Pediatric Residency Training Program

12

Neurology

Charles E. Niesen M.D.

  1. The Hypotonic Infant
  2. Definition

Hypotonia is the decreased resistance of movement during passive stretching of muscles. In contrast, weakness is the decreased or less than normal force generated by active contraction of muscles.

  1. Classification of hypotonia
  2. Central hypotoniais dysfunction ofupper motor neurons(i.e., cortical pyramidal neurons and their descending corticospinal pathways).
  3. Peripheral hypotoniais dysfunction oflower motor neurons(i.e., spinal motor neurons and distally to the muscle fibers).
  4. Clinical features
  5. Historymay reveal antenatal or neonatal problems. Decreased fetal movements and breech presentationmay be associated with a peripheral hypotonia. Seizures in the neonatal periodmay be associated with a central hypotonia.
  6. Physical examination findingsin both central and peripheral hypotonia may include a weak cry, decreased spontaneous movement, a frog-leg posture(the hips are externally rotated and flexed), and muscle contractures. When lifted up from under the axillae, the infant slips easily through the examiner's hands.
  7. In central hypotonia, there is an altered level of consciousness and increased deep tendon reflexes (DTRs), often with ankle clonus.
  8. In peripheral hypotonia, consciousness is unaffected, but muscle bulk and DTRs are decreased.
  9. In addition to hypotonia, patients withcongenital neuromuscular disordersmay have additional findings such as bilateral ptosis, ophthalmoplegia, flat mid-face, fish-shaped mouth, high-arched palate, chest wall abnormalities (e.g., bell-shaped chest, pectus excavatum or carinatum), and bilateral cryptorchidism.
  10. Etiology

Hypotonia may be caused by systemic pathology (e.g., sepsis, electrolyte abnormalities, hepatic or renal encephalopathy) or by neural

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pathology that may occur anywhere along the transmission route of a neural impulse (Figure 12-1).

  1. Evaluation
  2. Acute life-threatening causes, such as sepsis, meningitis, or an acute metabolic disorder, must be ruled out.
  3. When central hypotonia is suspected, it is necessary to consider:
  4. Head computed tomography (CT) scanto rule out acute central nervous system (CNS) injury or congenital malformation
  5. Serum electrolytes, calcium and magnesium levels, and ammonia, lactate, and pyruvate levels to rule out metabolic disorders
  6. High-resolution chromosome studiesand fluorescent in situ hybridization (FISH) tests for suspected genetic disorders (e.g., Prader-Willi syndrome)
 

Figure 12-1. Differential diagnosis of hypotonia.

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  1. When peripheral hypotonia is suspected, it is necessary to consider:
  2. Serum creatine kinase (CK)levels
  3. DNA testsfor spinal muscular atrophy (see section F.1)
  4. Electromyography (EMG).Nerve conduction studiesare crucial to identify myasthenic disorders.
  5. Muscle biopsy
  6. Specific peripheral hypotonic disorders

are described in more detail in the following discussion.

  1. Spinal muscular atrophy (SMA)
  2. Definition.SMA is anterior horn cell degeneration that presents with hypotonia, weakness, and tongue fasciculations.
  3. Epidemiology.Incidence is 1 in 10, 000–25, 000 live births. SMA is the second most common hereditary neuromuscular disorder after Duchenne muscular dystrophy.
  4. Classification
  5. Type 1or infantile form with onset < 6 months of age (also known as Werdnig-Hoffman disease)
  6. Type IIorintermediate form with onset at 6–12 months of age
  7. Type IIIorjuvenile form with onset > 3 years of age
  8. Etiology
  9. Autosomal recessive inheritance
  10. All three forms of SMA are caused by mutations in the survival motor neuron gene(SMN1) on chromosome 5.
  11. Pathologyof the spinal cord shows degeneration and loss of anterior horn motor neurons and infiltration of microglia and astrocytes.
  12. Clinical features
  13. Weak cry, tongue fasciculations, and difficulty sucking and swallowing
  14. Bell-shaped chest
  15. Frog-leg posturewhen in supine position, generalized hypotonia, weakness, and areflexia
  16. Normal extraocular movementsandnormal sensory examination
  17. Diagnosis
  18. DNA testingfor the abnormal gene is diagnostic in >90% of cases.
  19. Muscle biopsyshows a characteristic atrophy of groups of muscle fibers that were innervated by the damaged axons.
  20. Management. Treatment is supportive.There is no cure for this degenerative neuronal disorder. Supportive care includes gastrostomy tube feeding to ensure adequate nutrition, diligent surveillance and therapy of respiratory infections, and physical therapy to maintain range of motion and prevent contractures.
  21. Prognosis. For SMA type I, survival beyond the first year of life is unusual. Death occurs as a result of respiratory insufficiency or pneumonia.

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For SMA types II and III, survival until adolescent and adult years, respectively, is common.

  1. Infantile botulism
  2. Definition.Infantile botulism is bulbar weakness and paralysis that develops in infants during the first year of life secondary to ingestion ofClostridium botulinumspores and absorption of botulinum toxin.
  3. Etiology.The source of the botulinum toxin is infected foods, such as contaminated honey, or spores unearthed from the ground. The toxin prevents the presynaptic release of acetylcholine.
  4. Clinical features
  5. Onset of symptomsoccurs 12–48 hours after ingestion of spores.
  6. Constipation is the classic first symptom of botulism.
  7. Neurologic symptoms follow, including weak cry and suck, loss of previously obtained motor milestones, ophthalmoplegia, and hyporeflexia.
  8. Paralysis is symmetric and descending, and, at times, diaphragmatic paralysis may occur.
  9. Diagnosis.Diagnosis is based on suggestive history, neurologic examination, and identification of the toxin or bacteria in the stool. EMG is sometimes performed and shows brief, small-amplitude muscle potentials with an incremental response during high-frequency stimulation.
  10. Management. Treatment is supportivewith nasogastric feeding and assisted ventilation as needed.
  11. Botulism immune globulinimproves the clinical course.
  12. Antibiotics are contraindicatedand may worsen the clinical course.
  13. Prognosis.The outlook isexcellent, and complete recovery is expected. However, recovery may take weeks or even months.
  14. Congenital myotonic dystrophy
  15. Definitions
  16. Myotonia is the inability to relax contracted muscles.
  17. Congenital myotonic dystrophyis an autosomal dominant muscle disorder that presents in the newborn period with weakness and hypotonia.
  18. Epidemiology.Incidence is 1 in 30, 000 live births.
  19. Etiology.Myotonic dystrophy is a trinucleotide repeat disorder with autosomal dominant inheritance and variable penetrance. The gene has been identified on chromosome 19. Transmission to affected infants is through the affected mother in more than 90% of cases. The earlier the onset of the disease in the mother, the more likely she will have affected offspring.
  20. Clinical features
  21. Antenatal historymay reveal polyhydramnios caused by poor swallowing in utero and decreased fetal movements.

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  1. Neonatal historyis often significant for feeding and respiratory problems.
  2. Physical examinationof the neonate is notable for facial diplegia (bilateral weakness), hypotonia, areflexia, and arthrogryposis (multiple joint contractures).
  3. Myotonia is not present in the newborn, but develops later, almost always by 5 years of age.
  4. In adulthood, typical myotonic features include myotonic facies(atrophy of masseter and temporalis muscles), ptosis, a stiff, straight smile, and an inability to release the grip after handshaking (myotonia).
  5. Additional problemsinclude mental retardation, cataracts, cardiac arrhythmias, and infertility.
  6. Diagnosis
  7. This disorder should be suspected in all infants with hypotonia.The child's mother should also be examined; she will have the typical features of myotonic dystrophy.
  8. DNA testingto identify the gene can be performed to confirm the diagnosis. Because of the availability of DNA testing, EMG and muscle biopsy are no longer indicated.
  9. Management. Treatment is supportive.Infants may require assisted ventilation and gastrostomy tube feedings.
  10. Prognosis. Outlook is guarded.Infant mortality can be as high as 40% because of respiratory problems.
  11. All survivors have mental retardation (average intelligence quotient [IQ] of 50–65).
  12. Feeding problems tend to subside with time.
  13. Hydrocephalus
  14. Definition

Hydrocephalus is increased cerebrospinal fluid (CSF) under pressure within the ventricles of the brain. Hydrocephalus results from blockage of CSF flow, decreased CSF absorption, or, rarely, increased CSF production.

  1. Types of Hydrocephalus
  2. Noncommunicating hydrocephalusrefers to enlarged ventricles caused by obstruction of CSF flow through the ventricular system (e.g., aqueductal stenosis).
  3. Communicating hydrocephalusrefers to enlarged ventricles as a result of increased production of CSF (e.g., tumors) or decreased absorption of CSF (e.g., bacterial meningitis).
  4. Hydrocephalus ex vacuois not true hydrocephalus, but rather a term used to describe ventricular enlargement caused by brain atrophy.
  5. Etiology
  6. Congenital causes
  7. Chiari type II malformationis characterized by downward displacement

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of the cerebellum and medulla through the foramen magnum, blocking CSF flow. This malformation is often associated with a lumbosacral myelomeningocele.

  1. Dandy-Walker malformation, a combination of an absent or hypoplastic cerebellar vermis and cystic enlargement of the fourth ventricle, which blocks the flow of CSF.
  2. Congenital aqueductal stenosis(some cases of aqueductal stenosis are inherited as an X-linked trait and these patients may have thumb abnormalities and other CNS anomalies such as spina bifida)
  3. Acquiredcauses include intraventricular hemorrhage (most common in preterm infants), bacterial meningitis, and brain tumors.
  4. Clinical Features
  5. Increasing head circumferencethat crosses percentile lines, or head circumference > 97% for age.
  6. Infantswith open cranial sutures have the following clinical signs:
  7. Large anterior and posterior fontanelles and split sutures
  8. Sunset sign, a tonic downward deviation of both eyes caused by pressure from the enlarged third ventricles on the upward gaze center in the midbrain
  9. Older childrenwith closed cranial sutures have the symptoms and signs of increased intracranial pressure:
  10. Headache
  11. Nausea and vomiting
  12. Unilateral sixth nerve palsy
  13. Papilledema
  14. Brisk DTRs but with a usually downward plantar response.
  15. Evaluation

Increasing head circumference and signs or symptoms of increased intracranial pressure mandate an urgent head CT scan.

  1. Management

Hydrocephalus requires the surgical placement of aventriculoperitoneal shunt to divert the flow of CSF. Complications of ventriculoperitoneal shunts include shunt infectionandshunt obstruction.

  1. Prognosis

Outcome varies depending on the cause of the hydrocephalus.

  1. Patients with aqueductal stenosishave the best cognitive outcome.
  2. Patients with Chiari type II malformationmay have low-normal intelligence and language disorders.
  3. Patients with X-linked hydrocephalusmay have severe mental retardation.

III. Spina Bifida

  1. Definitions
  2. Spina bifida (SB)is a general term that refers to any failure of bone fusionin the posterior midline of the vertebral column.

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  1. Neural tube defectis a broad term that includes all forms of failure of neural tube closure, from anencephaly to sacral meningocele.
  2. Myelomeningoceleis the herniation of spinal cord tissue and the meninges through a bony cleft, most commonly in the lumbosacral region. Myelomeningocele is 20 times more common than meningocele.
  3. Meningoceleis the herniation of the meninges only through a bony cleft, most commonly in the lumbosacral region. Meningocele is usually not associated with any neural deficits.
  4. In SB occulta, there is no herniationof tissue through the vertebral cleft.
  5. Epidemiology

Incidence of neural tube defects varies with geographic location. The highest incidence is in Ireland (1 in 250 live births), and thelowest is in Japan (1 in 3, 000 live births).

  1. Etiology

The multifactorial etiology includes environmental, genetic, nutritional, and teratogenic factors.

  1. Mothers taking a multivitamin preparation that includes folic acidhave decreased incidence of SB. The mechanism of action of folic acid is uncertain.
  2. Teratogensthat cause SB include valproate, phenytoin, colchicine, vincristine, azathioprine, and methotrexate.
  3. Clinical Features
  4. SB occulta.The skin on the back (usually lumbosacral region) is epithelialized and a hairy patch or dimple often covers the area. No neurologic deficits are present.
  5. Meningocele.A fluctuant midline mass is present overlying the spine. The mass is filled with CSF and can be transilluminated. Neurologic deficits are usually not present or are only very mild.
  6. Myelomeningocele
  7. fluctuant midlinemass is present anywhere along the spine, but most commonly in the lumbosacral region.
  8. Neurologic defects are present and depend on the level of the lesion, varying from complete paraplegia (above L3) to preserved ambulation and variable bladder or bowel incontinence (S3 and below).
  9. Associated anomalies and complications
  10. Hydrocephalus. Ninety percent of lumbosacral myelomeningoceles are associated with Chiari type II malformation and hydrocephalus.Cervical and thoracic myelomeningoceles are not associated with hydrocephalus.
  11. Cervical hydrosyringomyelia(accumulation of fluid within the central spinal cord canal and with the cord itself)
  12. Defects in neuronal migration(e.g., gyral anomalies, agenesis of the corpus callosum)
  13. Orthopedic problems (e.g., rib anomalies, deformities of the lower extremities, lower extremity fractures from loss of sensation)
  14. Genitourinary defects

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  1. Diagnosis
  2. Prenatal diagnosis is common.
  3. α-Fetoprotein (AFP), the main serum protein in fetal life, is elevated in amniotic fluid and maternal serum in open neural tube defects and, when measured in maternal serum at 16–18 weeks gestation, detects 80% of spinal defects.
  4. Fetal sonographyis highly sensitive in detecting spinal defects.
  5. Diagnosis after birth
  6. SB occultais suggested by finding any skin abnormality overlying the spine and is confirmed by spinal radiographs.
  7. Meningoceleis suggested by physical examination findings and is confirmed by magnetic resonance imaging (MRI) of the spinal cord and spine.
  8. Myelomeningoceleis a clinical diagnosis based on physical examination at birth.
  9. Management
  10. SB occultadoes not require treatment.
  11. Meningocelerequires surgical repair.
  12. Myelomeningocelerequires urgent surgical repair within 24 hours of birth to reduce the morbidity and mortality from infection and to prevent further trauma to the exposed neural tissue.
  13. Prognosis
  14. SB occulta and meningocele have excellent prognosesas a result of the absence of neurologic deficits.
  15. Myelomeningocele.Ninety percent of patients survive to adolescence, but many are handicapped. Associated problems include wheelchair dependency, bladder or bowel incontinence, mental retardation, seizures, precocious puberty, pressure sores, and fractures.
  16. Approach to the Comatose Patient
  17. Definition

Coma is a state of unawareness of self and environment in which the patient lies with the eyes closed and is unarousable by external stimuli.

  1. Etiology

(Table 12-1)

  1. In children younger than 5 years of age, nonaccidental trauma and near-drowning are the most common causes of coma.
  2. In older children, drug overdose and accidental head injury are the most common causes of coma.
  3. Assessment

Thegoal of assessment of the comatose patient is to determine the depth of coma, to identify the neurologic signs that indicate the site and cause of the coma, and to monitor the patient's recovery.

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Table 12-1. Causes of Coma in Childhood and Adolescence

Focal lesions (abnormal neuroimaging studies)

 

Supratentorial lesions

 

 

Vascular: subarachnoid hemorrhage, multiple infarcts, thalamic infarct
Trauma: subdural hematoma, nonaccidental trauma
Tumors
Demyelination (e.g., postinfectious encephalitis)

 

Infratentorial lesions

 

 

Vascular: cerebellar hemorrhage
Trauma
Tumors

Diffuse lesions (often with normal neuroimaging studies)

 

Ingestion

 

 

Drugs:*

Atropine, scopolamine
Benzodiazepines, barbiturates
Ethanol, lithium
Opiates
Tricyclic antidepressants

 

 

Toxins:

Lead, mercury

 

Infection

 

 

Encephalitis

 

Hypoxemia

 

 

Near-drowning, carbon monoxide

 

Abnormal metabolites

 

 

Metabolic:

Hypo- or hyperglycemia
Hypo- or hypernatremia
Thiamine deficiency

 

 

Endocrine:

Hypo- or hyperthyroidism
Hypo- or hypercortisolism

 

Organ failure

 

 

Cardiac arrest, hepatic failure, uremia

 

Seizures

 

 

 

Nonconvulsive status epilepticus

 

 

Reye syndrome

 

*Amphetamine, cocaine, and hallucinogens (lysergic acid diethylamide [LSD], mescaline, phencyclidine hydrochloride [PCP]) cause agitation, confusion, delirium, and hallucinations but not coma.

 
  1. Glasgow Coma Scaleprovides a standard measure to monitor the level of consciousness (see Chapter 20, Table 20-1).
  2. Head and neck exam.The patient should be assessed for scalp injuriesbreath odors (for alcohol intoxication or ketosis caused by diabetic ketoacidosis), and nuchal rigidity(caused by meningitis). CSF or blood draining from the nose or auditory canal may indicate a basilar skull fracture.
  3. Abnormal motor responsesto stimuli can indicate the location of brain damage.
  4. Flaccidity or no movementsuggests severe spinal or brainstem injury.
  5. Decerebrate posturing (extension of arms and legs)indicates subcortical injury.
  6. Decorticate posturing (flexion of arms and extension of legs)suggests bilateral cortical injury.
  7. Asymmetric responsessuggest hemispheric injury.

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  1. Abnormal respiratory responsesmay indicate the location of brain injury or its cause.
  2. Hypoventilationsuggests opiate or sedative overdose.
  3. Hyperventilationsuggests metabolic acidosis (Kussmaul respirations, or rapid, deep breathing, may occur), neurogenic pulmonary edema, or midbrain injury.
  4. Cheyne-Stokes breathing(alternating apneas and hyperpneas) suggests bilateral cortical injury.
  5. Apneustic breathing(pausing at full inspiration) indicates pontine damage.
  6. Ataxic or agonal breathing(irregular respirations with no particular pattern) indicates medullary injury and impending brain death.
  7. Pupillary size and reactivitymay provide clues:
  8. Unilateral dilated nonreactive pupil suggests uncal herniation.
  9. Bilateral dilated nonreactive pupils suggest topical application of a dilating agent, a postictal state, or irreversible brainstem injury.
  10. Bilateral constricted reactive pupils suggest opiate ingestion or pontine injury.
  11. Other brainstem reflexesshould be assessed to determine the extent of injury to the brainstem.
  12. Oculocephalic maneuver (doll's eyes). When turning the head of an unconscious patient, the eyes normally look straight ahead and then slowly drift back to midline position because the intact vestibular apparatus senses a change in position. In an injured brainstem, movement of the head does not evoke any eye movement. This is termed anegative oculocephalic maneuveror negative doll's eyes.
  13. Caloric irrigation.When the oculocephalic response is negative or cannot be performed because of possible cervical cord injury, caloric testing should be performed. This involves angling the head at 30° and irrigating each auditory canal with 10–30 mL of ice water. An intact (normal) cold caloric response is reflected by eye deviation to the irrigated side. An abnormal response suggests pontine injury.
  14. Abnormal corneal and gag reflexesindicate significant brainstem injury.
  15. Evaluation

Once the airway, breathing, and circulation are stable, further diagnostic workup may begin.

  1. Glucose should be checked immediatelyin any comatose patient.
  2. Urine toxicology screen, serum electrolytes, and metabolic panelshould also be evaluated.
  3. Head CT scanshould be performed to identify mass lesions or trauma.
  4. Lumbar puncture to rule out meningoencephalitis should be consideredif the CT scan is negative.
  5. Urgent electroencephalography (EEG) should be considered, even in patients without a history of clinical seizures.

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  1. Seizure Disorders of Childhood
  2. Definitions
  3. seizureis a transient, involuntary alteration of consciousness, behavior, motor activity, sensation, or autonomic function caused by an excessive discharge from a population of cerebral neurons.
  4. Epilepsyis the occurrence of two or more spontaneous seizures without an obvious precipitating cause.
  5. Status epilepticusis a seizure that lasts > 30 minutes during which the patient does not regain consciousness.
  6. Epidemiology
  7. Four to six percent of children have a single afebrile seizure before 16 years of age.
  8. Fewer than one third of children who have a single seizure go on to develop epilepsy, which has an incidence of 0.5–0.8% during childhood.
  9. Etiology
  10. The seizure discharge is caused by an imbalance between excitatory and inhibitory input within the brain or abnormalities in the membrane properties of individual neurons.
  11. In some children, the cause of seizures is known (Table12-2).
  12. In 60–70%of cases, the cause is unknown.
  13. Classification of Seizures

Criteria for classification are the presence or absence of fever, the extent of brain involvement, whether consciousness is impaired, and the nature of the movements (Figure 12-2).

  1. Febrile seizuresare a common but benign type of seizure associated with fever (see section V.K).
  2. Afebrile seizuresare either generalized or partial, depending on whether both sides or one side of the brain are involved.
  3. Generalized seizuresare caused by the discharge from a group of neurons in both cerebral hemispheres. Two common types are tonic-clonic and absence seizures.

Table 12-2. Causes of Acute Seizures During Childhood

Head trauma

Cerebral contusion, subdural hematoma

Brain tumor

Astrocytoma, meningioma

Toxins

Amphetamines, cocaine

Infections

Meningitis, encephalitis, brain abscess, neurocysticercosis

Vascular

Cerebral infarction, intracranial hemorrhage

Metabolic disturbances

Hypocalcemia, hypoglycemia, hypomagnesemia, hypo- or
hypernatremia, pyridoxine deficiency

Systemic diseases

Hypertension, hypoxic-ischemic injury, inherited metabolic
disorder, liver disease, renal failure, neurocutaneous
disorders (tuberous sclerosis)

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  2. Tonic-clonic seizuresare the most common type of generalized seizure. These seizures are characterized by increased thoracic and abdominal muscle tone, followed by clonic movements of the arms and legs, eyes rolling upward, incontinence, decreased consciousness, and a postictal state of variable duration.
  3. Absence seizuresare brief staring spells that occur without loss of posture and with only minor motor manifestations (e.g., eye blinking or mouthing movements). The seizure lasts < 15 seconds, and there is no postictal state.
  4. Partial (focal) seizuresare caused by the discharge from a group of neurons in one hemisphere. Seizure symptoms may have predominately motor, sensory, or psychomotor features. There are two types, simple and complex.
  5. In simple partial seizures, consciousness is notimpaired.
  6. In complex partial seizures, consciousness is decreased.
 

Figure 12-2. Classification of seizures.

  1. Classification of epilepsy

Classification may be based on either the predominant seizure type or the site of origin of the epileptic discharge. For example, a child may have generalized or complex partial epilepsy, or it may be more convenient to refer to the site of the seizure discharge (e.g., frontal lobe epilepsy).

  1. Differential diagnosis

of seizurelike events (Table 12-3)

  1. Diagnosis

Epilepsy is diagnosed on the basis of history and physical examination. Other studies may be useful.

  1. EEGidentifies the focus and particular pattern of the epileptic discharge. However, an abnormal EEG is not required for the diagnosis of epilepsy (i.e., a normal EEG does not exclude the diagnosis of seizures or epilepsy).
  2. Video-EEG monitoringis a useful tool when clinical information is inadequate or incomplete(e.g., when patients are < 3 years of age, when

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seizurelike events occur during sleep, or when parents are poor historians).

Table 12-3. Differential Diagnosis of Seizurelike Events

Breath-holding spells (in infants)
Gastroesophageal reflux disease (Sandifer syndrome)
Syncope
Migraine
Vertigo
Movement disorder (e.g., tics, chorea)
Sleep disturbances (e.g., night terrors, somnambulism)
Transient ischemic attack
Rage attacks
Psychogenic seizures

  1. Neuroimaging studiesshould be performed in all children with epilepsy, except those with absence seizures or benign rolandic epilepsy (see sections V.L.4 and V.L.5).
  2. Evaluation
  3. Initial treatment starts with assessment of the patient's airway, breathing, and circulation (ABCs).
  4. Laboratory studiesare based on the patient's age, clinical features, and the physical examination.
  5. first-time afebrile seizurein an otherwise healthy child with a normal neurologic examination does not warrant further investigation.
  6. Serum electrolytes and neuroimagingshould be performed in a child who has had prior afebrile seizures.
  7. In a febrile seizure, CNS infection must be ruled outclinically or by examination of CSF. Other studies may include complete blood count (CBC), chest radiograph, and urine and blood cultures (see section V.K).
  8. Management
  9. Treatment of status epilepticus requires intravenous anticonvulsants, such as a short-acting benzodiazepine (e.g., lorazepam or diazepam) followed by a loading dose of either phenobarbital or phenytoin.
  10. Treatment of epilepsy
  11. Pharmacotherapy.Once the type of seizure has been determined, single-drug therapy is started with the antiepileptic drug that has the best combination of high efficacy and low toxicity. Recommended drugs include:
  12. Generalized epilepsy:valproic acid or phenobarbital
  13. Absence epilepsy:ethosuximide
  14. Partial epilepsy:carbamazepine or phenytoin
  15. Surgery

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  1. For medically intractable epilepsy, surgery to remove epileptic tissue may be an option.
  2. The best prognosis is for patients with temporal lobe lesions, 75% of whom have complete seizure control or remission after surgery.
  3. Alternative treatments.Patients with poorly controlled seizures for whom surgery is not an option have two additional choices.
  4. Vagal nerve stimulatoris a pacemaker-sized device that sends an electrical impulse to the vagus nerve. A common side effect is hoarseness.
  5. Ketogenic diet (a high-fat, low-carbohydrate diet) is thought to suppress seizure activity by producing a state of ketosis.
  6. Prognosis

Epilepsy is not a lifelong disorder. About 70% of epileptic children can be weaned off their medications after a 2-year seizure-free period and normalization of the EEG.

  1. Febrile Seizures
  2. Definition.A febrile seizure is any seizure that is accompanied by a fever owing to a non-CNS cause in patients from 6 months to 6 years of age.
  3. Epidemiology.Febrile seizures arecommonoccurring in 3% of all children.
  4. Etiology
  5. The pathophysiologic mechanism is unknown.
  6. Febrile seizures can be inherited, and several gene mutations have been found.
  7. Classification
  8. A simple febrile seizure lasts less than 15 minutes and is generalized.
  9. A complex febrile seizure lasts more than 15 minutes, has focal features, or recurs within 24 hours.
  10. Diagnosis
  11. The diagnosis of a febrile seizure is based on history, a normal neurologic examination, and the exclusion of any CNS infection.
  12. A lumbar punctureis necessary only if meningitis is suspected.
  13. Neither neuroimaging nor EEG is neededunless the neurologic examination is abnormal.
  14. Management
  15. First-time or occasional febrile seizuresare not treated with anticonvulsants.
  16. Aggressive antipyretic treatment of subsequent febrile illnesses may help prevent febrile seizures.
  17. Frequent, recurrent febrile seizuresdo pose a risk and may require additional treatment, including:
  18. Daily anticonvulsant prophylaxiswith valproic acid or phenobarbital
  19. Abortive treatment with rectal diazepam
  20. Prognosis. Approximately 30% of patients with one febrile

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seizure will have a recurrence.
 Recurrence risk decreases with increasing patient age. The risk of epilepsy is low (2%).

  1. Epileptic Syndromes
  2. Definition.Epileptic syndromes are epileptic conditions characterized by a specific age of onset, seizure characteristic, and EEG abnormality.
  3. Classification.More than 15 epileptic syndromes are recognized. Each syndrome has its own seizure severity and outcome. Three of the most common are infantile spasms, absence epilepsy of childhood, and benign rolandic epilepsy.
  4. Infantile spasms (West syndrome)
  5. Epidemiology. Age of onsetis typically 3–8 months. Infantile spasms are rare in children older than 2 years of age.
  6. Etiology. Tuberous sclerosis is the most commonly identified causeof infantile spasms. Other inherited and acquired causes include phenylketonuria, hypoxic-ischemic injury, intraventricular hemorrhage, meningitis, and encephalitis.
  7. Clinical features
  8. Brief, myoclonic jerks, lasting 1–2 seconds each, occurring in clusters of 5–10 seizures spread over 3–5 minutes.
  9. The jerks consist of sudden arm extension or head and trunk flexion (also known as jackknife seizuresor salaam seizures).
  10. Diagnosis.The EEG shows the characteristic hypsarrhythmia pattern, a highly disorganized pattern of high amplitude spike and waves occurring in both cerebral hemispheres.
  11. Management
  12. Adrenocorticotropic hormone (ACTH)intramuscular injections for a 4- to 6-week period are effective in more than 70% of affected patients.
  13. Valproic acidis the second-line drug of choice.
  14. Vigabatrinis the most effective drug for patients with infantile spasms associated with tuberous sclerosis.
  15. Prognosis. Outlook is poor.Despite the success of these different medications in suppressing seizures, children often develop moderate to severe mental retardation.
  16. Absence epilepsy of childhood
  17. Epidemiology. Age of onsetis between 5 and 9 years of age. There is a female-to-male predominance of 3:2.
  18. Etiology.Inheritance is autosomal dominant with age-dependent penetrance.
  19. Clinical features
  20. Absence seizures last 5–10 seconds.
  21. They occur frequently—tens to hundreds of times per day.
  22. They are often accompanied by automatisms, such as eye blinking and incomprehensible utterances.
  23. Loss of posture, urinary incontinence, and a postictal state do not occur.

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  1. Diagnosis.The EEG shows the characteristic generalized 3-Hz spike and wave discharge arising from both hemispheres.
  2. Management. Treatment includes ethosuximide(first-line drug) or valproic acid.
  3. Prognosis. Outlook is very good;the seizures usually resolve by adolescence without cognitive impairment.
  4. Benign rolandic epilepsy (benign centrotemporal epilepsy)
  5. Definition.Benign rolandic epilepsy involves nocturnal partial seizures with secondary generalization.
  6. Epidemiology
  7. Benign rolandic epilepsy is the most common partial epilepsy during childhood, accounting for 15% of epilepsy.
  8. It commonly presents at 3–13 years of age. Peak incidence is at 6–7 years. Boys are more likely to be affected.
  9. Etiology.Inheritance is autosomal dominant with variable penetrance.
  10. Clinical features
  11. Seizures occur in the early morning hourswhen patients are asleep with oral-buccal manifestations (i.e., moaning, grunting, pooling of saliva).
  12. Seizures spread to face and arm, then generalize into tonic-clonic seizures.
  13. Diagnosis. The EEGshows biphasic spike and sharp wave disturbance in the mid-temporal and central regions.
  14. Management.Treatment includes valproic acid (first-line drug) or carbamazepine.
  15. Prognosis. Outcome is excellent.Seizures remit spontaneously during adolescence with no adverse effects on development or cognition.
  16. Headaches in Childhood
  17. Etiology

Headaches may have intracranial or extracranial causes (Figure 12-3).

  1. Intracranial causes
  2. Primary headachesare caused by a primary dysfunction of neurons (e.g., migraine headaches) or muscles (e.g., tension headaches).
  3. Secondary headachesare caused by increased intracranial pressure (ICP; e.g., hydrocephalus) or meningeal irritation (e.g., meningitis, subarachnoid hemorrhage).
  4. Extracranial causes
  5. Local causesinclude sinusitis, perioral abscess, toothache, chronic otitis media, or refractive errors.
  6. Systemic causesinclude anemia and hypoglycemia in children, and depression and hypertension in adolescents.
  7. Important clinical information

about a patient's headache helps determine the cause.

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Figure 12-3. Causes of headache. ICP = intracranial pressure.

  1. Quality of pain.Throbbing or pounding pain suggests migraine headaches, whereas an aching feeling of pressure is more common in tension headaches.
  2. Site and radiation.Migraine headaches are usually unilateral and may begin in the periorbital area and spread to the forehead and occiput, whereas tension headaches are often generalized or bitemporal.
  3. Time of onset.Tension headaches occur toward the end of the day, whereas headaches from increased ICP occur in the morning.
  4. Duration.The shorter the headache duration, the less likely a serious disorder is responsible.
  5. Migraine Headaches
  6. Definition.Migraine headaches are prolonged (often > 1 hour), unilateral headaches that are associated with nausea, vomiting, or visual changes and are caused by changes in cerebral blood flow.
  7. Epidemiology
  8. Migraines are the most common cause of headaches in children and adolescents, occurring in up to 5% of school-age children.
  9. Age of onsetis younger than 5 years in 20% of patients.
  10. Before puberty, incidence is higher in males; after puberty, incidence is higher in females.
  11. Etiology

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  1. Inheritance is autosomal dominant.More than 80% of children with migraines have at least one affected parent.
  2. Changes in cerebral blood floware secondary to release of serotonin (5-HT), substance P, and vasoactive intestinal peptide from changes in neuronal activity.
  3. Classification
  4. Migraine without aura is the most common form of migraine in children.Headaches occur in the absence of any warning symptoms.
  5. Migraine with aura.The onset of the headache is preceded by transient visual changes (e.g., blurred vision, small areas of decreased vision [scotomata], streaks of light, or hemianopsia) or unilateral paresthesias or weakness.
  6. Migraine equivalent.In young children, the headache itself may be absent, but there is a prolonged, albeit transient, alteration of behavior that manifests as cyclic vomiting, cyclic abdominal pain, or paroxysmal vertigo.
  7. Migraines associated with focal neurologic signs.
  8. Ophthalmoplegic migraine.Unilateral ptosis or cranial nerve III palsy accompanies this headache.
  9. Basilar artery migraine.Vertigo, tinnitus, ataxia, or dysarthria may precede the onset of this headache.
  10. Precipitating factors.There is no obvious precipitating cause, although many migraine sufferers are sensitive to vasoactive substances in certain wines, cheeses, preserved meats, and chocolate. Some patients note that stress, fatigue, menstruation, or exercise induce the headache.
  11. Clinical features
  12. A prolonged, throbbing, unilateral headachestarts in the supraorbital area and radiates to the occiput. In young children, the headache is often bifrontal.
  13. Nausea and vomitingmay occur. A history of motion sickness is common.
  14. Visual disturbancesinclude blurred vision, scotomata, and jagged streaks of light that take on the outline of old forts (fortifications).
  15. Photophobia or phonophobiaoccurs. Many patients treat themselves by lying in a dark, quiet room.
  16. Over-the-counter analgesics are often ineffective.
  17. Symptoms are improved by sleep.
  18. Neurologic examination is normal.
  19. Diagnosis.Diagnosis is made by history and the presence of a normal neurologic examination.
  20. Management.Treatment includes rest and elimination of known triggers. Medications may be very helpful:
  21. Abortive treatmentincludes sumatriptan, a selective 5-HT agonist, available in injectable, intranasal, and oral forms.
  22. Propranolol is the drug of choice for prophylactic treatmentof frequent migraines.

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  1. Prognosis.Migraines can be a lifelong disorder with a waxing and waning course.
  2. Tension Headaches
  3. Definition.Tension headaches are bifrontal or diffuse, dull, aching headaches that are often associated with muscle contraction.
  4. Epidemiology.Tension headaches are unusual during childhood and extremely rare in children younger than 7 years of age.
  5. Clinical features
  6. Pain is described as dull, aching, and rarely throbbing, and it increases in intensity during the day.
  7. The pain is usually bifrontal but may be diffuse.
  8. Isometric contractionof the temporalis, masseter, or trapezius muscle often accompanies the headache.
  9. No vomiting, visual changes, or paresthesias occur.
  10. Diagnosis.Clinical presentation provides a clue to the diagnosis, although no laboratory or imaging study is diagnostic. Tension headaches are very rare in childhood, and therefore other diagnoses (e.g., migraines) should be preferentially considered.
  11. Management.Treatment includes reassurance and pain control (e.g., acetaminophen, ibuprofen). Stress and anxiety reduction may provide long-term relief.
  12. Cluster Headaches

These headaches are extremely rare during childhood. They are characterized by unilateral frontal or facial pain, accompanied by conjunctival erythema, lacrimation, and nasal congestion. The headaches usually last < 30 minutes but may recur several times in a day and then not occur again for weeks or months (hence the term “cluster”). Treatment includes abortive therapy with oxygen or sumatriptan. Prophylactic treatments include calcium-channel blockers and valproic acid.

VII. Approach to Unsteady Gait

  1. Definition

Ataxia is the inability to coordinate muscle activity during voluntary movement. It can involve the trunk or limbs and is caused by cerebellar or proprioceptive dysfunction.

  1. Differential diagnosis

A variety of neurologic problems can give the appearance of an unsteady gait.

  1. Cerebellar dysfunction.Children with a cerebellar gait have an unsteady, wide-based stance with irregular steps and veering to one side or the other. See Table 12-4 for the causes of cerebellar ataxia.
  2. Weakness.Any cause of muscle weakness, such as spinal cord lesions or acute disorders of the motor unit (e.g., Guillain-Barré syndrome, see section VII.D), can lead to an unsteady gait.
  3. Encephalopathy as a result of infection, drug overdose, or recent head traumamay cause decreased levels of consciousness, which may affect gait.

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Table 12-4. Differential Diagnosis of Cerebellar Ataxia

Brain tumors

Cerebellar astrocytoma
Cerebellar primitive neuroectodermal tumor (medulloblastoma)
Neuroblastoma

Trauma

Cerebellar contusion
Subdural hematoma

Toxins

Ethanol
Anticonvulsants

Vascular

Cerebellar infarction or hemorrhage

Infections

Meningitis
Encephalitis

Inflammatory

Acute cerebellar ataxia of childhood

Demyelination

Acute disseminated encephalomyelitis
Multiple sclerosis

  1. Seizures.During a seizure or while in the postictal period, the patient's gait is irregular and unsteady.
  2. Vision problemscan mimic the appearance of an unsteady gait.
  3. Vertigofrom migraines, acute labyrinthitis, and brainstem tumors may lead to unsteady walking.
  4. Acute Cerebellar Ataxia of Childhood
  5. Definition.Acute cerebellar ataxia is an unsteady gait secondary to a presumed autoimmune or postinfectious cause.
  6. Epidemiology
  7. Acute cerebellar ataxia is the most common cause of ataxia in children.
  8. Age of onsetis between 18 months and 7 years. Acute cerebellar ataxia rarely occurs in children older than 10 years of age.
  9. Etiology
  10. Common preceding infectionsinclude varicella, influenza, Epstein-Barr virus (EBV), and mycoplasma. The ataxia usually follows a viral illness by 2–3 weeks.
  11. The postulated cause is immune complex deposition in the cerebellum.
  12. Clinical features
  13. Truncal ataxiawith deterioration of gait is characteristic. Young children may refuse to walk for fear of falling.
  14. Slurred speech and nystagmusare often present, although hypotonia and tremors are less common.
  15. Fever is absent.
  16. Diagnosis. Diagnosis is by history and physical examination and by exclusionof other causes of ataxia. An urgent neuroimaging study is necessary in all patients suspected of cerebellar ataxia to rule out acute life-threatening causes, such as tumors or hemorrhage in the posterior fossa. Head CT scan is normal in this disorder.
  17. Management. Treatment is supportive.Complete resolution of symptoms may take as long as 2–3 months. Physical therapy may be useful.

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  1. Guillain-Barré Syndrome (acute inflammatory demyelinating polyneuropathy)
  2. Definition.Guillain-Barré syndrome is a demyelinating polyneuritis characterized by ascending weakness, areflexia, and normal sensation.
  3. Etiology.The most commonly associated infectious agent is Campylobacter jejuni, which causes a prodromal gastroenteritis. Many other infectious agents have been associated with Guillain-Barré syndrome, such as cytomegalovirus, EBV, herpes zoster virus, influenza, varicella, and coxsackievirus.
  4. Pathophysiology
  5. The principal sites of demyelinationare the ventral spinal roots and peripheral myelinated nerves.
  6. Injury is triggered by a cell-mediated immune responseto an infectious agent that cross-reacts to antigens on the Schwann cell membrane.
  7. Clinical features
  8. Ascending, symmetric paralysismay progress to respiratory arrest.
  9. No sensory loss occurs, although low back or leg pain may be present in 50% of patients.
  10. Cranial nerve involvement.Facial weakness occurs in 40–50% of patients.
  11. Miller-Fisher syndrome, a variantof Guillain-Barré syndrome, is characterized by ophthalmoplegia, ataxia, and areflexia.
  12. Diagnosis
  13. Lumbar punctureshows albuminocytologic dissociation (i.e., increased CSF protein in the absence of an elevated cell count), which is usually evident 1 week after symptom onset.
  14. EMGdemonstrates decreased nerve conduction velocity or conduction block.
  15. Spinal MRImay be necessary in children younger than 3 years of age to rule out compressive lesions of the spinal cord because the sensory examination in children of this age is often difficult to evaluate.
  16. Management.Treatment should be initiated as soon as the diagnosis is established because of the risk of respiratory muscle paralysis.
  17. Intravenous immune globulin (IVIG), given for 2–4 days, is the preferred treatment for childrenbecause of its relative safety and ease of use. The mechanism of action of IVIG is unknown.
  18. Plasmapheresisremoves the patient's plasma along with the presumed anti-myelin antibodies and is performed over a 4- to 5-day period.
  19. Prognosis. Complete recovery is the rule in childrenbut depends on the severity and extent of the weakness. Physical therapy may be necessary for several weeks or longer to aid recovery.

VIII. Movement Disorders

  1. Sydenham chorea

(St. Vitus' dance)

  1. Definition.Sydenham chorea is a self-limited autoimmune disorder associated with rheumatic fever (see Chapter 16, section VI) that

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presents with chorea (uncontrolled, restless proximal limb movements) and emotional lability.

  1. Epidemiology
  2. Sydenham chorea occurs in approximately 25% of patients with rheumatic fever.
  3. Onset is most common between 5 and 13 years of age.
  4. Pathophysiology.Sydenham chorea occurs secondary to antibodies that cross-react with membrane antigens on both group A β-hemolytic streptococcus and basal ganglia cells.
  5. Clinical features
  6. Immunologic responseusually follows the streptococcal pharyngitis by 2–7 months.
  7. Children appear restless.The face, hands, and arms are mainly affected, and the movements appear continuous, quick, and random. The chorea may begin as clumsiness of the hands.
  8. Speech is also affectedand can be jerky or indistinct.
  9. Patients are unable to sustain protrusion of the tongue (chameleon tongue).
  10. The wrist is held flexed and hyperextended at the metacarpal joints (choreic hand). On gripping the examiner's fingers, patients are unable to maintain the grip (milkmaid's grip).
  11. Emotional labilityis common.
  12. Gait and cognition are not affected.
  13. Differential diagnosis. Other conditions that may cause choreainclude many acquired and congenital conditions, including encephalitis, kernicterus, systemic lupus erythematosus, Huntington's disease, and Wilson's disease.
  14. Diagnosis.There is no single confirmatory test for Sydenham chorea. The diagnosis rests on presumptive evidence of rheumatic fever and the exclusion of other likely causes of chorea.
  15. Elevated antistreptolysin O (ASO) or anti-DNase B (ADB) titermay indicate a recent streptococcal infection.
  16. Neuroimaging
  17. Head MRImay show increased signal intensity in the caudate and putamen on T2-weighted sequences.
  18. Single-photon emission computed tomography (SPECT)may demonstrate increased perfusion to the thalamus and striatum.
  19. Management.Treatment involves the use of haloperidol, valproic acid, or phenobarbital.
  20. Prognosis.Symptoms may last from several months to 2 years. Generally, all patients recover.
  21. Tourette Syndrome
  22. Definitions
  23. Tourette syndrome is a chronic, lifelong movement disorderthat presents with motor and phonic tics before 18 years of age.

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  1. Tics are brief, stereotypical behaviorsthat are initiated by an unconscious urge that can be temporarily suppressed.
  2. Epidemiology.The prevalence of Tourette syndrome is 1 in 1, 000 live births. However, tics occur in 3% of children.
  3. Etiology.The cause of Tourette syndrome is unknown. In some patients, there is a genetic predisposition.
  4. Clinical features
  5. Motor ticscan be simple (e.g., eye blinking, head or shoulder shaking) or complex (e.g., bouncing, jumping, kicking).
  6. Phonic ticscan be simple (e.g., coughing, groaning, barking) or complex (e.g., echolalia, which is the repetition of heard words or phrases).
  7. Tics must be present ≥ 1 year, although their severity and frequency waxes and wanes.
  8. Absenceof any signs of a neurodegenerative disorder
  9. Coprolalia, the utterance of obscene words, is a dramatic symptom that occurs in 15% of patients but is rare at initial presentation.
  10. Associated findingsinclude learning disabilities, attention deficit/hyperactivity disorder, and obsessive-compulsive traits.
  11. Differential diagnosis. Disorders that may cause ticsinclude Wilson's disease, Sydenham chorea, partial seizures, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) (see Chapter 7, section IX.A.5.f.(4)), or simple habits. (Habits differ from tics in that habits are situation-dependent and are under voluntary control.)
  12. Diagnosis
  13. Tourette syndrome is a clinical diagnosis based on history and neurologic findings.
  14. No laboratory or imaging tests confirm the diagnosis.
  15. Management
  16. Pimozideis the drug of choice because it is effective with minimal extrapyramidal side effects.
  17. Clonidineis less effective than pimozide. The major side effect is sedation.
  18. Haloperidolwas the first drug used to treat Tourette syndrome, but the risk of tardive dyskinesia has limited its use.
  19. Hypnotherapyhas been effective in some patients.
  20. Prognosis
  21. Tics tend to decrease in adulthood.
  22. Pharmacotherapy is generally successful, but side effects from the medications may be limiting.
  23. Duchenne and Becker Muscular Dystrophies (DMD, BMD)
  24. Definition

DMD and BMD are progressive, X-linked myopathies characterized by myofiber degeneration. DMD is more severe than BMD.

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  1. Epidemiology
  2. These worldwide disorders occur in all ethnic groups.
  3. Prevalence is 1 in 25, 000 live births.
  4. Onsetof symptoms is between 2 and 5 years of age.
  5. Etiology

These X-linked disorders are caused by a deletion in the dystrophin gene.

  1. Pathophysiology
  2. Dystrophinis a high molecular weight cytoskeletal protein that associates with actin and other structural membrane elements.
  3. The absence of dystrophincauses weakness and eventually rupture of the plasma membrane, leading to injury and degeneration of muscle fibers.
  4. Pathology

Both DMD and BMD have the same appearance on light microscopy.

  1. Degeneration and regenerationof muscle fibers
  2. Infiltration of lymphocytesinto the injured area and replacement of damaged muscle fibers with fibroblasts and lipid deposits
  3. Clinical Features
  4. Slow, progressive weakness affecting the legs first
  5. In DMD, children lose the ability to walk by 10 years of age. In BMD, patients lose the ability to walk by 20 or more years of age.
  6. Pseudohypertrophy of calvesis present because of the excess accumulation of lipids, which replace the degenerating muscle fibers. This is more common in DMD than in BMD.
  7. Gowers' sign is present.Because of the weakness of pelvic muscles, patients arise from the floor in a characteristic manner by extending each leg and then “climbing up” each thigh until they reach an upright position.
  8. Cardiac involvement(e.g., cardiomegaly, tachycardia, or cardiac failure) occurs in 50% of patients.
  9. Mild cognitive impairment occurs in DMD, but normal intelligence is present in BMD.
  10. Diagnosis
  11. The presence of enlarged calf muscles in a young boy with muscle weakness suggests the diagnosis.
  12. CK levels are very high.
  13. EMGshows small, polyphasic muscle potentials with normal nerve conductions.
  14. Muscle biopsyshows the typical dystrophic pattern.
  15. Absent or decreased dystrophin levelsare present on immunocytochemistry or Western blot assay of muscle.
  16. DNA testingmay reveal the gene deletion in > 90% of patients.

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  1. Management

There is no cure but oral steroids can improve strength transiently when the disease is in the early stages. Gene replacement, myoblast transplantation, and dystrophin replacement have not been successful in clinical trials.

  1. Prognosis
  2. In DMD, patients are wheelchair dependent by 10 years of age and often die in their late teens from respiratory failure. Assisted ventilation may help individuals live longer.
  3. In BMD, patients become wheelchair dependent in their twenties. Life expectancy is in the fifties.
  4. Myasthenia Gravis
  5. Definition

Myasthenia gravis is an autoimmune disorder that presents with progressive weakness or diplopia.

  1. Etiology

Myasthenia gravis is caused by antibodies against the acetylcholine receptor (AChR) at neuromuscular junctions.

  1. Classification
  2. Neonatal myastheniais a transient weakness in the newborn period secondary to transplacental transfer of maternal AChR antibodies from a mother affected with myasthenia gravis.
  3. Juvenilemyasthenia gravis presents in childhood secondary to AChR antibody formation.
  4. Epidemiology

Juvenile myasthenia gravis affects girls two to six times more frequently than boys.

  1. Clinical Features
  2. In neonatal myasthenia, hypotonia, weakness, and feeding problemsare the most common findings.
  3. In juvenile MG, several findings are characteristic.
  4. Bilateral ptosis is the most common presenting sign.
  5. Characteristic increasing weaknessoccurs later in the day and with repetitive or sustained muscle activity.
  6. Diplopiasecondary to decreased extraocular movements may be the only manifestation.
  7. DTRs are preserved.
  8. Other autoimmune disorders, including juvenile rheumatoid arthritis, diabetes mellitus, and thyroid disease, may coexist.
  9. Diagnosis

Diagnosis is made by the following:

  1. Tensilon test. Intravenous injection of edrophonium chloride, a rapidly acting cholinesterase inhibitor, produces transient improvement of ptosis.
  2. Decremental responseto low-frequency (3–10 Hz) repetitive nerve stimulation
  3. Presence of AChR antibody titers

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  1. Management
  2. In neonatal myasthenia, treatment is often symptomatic, because the disorder is self-limited. If respiration is compromised, cholinesterase inhibitors or IVIG may be indicated.
  3. In juvenile myasthenia gravis, treatment involves the following:
  4. Cholinesterase inhibitorsare the mainstay of treatment.Pyridostigmine bromide is the drug of choice.
  5. Immunotherapy
  6. Corticosteroidsare used when cholinesterase inhibitors fail.
  7. Plasmapheresis lowers the level of AChR antibodies.It is useful when symptoms worsen, when respiratory effort is compromised, or when the patient is unresponsive to other therapies.
  8. IVIGalso may be effective.
  9. Thymectomyis often performed.
  10. Prognosis
  11. In neonatal myasthenia, symptoms are mild and generally resolve within 1–3 weeks.
  12. In juvenile myasthenia gravis, remission of symptoms can be as high as 60% after thymectomy.

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Review Questions and Answers

  1. You are called to the nursery to examine a “floppy” female infant born within the past 24 hours. The neonate is hypotonic with diminished deep tendon reflexes. There are no tongue fasciculations. When you greet the baby's mother, she is anxious and has difficulty releasing her grip after shaking your hand. Which of the following is the most likely diagnosis?

(A) Muscular dystrophy

(B) Congenital myotonic dystrophy

(C) Neonatal myasthenia gravis

(D) Spinal muscular atrophy, type 1

(E) Infantile botulism

  1. A 10-year-old girl is being evaluated for “weakness” of 3 days' duration. Medical history is significant for a 4-day episode of diarrhea 2 weeks before her current presentation. She is otherwise well with no chronic medical conditions and is taking no medications. Physical examination reveals symmetric weakness at the ankles and knees, with normal strength at the hip joints. Deep tendon reflexes are absent in the distal lower extremities. Sensory examination is normal. Which of the following statements is most consistent with the most likely diagnosis?

(A) This patient is most likely to have had a prodromal gastroenteritis with Salmonella typhi.

(B) Electromyography would be expected to show normal nerve conduction.

(C) Management should include intravenous immune globulin.

(D) This patient is likely to have elevated antistreptolysin O or anti-DNase B titers.

(E) The prognosis for complete recovery is poor.

  1. A 6-month-old male infant is evaluated for lethargy and poor feeding. Recent dietary changes include the introduction of cereals, fruits, and herbal tea with honey. Physical examination reveals an afebrile infant with normal vital signs. Neurologic examination is notable for decreased muscle tone and a weak suck. Which of the following statements regarding this infant's most likely diagnosis is most accurate?

(A) Infants typically present with ascending paralysis.

(B) Antibiotics should be administered immediately.

(C) Infants present with brisk deep tendon reflexes.

(D) Electromyography is not helpful in making the diagnosis.

(E) Constipation is the classic initial symptom in infants.

  1. An 8-year-old girl is noted by her teacher to have brief staring spells throughout the day. She is referred to you for further evaluation. Neurologic examination is normal. You order an electroencephalogram, which shows a generalized 3-Hz spike and wave discharge pattern arising from both hemispheres. Which of the following statements regarding the most likely diagnosis is most accurate?

(A) Further questioning would probably reveal that this patient loses control of her bladder during the event.

(B) This patient's condition is inherited in an autosomal recessive pattern.

(C) This patient's staring spells would be expected to last less than 10 seconds each.

(D) This patient is likely to have prolonged postictal periods.

(E) Phenobarbital is the drug of choice for this patient's condition.

  1. A 4-month-old female infant is brought to your office by her parents, who are concerned about some behaviors they have witnessed. They note that during the past week, she has had brief jerking episodes, lasting 1–2 seconds each, with sudden arm extension followed by flexion of the head. You order an electroencephalogram, which reveals a highly disorganized pattern of high-amplitude spike and waves in both cerebral hemispheres, consistent with a hypsarrhythmia pattern. Which of the following is the most commonly identified cause of the patient's disorder?

(A) Prior episode of bacterial meningitis

(B) Perinatal asphyxia

(C) Shaken baby syndrome

(D) Tuberous sclerosis

(E) Neurofibromatosis type 1

  1. A 6-year-old boy complains of a 4-day history of low back pain and difficulty walking. On examination, you note weakness in his lower extremities and absent lower extremity deep tendon reflexes. Sensation in the lower extremities is intact. A magnetic resonance imaging scan of the spine is normal. Which of the following is the most likely diagnosis?

(A) Duchenne muscular dystrophy

(B) Myasthenia gravis

(C) Acute cerebellar ataxia of childhood

(D) Guillain-Barré syndrome

(E) Becker muscular dystrophy

  1. A 2-year-old boy is brought to the office by his parents, who note that their son has had weakness in his legs for the past several months that appears to be getting worse. On examination, you note that the calf muscles are enlarged. Which of the following statements regarding this patient's likely condition is correct?

(A) DNA testing is normal.

(B) Dystrophin levels are normal.

(C) Progressive weakness leads to loss of ambulation before 10 years of age.

(D) Electromyography reveals delayed nerve conduction.

(E) Treatment with intravenous immune globulin can transiently improve symptoms.

  1. A previously healthy 3-year-old girl is brought to the emergency department with a 2-day history of unsteady gait and one episode of vomiting. Parents deny any history of trauma, medications, or ingestion. She has no other symptoms, and her last illness was an upper respiratory infection with cough 3 weeks ago. On examination, she is well appearing and afebrile and has normal deep tendon reflexes but refuses to walk. Which of the following is the next step in management?

(A) Obtain a complete blood count, serum electrolytes, and glucose.

(B) Perform a lumbar puncture.

(C) Order a head computed tomography scan.

(D) Order an electroencephalogram.

(E) Reevaluate her the next day to monitor her progress.

  1. Two hours ago a 2-year-old boy had a 5-minute episode of whole body shaking associated with a temperature of 103°F (39.4°C). The boy's parents state that their son has had runny nose and cough for the past 24 hours. He now acts normal except for his cold symptoms, according to his parents. The parents remind you that this is his second febrile seizure. Physical examination is normal, revealing no focal neurologic signs. Which of the following would be the most appropriate recommendation at this time?

(A) Order a stat head computed tomography scan.

(B) Order an electroencephalogram.

(C) Begin treatment with phenobarbital.

(D) Reassure the parents that no workup or medications are necessary at this point.

(E) Admit the patient to the hospital for overnight observation.

  1. A 12-year-old girl is brought to see you for evaluation of frequent headaches. She has had headaches three times per week for the past several months, and her parents are concerned that she may be having migraines. Which of the following statements would support this diagnosis?

(A) The headaches are bilateral, throbbing, and bitemporal in location.

(B) The neurologic examination is abnormal during the headache.

(C) The headaches awaken the patient in the early morning hours.

(D) The duration of the headache is > 1 hour.

(E) This patient is likely to have an aura with her headache.

  1. Examination of a comatose 13-year-old boy in the emergency department is significant for bilaterally nonreactive and dilated pupils. An oculocephalic maneuver is negative. Which of the following is the most likely diagnosis?

(A) Postictal state from status epilepticus

(B) Brainstem injury

(C) Subdural hematoma with herniation

(D) Opiate overdose

  1. A 2-month-old boy is brought to your office for evaluation with a 2-day history of poor feeding and vomiting. Parents deny fever, cold symptoms, or diarrhea. On physical examination, the child is well hydrated but has a large anterior and posterior fontanelle and a persistent downward deviation of both eyes. This patient's presentation is most consistent with which of the following diagnoses?

(A) Cerebral infarct

(B) Congenital myotonic dystrophy

(C) Myasthenia gravis

(D) Becker muscular dystrophy

(E) Infantile hydrocephalus

The response items for statements 13–15 are the same. You will be required to select one answer for each statement in the set.

For each patient, select the most likely diagnosis.

  1. A 4-month-old male infant has generalized weakness, hypotonia, areflexia, and tongue fasciculations.

(A) Dandy-Walker malformation

(B) X-linked hydrocephalus

(C) Infantile botulism

(D) Spinal muscular atrophy type 1 (Werdnig-Hoffman disease)

(E) Juvenile myasthenia gravis

(F) Congenital myotonic dystrophy

  1. An 8-month-old female infant with a 5-day history of constipation presents with a weak cry, hyporeflexia, ophthalmoplegia, and an inability to sit without support when she previously had been able to do so.

(A) Dandy-Walker malformation

(B) X-linked hydrocephalus

(C) Infantile botulism

(D) Spinal muscular atrophy type 1 (Werdnig-Hoffman disease)

(E) Juvenile myasthenia gravis

(F) Congenital myotonic dystrophy

  1. A 6-month-old male has had hypotonia, facial weakness, areflexia, and a history of feeding problems since birth.

(A) Dandy-Walker malformation

(B) X-linked hydrocephalus

(C) Infantile botulism

(D) Spinal muscular atrophy type 1 (Werdnig-Hoffman disease)

(E) Juvenile myasthenia gravis

(F) Congenital myotonic dystrophy

Answers and Explanations

  1. The answer is B[I.F.3]. This patient most likely has congenital myotonic dystrophy. Patients present with hypotonia and often have feeding and respiratory problems. Facial weakness and hyporeflexia are common. Infants acquire the disorder through autosomal dominant inheritance, most commonly from an affected mother. Mothers of infants with congenital myotonic dystrophy have myotonia, an inability to relax contracted muscles, which manifests as difficulty releasing a hand grip during a firm handshake. Muscular dystrophy rarely presents during infancy. Infants with botulism have constipation, hypotonia, problems with suck and swallow, and progressive weakness that may lead to paralysis. Neonatal myasthenia is a transient muscle disorder caused by the transplacental passage of acetylcholine receptor antibodies. Weakness and hypotonia may be present, but deep tendon reflexes are preserved. Infants with spinal muscular atrophy have hypotonia but also have characteristic tongue fasciculations.
  2. The answer is C[VII.D]. This patient's presentation is most consistent with Guillain-Barré syndrome. The diagnosis of Guillain-Barré syndrome should be considered in any child with ascending symmetric weakness or paralysis, absence of deep tendon reflexes, and a normal sensory examination. Management should be initiated as soon as the diagnosis is established because of the risk of respiratory muscle paralysis. Intravenous immune globulin is the preferred treatment in children. Many infectious agents have been associated with Guillain-Barré syndrome, but the most common infectious agent is Campylobacter jejuni, which causes a prodromal gastroenteritis. Electromyography would be expected to demonstrate decreased nerve conduction velocity or conduction block. There is no known association between Guillain-Barré syndrome and prior group A β-hemolytic streptococcal infection. The prognosis for children with Guillain-Barré syndrome is excellent, and complete recovery is likely.
  3. The answer is E[I.F.2]. Infantile botulism is caused by the ingestion of Clostridium botulinumspores and the release of botulinum toxin within the intestine. The toxin prevents the release of acetylcholine at peripheral cholinergic synapses, initiallycausing constipation, which is followed by a weak suck and swallow, cranial nerve palsies, and weakness. Patients with infantile botulism have a symmetric descending paralysis. Contaminated honey is a common source of the toxin. Physical examination is notable for diffuse weakness, hypotonia, and hyporeflexia (i.e., diminished deep tendon reflexes). The diagnosis is suggested by the history and physical examination findings and confirmed by the identification of the toxin or bacteria within the stool. Electromyography may also be helpful in diagnosis and may show brief, small-amplitude muscle potentials with an incremental response during high-frequency stimulation. Treatment includes supportive care and botulism immune globulin. Antibiotics are not helpful.
  4. The answer is C[V.L.4]. This patient's clinical presentation and electroencephalogram (EEG) are consistent with absence epilepsy of childhood. Patients usually present with multiple absence seizures, which are brief staring spells that occur without warning and are not followed by postictal drowsiness. Urinary continence and loss of posture are also not seen in absence seizures. Absence seizures last less than 10 seconds and have a very characteristic EEG pattern, showing a generalized 3-Hz spike and wave abnormality. Absence epilepsy of childhood is inherited in an autosomal dominant pattern with age-dependent penetrance. The antiepileptic medication of choice is ethosuximide.
  5. The answer is D[V.L.3]. This clinical presentation is consistent with infantile spasms (West syndrome). Patients with infantile spasms typically present with brief, myoclonic jerks, lasting 1–2 seconds each, occurring in clusters of 5–10 seizures spread out over 3–5 minutes. Patients may have sudden extension of the arms and sudden flexion of the head (jackknife or salaam seizures). A variety of different prenatal, perinatal, and postnatal insults to the central nervous system may result in infantile spasms. Tuberous sclerosis is the most commonly identified cause of this disorder. Perinatal asphyxia, intraventricular hemorrhage, and meningitis are other causes of infantile spasms. Neurofibromatosis type 1 is not typically associated with infantile spasms.
  6. The answer is D[VII.D]. Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy) typically presents with ascending paralysis without sensory loss. Despite this finding, about 50% of children complain of low back pain or discomfort in their legs. Deep tendon reflexes are absent, and spinal magnetic resonance imaging is normal. The diagnosis is based on the findings of albuminocytologic dissociation in the cerebrospinal fluid and by decreased nerve conduction velocity on electrophysiologic studies. In both Duchenne and Becker muscular dystrophy, the onset of weakness is slow and progressive. Myasthenia gravis, which is more common in girls, presents with weakness that increases during the day and normal deep tendon reflexes. Acute cerebellar ataxia of childhood presents with ataxia (unsteady gait or truncal unsteadiness) rather than weakness.
  7. The answer is C[IX.B, IX.E, IX.I.1]. This patient's presentation with increasing weakness in the lower extremities and calf enlargement is consistent with Duchenne muscular dystrophy, an X-linked progressive degenerative muscle disorder for which there is no cure. Children typically present between 2 and 5 years of age with gait problems and weakness, and they are often wheelchair dependent by their 10th birthday. On examination, patients have enlarged calf muscles as a result of fatty infiltration of the degenerating muscles, and laboratory studies reveal elevated creatine kinase levels. The diagnosis can be made by DNA testing of the dystrophin gene, which shows a deletion in more than 90% of patients. Electromyography shows small, polyphasic muscle potentials but normal nerve conduction velocities. Intravenous immune globulin has no role in the management of Duchenne muscular dystrophy.
  8. The answer is C[VII.C.2, VII.C.5]. Acute cerebellar ataxia of childhood is the most common cause of ataxia during childhood and is therefore the most likely diagnosis in this patient. However, because there are no diagnostic laboratory tests or imaging studies to confirm this diagnosis, acute cerebellar ataxia of childhood is a diagnosis of exclusion. Therefore, all patients who present with ataxia require an urgent neuroimaging study to rule out potentially life-threatening disorders of the posterior fossa, such as cerebellar tumors or hemorrhage. Electrolyte abnormalities do not cause gait disturbances. A lumbar puncture should be considered to evaluate for meningoencephalitis, but the absence of fever in this patient makes this diagnosis unlikely. Patients who have had seizures may have an unsteady gait after the seizure, and an electroencephalogram should therefore be a future consideration. Waiting to reevaluate this child may delay the diagnosis of significant underlying pathology.
  9. The answer is D[V.K.6]. Febrile seizures are defined as any seizure that accompanies a fever owing to a non-CNS cause in patients between the ages of 6 months and 6 years. Febrile seizures are benign events that are not generally associated with serious acute or long-term neurologic sequelae. A computed tomography scan is not indicated in the absence of papilledema or focal neurologic deficits. An electroencephalogram is useful whenthe diagnosis of epilepsy is being considered but not in recurrent febrile seizures. Anticonvulsant treatment is usually not initiated until a patient has multiple febrileseizures. Febrile seizures do not require inpatient observation.
  10. The answer is D[VI.B, VI.C]. Migraines are characterized by unilateral, or sometimes bilateral, frontal throbbing headaches that last for at least 1 hour. The neurologic examination of patients with migraines is usually normal. Headaches that occur on awakening in the morning are more characteristic of headaches resulting from increased intracranial pressure. Migraine without aura is the most common form of migraine in children.
  11. The answer is B[IV.C.6]. The physical examination of this patient's eyes, including both the negative oculocephalic test and bilateral dilated nonreactive pupils, is most consistent with brainstem injury. The oculocephalic maneuver is also termed doll's eyes, and an abnormal response (when the head is turned, the eyes follow the head and continue to look straight ahead rather than drifting to midline) suggests a damagedvestibular system. Pupils may also be dilated during and immediately after a seizure or after topical ophthalmic application of a dilating agent, but the vestibular nerve is usually unaffected in these situations (the oculocephalic maneuver would be positive). An enlarging subdural hematoma can cause uncal herniation with a unilateral dilated, nonreactive pupil. Opiate ingestion causes constricted pupils.
  12. The answer is E[II.D]. This patient's eye findings are termed the sunset sign, or a tonic downward deviation of the eyes. The sunset sign is suggestive of hydrocephalus. Increased pressure in the thirdventricle from noncommunicating hydrocephalus injures theupward gaze center in the mid-brain, causing this downward deviation of the eyes. In contrast, patients with myasthenia commonly present with ptosis. There are no specificeye abnormalities in congenital myotonic dystrophy, muscular dystrophy, or cerebral infarcts.

13–15. The answers are D, C, and F, respectively [I.F.1, 2, 3]. The 4-month-old infant hasspinal muscular atrophy type 1 (Werdnig-Hoffman disease), an autosomal recessive disorder that presents with hypotonia, weakness, problems with suck and swallow, and tonguefasciculations. It presents within the first 6 months of life. The 8-month-old infant has infantile botulism, an environmentally acquired disorder of the neuromuscular junction in which botulinum neurotoxin blocks release of acetylcholine at the neuromuscular junction. The toxin is released from the spores of Clostridium botulinum, which are found in contaminated honey or soil. Constipation is often the presenting symptom, followed by weakness, cranial nerve findings, poor abilities to feed, and paralysis. The 6-month-old infant has congenital myotonic dystrophy, an autosomal dominant disorder presenting in infancy with hypotonia, facial weakness, and feeding problems. The diagnosis may be missed if the mother of the patient is not seen or examined because the typical myotonia (i.e., inability to relax contracted muscles) is most apparent in adults.