Pediatric Neurology

CHAPTER 28
PEDIATRIC NEUROLOGY
Angus A. Wilfong, James Owens
NORMAL NEUROLOGIC GROWTH AND DEVELOPMENT

1. In addition to the routine questions asked during a neurologic interview, what
additional questions are important for a complete pediatric neurology history?
Antenatal history and risk factors
Perinatal history and risk factors
Neonatal history and complications
History of developmental milestones
2. List important features of the physical examination of infants and young children
that may not be included in the examination of adults.
Measurement of the fronto-occipital circumference (FOC)
Palpation of cranial sutures and fontanelles if open
Dysmorphic facial features (such as hypertelorism, absence of philtrum, or low-set ears)
Limb asymmetries and malformations (including dermatoglyphics)
Abnormal skin lesions concerning for a neurocutaneous syndrome
Developmental reflexes
3. List the common developmental reflexes. When do you expect them to be present?
See Table 28-1.
Table 28-1. Common Developmental Reflexes

REFLEX APPEARS DISAPPEARS
Lateral incurvation of trunk Birth 1-2months
Rooting Birth 3months
Moro Birth 5-6months
Tonic neck reflex Birth 5-6months
Palmar grasp Birth 6months
Crossed adduction Birth 7-8months
Plantar grasp Birth 9-10months
Extensor plantar responses Birth 6-12months
Parachute response 8-9months Persists
Landau reflex 10months 24months
4. What is the average FOC for a term newborn? What is the rate of growth over the
first year?
Average FOC of a term newborn is 35cm. Average FOC growth is 2cm per month for the first
3months, 1cm per month for the next 3months, and 0.5cm per month for the last 6months. Adult
head size averages approximately 57cm.
PRENATAL DISEASES AND DEVELOPMENTAL DEFECTS

5. What is the Apgar score?
The Apgar score is a clinical vitality rating scale applied to newborn infants in an attempt to identify
those at risk for certain neonatal complications. Apgar is an eponym (Virginia Apgar, US obstetrical
anesthesiologist), although it is often used as an acronym (Table 28-2).
389
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390Chapter 28 Pediatric Neurology
Table 28-2. Apgar Score

Score
SIGN 0 1 2
A Appearance (color) Blue, pale Acrocyanosis Pink
P Pulse (heart rate) Absent <100 >100
G Grimace (reflex No response Grimace Cry
irritability in re-
sponse to nasal
suctioning)
A Activity (muscle Limp Some flexion Active motion
tone)
R Respiration (respi- Absent Slow and irregular Strong crying
ratory effort)
Infants are routinely scored at 1 and 5minutes after birth. Further scores may be made at 10
and 20minutes if the infant appears to have been compromised.
6. How is neonatal intraventricular hemorrhage (IVH) classified?
See Figure 28-1.
Figure 28-1. Unenhanced axial computed tomography (CT): grade III, intraventricular hemorrhage (IVH) in a premature
newborn (32weeks gestation). Note acute ventricular distention with blood filling more than 50% of the ventricular
volume. There is no parenchymal extension of the hemorrhage.
Grade I: Localized subependymal hemorrhage into the germinal matrix

Grade II: Subependymal hemorrhage with extension into the ventricles (less than 50% of the
ventricular volume filled with blood)
Grade III: Subependymal hemorrhage with extension into the ventricles and acute ventricular dilata-
tion (greater than 50% of the ventricular volume filled with blood) (see Fig. 28-1)
Grade IV (now referred to as a periventricular hemorrhagic infarction): Subependymal, intraven-
tricular, and extension into the surrounding cerebral parenchyma
7. What risk factors are thought to play a role in the genesis of IVH?
The most important risk factor for the development of an IVH is prematurity. While only about 10% of
infants born at 28weeks will develop a severe IVH, the risk for infants born at 24weeks is closer to
25%. Birth weight (small, appropriate, or large for gestation age) is an independent risk factor. Other
risk factors include mechanical ventilation, pneumothoraces, rapid expansion of intravascular volume
(large or rapid IV infusions), rapid or wide fluctuations in blood pressure, hypoxic-ischemic injury,
hypernatremia and hyperosmolality, and administration of certain medications such as indomethacin.

Chapter 28 Pediatric Neurology 391
8. What complications may arise secondary to an IVH?

The most common complications of IVH include posthemorrhagic hydrocephalus, seizures, and the
parenchymal cerebral injury associated with periventricular hemorrhagic infarctions.
9. Does the neurologic prognosis correlate with the different IVHs?
Generally, grades I and II IVH are relatively benign with some studies showing no long-term adverse
developmental consequences. Grade III and periventricular hemorrhagic infarction (formerly grade IV)
are consistently associated with adverse outcomes, with grade IV having by far the greatest likelihood
of severe neurologic sequelae such as spastic quadriparesis, blindness, and cognitive impairment.
Unilateral hemorrhages are associated with better neurodevelopmental outcomes than bilateral
hemorrhages.
10. What are the most common causes of a floppy baby? What are the least
common?
By far the most frequent are the central causes involving the cerebellum, brain stem, basal ganglia,
and cerebral hemispheres. The least common causes of infantile hypotonia afflict the peripheral
nerves.
11. What is the difference between macrocephaly and megalencephaly?
Macrocephaly refers to a large head, whereas megalencephaly refers specifically to a large brain.
12. What is the differential diagnosis of macrocephaly in an infant?
Hydrocephalusobstructive or communicating
Extra-axial fluid collections
Thickened skull
Megalencephaly
13. What is the differential diagnosis of megalencephaly?

Toxic: cerebral edema from lead poisoning
White matter diseases such as Canavans disease and Alexanders disease
Genetic disorders such as Sotos syndrome
14. Name genes commonly implicated in brain overgrowth syndromes.
PIK3CA
AKT1
AKT3
MTOR
PTEN
TSC1 and TSC2
FGFR2 and FGFR3
These genes are all part of the receptor tyrosine kinase (RTK)phosphatidylinositol-3-kinase (PI3K)
AKT signaling pathway, which is an important regulator of cell growth.

15. What is hemimegalencephaly? What clinical manifestations are commonly associ-
ated with hemimegalencephaly?
Hemimegalencephaly is a rare brain malformation associated with cortical overgrowth on one hemi-
sphere. It is commonly associated with intractable partial seizures, significant developmental delay,
and progressive hemiparesis. Several genetic causes have been discovered including PIK3CA, PIK3R2,
AKT3, and MTOR. Surgical removal of the malformed hemisphere (hemispherectomy) may be neces-
sary to achieve seizure control.
16. In evaluating a child with microcephaly, what is the most important clinical
feature?
Is the microcephaly congenital or acquired? Serial measurements of FOC are helpful. Is the FOC
getting progressively worse (Retts syndrome in girls), returning to normal (catch-up growth after
a serious illness or prematurity), or remaining on the same percentile line (static process)? Review
the antenatal history carefully for evidence of intrauterine infection. Did the infant appear healthy
at birth? Any postnatal central nervous system (CNS) infections or trauma? Family history of
microcephaly?

Chapter 28 Pediatric Neurology391.e1
Hevner R: Brain overgrowth in disorders of RTK-PI3-AKT signaling: a mosaic of malformations. Semin

Perinatol 39(1):36-43, 2014.

17. Which laboratory tests, if any, would you order in a child with microcephaly?
A head computed tomography (CT) scan allows assessment of the skull (for premature closure
of the sutures) and also surveys for abnormal calcification (which may indicate infection with a
toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex [TORCH] agent, or earlier
hypoxic-ischemic injury). A magnetic resonance imaging (MRI) scan gives greater anatomic detail of
the brain parenchyma. In a neonate, TORCH titers may be measured if such an infection is suspected,
and a chromosomal analysisparticularly a chromosomal microarray or targeted gene analysis
depending on clinical suspicionmay be used to evaluate genetic causes. A basic metabolic screen
(serum amino acids, urine organic acids, ammonia, and lactate) could be considered as well.
K EY POIN T S: C AU S E S O F I N T R A UT E R I N E I N F EC T I O N
1 . TO=Toxoplasmosis, Other agents
2. R=Rubella
3. C=Cytomegalovirus
4. H=Herpes simplex virus
18. What are the most common complications of a lumbosacral myelomeningocele?

See Figure 28-2.
A B
Figure 28-2. A, Unenhanced midsagittal T1-weighted magnetic resonance image (MRI) in a 6-month-old boy with type
II ArnoldChiari malformation. Note herniation or downward displacement of the cerebellar tonsils through the foramen
magnum to the level of C2 and the associated obstructive hydrocephalus. B, Unenhanced midsagittal T1-weighted MRI
lumbosacral spine: extensive thoracolumbar myelomeningocele associated with the ArnoldChiari malformation in A. Note
the dorsal kyphosis, absence of posterior elements of the vertebrae, and the malformed spinal cord at the level of the
defect. A small syrinx in the cord is present above the defect.
Type II ArnoldChiari malformation resulting in hydrocephalus

CNS infectious complications are common and devastating
Renal failure due to chronic and repeated urinary tract infections and obstructive uropathy
Seizures
Progressive spasticity and weakness in the legs, worsening bladder and bowel function, progres-
sive scoliosis, or increasing low back pain and stiffness due to a tethered cord
19. Classify the ArnoldChiari malformations.
Type I: Downward displacement of the cerebellum with elongation of the medulla such that the
cerebellar tonsils egress through the foramen.

Type II: Associated with lumbosacral myelomeningocele and numerous other nervous system
malformations including:
Small posterior fossa
Cerebellar tonsil herniation through the foramen magnum
Elongated and thinned medulla
Characteristic beaking appearance of the quadrigeminal plate
Hydrocephalus
Syringomyelia and occasionally syringobulbia
Interdigitation of gyri along the interhemispheric fissure
T ype III: An occipital encephalocele with protrusion of cerebellar remnants into the overlying sac.
Type IV: Isolated hypoplasia of the cerebellum not associated with other nervous system
malformations.
20. List the major developmental abnormalities of cortical development.
Lissencephaly
Holoprosencephaly
Schizencephaly
Polymicrogyria
Pachygyria
Double cortex syndrome (laminar heterotopia)
Periventricular nodular heterotopia
Focal cortical dysplasia
21. What is Down syndrome?
Down syndrome is a chromosomal anomaly with trisomy 21 characterized by marked infantile
hypotonia with hyperflexibility of joints, cognitive impairment, brachycephaly with flat occiput,
up-slanting palpebral fissures, late closure of fontanelles, flattened nasal bridge, epicanthal folds,
speckling of iris (Brushfields spots), fine lens opacities, small ears, hypoplastic teeth, short neck,
brachydactyly with clinodactyly of fifth fingers, simian creases, wide space between first and second
toes, congenital heart disease (in 40%), and hypogonadism.
22. A school-aged child is referred for evaluation of possible absence epilepsy
because of constant day-dreaming and worsening grades. The mother and
teachers relate a history of short attention span for schoolwork but not for
television or video games, easy distractibility, impulsiveness, constant supervi-
sion needed to complete homework and chores, adventurous and risk-taking
behavior, and constant physical activity (as if driven by a motor). What is the
most likely diagnosis?
This is the usual presentation of a child with attention-deficit/hyperactivity disorder (ADHD). Some
children have the attention deficit without the hyperactivity. Affected children have unusually short
attention spans and are simply unable to concentrate for more than a few minutes for all but the most
stimulating and enjoyable activities. Their constant distractibility and day-dreaming may be confused
with the seizures of absence epilepsy.
23. What are the key diagnostic features of an autism spectrum disorder (ASD)?
Deficits in social communication and social interaction
Restricted, repetitive patterns of behavior, interests, or activities (such as repetitive move-
ments, stereotyped speech, highly restricted interests, or very inflexible adherence to
routines)
Motor development is generally not affected though patients may be clumsy
Symptoms are present from early in the developmental period
Discrete categories such as autistic disorder and Asperger syndrome have now been replaced
by one overarching diagnosis: ASD.

24. In addition to these key diagnostic features, name three common neurologic
comorbidities of ASD.
Sleep disturbanceparticularly insomnia with difficulty initiating and/or maintaining sleep
Epilepsywhich occurs at a much higher rate in ASD patients than in the general population
ADHDa disorder that may now be diagnosed in patients with an ASD

American Psychiatric Association: The diagnostic and statistical manual of mental disorders, 5th ed.
Arlington, VA, American Psychiatric Publishing, 2013.

NEURODEGENERATIVE DISORDERS
25. In general terms, how does a neurodegenerative disease affecting white matter
present?
Loss of motor skills, progressive spasticity, and ataxia. A disorder affecting the white matter is referred
to as a leukodystrophy.
26. In general terms, how does a neurodegenerative disease affecting gray matter
present?
Loss of intellectual skills (dementia), seizures, and blindness. A disorder affecting gray matter was
once called a poliodystrophy.
27. Name a neurodegenerative disorder that affects both the CNS and the peripheral
nervous system.
Krabbes disease (globoid cell leukodystrophy) is an autosomal recessive enzyme defect in galacto-
sylceramide beta-galactosidase that results in irritability, increased tone, optic atrophy, cortical blind-
ness, and peripheral nerve segmental demyelination. Metachromatic leukodystrophy is an autosomal
recessive lysosomal storage disorder caused by a mutation in arylsulfatase A that also affects both
central and peripheral myelin.
28. Which leukodystrophy is virtually always associated with a particular endocrino-
logic deficiency?
See Figure 28-3. Adrenoleukodystrophy, an X-linked recessive disorder, is one of the peroxisomal
disorders. It is characterized by impaired beta-oxidation of the very long-chain (C26) fatty acids,
leading to their accumulation. In addition, patients also have adrenocortical insufficiency. Onset is
usually between 4 and 6years of age. An adult form of the disease called adrenomyeloneuropathy is
characterized by progressive spastic paraparesis and peripheral neuropathy.
Figure 28-3. Unenhanced axial T2-weighted magnetic resonance image (MRI) in a 9-year-old boy with adrenoleuko-
dystrophy. Note extensive dysmyelination involving the anterior centrum semiovale, subcortical white matter, genu of the
corpus callosum, and internal capsule. The cerebral cortex, basal ganglia, and thalami are unaffected.
29. How often does multiple sclerosis present in children?

Approximately 3% to 5% of all patients with multiple sclerosis (MS) have onset of symptoms in
childhood. The majority of affected children (more than 90%) are older than 10years of age, but MS
cases have been described in patients younger than 3years of age.

30. What is a cherry-red spot?
Cherry-red spot is the bright red appearance of the fovea centralis of the eye as seen by funduscopy
in children with certain gray matter storage diseases, classically TaySachs disease. As the storage

Waubant E, Chabas D: Pediatric multiple sclerosis. Curr Treat Options Neurol 11:203-210, 2009.

material accumulates in the nerve fiber layer, the retina takes on a grayish-white appearance.
Because there are very few fibers traversing the fovea, it retains its normal color and continues to
reflect the bright red vascular choroid underneath.
31. What are the neuronal ceroid lipofuscinoses (NCL)?
NCL are a group of autosomal recessively inherited lysosomal storage disorders characterized by
excessive neuronal accumulations of the lipid pigments, ceroid, and lipofuscin. They present as classic
gray matter diseases with intractable seizures, progressive dementia, and blindness. Together they
represent the most commonly diagnosed pediatric neurodegenerative disorder. The genetic basis of
these diseases is increasingly understood with 13 genes presently implicated.
32. Which endocrinologic disorder may present as a gray matter neurodegenerative
disease if it is missed on the newborn screening?
Congenital hypothyroidism (cretinism) is extremely difficult to detect clinically at birth, and the diag-
nosis may not be suspected until it is too late for replacement therapy to be maximally efficacious.
Left untreated, these children develop prolonged jaundice, abdominal distention with umbilical hernia,
large fontanelles, hypotonia, impaired bony development, large tongue, psychomotor retardation,
seizures, spasticity, ataxia, and deafness.
33. What are ragged-red fibers?
In some of the mitochondrial cytopathies, mitochondria become clumped beneath the skeletal muscle
sarcolemmal membrane. When the muscle biopsy specimen is prepared with modified Gomoris
trichrome stain and viewed by light microscopy, the clumps of mitochondria stain red and give the
muscle fibers a ragged appearancehence the term ragged-red fibers.
NEUROCUTANEOUS SYNDROMES
34. What is the most common neurocutaneous syndrome?
Neurofibromatosis (NF) type I has an incidence of 1/3000 to 4000 of the population. Inheritance is
autosomal dominant and the spontaneous mutation rate (chromosome 17) is very high (30% to 50%).
Clinical characteristics include caf-au-lait spots, neurofibromas, axillary/inguinal freckling, optic
gliomas, megalencephaly, mental retardation, seizures, and characteristic bony lesions.

35. Which neurocutaneous syndrome is associated with infantile spasms and a
hypsarrhythmia pattern on electroencephalogram?
Tuberous sclerosis (TS), an autosomal dominant disorder with genetic heterogeneity (similar pheno-
type with mutation on either chromosome 9 or 16). Incidence is 1/10,000 with a high-spontaneous
mutation rate. Clinical features include mental retardation, seizures, adenoma sebaceum, ash-leaf
spots, shagreen patches, caf-au-lait spots, subungual and periungual fibromas (Koenens tumors),
gingival fibromas, dental enamel pits, retinal tumors (mulberry tumor of the optic disc), cardiac
rhabdomyomas, renal angiomyolipomas, and CNS cortical tubers and subependymal hamartomas that
calcify.
36. Of the more common neurocutaneous syndromes, which has no clear pattern of
inheritance?
SturgeWeber syndrome (encephalofacial angiomatosis), which is less common than NF or TS.
Patients have a facial port-wine stain (nevus) that is usually unilateral involving the V1 segment of the
trigeminal nerve. The nevus may involve the ocular choroidal membrane, causing glaucoma. Arteri-
ography reveals extensive arteriovenous malformation involving the ipsilateral cerebral hemispheric
dura.
37. In addition to brain and skin involvement, which other neurocutaneous syndrome
has an immune disorder and a high propensity for malignancy?
Ataxia-telangiectasia is an autosomal recessive disorder with an incidence of 1/100,000.
Affected individuals develop telangiectasias by 2 to 4years of age on exposed areas of skin and
conjunctiva. Progressive cerebellar ataxia begins within the first few years of life. Patients have
decreased or absent IgA and IgE and decreased IgG2 and IgG4. Defective cellular DNA repair
leads to increased spontaneous and radiation-induced chromosomal aberrations, inducing
various neoplasias. The disorder is caused by inactivation of the ataxia-telangiectasia-mutated
protein kinase involved in detecting double-stranded DNA breaks and helping to coordinate repair.


Kandit RS: Tuberous sclerosis complex and neurofibromatosis type 1: the two most common neurocutane-
ous diseases. Neurol Clin 20:941-964, 2002.
Lavin M: Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signaling and cancer. Nat Rev Mol
Cell Biol 9(10):759-769, 2008.

INFECTIONS AND INFESTATIONS

38. What are the most common bacterial pathogens for acute meningitis in neonates
and children?
Neonatal
Group B beta-hemolytic streptococci
Escherichia coli
Listeria monocytogenes
Klebsiella pneumoniae
Childhood
Haemophilus influenzae type B
Streptococcus pneumoniae
Neisseria meningitides
While vaccination has largely eliminated H. influenzae type B, nontypable H. influenzae is still seen.
Worldwide these three bacteria are responsible for approximately 90% of acute bacterial meningitis in
childhood.
39. What are the usual signs and symptoms of neonatal meningitis?
Lethargy
Irritability
Hypothermia or hyperthermia
Poor feeding
Bulging fontanelle (a later sign)
Seizures
40. What are the usual signs and symptoms of an older infant or child with acute
meningitis?
Fever
Headache
Altered mental status
Stiff neck
Nausea and vomiting
Seizures
41. How does the presentation of tuberculous meningitis differ from acute bacterial
meningitis?
Tuberculous meningitis is difficult to diagnose in its earliest stages as the symptoms tend to be
nonspecific, mild to moderate in severity, and persistent (weeks). Poor weight gain, low-grade
fever, and listlessness may be seen in young children while older children may manifest headache
and emesis. As the disease progresses the symptoms become more severe with obtundation
and evidence of meningeal irritation. As tuberculosis tends to cause a basilar meningitis, cranial
neuropathies are often seen in later stages. Cerebrovascular disease with ischemic strokes is also
seenlikely due to the proximal anterior circulation passing through the inflammatory infectious
exudate.
42. A child from Central America presents with a prolonged partial motor seizure.
Neurologic examination reveals no focal or lateralizing findings; however, fundu-
scopic examination reveals early papilledema. CT scanning of the brain discloses
a number of small, densely calcified lesions scattered along the graywhite junc-
tion of the cerebral hemispheres. What is the most likely diagnosis and how might
you confirm your suspicions?
The pork tapeworm, Taenia solium, is endemic in Central America. When a human (rather than the pig)
becomes the intermediate host, he may develop neurocysticercosis. This occurs when the ingested T.
solium ova become partially digested, releasing onchospheres that gain access to the circulation and
are carried throughout the body. They then become larvae (cysticerci) in subcutaneous tissue, muscle,
and brain where the majority die and become densely calcified. The diagnosis can be confirmed by
serum or cerebrospinal fluid (CSF) antibody and antigen detection methods and in certain cases by
tissue biopsy (Fig. 28-4).


Garcia HH, Nash TE, Del Brutto OH: Clinical symptoms, diagnosis, and treatment of neurocysticercosis.
Lancet Neurol 13(12):1202-1215, 2014.

Figure 28-4. Enhanced axial computed tomography (CT): neurocysticercosis in a 7-year-old girl. Note the solitary, densely
enhancing lesion with surrounding edema.
VASCULAR DISORDERS
43. What is the most common hemoglobinopathy associated with cerebrovascular
disease?
Approximately one-fourth of all patients with sickle cell disease experience cerebrovascular complica-
tions; the vast majority are children. When strokes occur in adults, they are more likely to be intra-
cerebral hemorrhages as opposed to the infarctions that affect children. In addition to small vessel
occlusion by sickled red cells, endothelial proliferation is also thought to be an important mechanism
in the genesis of these strokes.
NEOPLASMS
44. Where are brain tumors most common in infants, children, and adults?
In infants less than 1year of age, supratentorial brain tumors predominate. In children older than
1year, infratentorial tumors are more common. In adults, supratentorial tumors are again more
frequently encountered. Brain tumors are the second most common malignancy in children.

45. What are primitive neuroectodermal tumors (PNET)?
These are highly malignant, small, blue cell tumors. If a PNET is completely undifferentiated and is in the
midline posterior fossa, it is often referred to as a medulloblastoma. PNET may show varying degrees of
differentiation along different cell lines, including glial, ependymal, pineal, and neuronal (Fig. 28-5).
46. A school-aged child complains of recurrent headaches and recent onset of
marked polyuria and polydipsia. Examination reveals bitemporal homonymous
hemianopsia and papilledema. Laboratory tests are consistent with diabetes
insipidus. Where is the lesion?
The anatomic location of this lesion must be in the parasellar region. The visual field defect is pro-
duced by compression of the optic chiasm. The diabetes insipidus is produced by compression of the
pituitary stalk (Fig. 28-6).
47. What is the differential diagnosis of parasellar tumors in children?
Craniopharyngioma
Germ cell tumor, including teratoma
Pituitary adenoma
Optic glioma

Chintagumpala M, Gajjar A: Brain tumors. Pediatr Clin North Am 62(1):167-178, 2015.

Figure 28-5. Enhanced midsagittal T1-weighted magnetic resonance image (MRI) reveals a posterior fossa primitive
neuroectodermal tumor (PNET) in a 5-year-old boy. Note the brightly enhancing tumor mass extending upward through
the fourth ventricle into the cerebral aqueduct and downward through the foramen magnum. There is compression of the
medulla and marked displacement of the cerebellum. Early obstructive hydrocephalus is developing.
Figure 28-6. Enhanced midsagittal T1-weighted magnetic resonance image (MRI) demonstrates a craniopharyngioma in a
3-year-old girl. Note the large, multilobulated tumor extending from the parasellar region through the midbrain. The tumor
has brightly enhancing solid areas and fluid-filled cysts. There is associated obstructive hydrocephalus.
Hypothalamic glioma
Chordoma of the clivus
48. Most posterior fossa tumors in children have a poor prognosis except for one,
which has an excellent prognosis. What is it?
Juvenile cerebellar pilocytic astrocytoma has virtually a 100% 5-year survival rate. This tumor devel-
ops in the cerebellar hemispheres of school-aged children. Histologically, the tumor cells are hair-like
(pilocytic). The tumor is classified as a grade 1 neoplasm, which is a well-circumscribed neoplasm
without local invasiveness. Complete resection is curative.

49. An older child with medically intractable complex partial seizures has an MRI
scan performed. The scan reveals a partially calcified mass in the right mesial
temporal lobe without associated edema. What is the most likely diagnosis?
Gangliogliomas, oligodendrogliomas, and dysembryoplastic neuroepithelial tumors are slow-growing
neoplasms whose only clinical signs may be intractable seizures.
INJURY BY PHYSICAL AGENTS AND TRAUMA

50. Does age have any effect on whether or not cranial irradiation would be consid-
ered as treatment for cancer?
Children who received cranial X-ray therapy (XRT) prior to 3years of age have significantly reduced
intelligence quotients later in life.
51. What are some of the other adverse effects that may be encountered in children
who receive cranial XRT?
Transient somnolence, headaches, and anorexia 6 to 8weeks after initiation of XRT are common.
Radiation necrosis (radionecrosis) may occur 1 to 3years post-XRT and can mimic a mass effect,
making it difficult to distinguish tumor recurrence from radionecrosis. Pathologically the lesion
involves hyalinization of blood vessels with infarction and necrosis of brain tissue.
Hypothalamicpituitary dysfunction, which usually involves decreased production of growth hor-
mone and thyroid-stimulating hormone.
Formation of cataracts if the ocular globes were exposed to radiation.
Induction of a second malignancy that may appear years later.
52. A 6-month-old infant presents with obtundation and recent seizures. Examination
reveals no fever, anterior fontanelle slightly bulging, depressed level of conscious-
ness, and hypotonia. On funduscopic examination, extensive, bilateral retinal
hemorrhages and mild papilledema are observed. What is your leading diagnosis?
Child abuse, specifically the shaken-baby syndrome or nonaccidental trauma, needs to be first on the
list of diagnostic possibilities. Because of the violent shaking of the body and head, these infants sus-
tain subarachnoid hemorrhages and associated retinal hemorrhages. This commonly leads to seizures
and may cause cortical infarctions as the cerebral vessels spasm.
53. What is a growing skull fracture?
This is a rather rare complication of linear skull fractures, usually occurring in children younger than
3years of age. Because of brain and CSF pulsations, the opposing edges of bone along the fracture
do not fuse. Resorption of bone along the edges occurs so that the fracture opening progressively
enlarges, producing a growing skull fracture.
SEIZURES AND OTHER PAROXYSMAL DISORDERS

54. What is a complex febrile seizure?
The seizure has focal features, lasts longer than 15minutes or recurs within 24hours, or occurs in a
child younger than 6months or older than 5years of age.
K EY POIN T S: SIM P L E F E B R I L E S E I Z UR E
1 . A generalized tonic or tonicclonic seizure
2. Between 3months and 5years of age
3. Fever greater than 38C not associated with a CNS infection
4. Lasting less than 15minutes, no focal features, does not recur within 24hours
5. No postictal neurologic abnormalities
55. Does having had a simple febrile convulsion increase the risk for later develop-
ment of epilepsy (recurrent nonfebrile seizures)?
The risk is minimally elevated, if at all. At worst the risk rises from the background rate of 1% to a rate
of 2% (meaning that 98% of patients with simple febrile seizures do not develop epilepsy). The risk for
patients with complex febrile seizures is higher: 4% to 6%.


Pavlidou E, Hagel C, Panteliadis C: Febrile seizures: recent developments and unanswered questions. Childs
Nerv Syst 29(11):2011-2017, 2013.

56. What is generalized epilepsy with febrile seizures plus GEFS+?

GEFS+ is an epilepsy syndrome with a highly variable phenotype. Within a single family some affected
members may have febrile seizures alone, some may have febrile seizures and afebrile seizures, and
others may have only afebrile seizures. The understanding of GEFS+ has been significantly advanced
by the discovery of several associated genes including SCN1A, SCN1B, and GABARG2. Given that
these genes encode ion channel or ionotropic receptor subunits, GEFS+ is presently considered a
channelopathy.
57. A 16-month-old child is being seen for difficult-to-control seizures. He was born
at term with no neurodevelopmental concerns until a prolonged febrile seizure
at 6months of age. This febrile seizure was soon followed by another episode of
febrile status epilepticus, and then the patient began having generalized tonic
clonic seizures as well as apparently focal seizures. Despite trials of several
anticonvulsants he continues to have frequent seizures. His developmental
trajectory, which was initially normal, has now slowed. What gene mutation does
this patient most likely have?
The history of early prolonged febrile seizures followed by difficult-to-control afebrile generalized and
focal seizures in a previously normal child would be consistent with Dravet syndrome, also called severe
myoclonic epilepsy in infancy. The patients acquired developmental delay would also be consistent.
Patients go on to develop other types of seizures including atypical absence and myoclonic seizures.
Approximately 70% to 80% of patients with Dravet syndrome have a mutation in the SCN1A gene, which
codes for the neuronal type 1 alpha subunit of the voltage-gated sodium channel. Interestingly, mutations
in this same gene can cause GEFS+, which is usually associated with a much better prognosis.

58. An 18-month-old child is referred for possible epilepsy. The mother relates a history
of paroxysmal spells that have occurred over the past month. Each spell consists of
the child turning red, then blue in the face, and then passing out with a few clonic
jerks of the extremities. Immediately before each spell, the child had been startled,
frightened, or frustrated and began crying. What is the probable diagnosis?
This is a typical history of blue breath-holding spells, a form of infantile syncope. Breath-holding
spells occur in 4% to 5% of children; there is a positive family history in 25% of cases. Two-thirds
have cyanotic or blue breath-holding spells, 20% have pallid breath-holding spells, and the remain-
der have a mixture of the two. The peak incidence is between 1 and 2years of age and resolution
usually occurs by 6years of age. The spells follow minor injuries, fright, or frustration. Patients
with a history of breath-holding spells are more likely to have symptomatic orthostatic syncope as
adolescents.

HEAD PAIN
59. What are the clinical features of childhood migraine headaches?
Migraine headaches in children are common (prevalence of 1% to 3% in 3- to 7-year-olds and
almost 25% of adolescents).
Fifty percent of all individuals who develop migraine had the onset of their attacks before 20years
of age.
Boys are more frequently affected until puberty, after which time the incidence is considerably
higher in girls.
Younger children usually complain of a generalized, bifrontal, or bitemporal headache, rather than
the hemicranial pain characteristically present in the older child or adult.
Abdominal distress with nausea and sometimes vomiting is prominent.
The child often appears pale and frequently stops all activities and lies down.
Photophobia and phonophobia are usually present but may need to be inferred from behavior in
younger children.
If the child is able to fall asleep, the headache is usually gone upon awakening.
Family history for migraine is positive in 70% to 90% of cases.


Dravet C, Oguni H: Dravet syndrome (severe myoclonic epilepsy in infancy). Handb Clin Neuro 111:627-633,
2013.
Kolkiran A, Tutar E, Atalay S, etal: Autonomic nervous system functions in children with breath-holding
spells and effects of iron deficiency. Acta Paediatr 94:1227-1231, 2005.
Maytal J, Young M, Shechter A, Lipton RB: Pediatric migraine and the International Headache Society
Criteria. Neurology 48:602-607, 1997.

60. What are the different types of migraine headaches in children?

Migraine without aura (formerly common migraine): accounts for up to three-quarters of all
migraine attacks. Clinical manifestations are those listed in the preceding answer.
Migraine with aura (formerly classic migraine): same as above except these individuals experi-
ence an aura just before the onset of the headache.
Complicated migraine: migraine headache associated with various transient neurologic phenom-
ena. These include hemiplegic migraine, ophthalmoplegic migraine, vertebrobasilar migraine, and
acute confusional migraine.
Migraine variants or equivalents: benign paroxysmal vertigo of childhood, paroxysmal torticollis,
and cyclical vomiting of childhood are syndromes thought to be related to migraine.
61. What are the most important pharmacologic agents used in treating migraine?
Symptomatic treatments: Analgesics that have no action on the underlying cause of the migraine
headache. Examples include aspirin, ibuprofen, acetaminophen, codeine, and meperidine. It is usu-
ally best to avoid narcotic preparations in the treatment of chronic illnesses if at all possible.
Abortive therapies: Vasoactive agents that modify the vasculature so that the migraine headache
is aborted before becoming fully developed. Serotonin receptor partial agonists (triptans) such
as sumatriptan are most commonly used, though ergotamine derivatives are also sometimes
employed, particularly in the management of prolonged or refractory headaches.
Prophylactic medications: Drugs that prevent the migraine headaches from occurring. Examples
include beta-blockers, calcium channel blockers, antiepileptic medications (sodium valproate and
topiramate), tricyclic antidepressants (amitriptyline), and cyproheptadine (an antihistamine that is
also a serotonin receptor antagonist).

K EY POIN T S: HE AD AC H ES C O N C ER N I N G F O R A N I N T RACRANIAL MAS S

1 . Recent onset of headaches or change in character of chronic headaches
2. Headaches that awaken the patient from sleep or are present on awakening in the morning
3. Association with altered mental status, vomiting, constriction of visual fields, or focal neurologic deficits
NEUROMUSCULAR DISORDERS
62. What protein is missing in Duchenne muscular dystrophy (DMD)?
The missing gene product is a protein called dystrophin. Dystrophin is a structural protein that helps to link
extracellular matrix proteins, via the sarcoglycan complex, with actin and myosin. It is important in several
tissues, including skeletal muscle, cardiac muscle, and brain. Certain mutations of the dystrophin gene lead
to essentially no dystrophin production and result in DMD. Other mutations allow for the production of some
dystrophin and cause the less severe and late-onset Becker muscular dystrophy.
63. What are the clinical manifestations of DMD?
Affected children are normal through the first year of life. The first clue is that the child may walk
later than expected, but detectable weakness is not present until 3 to 4years of age. The pelvic girdle
weakens first and gives rise to the characteristic Gowers sign. Soon widespread weakness is appar-
ent, and relentless progression ensues. Most children become unable to walk by the end of their first
decade. Once the patient is wheelchair bound, flexion contractures and progressive scoliosis develop.
Cardiac involvement is invariable. Mild intellectual impairment is also common in these patients.
Death from pulmonary infection, respiratory failure, or cardiac failure usually occurs by age 30years.
64. What treatment is available for children with DMD?
Treatment with daily oral corticosteroids from the time of diagnosis until the time the child requires a
wheelchair appears to slow the course of DMD.
65. What are the most common congenital myopathies?
Central core disease
Centronuclear myopathy
Nemaline myopathy
Minimal change myopathy
Congenital fiber type disproportion


Gelfand AA: Migraine and childhood periodic syndromes in children and adolescents. Curr Opin Neurol
26(3):262-268, 2013.
Sharma MC, Jain D, Sarkar C, Goebel HH: Congenital myopathiesa comprehensive update of recent
advancements. Acta Neurol Scand 119:281-292, 2009.

66. What are the clinical manifestations of myotonic muscular dystrophy type 1?
Myotonic dystrophy type 1 is caused by a trinucleotide (CTG) expansion in the DMPK gene. Myo-
tonic dystrophy type 2 is less common and is caused by a tetranucleotide (CCTG) expansion in the
CCTG gene.
Clinical manifestations of myotonic dystrophy type 1 usually begin in adolescence or early adult life
with distal muscle weakness and myotonia. Given the phenomenon of anticipation the disease may
manifest in childhood if the inherited repeat size is large.
Muscle wasting about the face and sternocleidomastoids, in combination with facial weakness,
leading to the distinctive hatchet-face appearance
Partial ptosis, swan-like posture of the neck, enlarged paranasal sinuses, early prominent male-
pattern balding in both sexes
Cataracts, cardiac conduction abnormalities, hypogonadism with testicular atrophy, and abnormal
glucose tolerance

67. What is a common complication of neonates born to mothers with myotonic mus-
cular dystrophy?
Some newborns who have inherited the myotonic dystrophy gene from their mothers experience
profound weakness, with respiratory failure and bulbar insufficiency requiring endotracheal intubation
and mechanical ventilation. The mortality rate may be as high as 30% to 40%. Should the neonate
survive, the weakness resolves spontaneously. The occurrence of the neonatal syndrome has no effect
on the severity of the adult expression of the disease.
68. What are the two types of myasthenia that may affect the newborn or young
infant?
Transient neonatal myasthenia gravis. Affected neonates are born to mothers with autoimmune
myasthenia gravis. Because of transplacental transfer of maternal antiacetylcholine (ACh) receptor
antibodies, newborns experience transient weakness and hypotonia, which may be severe and life
threatening.
Nonautoimmune congenital myasthenia syndromes
69. Which types of myasthenia are not due to autoimmune production of antibodies
against the ACh receptor?
Defects in ACh synthesis or mobilization
End-plate acetylcholinesterase deficiency
Slow-channel syndrome
End-plate ACh receptor deficiency
70. A school-aged child presents with a few days history of progressive weakness
in his legs. This ascending paralysis was first noted at his ankles and now has
spread to involve his hips. List the differential diagnoses.
GuillainBarr syndrome
Acute spinal cord lesion
Tick bite paralysis
West Nile virus
Poliomyelitis (usually asymmetrical weakness)
Periodic paralysis (usually episodic)
Acute cerebellar ataxia
Myasthenia gravis (usually waxing and waning)
Botulism (usually descending)
References available online at expertconsult.com.
Bibliography
1. Dubowitz V: Muscle Disorders in Childhood, 3rd ed. Philadelphia, WB Saunders, 2001.
2. Fenichel GM: Clinical Pediatric Neurology: A Signs and Symptoms Approach, 7th ed. Philadelphia, Elsevier, 2013.
3. McMillan JA, Feigin RD, DeAngelis CD, Jones MD, (eds): Oskis Pediatrics, 4th ed. Philadelphia, Lippincott Williams &
Wilkins, 2006.
4. Menkes JH, Sarnat HB, (eds): Child Neurology, 7th ed. Philadelphia, Lippincott Williams & Wilkins, 2005.
5. Swaimann KF, Ashwal S, Ferriero DM, Schor NF, (eds): Pediatric Neurology: Principles and Practice, 5th ed. Philadelphia,
Mosby, 2012.
6. Volpe JJ: Neurology of the Newborn, 5th ed. Philadelphia, Saunders, 2008.
Meola G: Clinical aspects, molecular pathomechanisms and management of myotonic dystrophies. Acta
Myol 32(3):154-165, 2013.


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CHAPTER 28

NORMAL NEUROLOGIC GROWTH AND DEVELOPMENT

Table 28-1. Common Developmental Reflexes

PRENATAL DISEASES AND DEVELOPMENTAL DEFECTS

Table 28-2. Apgar Score

Grade I: Localized subependymal hemorrhage into the germinal matrix

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8. What complications may arise secondary to an IVH?

13. What is the differential diagnosis of megalencephaly?

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Hevner R: Brain overgrowth in disorders of RTK-PI3-AKT signaling: a mosaic of malformations. Semin

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18. What are the most common complications of a lumbosacral myelomeningocele?

Type II ArnoldChiari malformation resulting in hydrocephalus

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29. How often does multiple sclerosis present in children?

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INFECTIONS AND INFESTATIONS

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Chintagumpala M, Gajjar A: Brain tumors. Pediatr Clin North Am 62(1):167-178, 2015.

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INJURY BY PHYSICAL AGENTS AND TRAUMA

SEIZURES AND OTHER PAROXYSMAL DISORDERS

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56. What is generalized epilepsy with febrile seizures plus GEFS+?

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60. What are the different types of migraine headaches in children?

K EY POIN T S: HE AD AC H ES C O N C ER N I N G F O R A N I N T RACRANIAL MAS S

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References available online at expertconsult.com.

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You might also like

Table 28-1. Common Developmental Reflexes

Table 28-2. Apgar Score

Grade I: Localized subependymal hemorrhage into the germinal matrix

8. What complications may arise secondary to an IVH?

13. What is the differential diagnosis of megalencephaly?

18. What are the most common complications of a lumbosacral myelomeningocele?

Type II ArnoldChiari malformation resulting in hydrocephalus

29. How often does multiple sclerosis present in children?

56. What is generalized epilepsy with febrile seizures plus GEFS+?

60. What are the different types of migraine headaches in children?