Developmental and Hereditary Disorders Flashcards
Developmental and Hereditary Disorders
1
Q
- In Hirschsprung’s disease, neural crest cells fail to migrate normally
early in fetal development and produce potentially fatal complications
within months of birth because of disturbed
a. Intestinal motility
b. Bladder control
c. Swallowing
d. Bile secretion
e. Cardiac rhythms
A
- The answer is a. (Victor, p 574.) Infants with this defect in development
of the myenteric plexus are susceptible to intestinal obstruction and
megacolon development. The affected infants are often misconstrued as
merely colicky shortly after birth, but recurrent bouts of constipation, diarrhea,
and vomiting point to more serious disturbances of intestinal motility.
Intestinal obstruction is likely to become complete within the first year
of life and may be fatal if not surgically corrected. The failure of migration
of neural crest cells has been linked to a defect on chromosome 10.
2
Q
287. A newborn infant has a cystic swelling at the base of the spine that is covered with hyperpigmented skin and some coarse hair. Which of the following is the most likely explanation? a. Mongolian spot b. Spina bifida occulta c. Nevus flammeus d. Meningocele e. Encephalocele
A
- The answer is d. (Victor, p 1062.) The Mongolian spot is a benign
discoloration of the newborn’s skin at the base of the spine. It is usually
oval, well circumscribed, flat, and slightly hyperpigmented or otherwise
discolored. Spina bifida occulta is a defect in the superior elements of the
spinal column that is unassociated with meningeal or spinal cord abnormalities.
It may be evidenced superficially by a dimple in the skin or a
tuft of hair overlying the base of the spine. When there is evagination of
the meninges (dura mater and pia arachnoid) about the cord or cauda
equina through the defect in the spine, the condition is called a meningocele.
Extrusion of meningeal and neural elements together is called a
meningomyelocele. An encephalocele is a defect in the skull with extrusion
of brain. Nevus flammeus is a congenital, port-wine spot, usually
developing on the face.
3
Q
Items 288–289
At age 5, a child is noted to have the loss of ankle jerks. At age 10, limb
ataxia develops, followed by a peripheral neuropathy. During adolescence,
retinitis pigmentosa develops. Acanthocytosis is present.
288. These are all characteristic of which of the following?
a. Multiple sclerosis (MS)
b. Sickle cell disease
c. Abetalipoproteinemia
d. Progressive multifocal leukoencephalopathy (PML)
e. HIV subacute encephalomyelitis
A
- The answer is c. ( Rowland, pp 552–553.) Abetalipoproteinemia
(Bassen-Kornzweig syndrome) usually becomes symptomatic during
early childhood. The peripheral blood smear will exhibit abnormally
shaped erythrocytes (acanthocytes), and the plasma lipid profile will
reveal a very low cholesterol and triglyceride content. Acanthocytes are
spiked or crenated RBCs. These are an unusual hematologic finding in
patients with ataxia and are often diagnostic of abetalipoproteinemia.
Autopsy examination of the CNS in patients with abetalipoproteinemia reveals posterior column and spinocerebellar tract degeneration. The initial
complaints are similar to the spinocerebellar signs of Friedreich’s disease.
Position sense is lost and extensor plantar responses develop as the
disease progresses. As is true for Friedreich’s disease, dementia is not an
obvious part of the syndrome. Deficits accumulate over the course of
years. Vitamin E supplementation may retard the disease’s progression.
The differential diagnosis of retinitis pigmentosa is broad, and includes
many other conditions besides abetalipoproteinemia: mitochondrial diseases,
Bardet-Biedl syndrome, Laurence-Moon syndrome, Friedreich’s
ataxia, and Refsum’s disease. It may also occur alone as a hereditary disorder
linked to chromosome 3. It is characterized by a degeneration of all
layers of the retina. Because it is a noninflammatory condition, retinitis is
actually something of a misnomer.
4
Q
At age 5, a child is noted to have the loss of ankle jerks. At age 10, limb
ataxia develops, followed by a peripheral neuropathy. During adolescence,
retinitis pigmentosa develops. Acanthocytosis is present.
- In this disorder, chylomicrons, very-low-density lipoprotein (VLDL),
and low-density lipoprotein (LDL) are largely absent in the serum as a consequence
of a mutation in which gene?
a. Microsomal triglyceride transfer protein (MTP)
b. Huntingtin
c. Amyloid precursor protein
d. Dystrophin
e. Transfer RNA (tRNA)
A
- The answer is a. (Rowland, pp 552–553.) This disorder appears to be
due to a mutation in the gene that encodes a subunit of the MTP, which
results in impaired VLDL formation and consequent decreased vitamin E
delivery to the peripheral and central nervous system. In addition to an
abnormal plasma lipid profile, patients have disturbed fat absorption. Presumably,
it is the disturbed lipid that deforms the erythrocyte cell wall, but
erythrocyte production levels are relatively normal. Fat is increased in the
liver, and patients exhibit lactose intolerance. Central nervous system amyloid
collections develop in Alzheimer’s disease.
5
Q
- A 5-year-old boy has mental retardation, homonymous hemianopsia,
and hemiparesis. He had infantile spasm and still has epilepsy. Head CT
reveals calcifications in the cerebral cortex in a railroad track pattern.
Which of the following does this child most likely have?
a. Glioblastoma multiforme
b. Oligodendroglioma
c. Acoustic schwannoma
d. Craniopharyngioma
e. Sturge-Weber syndrome
A
- The answer is e. (Greenberg, 2/e, p 601.) All of these disturbances
will produce intracranial calcifications in some cases. The calcifications in
Sturge-Weber syndrome follow the gyral pattern of the cerebral cortex and
consequently produce the railroad track pattern that is evident on plain
x-ray of the skull. Calcium is deposited in the brain of the patient with
Sturge-Weber syndrome, presumably because the abnormal vessels overlying
the brain allow calcium, as well as iron, across the defective bloodbrain
barrier. Craniopharyngioma and acoustic schwannoma produce
calcifications, but these are obviously outside the cerebral cortex.
6
Q
294. A 35-year-old woman has prenatal testing done. The testing reveals that her child will have phenylketonuria (PKU). With PKU, serum may exhibit dangerously high levels of a. Creatine phosphokinase (CPK) b. Nicotinamide c. Phenylketone d. Lactate dehydrogenase e. Phenylalanine
A
- The answer is e. (Victor, pp 1008–1009.) Phenylketonuria is inherited
as an autosomal recessive trait. It occurs in at least two forms. In one
form, intolerance of phenylalanine is extreme, and dietary intake of that
amino acid must be restricted from birth. Alternatively, some persons have
hyperphenylalaninemia without PKU. This latter group does not suffer the
CNS damage seen with in utero exposure to high phenylalanine levels.
Such in utero exposure will occur if the mother is homozygous for PKU. If
the mother is normal, infants with PKU are born with essentially normal
nervous systems. Damage develops after birth in the susceptible group as
serum phenylalanine levels rise.
7
Q
- A 4-year-old previously healthy girl develops an intermittent red,
scaly rash over her face, neck, hands, and legs. This is followed by developmental
delay, emotional lability, and episodic cerebellar ataxia. She is
diagnosed with Hartnup’s disease. Her condition may respond to large supplementary
doses of
a. Vitamin C
b. Nicotinamide
c. Thiamine
d. Pyridoxine
e. α tocopherol
A
- The answer is b. (Victor, pp 1009–1010.) With Hartnup’s disease
there is intestinal malabsorption of tryptophan and other neutral amino
acids. Tryptophan serves as a precursor for nicotinamide, but with more
than 400 mg of nicotinamide daily, the tryptophan malabsorption becomes
less problematic. Inheritance appears to be autosomal recessive. Affected
children develop a scaly erythematous rash on the face similar to that seen
with pellagra. The ataxia exhibited may be episodic.
8
Q
- Hepatosplenomegaly is most likely with
a. Tay-Sachs disease
b. Niemann-Pick disease
c. Alpers’ disease
d. Subacute necrotizing encephalopathy
e. Wilson’s disease (hepatolenticular degeneration)
A
- The answer is b. (Victor, pp 997–998.) Niemann-Pick disease is
inherited as an autosomal recessive trait. By 9 months of age, patients with
the infantile form usually have prominent hepatosplenomegaly. A deficiency
of sphingomyelinase in hepatocytes is diagnostic for the disease.
9
Q
297. A 25-year-old woman with epilepsy is taking divalproex sodium during the first trimester of pregnancy. She is at slightly increased risk of having children with which of the following? a. Holoprosencephaly b. Defects of neural tube closure c. Medulloblastoma d. Agenesis of the corpus callosum e. Kallmann syndrome
A
- The answer is b. (Greenberg, 5/e, p 274.) To what extent the
antiepileptic divalproex sodium increases the risk of defects of neural tube
closure, such as meningomyelocele, is debatable, but there is at least a
slight increase in the risk. Many agents have been linked to problems with
neural tube formation or closure, but none causes problems in a large segment
of the population. Colchicine, papaverine, and caffeine, as well as
irradiation, hyperthermia, antimetabolites, and salicylates, may increase
the risk of neural tube malformations. The vitamin most clearly implicated
in cases involving hypervitaminosis is vitamin A. Congenital malformations
as a group are slightly increased in the offspring of women with
epilepsy even if they are not taking antiepileptic drugs before or during
pregnancy. The importance of folate supplementation in women with a
prior history of neural tube defect has been shown in several studies and is
the basis of the recommendation for the use of folate supplementation during
the first trimester of pregnancy. Agenesis of the corpus callosum is a
component of several developmental disorders of the CNS, including
Chiari syndromes. Kallmann syndrome is a congenital disturbance of the
hypothalamus that results in anosmia, hypogonadism, and other maturational
problems that become more evident when puberty fails to occur.
10
Q
- With agenesis of the corpus callosum, magnetic resonance imaging
(MRI) will reveal
a. Atrophy of the frontal lobes
b. Abnormally shaped lateral and third ventricles
c. Cerebellar aplasia
d. Schizencephaly
e. Encephaloclastic porencephaly
A
- The answer is b. (Greenberg, 2/e, p 586–587.) On coronal sections of
the brain, the lateral ventricles will have a typical batwing conformation if
the patient has agenesis of the corpus callosum. The third ventricle may be
dilated and may open onto the surface of the brain. Patients with this congenital
anomaly may be asymptomatic or may exhibit a variety of cognitive
212 Neurology
disorders. In Aicardi syndrome, agenesis of the corpus callosum is associated
with retardation, epilepsy, vertebral anomalies, and chorioretinitis.
11
Q
Items 299–300
A boy has the onset of difficulty walking at 16 months. Reflexes are
decreased. Over the course of several months, the patient becomes dysarthric
and mental functioning decreases. Testing reveals that the patient has a deficiency
of arylsulfatase A.
299. Which of the following does this patient most likely have?
a. Sandhoff’s disease
b. Tay-Sachs disease
c. Gaucher’s disease
d. Metachromatic leukodystrophy
e. McArdle’s disease
A
- The answer is d. (Rowland, pp 521–523.) Hexosaminidase deficiencies
produce Sandhoff’s and Tay-Sachs diseases. Glucocerebrosidase is deficient
in Gaucher’s disease. Phosphofructokinase deficiency is usually
symptomatic as a disturbance of skeletal muscle function. The enzymatic
defect in metachromatic leukodystrophy is transmitted in an autosomal
recessive fashion. The affected person usually has retardation, ataxia, spasticity,
and sensory disturbances, but individual elements of this disorder
may appear alone in less serious cases. The disease is usually symptomatic
during infancy.
12
Q
Items 299–300
A boy has the onset of difficulty walking at 16 months. Reflexes are
decreased. Over the course of several months, the patient becomes dysarthric
and mental functioning decreases. Testing reveals that the patient has a deficiency
of arylsulfatase A.
- This diagnosis can usually be made on the basis of which of the following?
a. MRI
b. Nerve biopsy
c. Red blood cell (RBC) morphology
d. Cerebrospinal fluid (CSF) cell morphology
e. Electroencephalography (EEG)
A
- The answer is b. (Rowland, pp 521–523.) Sulfatide granules may be
evident in nerve tissue, as well as in tissue outside the nervous system, in
persons with metachromatic leukodystrophy. The disease is usually fatal
within a few years of obvious symptoms. At autopsy, there may be evidence
of dysmyelination or demyelination in the CNS, as well as in the peripheral
nervous system.
13
Q
Items 301–302
301. A 15-year-old boy has moderate mental retardation, attention deficit
disorder, a long face, enlarged ears, and macroorchidism. Development has
been steady but always at a delayed pace. The most likely cause for this
patient’s low intelligence is which of the following?
a. Turner syndrome
b. Klinefelter syndrome
c. Fragile X syndrome
d. Reye syndrome
e. Tuberous sclerosis
A
- The answer is c. (Bradley, p 83.) With the fragile X syndrome, the
terminal elements of the long arm of the abnormal X chromosome appear
stretched or broken away from the rest of the chromosome. Retardation
usually becomes evident during childhood. Affected men have large ears, a
high-arched palate, hypotelorism, and large testes. Autism also occurs
among affected men.
14
Q
Items 301–302
301. A 15-year-old boy has moderate mental retardation, attention deficit
disorder, a long face, enlarged ears, and macroorchidism. Development has
been steady but always at a delayed pace. The most likely cause for this
patient’s low intelligence is which of the following?
302. Women carrying chromosomes for this disorder
a. Are invariably normal
b. Have mild retardation in about one-half of cases
c. Have high-arched palates and hypotelorism
d. Have hyperextensible joints
e. Have prominent thumbs
A
- The answer is b. (Victor, p 1067.) Men with the fragile X syndrome
have hyperextensible joints and prominent thumbs, but carrier women
may appear quite normal. The abnormal chromosome may be detected in
fetal lymphocytes and fibroblasts, thereby allowing for prenatal screening.
Epilepsy develops in many affected persons, but the seizures are usually
easily controlled, unlike the case with other hereditary causes of epilepsy.
15
Q
Items 303–306
A 35-year-old man complains of stumbling and slurred speech. His
problem started several months ago and has progressed slowly but consistently.
On neurologic examination, he is found to have scanning speech,
nystagmus, limb dysmetria, and kinetic tremor. His intellectual function is
normal.
- The most appropriate initial investigation is
a. Lumbar puncture
b. Serum drug screen
c. Routine urinalysis
d. Posterior fossa myelogram
e. Precontrast CT scan
A
- The answer is e. (Swaiman, pp 539–540.) This man has signs of
cerebellar dysfunction. That the deficit has been slowly progressive and is
not associated with cognitive dysfunction makes it especially likely that a
structural lesion in the posterior fossa is responsible for the deficit. Because
Developmental and Hereditary Disorders
the lesion need not disturb the external shape of the cerebellum, a posterior
fossa myelogram will not necessarily yield an answer. The CT scan will
show if there is an intraparenchymal or extraparenchymal lesion. Drug
abuse is not likely to be a factor in this cerebellar syndrome, because all the
phenomena that are observed on examination are coordination problems
rather than combined cognitive and motor functions.
16
Q
Items 303–306
A 35-year-old man complains of stumbling and slurred speech. His
problem started several months ago and has progressed slowly but consistently.
On neurologic examination, he is found to have scanning speech,
nystagmus, limb dysmetria, and kinetic tremor. His intellectual function is
normal.
- Admission studies include a hematocrit of 55% and a routine urinalysis,
which reveals excess protein and some RBCs in the urine. Urine culture
is negative. The initial physical examination reveals an enlarged liver
and spleen. Additional physical findings will most likely include
a. A Kayser-Fleischer ring around the cornea
b. Hypopigmented (ash leaf) spots on the trunk
c. Telangiectasias in the fundi on retinal examination
d. Bilateral hearing loss
e. Generalized hyporeflexia
A
- The answer is c. (Swaiman, pp 539–540.) The association of erythrocytosis
with cerebellar signs, microscopic hematuria, and hepatosplenomegaly
suggests von Hippel-Lindau syndrome. This hereditary disorder is
characterized by polycystic liver disease, polycystic kidney disease, retinal
angiomas (telangiectasia), and cerebellar tumors. This is an autosomal dominant
inherited disorder with variable penetrance. Men are more commonly
affected than women. Although neoplastic cysts may develop in the cerebellum
in persons with von Hippel-Lindau syndrome, these usually do not
become sufficiently large to cause an obstructive hydrocephalus. Other
abnormalities that occur with this syndrome include adenomas in many
organs. Hemangiomas may be evident in the bones, adrenals, and ovaries.
Hemangioblastomas may develop in the spinal cord or brainstem, as well as
in the cerebellum. This syndrome is not associated with acoustic schwannomas
that could cause bilateral hearing loss, and it is not accompanied by
peripheral neuropathy, which could cause diffuse hyporeflexia.
17
Q
Items 303–306
A 35-year-old man complains of stumbling and slurred speech. His
problem started several months ago and has progressed slowly but consistently.
On neurologic examination, he is found to have scanning speech,
nystagmus, limb dysmetria, and kinetic tremor. His intellectual function is
normal.
- A postcontrast computed tomography (CT) scan reveals a cyst and
two smaller masses in the left cerebellar hemisphere. Your recommendation
is that the patient
a. Submit to surgical resection of the cerebellar lesions as soon as possible
b. Submit to radiation therapy of the cerebellar lesions immediately
c. Have follow-up MRI to look for involution of the lesions
d. Have a diagnostic lumbar puncture to look for evidence of parasitic infestation
of the brain
e. Have a needle biopsy of the cerebellum to establish the histology of the cystic
lesion
A
- The answer is a. (Swaiman, pp 539–540.) The cystic lesion and the
other cerebellar lesions are most likely hemangioblastomas. These hemangioblastomas
often bleed and produce potentially lethal intracranial
hematomas. Radiation therapy and needle biopsies would increase the risk
of bleeding. Rather than spontaneously involuting, these lesions generally
enlarge and become more unstable as time passes. Intracerebellar hemorrhage
is increasingly likely as time passes.
18
Q
Items 303–306
A 35-year-old man complains of stumbling and slurred speech. His
problem started several months ago and has progressed slowly but consistently.
On neurologic examination, he is found to have scanning speech,
nystagmus, limb dysmetria, and kinetic tremor. His intellectual function is
norma
306. Within 6 years of his initial visit, the patient returns with a pathologic fracture of his spine. Biopsy reveals metastatic cancer. The source of the tumor is most likely the a. Cerebral hemisphere b. Cerebellar hemisphere c. Liver d. Kidney e. Spleen
A
- The answer is d. (Swaiman, pp 539–540.) Von Hippel-Lindau syndrome
is associated with a high incidence of renal carcinomas. These
malignant renal tumors usually develop years after the cerebellar hemangioblastomas,
liver disease, or polycystic renal disease becomes symptomatic.
People surviving intracranial hemorrhages caused by the
intracerebellar hemangioblastomas often succumb to metastatic renal carcinoma. Treating the intracranial lesions does nothing to reduce the risk of
metastatic renal cancer.
19
Q
Items 307–308
An infant has a head CT performed because of a large head and failure
to thrive. The diagnosis of hydrocephalus is made.
307. Congenital hydrocephalus may develop as a consequence of which first-trimester maternal disorder? a. Complicated migraine b. Viral infection c. Pseudotumor cerebri d. Chorea gravidarum e. Intervertebral disk herniation
A
- The answer is b. (Greenberg, 2/e, p 597. Rowland, pp 5142–5143.) A
maternal infection with mumps or rubella virus may produce aqueductal
stenosis and, as a consequence, hydrocephalus. The aqueduct of Sylvius
connects the third ventricle to the fourth ventricle. The lateral and third
ventricles enlarge as the choroid plexus produces fluid that cannot migrate
to the subarachnoid space to be reabsorbed.
20
Q
Items 307–308
An infant has a head CT performed because of a large head and failure
to thrive. The diagnosis of hydrocephalus is made.
308. Uncorrected congenital hydrocephalus will usually produce which of the following? a. Dolichocephaly b. Brachycephaly c. Holoprosencephaly d. Macrocephaly e. Microcephaly
A
- The answer is d. (Victor, pp 661–662.) Congenital hydrocephalus
usually requires shunting to avoid progressive enlargement of the head and
thinning of the brain mantle. Dolichocephaly and brachycephaly refer to
head shapes, the former being a long, narrow head and the latter a broad
head. Neither of these is necessarily associated with any abnormality. Holoprosencephaly
is a failure in development of the midline division of the
brain, which may give rise to a stillborn cyclops. A variety of conditions
will produce congenital hydrocephalus, and any condition that produces
apparent hydrocephalus at birth may produce mental retardation. Correction
of the hydrocephalus at or soon after birth reduces the probability of
retardation as a direct effect of the hydrocephalus, but conditions that
cause damage to the brain as well as obstruct the flow of CSF may leave the
patient retarded. An uncorrected hydrocephalus may not be lethal for
many years.
21
Q
- A 6-month-old child is noted to have head lag, tongue fasciculations,
and bilateral abducens palsies. MRI scan reveals a type 2 Chiari malformation.
Which of the following defects would this child be likely to have?
a. A renal cyst
b. Pulmonary atelectasis
c. Spina bifida
d. Holoprosencephaly
e. A hepatic cyst
A
- The answer is c. (Victor, pp 1064–1065.) Spina bifida may be
extreme in some of the children affected by the Arnold-Chiari (type 2
Chiari) malformation. A myelomeningocele may be present at the level of
the spina bifida. Spinal cord tissues may extend into this mass and lie just
under the skin covering the neural tube defect. Children with obvious
spinal defects usually have persistent problems with leg movements and
bladder and bowel control.
22
Q
Items 310–313
A 7-year-old boy is taken by his parents to see a dermatologist. They
have noticed nodules on his face and are concerned. The dermatologist
tells them that their child has adenoma sebaceum.
310. Adenoma sebaceum of the face is especially common with which of
the following diseases?
a. Neurofibromatosis
b. Sturge-Weber syndrome
c. Tuberous sclerosis
d. Ataxia telangiectasia
e. Fragile X syndrome
A
- The answer is c. (Victor, pp 1069–1073.) Adenoma sebaceum occurs
in about 90% of patients with tuberous sclerosis. A depigmented lesion,
called a shagreen patch, occurs in only about 20% of these patients. Adenoma
sebaceum usually becomes apparent over the malar eminences of the
Developmental and Hereditary Disorders
face between 2 and 5 years of age and may evolve into difficult-to-treat
angiofibromas of the skin. In ataxia telangiectasia, facial telangiectasias may
develop. Sturge-Weber syndrome is characteristically associated with a portwine
spot over part of the face. Patients with neurofibromatosis often have
café au lait spots, but these do not usually occur on the face.
23
Q
Items 310–313
A 7-year-old boy is taken by his parents to see a dermatologist. They
have noticed nodules on his face and are concerned. The dermatologist
tells them that their child has adenoma sebaceum.
- This disease is inherited in
a. A sex-linked recessive pattern
b. An autosomal dominant pattern
c. An autosomal recessive pattern
d. A pattern most consistent with newly arising mutations
e. A pattern suggesting a mitochondrial gene defect
A
- The answer is b. (Victor, pp 1069–1073.) Although the inheritance
pattern of tuberous sclerosis is autosomal dominant, the penetrance is variable.
A severely impaired child may be born to a negligibly affected parent.
Despite the consensus that inheritance is autosomal dominant, estimates of
spontaneous mutations in affected persons are as high as 70%.
24
Q
Items 310–313
A 7-year-old boy is taken by his parents to see a dermatologist. They
have noticed nodules on his face and are concerned. The dermatologist
tells them that their child has adenoma sebaceum.
- Retinal problems with this disease
a. Include retinal phakomas
b. Include retinitis pigmentosa
c. Include retinal telangiectasias
d. Include retinoblastomas
e. Are generally not part of the disease
A
- The answer is a. (Victor, p 1071.) Retinal phakomas, which require
no treatment, are a principal criterion for making the diagnosis of tuberous
sclerosis. Along with adenoma sebaceum and periventricular tubers, they
are virtually pathognomonic. Other findings that are typical of tuberous
sclerosis include ash leaf spots, shagreen patches, CNS calcifications, renal
tumors, cardiac rhabdomyomas, and seizure disorders.
25
Q
Items 310–313
A 7-year-old boy is taken by his parents to see a dermatologist. They
have noticed nodules on his face and are concerned. The dermatologist
tells them that their child has adenoma sebaceum.
313. Calcifications evident on the skull x-ray or CT scan of a patient with this disease usually represent a. Calcified subependymal glial nodules b. Calcified meningeal adhesions c. Meningeal psammoma bodies d. Calcified astrocytomas e. Calcified granulomas
A
- The answer is a. (Victor, pp 1071–1073.) By 5 years of age, more than
half of patients with tuberous sclerosis will have subependymal glial nodules
that have calcified. These nodules usually do not become malignant,
but they may enlarge sufficiently to produce an obstructive hydrocephalus.
Ventriculoperitoneal shunting may be needed if obstruction develops.
26
Q
- A 50-year-old man complaining of dizziness is found to have a cyst
occupying 50% of his posterior fossa and incomplete fusion of the cerebellar
elements inferiorly. There is no evidence of an obstructive hydrocephalus.
His longevity can be estimated to be
a. Less than 3 months
b. Less than 1 year
c. Less than 5 years
d. Less than 10 years
e. Unaffected by this finding
A
- The answer is e. (Greenberg, 2/e, pp 587–588.) That the cerebellar
elements are not fused in the midline suggests an asymptomatic Dandy-
Walker malformation. This congenital disorder of brain formation may
become symptomatic soon after birth if an obstructive hydrocephalus
develops as one facet of the anomaly. In the absence of an obstructive
hydrocephalus, the patient may remain asymptomatic throughout life.
27
Q
- The treatment of choice for children with infantile spasms is
a. Carbamazepine (Tegretol)
b. Phenobarbital
c. Phenytoin (Dilantin)
d. Divalproex sodium (Depakote)
e. Adrenocorticotropic hormone (ACTH)
A
- The answer is e. (Rowland, p 815.) Adrenocorticotropic hormone is
usually given as a gel intramuscularly to control infantile spasms in children
with tuberous sclerosis; 40 to 80 mg is divided into two doses. Treatment
continues until the infantile spasms abate or the EEG pattern of
hypsarrhythmia resolves. This usually requires 6 to 8 weeks of treatment.
The ACTH should not be stopped abruptly.
28
Q
- A 9-year-old boy has been generally healthy. However, his parents are
concerned that his many areas of hyperpigmented skin may have some significance.
They have been told that these are café au lait spots. Café au lait
spots are commonly found on patients with
a. Tuberous sclerosis
b. Neurofibromatosis
c. MS
d. Sturge-Weber syndrome
e. Ataxia telangiectasia
A
- The answer is b. (Victor, pp 1073–1077.) Café au lait spots in
patients with neurofibromatosis are usually larger than a few centimeters
and occur in several locations in individual patients. Some have ragged
edges and are called coast of Maine spots. They occur with both type 1 and
type 2 neurofibromatosis, but are much more common with type 1.
29
Q
- The newborn infant with motor neuron disease is likely to exhibit
a. Seizures
b. Hypotonia
c. Hypsarrhythmia
d. Moro reflexes
e. Spina bifida
A
- The answer is b. (Swaiman, pp 1164–1169.) The child with congenital
weakness, hypotonia, and muscle atrophy may have Werdnig-
Hoffmann disease, a congenital motor neuron disease. This is an especially
lethal form of motor neuron disease and may limit the child’s life
expectancy to weeks or months. A similar pattern of disease that appears in
older children is less lethal and is called Kugelberg-Welander disease.
These types of motor neuron diseases are also known as spinal muscular
atrophies (SMAs). Anterior horn cell disease is presumed to be a pivotal
feature of diseases in this category.
30
Q
- Many children with Tay-Sachs disease develop blindness before they
die, with retinal accumulation of gangliosides that produces
a. Optic neuritis
b. Cherry red spots
c. Chorioretinitis
d. Retinal detachments
e. Waxy exudates
A
- The answer is b. (Victor, pp 996–997.) More than 90% of children
with Tay-Sachs disease develop cherry red spots on the retina. The red
spot at the fovea develops as retinal ganglion cells become distended with
glycolipid. There are no ganglion cell bodies overlying the fovea, and so
the red color of the vascular choroid is apparent in this region but
obscured by more opaque glycolipid-engorged cells over the remainder
of the retina.
31
Q
- The parents of a 10-year-old boy bring their child in to see you. The
child has been diagnosed with cerebral palsy, and the parents do not really
understand what this means. As part of your explanation, you tell them
that cerebral palsy is a static encephalopathy because
a. Deficits do not appear after birth
b. The injury to the brain does not progress
c. Affected persons fail to reach any developmental milestones on time
d. Affected persons have resting tremors
e. The EEG exhibits a disorganized background rhythm
A
- The answer is b. (Rowland, p 476.) A static encephalopathy is one in
which brain damage has been arrested but neurologic problems persist.
Establishing that the brain lesion is not progressive may require extensive
testing. A young child with a static motor disorder is said to have CP. Neurodegenerative
diseases with slow or stepwise progressions may appear to
be static encephalopathies over the course of months, but prove to be progressive
encephalopathies over the course of years. The brain lesion with
CP is static, but the deficits associated with CP may evolve as the child
matures.
32
Q
- A 6-year-old child is brought to the neurologist because of developmental
delay. Her morphological features are typical and chromosome
analysis confirms a diagnosis of Down syndrome (trisomy 21). The brain of
this patient is expected to be
a. Smaller than normal for age and body size
b. Larger than normal for age and body size
c. Abnormally long in anteroposterior measurements
d. Hydrocephalic
e. Excessively convoluted
A
- The answer is a. (Victor, p 1067.) The brain of the patient with
Down syndrome (trisomy 21) is typically foreshortened. The gyral pattern
is simplified, and the frontal lobes are small. The occipital lobes may be
slanted, and the overall shape of the skull is abnormal.
Developmental and Hereditary Disorders
33
Q
- Porencephaly usually develops as a consequence of
a. Fetal alcohol syndrome
b. Vascular or other destructive injuries to the fetal brain
c. Trisomy 13
d. Trisomy 21
e. Dandy-Walker syndrome
A
- The answer is b. (Osborn, pp 52–56.) In utero damage to the fetal
brain may be evident at birth as large cysts in the brain. The presence of
one or more of these intracerebral cysts is called porencephaly. Some
pathologists believe that schizencephaly, a related abnormality in which
brain segmentation is abnormal, is caused by similar phenomena, which
include incidents such as strokes and viral encephalitides in the fetal brain.
34
Q
322. What percentage of patients with tuberous sclerosis have mental retardation? a. 1 b. 10 c. 25 d. 65 e. 99
A
- The answer is d. (Swaiman, p 534.) Of the 65% of patients with
tuberous sclerosis who are retarded, half are severely retarded. Seizures are
invariably associated with retardation. About 20% of patients with tuberous
sclerosis develop the Lennox-Gastaut syndrome with persistent
seizures and significant mental retardation. These children usually have a
mixed seizure disorder, whereas those without Lennox-Gastaut syndrome
most often have complex partial seizures.
35
Q
- A child is born to a 19-year-old woman who has had two to eight
drinks per day throughout her pregnancy. What is the major pathologic
effect of alcohol on the central nervous system of the developing fetus?
a. Cerebral ischemia
b. Periventricular hemorrhage
c. Macrocephaly
d. Impaired neuronal migration
e. Holoprosencephaly
A
- The answer is d. (Victor, pp 1247–1248.) Alcohol abuse in pregnant
women is associated with three major kinds of abnormalities in the developing
fetus: intrauterine and postpartum growth retardation, dysmorphic facies
in the newborn, and effects on the development of the CNS. The broad range
of neurologic and systemic abnormalities observed in children born to
alcohol-abusing women is referred to as the fetal alcohol syndrome. Alcohol
is teratogenic at high doses and may interfere measurably in fetal development
with exposure at any dose. Although the mechanism of alcohol’s effect
on the developing brain is not entirely clear, it appears that alcohol acts
primarily to impair neuronal migration. This may result in formation of heterotopias
(collections of cortical neurons in abnormal locations), cortical disorganization,
and malformations of the cerebellum and brainstem. Mental
retardation, learning disabilities, hyperactivity, and microcephaly, not macrocephaly,
are the common clinical neurologic consequences of fetal alcohol
syndrome. Ischemia and hemorrhagic complications are not part of the syndrome.
Holoprosencephaly refers to a failure of the two sides of the frontal
cerebrum to separate properly, leading to a fusion of the frontal poles and
hippocampi with no interhemispheric fissure.
36
Q
- A 37-year-old man has an MRI performed by his primary care doctor
because of a long history of headaches. It is notable only for the finding
of a type 1 Chiari malformation. He is sent to a neurologist for further evaluation.
A type 1 Chiari malformation usually becomes symptomatic as
which of the following in adults?
a. Epilepsy
b. Hydrocephalus
c. Ataxia
d. Dementia
e. Psychosis
A
- The answer is c. (Osborn, pp 15–18.) Both type 1 and type 2 Chiari
malformations are primarily abnormalities of hindbrain development. With
the type 1, or adult, abnormality, the cerebellar tonsils extend below the
foramen magnum. Affected persons do not usually become symptomatic
218 Neurology
until they are adults, and then the symptoms are largely referable to the
cerebellum. With the type 2 malformation, cerebellar anatomy is usually
much more deranged, and the cerebellar vermis lies well below the foramen
magnum. Type 2 malformations most often become symptomatic at birth or
during infancy and may produce hydrocephalus with retardation.
37
Q
- A 25-year-old mother develops an illness during pregnancy. A diagnosis
of cytomegalovirus (CMV) infection is made by serology. Prenatal
CMV infections may produce which retinal disturbance?
a. Chorioretinitis
b. Cherry red spot
c. Microaneurysms
d. Hypervascularity
e. Hemorrhage
A
- The answer is a. (Victor, p 1071.) Microaneurysms and hypervascularity
are typically seen with diabetic retinopathy rather than developmental
disease. Hemorrhages in the retina would be more typical of
hypertensive encephalopathy or a coagulopathy. Neurologic problems that
develop in the infant with a prenatal CMV infection include retardation,
microcephaly, seizures, and hearing deficits. The virus often causes chorioretinitis,
optic atrophy, and architectural changes throughout the brain.
