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This chapter is designed to help the pediatrician feel comfortable and confident with the assessment of neurologic disease. More detailed discussions of individual diseases are given in other chapters.
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When tackling any case, accurate diagnosis and management start with the history. The information found in the history, starting with the chief complaint, allows the practitioner to then focus on certain elements of the neurologic examination. At the end of the encounter, the combination of information found in the history and neurologic examination will direct the practitioner to determine if specialized neurologic care is needed and, if so, whether that care can be provided in an outpatient setting or if inpatient/emergent care is needed.
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The following sections will be divided into a variety of neurologic chief complaints a pediatrician could encounter. Also presented are additional elements of the history and physical examination that need to be elicited to ensure proper localization of the disease process. Once a neurologic lesion has been confidently localized, appropriate management can begin.
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To understand the magnitude of potential etiologies for weakness, one must have an understanding of the intricate nature of the neurologic axis. At the time of first encounter for weakness, one should attempt to localize the lesion to the brain (cortex, white matter, basal ganglia, thalamus, brain stem), the spinal cord, the anterior horn cell, the nerve root, the nerve (axon or myelin or both), the neuromuscular junction, the muscle, or multiple components of the aforementioned.
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The acuity of onset and whether the weakness is static or progressive are extremely important factors in determining the plan of care. Weakness that is long-standing (ie, months to years) is rarely going to represent a disease process that requires emergent care, and outpatient neurology follow-up should be sufficient. However, weakness that is acute to subacute in onset (minutes, hours, or days to weeks) may represent a neurologic condition requiring emergent care.
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CEREBRAL LESIONS REQUIRING EMERGENT EVALUATION
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Altered mental status, or encephalopathy, can occur when there is a bilateral hemispheric disturbance involving the cerebral cortex. Language dysfunction and impaired fluency or comprehension can occur if the cortices of the frontal or temporal lobes are affected, respectively. Finally, since seizures frequently originate from the cerebral cortex, lesions affecting the cortex can give rise to seizures. Neurologic disease giving rise to weakness in the setting of any of the aforementioned symptoms would suggest a disease process affecting the cerebral cortex. The differential of such a case includes intracranial hemorrhage, cerebral infarct (stroke), infectious/inflammatory encephalitis, demyelinating processes such as acute disseminating encephalomyelitis, and neoplastic processes. To evaluate for these processes, emergent imaging in the form of computed tomography (CT) scans or magnetic resonance imaging (MRI) of the brain should be pursued. Alteration of mental status will be discussed in more detail later in the chapter.
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SPINAL CORD LESIONS REQUIRING EMERGENT EVALUATION
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Bowel and bladder incontinence along with extremity weakness and a sensory level may indicate a spinal cord lesion, and emergent care should be sought. These lesions may be neoplastic, vascular, inflammatory, infectious, or degenerative in origin and may necessitate immunomodulatory/surgical treatment.
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Weakness associated with back pain may also be indicative of a spinal cord neoplastic process or epidural abscess. The weakness within these 2 disease processes will potentially arise subacutely; however, emergent care should still be sought.
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An emergent MRI of the spinal cord will be of use in characterizing spinal cord lesions.
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NEUROPATHIES REQUIRING EMERGENT EVALUATION
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Worsening acute/subacute lower extremity weakness that ascends from the feet is worrisome for acute inflammatory polyneuropathy or Guillain-Barré syndrome (GBS). Absent reflexes generally localize the lesion to the peripheral nervous system (anterior horn cell, nerve, neuromuscular junction, and/or muscle). GBS represents an umbrella term for a polyneuropathy secondary to an autoimmune disorder, and the autoantibodies produced with GBS can react with the myelin, axonal, or both components of the nerve. The location and severity of this reaction give rise to the many variants of GBS. The clinical course of GBS can often involve respiratory compromise and autonomic instability, rendering the early recognition of GBS and immediate hospitalization and workup imperative. (See also Chapter 561.)
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WEAKNESS IN THE NEONATE AND INFANT
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While it is possible for a neurologic disease to be present from birth, the diagnosis is sometimes delayed because of the difficulty in properly assessing all components of the neurologic examination. Subtle clues in the developmental screen and neurologic examination may allow the examiner to establish an earlier diagnosis, allowing for improved care of the child.
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Weakness can take on many forms in infancy. Weakness may manifest as subtle delays in achieving motor milestones such as rolling over, sitting up, or crawling or as a preference to use one hand over the other before the age of 1. In extreme cases, a newborn child may have difficulty with vital tasks such as breathing and feeding, and on occasion, joint contractures may be present secondary to immobility in utero. On examination, there may be hypotonia (decreased resistance of muscle to stretch). The family may describe this finding as their child being “too loose” or “floppy.” These findings are fairly nonspecific in terms of identifying where along the neurologic axis the lesion exists; the lesion could exist in either the central or peripheral nervous system, and, thus, more information is needed. The presence of weakness in the setting of hypotonia, areflexia, and fasciculations typically points to an anterior horn cell disease such as spinal muscular atrophy. The presence of weakness and hypotonia but preserved reflexes should raise the possibility of a disorder of neuromuscular transmission such as infantile botulism or transient myasthenia gravis (especially in a newborn with a maternal history of myasthenia gravis). Congenital myotonic dystrophy should be considered in a newborn or infant with hypotonia and weakness with a maternal history of myotonic dystrophy. These are just a few examples of diseases that can cause early hypotonia and weakness, but consideration should also be given to genetic conditions such as trisomy 21 and Prader-Willi syndrome.
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Consideration should also be given to cerebral lesions (eg, anoxic brain injury or remote intracranial hemorrhage), especially in the neonate/infant with an alteration of mental status as evident by lethargy, irritability, and/or feeding difficulties. Polyneuropathies, congenital myopathies, metabolic myopathies, mitochondrial myopathies, and muscular dystrophies are also within the differential. Focal upper extremity weakness from birth can also be indicative of a brachial plexopathy. An MRI of the brain, serum creatine kinase, electromyogram and nerve conduction studies (EMG/NCS), and genetic testing can help differentiate between the many etiologies giving rise to weakness in the neonate and infant.
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Seizures are an abnormal and hypersynchronous discharge of a population of neurons. Epilepsy is defined as 2 or more unprovoked seizures. An unprovoked seizure excludes febrile seizures and seizures in the setting of acute precipitating causes such as head trauma or metabolic disturbances. It is important to first distinguish between febrile and afebrile seizures (or unprovoked seizures) as the difference in management between the 2 is different.
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RELEVANT MEDICAL HISTORY
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The history obtained for a patient with a seizure will help the physician in determining a potential etiology for the patient’s seizure activity. The pregnancy history including maternal drug use or infection should be obtained. Birth history is very important, especially if it was noted the baby was born premature or underwent any resuscitative measures. A child who is developmentally delayed may be delayed secondary to seizure activity, or the process that has caused the child to be delayed may also serve as the etiology for the patient’s seizure activity. A family history of seizures may point to a genetic etiology for the patient’s epilepsy.
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CLINICAL CHARACTERIZATION OF SEIZURES
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Once a seizure is determined to be unprovoked, it is important to distinguish whether or not the seizure was partial or generalized. A generalized seizure is characterized by an alteration of consciousness and involvement of both left and right hemispheres. This can manifest as motor activity such as generalized tonic-clonic seizure or as staring spells with an immediate return to baseline after the episode (absence seizure); “drop attacks,” as is the case in atonic seizures; or generalized myoclonic jerks. Partial seizures are characterized by a preservation of consciousness. Patients or family members may describe unilateral extremity jerking, forced deviation of the head, or forced deviation of the eyes if motor activity is present. Other patients may describe a rising epigastric sensation, a feeling of déjà vu, sensory involvement, nausea, vomiting, and autonomic and/or visual symptoms depending on the origin of the seizure. It is also important to note that it is possible for a seizure to start as a partial seizure and secondarily generalize to involve all of the brain.
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Seizures can be much more subtle in a neonate and an infant. For example, seizures in the neonate can be as subtle as chewing movements or pedaling motions. Paying special attention to eye movements in the neonate can be helpful in determining if an event is truly epileptic. Neonates with seizures can present with sustained opening of the eyes with ocular fixation or with tonic horizontal deviation of the eyes. Clonic jerking and movements that do not cease with passive flexion are also characteristic of neonatal seizures. If seizures in the neonate are suspected, emergent care should be sought given the potential that the seizures represent an underlying neurologic disturbance such as central nervous system infection, intracranial hemorrhage, and stroke.
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Seizures in infants can still appear different from the more frequently seen generalized tonic-clonic seizures of childhood. One such seizure type is an infantile spasm that appears as a sudden flexion or extension of the head, trunk, and extremities. Behavioral arrest during the seizure is characteristic of infantile spasms. An alternative clue that an infant may be experiencing seizures including spasms is the presence of developmental arrest or regression. Urgent evaluation for infantile seizures should be sought given that seizures could represent an underlying neurologic disturbance such as a neuronal migration disorder, metabolic disorder, or an underlying genetic epilepsy, and urgent treatment of infantile spasms has the potential to improve developmental outcome. MRI of the brain, electroencephalogram (EEG), and metabolic and genetic testing can help clarify the diagnosis.
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The etiologies of epilepsy are varied. Injuries in the form of anoxic brain injury or intracranial hemorrhage can leave a neonate susceptible to seizures. Central nervous system infections also serve as a potential etiology for seizure activity. Genetic syndromes such as childhood absence epilepsy, benign rolandic epilepsy, and juvenile myoclonic epilepsy are also within the differential. Brain malformations such as cortical dysplasias, lissencephaly, and gray matter heterotopias increase risk for epilepsy. Neoplasms can predispose to seizures and can be easily identified by neuroimaging. Neuroinflammatory disorders such as viral or postviral encephalitis are potentially treatable causes of seizures. Finally, several inborn errors of metabolism will place a child at risk for epilepsy.
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Cerebrospinal fluid (CSF) studies should be pursued if there is concern for central nervous system infection, and an EEG should be obtained for all first-time unprovoked seizures, and it may help determine the need for anticonvulsant medications. An MRI of the brain should be obtained for any child with developmental delay, in children younger than 1 year old with seizures, and in children with an abnormal neurologic examination or focal components to the seizure. Genetic testing is usually reserved for patients with refractory epilepsy or who have a strong family history of epilepsy.
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Daily administration of anticonvulsants is usually reserved for patients who have had 2 or more unprovoked seizures. An anticonvulsant can be started after the first unprovoked seizure if it is deemed that the child is at high risk for having additional seizures. This may be the case in patients who have an abnormal EEG, abnormal brain MRI, or a strong family history of epilepsy.
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ALTERED MENTAL STATUS (ENCEPHALOPATHY)
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Encephalopathy simply refers to an altered state of consciousness. Encephalopathy may be clinically evident on examination as difficulty maintaining arousal (lethargy) or as an unresponsiveness to pain (comatose state). It may also present as a change in behavior in which there is agitation, confusion, delusions, or hallucinations. Patients with encephalopathy should prompt an emergent workup for an underlying disease process, including localized cerebral pathology, ingestion of toxins, infection, or inflammation. Given that life-threatening conditions such as intracranial hemorrhage, bacterial meningitis, and sepsis can lead to an encephalopathic patient, it is extremely important that such a patient be evaluated in an emergent setting where appropriate resuscitative measures can be taken if necessary.
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All encephalopathic patients should be evaluated for signs of increased intracranial pressure as it may warrant emergent neurosurgical intervention. Aspects of the history that may point to raised intracranial pressure include projectile vomiting, seizure activity, or acutely worsening headache. On examination, visual changes, papilledema, and ocular nerve palsies may be present. In a child with an open fontanelle, the presence of a bulging fontanelle may also be indicative of increased intracranial pressure. Rapidly enlarging head circumference may also be a finding of increasing intracranial pressure. The findings of increased intracranial pressure may be seen in patients with intracranial tumors, infections, hemorrhages, or the presence of hydrocephalus and warrant emergent evaluation usually with a CT scan.
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Once a patient has been stabilized, the search can then focus on an etiology of encephalopathy. The presence of encephalopathy in the setting of focal neurologic deficits such as hemiparesis suggests a diagnosis of cerebral infarct. MRI of the brain can evaluate for the presence of a stroke. The presence of fever in conjunction with meningeal signs suggests a diagnosis of central nervous system infection. CSF studies and MRI of the brain can evaluate for signs of a central nervous system infection or postinfectious encephalomyelitis. The presence of altered mental status (with prominently psychiatric disturbances) in the setting of seizure activity is suggestive of a paraneoplastic or autoimmune encephalitis. This diagnosis is confirmed with paraneoplastic and autoimmune biomarkers. A patient with known epilepsy found to be encephalopathic would suggest postictal phenomenon versus ongoing status epilepticus. An EEG should be obtained for an epileptic with encephalopathy who has not returned to baseline in a timely manner to evaluate for ongoing epileptic activity. The differential also includes metabolic disturbances such as hypoglycemia and hyponatremia. Inborn errors of metabolism, endocrine disorders, hepatic disease, renal disease, and toxic ingestion can present as encephalopathy as well. Treatment of encephalopathy requires treatment of the underlying medical condition.
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Encephalopathy in the neonate can be subtle and difficult to diagnose. We assess the mental status of a neonate by ensuring a neonate can readily arouse to tactile stimuli, as well as eye opening, spontaneous movement of all 4 extremities, and vocalizations. In infants and toddlers, lethargy, agitation, and/or irritability may be the signs of altered mental status. It is not until a child gets older that he or she may be able to communicate the presence of visual and auditory hallucinations or delusions.
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Paresthesias are sensory disturbances of the skin sometimes described as “tingling” or “burning” or “pins and needles” sensations. Although the differential is broad, the presence of paresthesias can, when combined with other neurologic signs and symptoms, provide a sense of where the lesion may exist. Starting most distally in the sensory pathway, paresthesias and sensory loss in the sensory distribution of a nerve with or without weakness can be indicative of a peripheral neuropathy. Lesions involving nerve roots will present with pain, along with paresthesias that radiate down the limb. An EMG/NCS can be beneficial in evaluating for either of these conditions. The sensation of electricity moving from the neck into the extremities upon neck flexion is worrisome for a cervical spinal cord lesion. A cervical spine MRI will be helpful in evaluating for such a lesion. Sensory changes that are not in typical anatomic patterns or in multiple locations or occurring during distinct episodes, especially in adolescent children, could be presenting symptoms of multiple sclerosis, and brain and spine MRI would be useful to identify the typical lesions. Finally, lesions of the thalamus and parietal lobe (which can be seen with an acute cerebral infarct) may present as a contralateral face and body sensory loss. Lesions involving only the thalamus will produce an isolated sensory syndrome, whereas lesions involving the parietal lobe may present additionally with language deficits and a contralateral neglect.
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In order for a visual stimulus to be perceived, light must travel through the eye and be directed onto photoreceptor cells (rods and cones) on the retina. From the retina, the signal passes through the optic nerve to the optic chiasm and then through the optic tract to the thalamus. From here, the signal is carried to the occipital cortex through optic radiations that exist in subcortical white matter. Thus, visual disturbances may represent an underlying neurologic disease that involves 1 or many components of the nervous system.
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A neurologically intact infant should be able to fixate and follow the examiner horizontally and vertically. Assessing the visual system becomes easier as the child grows, when the Snellen Chart can be used to assess visual acuity. Visual changes may be difficult to communicate in an infant or toddler, but at the very least, the initial examination should involve testing the child for the ability to track, checking for a blink reflex to light, testing for a blink to visual threat, and finally, checking for pupillary constriction to light stimulus. If there are any concerns regarding functioning of the above, a neurologic and ophthalmologic workup should be initiated.
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Acute visual changes including diplopia, reduced visual acuity, increased central scotoma, loss of color discrimination, patchy visual loss, and complete monocular or binocular visual loss all warrant emergent evaluation in consultation with ophthalmology and neurology. Visual changes are often accompanied by additional neurologic and nonneurologic symptoms. They include headache, painful eye movements, additional cranial neuropathies, neck and back pain, vomiting, and hemiparesis. These are additional worrisome signs and can point to specific diagnoses, as described below.
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Patients with acute visual disturbances in the setting of headaches should be fully evaluated immediately as these disturbances may be indicative of increased intracranial pressure. Funduscopic examination can reveal papilledema, confirming increased intracranial pressure, although papilledema may not always be present. There can be many causes of elevated intracranial pressure including neoplasm, intracranial hemorrhage, meningitis, encephalitis, and so on. Only if all of these causes are ruled out, usually with neuroimaging, can a diagnosis of idiopathic intracranial hypertension or pseudotumor cerebri be considered (see Chapter 546). The diagnosis of increased intracranial pressure is confirmed with the finding of elevated opening pressure with a lumbar puncture.
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Patients with acute to subacute monocular or binocular visual changes (decreases in visual acuity, change in color vision) along with eye pain that is worsened with eye movements may have optic neuritis. Pupillary examination will potentially reveal a relative afferent pupillary defect, and blurring of the disc margins may be seen on funduscopic examination. The diagnosis is made clinically but may be confirmed with an MRI of the brain and orbits demonstrating contrast enhancement of the optic nerves. Demyelinating diseases that can cause optic neuritis include multiple sclerosis and neuromyelitis optica, but optic neuritis can occur in isolation. Infectious and postinfectious diseases can serve as the etiology for optic nerve impairment. If suspected, cases of optic neuritis should be referred to the emergency department immediately where intravenous methylprednisolone may be used for treatment.
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Acute visual disturbances in combination with headaches and possibly seizures or altered mental status should also raise suspicion for reversible posterior leukoencephalopathy syndrome (also known as posterior reversible encephalopathy syndrome [PRES]). Patients who have a history of hypertension or who are on chemotherapeutic agents are at higher risk of developing PRES. An MRI of the brain will be useful in characterizing this disease process.
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Gradual onset of visual disturbances in combination with developmental regression is concerning for a leukodystrophy, a group of neurodegenerative conditions involving progressive degeneration of cerebral white matter. An MRI of the brain in combination with specific metabolic and genetic testing can help with the diagnosis of the different leukodystrophies.
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The differential diagnosis for developmental delay is broad, and a thorough history (including developmental history) and physical examination are crucial to narrowing down the potential diagnosis. Development can be assessed by evaluating gross motor, fine motor, language, and social milestones. A maternal history should be obtained reviewing chronic illnesses, infections, and history of miscarriages. Maternal exposure to drugs, alcohol, cigarettes, or prescription medications during pregnancy should also be reviewed. Details of the pregnancy itself, including markers of fetal well-being such as fetal movement, should be reviewed. A child who is found to be developmentally delayed in the presence of a history of decreased fetal movement and hypotonia should raise the suspicion of a neuromuscular condition. A perinatal history should also be obtained including mode of delivery and circumstances leading to delivery (placental abruption, trauma, nonreassuring fetal heart tones—any of which can predispose a neonate to hypoxic injury). If a patient is found to be developmentally delayed and the history and/or the neurologic examination is suggestive for toxic exposures in utero, intrauterine infections, or anoxic brain injury, an MRI of the brain should be obtained to assess for the presence of central nervous system injury. A neonatal history should also be reviewed for the presence of intracranial hemorrhages or meningitis/encephalitis, which can predispose a child to developmental delay. The presence of dysmorphic features in combination with developmental delay should prompt genetic testing to assess for chromosomal abnormalities such as fragile X syndrome or trisomy 21. A family history including the presence of consanguinity may also point to genetic etiologies of developmental delay. The presence of skin lesions in the presence of developmental delay may be indicative of neurocutaneous syndromes such as neurofibromatosis type 1 and tuberous sclerosis.
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While taking a developmental history, special attention should be paid to autistic features including impairments in language, impairments in social skills, and restricted patterns of behavior or interests. Poor eye contact, parallel play, and preoccupation with certain toys are just a few signs suggestive of autistic features. Genetic conditions such as Phelan-McDermid syndrome can present with autistic features. Patients with metabolic conditions and epileptic syndromes (such as Dravet syndrome) may also present with autistic features, and these disorders should be suspected when there has also been developmental regression. The presence of developmental regression can also be indicative of a progressive neurodegenerative condition prompting urgent neurologic evaluation. Language delay should prompt a thorough audiologic evaluation to ensure there are no impairments in hearing contributing to the language delays.
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Developmental delay often requires a multidisciplinary approach to diagnosis, medical treatment, and management to ensure that the associated disabilities are addressed. The goal for the pediatrician and neurologist is to involve (where appropriate) the services of physical medicine and rehabilitation, orthopedics, therapies (speech, physical, and occupational), and neuropsychologists to ensure the patient can meet his or her developmental potential.
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DISTURBANCES OF HEAD GROWTH
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Growth of the head usually is driven by growth of the brain parenchyma; hence, the importance of the serial measurement of head circumference in neonates and infants. In addition to absolute head circumference, trends in the growth of head circumference are also important to note, especially in the neonate or infant. The presence of a rapidly enlarging head circumference in conjunction with a change in mental status and vomiting may point to increasing intracranial pressure and hydrocephalus, warranting emergent neurologic care, whereas decelerating head growth in a girl with loss of purposeful hand movements would point to Rett syndrome.
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Microcephaly is the result of reduced brain growth. It can occur in certain genetic conditions, neural tube defects (eg, encephalocele), midline cerebral abnormalities (eg, holoprosencephaly), or disorders of neuronal migration (eg, lissencephaly or polymicrogyria). Microcephaly also can occur as the result of a destructive or degenerative process of the brain that is forming, which can occur with toxic exposures in utero, congenital infections, anoxic brain injuries, and chronic systemic diseases (see also Chapter 543).
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Macrocephaly can have numerous etiologies including overgrowth of the brain, increased CSF, and intracranial bleeding (see also Chapter 543). Increase in brain tissue, also known as megalencephaly, can be seen with neurocutaneous disorders such as neurofibromatosis type 1 and tuberous sclerosis. In cases in which there is developmental delay or regression along with megalencephaly, neurodegenerative conditions such as Tay-Sachs disease, Canavan disease, and Alexander disease should be considered. The presence of megalencephaly can also be benign (benign familial megalencephaly), and, thus, a child with macrocephaly should prompt the measurement of the parents’ head circumference.
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Hydrocephalus can cause macrocephaly. Obstruction to the CSF circulation (eg, Dandy-Walker malformation or aqueduct stenosis) can lead to a noncommunicating hydrocephalus. An inability to resorb CSF (eg, intraventricular hemorrhage or meningitis) causes communicating hydrocephalus. Benign enlargement of the subarachnoid space can occur when there is a buildup of CSF in the extraventricular system and can lead to macrocephaly. Finally, intracranial bleeds such as intraventricular, epidural, and subdural hemorrhages can give rise to macrocephaly.
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Neuroimaging (brain MRI) can help in the assessment and further workup and management (eg, surgical) of the cause of micro- or macrocephaly.
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Blumenfeld
H. Neuroanatomy Through Clinical Cases. 2nd ed. Sunderland, MA: Sinauer Associates; 2010.
+
Piña-Garza
JE. Fenichel’s Clinical Pediatric Neurology: A Signs and Symptoms Approach. 6th ed. Philadelphia, PA: Saunders Elsevier; 2009.
+
Posner
JB, Saper
CB, Schiff
N, Plum
F. Plum and Posner’s Diagnosis of Stupor and Coma. 4th ed. Oxford, United Kingdom: Oxford University Press; 2007.
+
Shevell
M, Ashwal
S, Donley
D,
et al. Practice parameter: evaluation of the child with global developmental delay.
Neurology. 2003;60(3):367–380.
[PubMed: 12578916]
+
Subcommittee on Febrile Seizures, American Academy of Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure.
Pediatrics. 2011;127(2):389–394.
[PubMed: 21285335]
+
Volpe
JJ. Neurology of the Newborn. 5th ed. Philadelphia, PA: Saunders Elsevier; 2008.