290. A 13-year-old girl has had a gradually worsening ataxia over the past 6 years. She also reports generalized weakness. Examination findings include height and weight to be at the 50th percentile for a 10-year-old, and a peripheral neuropathy. Serum and red-cell lipid profiles are abnormal, suggesting the diagnosis of abetalipoproteinemia. Chylomicrons, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) would be largely absent in the serum as a consequence of a mutation in which gene?
a. Microsomal triglyceride transfer protein
b. Huntingtin
c. Amyloid precursor protein
d. Dystrophin
e. Transfer RNA (tRNA)
291. 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
292. A 26-year-old man diagnosed with von Hippel-Lindau syndrome has a postcontrast computed tomography (CT) scan that reveals a cyst and two smaller masses in the left cerebellar hemisphere. Which of the following is the best recommendation to this patient?
a. Surgical resection of the cerebellar lesions as soon as possible
b. Radiation therapy of the cerebellar lesions immediately
c. Follow-up magnetic resonance imaging (MRI) in 6 months to look for involution of the lesions
d. Diagnostic lumbar puncture to look for evidence of parasitic infestation of the brain
e. Needle biopsy of the cerebellum to establish the histology of the cystic lesion
293. In Hirschsprung disease, neural crest cells fail to migrate normally early in fetal development and produce potentially fatal complications within months of birth because which of the following is disturbed?
a. Intestinal motility
b. Bladder control
c. Swallowing
d. Bile secretion
e. Cardiac rhythms
Questions 294 and 295
294. In the tomogram below showing the base of the skull, which of the following is true regarding the first cervical vertebra?
a. It is unremarkable.
b. It is fused to the base of the skull.
c. It is completely absent.
d. It is displaced dorsally.
e. It is incorporated into the odontoid process (od).
295. In the above x-ray, the second cervical vertebra extends above the level of the foramen magnum and places the patient at high risk of having which of the following?
a. A meningoencephalocele
b. A myelomeningocele
c. Syringobulbia
d. Syringomyelia
e. Brainstem compression
296. A 22-year-old healthy woman has a history of mental retardation in her family. Testing has revealed fragile X syndrome as the etiology. She has brought her husband to the office visit, and they have many questions. Which of the following is true regarding women carrying chromosomes for fragile X syndrome?
a. They are invariably normal.
b. They have mild retardation in about one-half of cases.
c. They have high-arched palates and hypotelorism.
d. They have hyperextensible joints.
e. They have prominent thumbs.
297. 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 which of the following?
a. Creatine phosphokinase (CPK)
b. Nicotinamide
c. Phenylketone
d. Lactate dehydrogenase
e. Phenylalanine
298. A 17-month-old boy had developed normally until approximately 13 months of age, when he began having progressive gait problems. On examination, the patient is spastic, yet nerve conduction studies (NCS) reveal slowed motor and sensory conduction velocities. Cerebrospinal fluid (CSF) protein is elevated. MRI reveals white matter abnormalities. Leukocyte testing reveals deficient arylsulfatase A activity. Which of the following tests may also provide useful diagnostic information in this condition?
a. CT
b. Nerve biopsy
c. Red blood cell (RBC) morphology
d. CSF cell morphology
e. Electroencephalogram (EEG)
299. A 25-year-old woman with epilepsy is taking divalproex sodium during the first trimester of pregnancy. She is at increased risk of having a child with which of the following?
a. Holoprosencephaly
b. Defects of neural tube closure
c. Medulloblastoma
d. Agenesis of the corpus callosum
e. Kallmann syndrome
300. With agenesis of the corpus callosum, MRI will reveal which of the following?
a. Atrophy of the frontal lobes
b. Abnormally shaped lateral and third ventricles
c. Cerebellar aplasia
d. Schizencephaly
e. Encephaloclastic porencephaly
301. 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. Which of the following is the most likely diagnosis?
a. Sandhoff disease
b. Tay-Sachs disease
c. Gaucher disease
d. Metachromatic leukodystrophy
e. McArdle disease
302. 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 disease. Her condition may respond to large supplementary doses of which of the following?
a. Vitamin C
b. Nicotinamide
c. Thiamine
d. Pyridoxine
e. α-Tocopherol
303. 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. Which of the following is the most likely cause for this patient’s low intelligence?
a. Turner syndrome
b. Klinefelter syndrome
c. Fragile X syndrome
d. Reye syndrome
e. Tuberous sclerosis
304. 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
305. A 35-year-old man has stumbling and slurred speech. His symptoms started several months ago and have progressed slowly but consistently. On neurological examination, he is found to have scanning speech, nystagmus, limb dysmetria, and kinetic tremor. His intellectual function is normal. Which of the following is the most appropriate initial investigation?
a. Lumbar puncture
b. Serum drug screen
c. Routine urinalysis
d. EEG
e. Brain MRI
306. A 29-year-old woman has progressive gait disorder and dysmetria. Laboratory 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 which of the following?
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
307. 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. 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
308. A 2-year-old boy with severe epilepsy is diagnosed with tuberous sclerosis. His mother has some skin findings suggesting that she is a relatively asymptomatic carrier of the disease. The child’s parents would like to understand the risk that their future offspring may develop tuberous sclerosis. This condition is inherited in which of the following patterns?
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
309. An infant has a head CT performed because of a large head and failure to thrive. The diagnosis of hydrocephalus is made. Congenital hydrocephalus may develop as a consequence of which of the following first-trimester maternal disorders?
a. Complicated migraine
b. Viral infection
c. Pseudotumor cerebri
d. Chorea gravidarum
e. Intervertebral disk herniation
310. In the preceding patient, uncorrected congenital hydrocephalus will usually produce which of the following?
a. Dolichocephaly
b. Brachycephaly
c. Holoprosencephaly
d. Macrocephaly
e. Microcephaly
311. A 6-month-old child has 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
312. 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. 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
313. Within 6 years of his initial visit, a patient with von Hippel-Lindau syndrome returns with a pathologic fracture of his spine. Biopsy reveals metastatic cancer. Which of the following is the likely source of the tumor?
a. Cerebral hemisphere
b. Cerebellar hemisphere
c. Liver
d. Kidney
e. Spleen
314. Which of the following retinal problems tend to occur in people with tuberous sclerosis?
a. Retinal phakomas
b. Retinitis pigmentosa
c. Retinal telangiectasias
d. Retinoblastomas
e. Retinal problems are generally not part of the disease
315. Calcifications evident on the skull x-ray or CT scan of a patient with tuberous sclerosis usually represent which of the following?
a. Calcified subependymal glial nodules
b. Calcified meningeal adhesions
c. Meningeal psammoma bodies
d. Calcified astrocytomas
e. Calcified granulomas
316. A 50-year-old man presenting with “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 which of the following?
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
317. A 1-year-old girl is evaluated for developmental delay. Examination and testing reveal that she is having hundreds of seizures per day. The clinical manifestations are somewhat subtle and consist of sit-up like movements. Interictal EEG shows multifocal, high-amplitude spikes (hypsarrhythmia) and slowing. Which of the following is the treatment of choice for this patient?
a. Carbamazepine
b. Phenobarbital
c. Phenytoin
d. Divalproex sodium
e. Adrenocorticotropic hormone (ACTH)
318. A 9-year-old boy has been generally healthy. However, there is a family history of neurological disease, and his parents are concerned that his many areas of hyperpigmented skin (some more than 2.5 in. in diameter) may have some significance. This dermatological manifestation is commonly found on patients with which of the following diseases?
a. Tuberous sclerosis
b. Neurofibromatosis
c. MS
d. Sturge-Weber syndrome
e. Ataxia telangiectasia
319. The newborn infant with motor neuron disease is likely to exhibit which of the following?
a. Seizures
b. Hypotonia
c. Hypsarrhythmia
d. Moro reflexes
e. Spina bifida
320. Many children with Tay-Sachs disease develop blindness before they die, with retinal accumulation of gangliosides that produces which of the following?
a. Optic neuritis
b. Cherry red spots
c. Chorioretinitis
d. Retinal detachments
e. Waxy exudates
321. 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, which of the following would you tell them?
a. Cerebral palsy is a static encephalopathy because deficits do not appear after birth.
b. Cerebral palsy is a static encephalopathy because the injury to the brain does not progress.
c. Cerebral palsy is a static encephalopathy because affected persons fail to reach any developmental milestones on time.
d. Cerebral palsy is a static encephalopathy because affected persons have resting tremors.
e. Cerebral palsy is a static encephalopathy because the EEG exhibits a disorganized background rhythm.
322. 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 have which of the following characteristics?
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
323. A 7-year-old child has a head CT ordered because of recent headaches. The scan is significant for a right parietal parenchymal defect that is continuous with the ventricle and does not appear to be lined with gray matter. This type of lesion usually develops as a consequence of which of the following?
a. Fetal alcohol syndrome
b. Vascular or other destructive injuries to the fetal brain
c. Trisomy 13
d. Trisomy 21
e. Dandy-Walker syndrome
324. What percentage of patients with tuberous sclerosis have mental retardation?
a. 1%
b. 10%
c. 25%
d. 65%
e. 99%
325. 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
326. 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
327. 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
290. The answer is a. (Swaiman, pp 1906-1907.) This disorder appears to be caused by a mutation in the gene that encodes a subunit of the microsomal triglyceride transfer protein, 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. CNS amyloid collections develop in Alzheimer disease.
291. The answer is d. (Swaiman, p 368.) 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.
292. The answer is a. (Swaiman, pp 784-785.) The cystic lesion and the other cerebellar lesions are most likely hemangioblastomas. These hemangioblastomas often bleed and produce potentially lethal intracranial hematomas. Radiation therapy is not the best choice, although stereotactic radiosurgery may be an option. Needle biopsy 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.
293. The answer is a. (Swaiman, p 2287.) 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.
294. The answer is b. (Yousem, pp 515-518.) In the tomogram, the first cervical vertebra, or atlas, is incompletely formed. The most ventral elements are apparent to the left of the left-pointing arrowhead, but the cortical bone of these elements is continuous with that of the skull. The elements of C1 that have formed have simply fused to the base of the skull. This assimilation of the atlas to the base of the skull is a congenital abnormality. It is often associated with a Chiari malformation of the hindbrain.
295. The answer is e. (Yousem, pp 515-518.) This abnormally situated axis (C2) qualifies as basilar invagination of the skull. If the medulla oblongata is situated at a normal level, it is at risk of compression, but posterior fossa contents may be so caudally displaced that pontine structures are also at risk of compression. Hydrocephalus may develop with this degree of basilar invagination by virtue of obstruction of the flow of CSF through the foramen magnum. Syringomyelia and syringobulbia are occasionally associated with this anatomic variant, but they probably develop as a consequence of cervical cord or brainstem damage.
296. The answer is b. (Ropper, pp 974-976.) 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 some other hereditary causes of epilepsy.
297. The answer is e. (Swaiman, pp 569-574.) 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 have 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.
298. The answer is b. (Swaiman, pp 680-682.) The patient has metachromatic leukodystrophy. Sulfatide may be evident in Schwann cells as prismatic and tuffstone inclusions, as well as in tissue outside the nervous system. 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.
299. The answer is b. (Swaiman, pp 2197-2198.) All antiepileptic drugs increase the risk for birth defects. The risk is approximately 8% as opposed to 2% in the general population. Divalproex sodium appears to pose a greater risk than other antiepileptic drugs. 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. 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.
300. The answer is b. (Yousem, p 2887.) 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 disorders. In Aicardi syndrome, agenesis of the corpus callosum is associated with retardation, epilepsy, vertebral anomalies, and chorioretinitis.
301. The answer is d. (Swaiman, pp 680-682.) Hexosaminidase deficiencies produce Sandhoff and Tay-Sachs diseases. Glucocerebrosidase is deficient in Gaucher 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.
302. The answer is b. (Swaiman, pp 584-585.) With Hartnup 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.
303. The answer is c. (Swaiman, pp 559-561.) 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.
304. The answer is e. (Swaiman, pp 782-784.) 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 blood-brain barrier. Craniopharyngioma and acoustic schwannoma produce calcifications, but these are obviously outside the cerebral cortex.
305. The answer is e. (Swaiman, pp 1241-1246.) 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. The cerebellum makes no significant contribution to the routine scalp EEG. The MRI 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.
306. The answer is c. (Swaiman, pp 784-786.) 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.
307. The answer is c. (Swaiman, pp 1906-1907.) 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 disease. Position sense is lost and extensor plantar responses develop as the disease progresses. As is true for Friedreich 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 ataxia, and Refsum 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.
308. The answer is b. (Swaiman, pp 777-782.) 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%.
309. The answer is b. (Yousem, pp 251-254.) 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.
310. The answer is d. (Swaiman, pp 425-433.) 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.
311. The answer is c. (Swaiman, pp 375-376.) 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.
312. The answer is c. (Swaiman, p 779.) 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 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 port-wine spot over part of the face. Patients with neurofibromatosis often have café au lait spots, but these do not usually occur on the face.
313. The answer is d. (Swaiman, pp 784-786.) 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.
314. The answer is a. (Swaiman, p 780.) Retinal phakomas are gliomatous tumors that require no treatment and 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 epilepsy.
315. The answer is a. (Swaiman, pp 777-782.) 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.
316. The answer is e. (Greenberg, 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.
317. The answer is e. (Swaiman, pp 1066-1070.) 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.
318. The answer is b. (Swaiman, pp 772-773.) 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.
319. The answer is b. (Swaiman, pp 1862-1868.) 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. Anterior horn cell disease is presumed to be a pivotal feature of diseases in this category.
320. The answer is b. (Swaiman, pp 667-669.) 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.
321. The answer is b. (Swaiman, pp 491-500.) A static encephalopathy is one in which brain damage has been arrested but neurological 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 cerebral palsy (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.
322. The answer is a. (Swaiman, pp 551-553.) 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.
323. The answer is b. (Lee, pp 163-165.) 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.
324. The answer is d. (Swaiman, pp 777-782.) 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.
325. The answer is d. (Swaiman, pp 402, 2197.) 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 neurological 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 neurological 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.
326. The answer is c. (Lee, pp 143-148.) 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 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.
327. The answer is a. (Swaiman, pp 1606-1607.) 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. Neurological 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.