGR is restricted growth affecting weight and sometimes length but with normal head growth (“head sparing”). This is thought to reflect a protective mechanism in the face of extrinsic factors, by which the developing fetal brain is spared at the cost of other aspects of growth. Symmetric IUGR refers to restricted growth in all dimensions of growth, including head circumference, and carries a more worrisome neurologic prognosis.

The examination of the anterior fontanel is somewhat subjective and inexact, but it is useful nonetheless. The anterior fontanel should be slightly depressed and pulsatile when a neonate is sleeping comfortably. Sitting the baby up should depress the fontanel further in a normal newborn. A sunken anterior fontanel suggests dehydration. When the anterior fontanel is bulging, increased intracranial pressure may be a cause of concern. The normal anterior fontanel should remain open for at least the first 6 months. Premature closure is a concern for craniosynostosis.

The neonate with increased ICP may show poor feeding, lethargy, and irritability. Vomiting may increase or become more forceful. Bulging of the anterior fontanel, particularly while the baby is calm, is worrisome because ICP may be increased. With progression there may be bulging at the posterior fontanel or separation of the cranial sutures. Changes in pupils, eye movements, and autonomic function are late signs of increased ICP in the neonate. Although the open anterior fontanel may offer a limited outlet for increased ICP (when bulging), neonates can incur permanent injury or death from increased ICP.

Craniosynostosis is the result of premature closure of a cranial suture. Normal cranial sutures are shown in Figure 14-4. Premature closure results in the arrest of growth perpendicular to the affected suture. Types of craniosynostosis and their appearance are illustrated in Figure 14-5. They involve the following:

See Table 14-3.

Fortunately, spinal cord injury is uncommon in neonates. One instance in which it can occur, however, is when excessive traction is applied to the neck during a difficult delivery, especially if there is shoulder dystocia. The resulting cord injury causes a flaccid quadriplegia with sparing of the face and cranial nerves. Secondly, an indwelling umbilical arterial catheter misplaced at T11 can obstruct the artery of Adamkiewicz, which feeds the anterior spinal artery. The resulting cord ischemia causes an irreversible paraplegia.

Erb palsy is an injury to the brachial plexus, particularly the upper trunk. This causes weakness in flexion at the shoulder and elbow. At rest, the arm of a baby with Erb palsy hangs by the side and is internally rotated, and there are limited or no spontaneous movements of the hand. The most common cause is injury to the brachial plexus during delivery, particularly in babies who are large for gestational age, or in cases of shoulder dystocia ( Table 14-4).

Most babies with brachial plexus injury recover well, although this may take as long as 6 months. As many as 30% of cases may have lasting deficits or will require intervention. In the initial weeks and months, physiotherapy may be useful. If problems persist, nerve and muscle transfer surgery may be warranted. ⁹

Malformations of the Central Nervous System

A meningocele is the protrusion of only the meninges through a bony defect in the spine, whereas in meningomyelocele, both meninges and spinal cord protrude through bone. Spina bifida occulta is a vertebral cleft without spinal cord or meningeal herniation; it is a frequent incidental finding when neuroimaging the lumbar spinal region.

The incidence of meningomyelocele is approximately 0.5 to 1 per 1000 live births. Prophylaxis is accomplished in most cases by the intake of 0.4 mg of folic acid daily, starting, if possible, before the pregnancy begins. If the parents have had a previous child with spina bifida, 4 mg/day is recommended. With supplementation there has been a significant decrease in neural tube defects in the United States.

Until recently, standard treatment for meningomyelocele was surgery after birth. However, a randomized trial showed that prenatal surgery (i.e., fetal surgery performed before 26 weeks of gestation) led to a reduction in the need for CSF shunt in the first year and improved motor outcomes at 30 months. Because of the maternal and fetal risks of this operation, treatment is now available only at highly specialized fetal surgery centers. ¹⁰

The Arnold–Chiari type II (ACTII) malformation is frequently associated with meningomyelocele. ACTII consists of a low-lying cerebellar vermis and a ventral medulla that often protrudes into the foramen magnum. By obstructing the flow of CSF, it leads to hydrocephalus. Aqueductal stenosis may be found with ACTII malformation or in isolation, again leading to CSF flow obstruction. Agenesis of the corpus callosum can also be associated with meningomyelocele.

Many factors should be considered in formulating a neurologic prognosis. In general, the lower the level of the lesion, the better the prognosis. However, the presence and degree of hydrocephalus present at birth, in addition to the need for and any complications in shunting procedures (e.g., infection), also significantly affect outcomes. Any associated central nervous system (CNS) malformations, including agenesis of the corpus callosum, also contribute to morbidity. A child with a relatively low-lying lesion with an ACTII lesion and who has hydrocephalus is likely to have cognitive development in the normal range if there are no complications related to the shunting procedure. ¹¹

This assessment is accomplished by determining motor level and reflex level on examination ( Table 14-5). Sensory level assessment is less reliable in the newborn.

A tethered cord is a low-lying lumbosacral cord anchored posteriorly by a thickened filum terminale. It can occur in association with meningomyelocele or with other lumbosacral abnormalities such as lipomeningocele. It may be overlain by a dermal defect such as a hair tuft or sacral dimple. The lesion may be asymptomatic, but with growth it may lead to problems with sphincter control and walking and may also cause lumbar back pain. When a newborn has a sacral tuft or dimple suspicious for underlying cord abnormality, ultrasound is often used for immediate assessment, and magnetic resonance imaging (MRI) provides a definitive diagnosis.

The components of the Dandy–Walker malformation are cystic dilation of the fourth ventricle, partial or complete agenesis of the cerebellar vermis, and enlargement of the posterior fossa with a high attachment of the tentorium cerebelli. The Dandy–Walker malformation is frequently associated with hydrocephalus, which may not be present at birth but develops in the first year of life. Agenesis of the corpus callosum or cortical migrational defects (or both) coexist in many cases and increase the risk for intellectual disability when present. Treatment consists of observation and shunting of the ventricles. Sometimes the cyst itself needs to be shunted.

Porencephaly is an acquired abnormality that is seen as CSF-filled cysts at the site of injury, often adjacent to or connecting with the ventricular system. It usually is the result of an early parenchymal bleed, infarction, or infection. Schizencephaly represents a “split” or “cleft” in the cortex resulting from a congenital migrational defect and appears in one or both hemispheres from the surface of the brain down to the ventricular surface. In schizencephaly the walls of the cleft are lined with abnormal cortex (e.g., polymicrogyria), further dinstinguishing it from porencephaly.

Lissencephaly means “smooth brain.” With this condition there are few if any gyri formed on the brain’s surface. Lissencephaly is a severe migrational disorder of genetic etiology. There are two basic types. Type I is characterized by diffuse failure of migration on histology. These infants have an initially normal head size, but they also have hypotonia and seizures. A majority of these cases are caused by mutations affecting the genes LIS1, XLIS, or DCX. Type II lissencephaly is characterized by a “bumpy” or “pebbly” brain surface on pathology and is associated with congenital muscular dystrophy.

Holoprosencephaly reflects an early failure of the rudimentary forebrain to divide into two halves, resulting in various kinds of single-ventricle anomalies. These range in severity from alobar, in which there are no distinct cerebral hemispheres, to lobar variants, in which division between cerebral lobes is incomplete. The alobar form is particularly severe in terms of neurologic dysfunction, may result in a wide spectrum of facial abnormalities, and may be observed in infants with trisomy 13 or 18 syndrome. ¹²

Hydrocephalus is a build-up of CSF, usually owing to obstruction in the outflow of the CSF pathways. By conventional definitions, the obstruction can be “communicating,” in which the block is outside the ventricular system, or “noncommunicating,” in which the block is within the ventricular system. Choroid plexus papillomas (90% benign) are a rare cause of nonobstructive hydrocephalus; these tumors oversecrete CSF and lead to hydrocephalus that is often present at birth.

Structural malformations, such as aqueductal stenosis and ACTII malformation (usually associated with meningomyelocele and the Dandy–Walker malformation), are the most common causes of fetal hydrocephalus ( Table 14-6).

With hydrocephalus the CSF is under pressure, causing a dilation of the ventricles proximal to the cause of obstruction. This condition will often worsen until surgical correction of the obstruction or placement of a CSF shunt. Ventriculomegaly, in contrast, occurs when ventricles are of a larger size than normal, but no evidence of increased CSF pressure exists. In cases of ventriculomegaly the cause is an underlying difference in brain development, and surgery is not indicated.

Posthemorrhagic hydrocephalus resulting from intraventricular hemorrhage (IVH) is by far the most frequent cause of acquired hydrocephalus in the neonatal period. Other causes of hydrocephalus include blocked reabsorption of CSF by the meninges, as occurs with inflammation associated with subarachnoid hemorrhage or meningitis.

The vein of Galen malformation is rare overall, but it accounts for 30% of intracranial pediatric vascular abnormalities. A characteristic feature of the malformation is the presence of an arteriovenous shunt, which typically presents as high-output congestive heart failure in the neonatal period. There may be a bruit, sometimes quite loud, best heard over the posterior aspect of the newborn’s head. Sometimes there is head enlargement caused by an extrinsic aqueductal stenosis produced in the pons and midbrain by the bulk of the malformation. Only very rarely do these malformations present as bleeds at birth. Diagnosis is through neuroimaging (color Doppler and MRI and magnetic resonance angiography); ultimate treatment is through intravascular embolization or neurosurgery. ¹³

Neurocutaneous Syndromes

The term phakomatosis is derived from the Greek phakos, meaning “lentil” or “lens,” and refers to the patchy, circumscribed dermatologic lesions that are their hallmark. Because both skin and CNS tissue arise from the same ectodermal precursors, conditions that affect the CNS may have pathognomonic skin features. In addition to dermatologic features, these syndromes have hamartomata (errors in development) with involvement of multiple tissues. More commonly, the term neurocutaneous syndrome is used when referring to this group of diseases.

Neurofibromatosis (NF) and tuberous sclerosis complex (TSC) are both autosomal dominant conditions; the majority are sporadic. The prevalence of NF1 is about 1 in 3000 live births, and the incidence of NF2 is 1 in 100,000 live births. The prevalence of TSC is 1 in 6000.

Café-au-lait spots are present in as many as 2% of infants; these vary in prevalence and are not always indicative of NF. Children with NF1 may have few or no café-au-lait spots at birth; these may become more obvious within the first year. Because of the high spontaneous mutation rate for this autosomal dominant disease, only about 50% of newly diagnosed cases of NF1 are associated with a positive family history. ¹⁴¹⁵

NF1 is an autosomal dominant disorder of a tumor-suppressor gene located on chromosome 17q11.2 that encodes neurofibromin, a negative regulator of the Ras oncogene. Characteristic café-au-lait-spots may appear at birth. Osseous lesions are usually apparent within the first year of life, and tumors of the optic chiasm present relatively early in life. Axillary freckling and peripheral, spinal, or central nerve NFs may develop in later childhood. Early ascertainment is difficult, and almost half of infants younger than 1 year of age do not fulfill the full criteria for this disorder. ¹⁶

TSC is characterized by multiple and variable organ involvement. Commonly recognized clinical features include hypomelanotic skin macules, facial angiofibromas, periungual fibromas, delayed development, epilepsy, and autism. The kidney, heart, and retina are among other commonly affected organs. Abnormalities on brain imaging include subependymal nodules, cortical tubers, radial white matter lines, and subependymal giant cell astrocytomas (SEGAs). In 2010 everolimus was approved for the nonsurgical treatment of SEGAs (U.S. Food and Drug Administration Bulletin 2010). Sometimes computed tomography (CT) may be superior to MRI in detecting calcified cortical tubers. Seizures may begin in the neonatal period and are one example of a “well baby with seizures.” At the same time, symptoms for a given individual may be subtle; it is possible for a parent to have undiagnosed TSC come to light only when their affected baby is born.

Port-wine stains can occur as isolated cutaneous birthmarks or in association with structural abnormalities