McGraw-Hill Specialty Board Review Pediatrics, 2nd Edition

Chapter 16. NEUROLOGY

CASE 131: A 6-YEAR-OLD GIRL WITH STARING SPELLS

The teacher of a 6-year-old African American girl refers her to your clinic for an evaluation of frequent episodes of staring. The episodes occur daily and are brief, lasting no more than 5-8 seconds. She typically has several events per day. Occasionally, when the children are playing during recess, the child will stop what she is doing and exhibit a blank facial expression. She often picks at her clothes during these episodes. Following the event, she resumes her activity. Her mother states that she has not noticed any of these particular spells but notes that the child frequently “daydreams” at home, during which she is unresponsive to verbal stimuli. The child was born at full term without complications. There is no history of bowel or bladder incontinence, headache, or emesis. The child states that she is unaware of the episodes, but believes there are times when she has missed things that have been said to her. She denies any aura. There is no history of febrile seizures, central nervous system (CNS) infections, or head trauma.

On reviewing her family history, you discover that the child has a maternal great-aunt with “terrible seizures” unresponsive to medications. Her mother recalls having similar “daydreaming episodes” as a child for which she was treated with medication until high school. There is a strong family history of depression.

On physical examination, she has a large café au lait spot on her back. On neurologic examination, she has normal intelligence. Her cranial nerve examination is unremarkable. She has normal strength in both the upper and lower extremities. Her deep tendon reflexes are symmetric at 2+ of 4. Her gait is normal.

SELECT THE ONE BEST ANSWER

1. Based on the clinical history, this child most likely has which of the following diagnoses?

(A) depression

(B) absence seizures

(C) complex partial seizures

(D) juvenile myoclonic epilepsy

(E) attention deficit disorder

2. To establish the diagnosis in the clinic, which of the following actions would be the most helpful?

(A) assessment of risk factors for depression

(B) Connor scales

(C) visual screening

(D) hyperventilation

(E) none of the above

3. Which of the following diagnostic studies would be the most helpful in establishing the diagnosis?

(A) electroencephalogram (EEG) with hyperventilation and photic stimulation

(B) magnetic resonance imaging (MRI) of the brain, with and without contrast

(C) urine toxicology screen

(D) electrolytes

(E) polysomnogram

4. The drug treatment of choice for this patient would be which of the following medications?

(A) lamotrigine

(B) ethosuximide

(C) carbamazepine

(D) methylphenidate

(E) fluoxetine

5. A child presents to your office with the chief complaint of staring lasting up to 80 seconds. During the event, the child exhibits lip smacking and is unresponsive to verbal and tactile stimuli. The child states that on occasion a “strange feeling” precedes the episodes. He has had one generalized tonic-clonic seizure observed by the school nurse. The child most likely has which of the following diagnoses?

(A) migraines with aura

(B) complex partial seizures

(C) absence seizures

(D) juvenile myoclonic epilepsy

(E) depression

6. A 5-year-old girl comes to your office because she has started to lose the ability to speak. Her mother states that she was born full term and developed normally, speaking in full sentences by 3 years of age. She has a normal physical examination, including her head circumference that has been at the 50th percentile. A head computed tomography (CT) without contrast was within normal limits. Which of the following studies is most likely to yield the diagnosis?

(A) MRI of the brain with and without contrast

(B) lumbar puncture

(C) 24-hour long-term video EEG monitoring

(D) methyl CpG-binding protein 2 (MECP2) gene mutation analysis

(E) hearing test

7. A 15-year-old boy with a history of complex partial seizures recently moves into your practice area. He comes into your office for a general physical examination. During the visit, he states he has been seizure-free for approximately 21/years. His spells consisted of staring with automatisms, but occasionally they would progress to generalized tonic-clonic seizures. Because he is concerned about driving next year, he asks you when he can go off his medication. He is currently treated with carbamazepine. The most appropriate response would be which of the following?

(A) “let’s obtain an EEG. If that test is normal, there is an approximately 70% chance you will be seizure-free upon weaning off the carbamazepine”

(B) “never; epilepsy is a lifelong condition”

(C) “children with complex partial seizures need to be seizure-free for at least 5 years before a decision can be made”

(D) “it all depends on the epilepsy syndrome or type; complex partial seizures seldom go into remission”

(E) none of the above

8. Which of the following antiepileptic drugs are generally considered the first- and second-line therapies for neonatal seizures?

(A) diazepam and phenobarbital

(B) phenobarbital and phenytoin

(C) phenytoin and midazolam

(D) phenobarbital and lorazepam

(E) phenobarbital and valproic acid

9. Which of the following is the most common form of childhood seizures?

(A) complex partial seizures

(B) absence seizures

(C) infantile spasms

(D) benign rolandic epilepsy

(E) febrile seizures

10. A child with a 2-year history of epilepsy has been seizure free on his current antiepileptic regimen for 18 months. Recently, he was diagnosed with attention deficit hyperactivity disorder (ADHD). He was started on methylphenidate and a few days later experienced a complex partial seizure. The most likely explanation for this breakthrough seizure is which of the following?

(A) the child has developed a new seizure type

(B) the child has stopped taking his antiepileptic medications

(C) the child is now depressed regarding the new diagnosis

(D) the event represents a pseudoseizure

(E) methylphenidate can lower the seizure threshold

11. Which of the following statements is not true about febrile seizures?

(A) a febrile seizure is considered “complex” if it is prolonged, focal, or occurs multiple times per febrile illness

(B) a family history of febrile seizures in a first- or second-degree relative is a risk factor for the development of febrile seizures

(C) developmental delay is a risk factor for the development of a first febrile seizure

(D) up to 10% of patients with febrile seizures develop epilepsy

(E) carbamazepine and phenytoin are equally effective in the treatment of febrile seizures should one consider treatment

12. Which of the following are causes of neonatal seizures?

(A) a hypoxic-ischemic episode

(B) metabolic abnormalities

(C) infection

(D) inborn errors of metabolism

(E) all of the above

MATCH EACH OF THE FOLLOWING ANTIEPILEPTIC DRUGS WITH ITS COMMONLY REPORTED SIDE EFFECT

13. lamotrigine     (A) gingival hyperplasia

14. valproic acid  (B) Stevens-Johnson syndrome

15. phenytoin      (C) hepatotoxicity

16. carbamazepine    (D) weight loss

17. phenobarbital      (E) agranulocytosis

18. topiramate     (F) hyperactivity

ANSWERS

1. (B) This patient most likely has absence seizures (petit mal). Absence seizures are relatively uncommon, accounting for less than 10% of all seizure types. They tend to be more common in females than males. The average age of onset is approximately 4 years, and they are rarely seen before the age of 2 years. In typical absence seizures, patients exhibit brief (<30 seconds) staring spells; however, motor, behavioral, and autonomic phenomena are frequently observed. The child can have multiple spells per day. Automatisms, such as chewing, grimacing, or lip licking, may be observed. They are never associated with an aura, bowel or bladder incontinence, or postictal impairment. Most children with typical absence seizures have normal intelligence and a normal physical examination. There is a strong genetic predisposition. An EEG typically demonstrates generalized 3-Hz spikewave activity. The prognosis of typical absence seizures is favorable with approximately 80% achieving remission by 10-11 years of age. Atypical absence seizures are similar to typical absence seizures but are more likely to have diminished postural tone and tonic or myoclonic activity as part of their initial clinical presentation. Automatisms are less likely. Many children go on to develop Lennox-Gastaut syndrome. The EEG demonstrates asymmetric less than 2.5-Hz spike-wave activity with multifocal spikes and sharp waves. In contrast, complex partial seizures tend to last much longer (>1 minute on average), are frequently associated with an aura, and can be followed by a postictal state. The EEG usually demonstrates rhythmic focal spikes or sharp waves over the temporal or frontal regions during a seizure. Juvenile myoclonic epilepsy (JME) typically occurs between the ages of 12 and 18 years. Children as young as 8 years have been reported to develop JME. JME is a familial, generalized seizure disorder in which patients demonstrate jerks of the shoulders and arms, typically occurring shortly after awakening. Loss of consciousness is seldom noticeable. Many of these patients respond to valproic acid.

2. (D) Hyperventilation is a strong activator of typical absence seizures. The child is asked to hyperventilate for 3-5 minutes, during which a seizure is induced. Photic stimulation is also used to induce generalized seizure disorders but does not appear to be as effective an activator in typical absence seizures as hyperventilation. Connor scales are used to screen for attention deficit disorder.

3. (A) The differential diagnosis of absence seizures includes complex partial seizures, daydreaming, and pseudoseizures. The most effective way of establishing the classification of a seizure or establishing a diagnosis is to capture a spell while performing an EEG. In this case, hyperventilation can be used to precipitate a seizure, enabling the physician to capture the spell while recording. Bilateral, synchronous 3-Hz spike-wave activity would confirm the diagnosis of typical absence seizure (see Figure 131-1). In complex partial seizures, one may observe intermittent spikes or sharp waves over the temporal or frontal regions during the interictal (between seizures) stage, and rhythmic activity over these regions during the seizure. The EEG should be normal in daydreaming and pseudoseizures. MRI of the brain, urine toxicology, and electrolyte analysis can be important in the diagnosis and management of seizures, but given the clinical history, an EEG with hyperventilation has the highest yield. The brain MRI, urine toxicity screen, and electrolytes are normal in typical absence seizures.

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FIGURE 131-1Absence seizures. Record of four cortical EEG leads from a 6-year-old boy who, during the recording, had one of his “blank spells” in which he was transiently unaware of his surroundings and blinked his eyelids. Time is indicated by the horizontal calibration line. (1 s = 1 second). (Reproduced, with permission, from Waxman SG. Clinical Neuroanatomy, 25th ed. New York: McGraw-Hill; 2003.)


4. (B) Three drugs are primarily used in the treatment of absence seizures: ethosuximide, valproic acid, and lamotrigine. For typical absence seizures, most neurologists would start therapy with ethosuximide given its side-effect profile compared with that of valproic acid. It is not useful for patients who have generalized tonic-clonic seizures with their absence seizures. In this case, valproic acid is preferred. Carbamazepine is used in the treatment of complex partial seizures. In primary generalized seizure disorders, such as absence seizures, it may make the patient worse. Methylphenidate is used in the treatment of ADHD; fluoxetine is used to treat anxiety, depression, and obsessive-compulsive disorders (OCDs).

5. (B) This child most likely has complex partial seizures with secondary generalization given the single generalized tonic-clonic seizure and clinical history. The “strange feeling” likely represents an aura or a simple partial seizure. Simple partial seizures can precede complex partial seizures. Complex partial seizures are distinguished from simple partial seizures in that the patient has loss of consciousness with the former. In contrast to partial seizures, an aura is not observed in primary generalized seizures, such as absence epilepsy. Automatisms, such as lip smacking, can be observed during the period of altered consciousness. An EEG will most likely demonstrate anterior temporal spikes between seizures.

6. (C) This child most likely has an acquired epileptiform aphasia, such as Landau-Kleffner syndrome (LKS). LKS often occurs between the ages of 5 and 7 years. Children afflicted with LKS typically develop an abrupt or gradual loss of language ability. Expressive and receptive language dysfunction is observed. These children can also have behavioral and psychomotor disturbances, such that they resemble an autistic child. The EEG most commonly demonstrates sharp wave and spike-wave activity over the temporal or parietal-occipital regions bilaterally more commonly observed during sleep, which is most likely to be captured with 24-hour long-term video EEG monitoring. Electrical status of slow-wave sleep is a condition similar to LKS in which spike-wave activity is the dominant pattern observed during sleep. This disorder occurs with a peak age of onset between 4 and 5 years of age. The prognosis for both conditions is variable. Although some may recover fully, others continue to have speech and cognitive impairments. To capture slow-wave sleep (stage 4), a 24-hour EEG is usually required. MECP2 gene mutation is associated with Rett syndrome.

7. (A) If a child is seizure free for approximately 2 years, there is about a 70% chance the child will go into remission. Generalized seizures, a normal neurologic examination, and age of onset before approximately 12 years predict a more favorable outcome. Some studies suggest that a normal EEG or resolution of interictal spikes also predicts a favorable outcome.

8. (B) It is generally accepted among pediatric neurologists and neonatologists that phenobarbital is the firstline therapy for neonatal seizures, and phenytoin is the second-line therapy. Although many centers prefer to use fosphenytoin, a benzodiazepine is considered third-line therapy. Caution must be exercised when using phenobarbital in conjunction with a benzodiazepine because respiratory suppression, a potential side effect of both medications, is more likely.

9. (E) The most common form of childhood seizures are febrile seizures, occurring in 2-4% of the population in the United States.

10. (E) Children with epilepsy occasionally have comorbid conditions such as ADHD, depression, and tics. Many of the medications used to treat these comorbid conditions, such as methylphenidate, fluoxetine, risperidone, and haloperidol, can lower the seizure threshold. Atomoxetine, a selective norepinephrine reuptake inhibitor used to treat ADHD, does not seem to lower the seizure threshold. Although noncompliance with antiepileptic medications is always a concern in the treatment of pediatric epilepsy, the fact that the child went 18 months without a clinical seizure before initiation of methylphenidate makes it less likely this was an issue.

11. (E) Febrile seizures are considered complex if they are prolonged, lasting more than 10-15 minutes, are focal, or occur multiple times per febrile illness. Risk factors for a first febrile seizure include developmental delay, admission to the neonatal intensive care unit for longer than 30 days, attendance at day care, and having a family history of febrile seizures in a first- or second-degree relative. Based on data obtained from several large studies of children with febrile seizures, the risk of developing subsequent epilepsy is approximately 2-10%. Although treating febrile seizures remains controversial, daily phenobarbital has been shown effective in reducing the risk of recurrent febrile seizures. Diazepam given orally or rectally at the onset of a febrile illness reduces the probability of a febrile seizure. Carbamazepine and phenytoin are not effective in the treatment of febrile seizures.

12. (E) The causes of neonatal seizures are diverse and must be investigated to ensure adequate treatment. For example, seizures resulting from hypoglycemia require adequate glucose replacement.

13. (B) Stevens-Johnson syndrome secondary to lamotrigine administration occurs in 1-2% of children and 0.1% of adults. Other side effects of lamotrigine include dizziness, diplopia, and blurred vision.

14. (C) Fatal hepatotoxicity can occur in children treated with valproic acid. Children between the ages of 0 and 2 years are particularly at risk: 1 in 118,000 for patients on monotherapy and 1 in 800 on therapy with multiple anticonvulsants. Other side effects of valproate include weight gain in some children and thrombocytopenia.

15. (A) Long-term administration of phenytoin has been associated with gingival hyperplasia, hirsutism, acne, and rash (Stevens-Johnson syndrome). Toxic serum levels of phenytoin may result in ataxia, nystagmus, diplopia, and incoordination.

16. (E) Although serious hematologic complications with carbamazepine therapy are very rare, thrombocytopenia, aplastic anemia, agranulocytosis, and pancytopenia have been reported. Drowsiness, ataxia, dyskinesia, dizziness, and visual disturbances may also be observed.

17. (F) Behavioral side effects, especially hyperactivity and aggressiveness, can be seen in almost half the children taking phenobarbital. Dose-dependent side effects include sedation and respiratory depression.

18. (D) Weight loss has been reported as a side effect of topiramate therapy, usually beginning during the first few months of administration and peaking at 12-18 months.


SUGGESTED READING

Baram TZ. Myoclonus and myoclonic seizures, and infantile spasms. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1063.

Conway JM, Kriel RL, Birnbaum AK. Antiepileptic drug therapy in children. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1105.

Holmes GL. Generalized seizures. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1019.

Shinnar S. Febrile seizures. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1079.

Wyllie E, ed. The Treatment of Epilepsy: Principles & Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.

CASE 132: A 5-MONTH-OLD BOY WITH SEIZURES AND A BIRTH MARK

You are called to the emergency department to evaluate a 5-month-old infant boy who presents with the chief complaint of “unusual leg movements” on awakening. The patient was born at full term by normal spontaneous vaginal delivery. The pregnancy was unremarkable except for maternal spotting in the first trimester. Developmentally, his mother states he is not yet rolling over. He startles to loud noises and occasionally vocalizes. Although he smiled responsively at 2 months of age, she has noticed he no longer seems to smile. His mother states that he often “spits up” after feeds. There is no family history of seizures.

During the evaluation, you observe a cluster of spells as the baby awakens. The spells consist of flexion of the head and body with extension of the legs. You are unable to stop the movements by applying gentle pressure. The baby was given a bottle feed approximately 1 hour ago.

On physical examination, his temperature is 98.2°F (36.8°C), the heart rate is 164, the respiratory rate is 32, and the blood pressure is 78/51 mm Hg. The tympanic membranes are normal. He has an irregular heartbeat. His lungs are clear to auscultation. Examination of his skin reveals 3 hypopigmented lesions over his abdomen and back. On neurologic examination, his tone is decreased centrally. He has a poor response to traction with a significant head lag. His reflexes are brisk symmetrically. His plantar reflexes are extensor.

SELECT THE ONE BEST ANSWER

1. An echocardiogram is most likely to reveal which of the following diagnoses?

(A) cardiac rhabdomyoma

(B) fibroma

(C) teratoma

(D) myxoma

(E) hemangiomas

2. The EEG demonstrates hypsarrhythmia; the head CT reveals periventricular calcifications. A small mineralized subependymal nodule is also observed. The most likely diagnosis is which of the following?

(A) Fahr disease

(B) neurofibromatosis (NF) type 1

(C) tuberous sclerosis complex (TSC)

(D) toxoplasmosis

(E) incontinentia pigmenti achromians (hypomelanosis of Ito)

3. This patient is at risk for developing which of the following complications?

(A) hydrocephalus

(B) renal cell carcinoma

(C) bony involvement

(D) giant cell astrocytoma

(E) all of the above

4. Which of the following is considered the most effective in the treatment of this patient’s seizure?

(A) topiramate

(B) phenobarbital

(C) primidone

(D) adrenocorticotropic hormone (ACTH)

(E) phenytoin

5. Which of the following statements is true regarding the genetics of TSC?

(A) it is transmitted as an autosomal recessive trait

(B) it is transmitted as an autosomal dominant trait with variable penetrance

(C) the disorder demonstrates an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) relatively little is known about the mode of transmission of this disorder

6. Which of the following seizure types is not more common in TSC?

(A) infantile spasms

(B) complex partial seizures

(C) absence seizures

(D) simple partial seizures

(E) atonic seizures

7. When would you most likely expect adenoma sebaceum (facial angiofibromas) to present in this child?

(A) shortly after birth

(B) between 1 and 4 years

(C) between 6 and 9 years

(D) during puberty

(E) adulthood

8. An 18-month-old girl presents to your clinic for continued pediatric care. Her family recently moved to your area and you haven’t yet received her medical records. On physical examination, she has a nevus flammeus (port wine stain) over the left side of her face and a contralateral hemiparesis. This patient is most likely to have which of the following?

(A) ipsilateral leptomeningeal angioma

(B) intracranial calcifications on head CT

(C) glaucoma

(D) A and B

(E) all of the above

9. Which of the following statements is true regarding the genetics of Sturge-Weber syndrome?

(A) it is transmitted as an autosomal recessive trait

(B) it is transmitted as an autosomal dominant trait

(C) the disorder demonstrates an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) relatively little is known about the mode of transmission of this disorder

10. Each of the following neurocutaneous disorders is transmitted as an autosomal dominant trait except for

(A) NF 1

(B) Von Hippel-Lindau disease

(C) TSC

(D) ataxia-telangiectasia

(E) NF 2

11. A 26-month-old boy presents to your clinic for an evaluation of multiple café au lait spots. On close inspection, you determine that he has 6 spots larger than 0.8 cm over the trunk. On funduscopic examination, you notice optic disc pallor in the left eye. The most likely cause of the optic disc pallor and atrophy is which of the following?

(A) optic neuritis

(B) papilledema

(C) optic nerve glioma

(D) meningioma

(E) retinal artery infarction

12. The father of the patient in question 11 offers that he has similar birthmarks to that of his son. The most likely diagnosis is which of the following?

(A) NF 2

(B) NF 1

(C) ataxia-telangiectasia

(D) neurocutaneous melanosis

(E) linear sebaceous nevus

13. Which of the following is the most common CNS tumor observed in NF 1?

(A) low-grade astrocytoma

(B) meningioma

(C) medulloblastoma

(D) ependymoma

(E) primitive neuroectodermal tumors

14. Which of the following is not a diagnostic criterion of NF1?

(A) two or more Lisch nodules

(B) optic nerve glioma

(C) five or more café au lait spots 1.5 cm or larger in postpubertal individuals

(D) a first-degree relative with NF1

(E) two or more neurofibromas or one or more plexiform neurofibroma

MATCH EACH OF THE FOLLOWING DIAGNOSTIC FEATURES WITH ITS NEUROCUTANEOUS DISORDER

15. Bilateral acoustic neuromas  (A) neurofibromatosis 1

16. Periungual fibroma (B) Von Hippel-Lindau disease

17. Retinal hemangioblastoma    (C) NF 2

(D) ataxia-telangiectasia

18. Decreased
immunoglobulin A
and E levels    (E) TSC

19. Café au lait spots

ANSWERS

1. (A) This patient most likely has infantile spasms given the clinical history and observations. Infantile spasms typically occur between 3 and 8 months of age. Although there are many causes of infantile spasms, such as intrauterine infections and perinatal asphyxia, it is the most common seizure type seen in tuberous sclerosis complex (TSC). Patients typically have myoclonic jerks in clusters that usually occur on awakening. The seizures can consist of head and body flexion or extension. The movements observed in this child are the more common presentation. As seen in this child, the loss of milestones and developmental arrest are not uncommon at the onset of infantile spasms. The presence of hypopigmented spots supports the diagnosis of TSC and, to some extent, infantile spasms. Approximately half the patients with TSC can have cardiac rhabdomyomas. The cardiac rhabdomyomas affect the myocardium and can be solitary, multiple, or infiltrative. Cardiac rhabdomyomas can cause arrhythmias, congestive heart failure, obstruction to blood flow, or even sudden death. The arrhythmias include ventricular tachycardia, supraventricular tachycardia (SVT), and Wolff-Parkinson-White syndrome. It is important to clarify the arrhythmia and begin the necessary treatment. An echocardiogram will probably reveal a cardiac rhabdomyoma.

2. (C) To make a definite diagnosis of TSC, 2 of 11 major features or 1 major feature plus 2 of 9 minor features must be present. The features are listed here (slightly modified from Kandt, 2002):

Major diagnostic features:

Cardiac rhabdomyoma

Renal angiomyolipoma

Lymphangiomyomatosis

Facial angiofibromas

Ungual fibroma

Shagreen patch

Cortical tuber

Three or more hypomelanotic macules

Multiple retinal nodular hamartomas

Subependymal giant cell astrocytoma

Subependymal nodule

Minor diagnostic features:

Multiple renal cysts

Retinal achromic patch

Multiple dental pits

Bone cysts

Nonrenal hamartoma

Gingival fibromas

“Confetti” skin lesions

Cerebral white matter radial migration lines

Hamartomatous rectal polyps

Patients who have the hypomelanosis of Ito have hypopigmented skin lesions, which vary from linear streaks following a dermatomic distribution to whorls with irregular margins. Females are more frequently affected than males. Periventricular calcifications, tubers, and subependymal nodules are not observed. Fahr disease (familial basal ganglia calcification) is a hereditary condition in which calcification is particularly observed in the dentate and lenticular nuclei. The disease is not associated with hypopigmented skin lesions. Toxoplasmosis is caused by the protozoan Toxoplasma gondii. The major reservoir for this organism in the United States is the cat, which excretes oocysts in the feces. The disease is associated with cerebral calcification in approximately 60% of affected individuals. Although seizures, hydrocephalus, microcephaly, chorioretinitis, and psychomotor retardation are seen in toxoplasmosis, skin lesions are not described.

3. (E) Patients with TSC are at risk for developing all of the complications described. Most renal tumors are renal cysts or renal angiomyolipomas. However, a small percentage of patients (<2%) develop renal carcinoma. For reasons that are unclear, female patients are at risk to develop pulmonary complications. Tubers can obstruct normal cerebrospinal fluid (CSF) flow if located near the foramen of Monro or the Sylvian aqueduct.

4. (D) The American Academy of Neurology recently published a practice parameter reviewing the medical treatment of infantile spasms. The recommendation is that ACTH is probably effective in the short-term treatment of infantile spasms. Vigabatrin may be useful in the treatment of infantile spasms, particularly caused by TSC. However, this medication is not Food and Drug Administration approved because it causes retinal toxicity.

5. (B) TSC is transmitted as an autosomal dominant trait with variable penetrance. However, spontaneous mutation rates may be observed in more than 50% of patients.

6. (C) Absence seizures cause a primary generalized seizure disorder and are not seen more frequently in TSC.

7. (B) Some lesions seen in TSC occur at various developmental stages. Adenoma sebaceum typically develops at 1-4 years. It rarely is seen at birth.

8. (E) This patient probably has Sturge-Weber syndrome, which is characterized by a facial angioma (nevus flammeus, or port wine stain) and ipsilateral leptomeningeal angioma. The facial angioma typically involves the upper face and occasionally the nasopharynx, mucous membranes, and/or ocular choroidal membrane (see Figure 132-1). Choroidal membrane involvement can lead to glaucoma in approximately 25% of patients. Neuroimaging studies demonstrate calcium deposits in the walls of some small cerebral vessels and outer cortical layers. This is best observed on head CT. In one study, seizures occurred in three-quarters of the cases. Patients can have a contralateral hemiparesis with hemiatrophy. Hemianopsia is also observed.

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FIGURE 132-1. Extensive right facial capillary malformation (A) involving the ophthalmic and maxillary branches of the trigeminal nerve in a 6-month-old girl affected with Sturge-Weber syndrome. Choroid capillary-venous malformation (B) causing vision loss in a 50-year-old man with Sturge-Weber syndrome. (Reproduced, with permission, from Wolff K, Goldsmith LA, Katz SI, et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill; 2008: Fig. 173-4A,B.)


9. (E) No clear evidence of heredity has been discovered for this disorder.

10. (D) Ataxia-telangiectasia is a neurocutaneous disorder characterized by progressive cerebellar ataxia, immune defects, oculocutaneous telangiectasis, and a predisposition to malignancy (see Figure 132-2). Patients have a tendency to develop sinopulmonary infections and skin infections. Cellular and humoral immunity can be impaired. The disease is transmitted in a sporadic or autosomal recessive manner.

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FIGURE 132-2Ataxia-telangiectasia. Telangiectases inside and on the helix. (Reproduced, with permission, from Wolff K, Goldsmith LA, Katz SI, et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill; 2008: Fig. 144-10.)


11. (C) Approximately 50% of children with optic nerve gliomas have NF 1. Most of the children present with optic pallor and atrophy, as well as decreased visual acuity. Depending on the location of the tumor, the child can present with visual field defects.

12. (B) To make a diagnosis of NF1, 2 or more of the following criteria are required:

• Two or more neurofibromas of any type or one or more plexiform neurofibromas

• Optic nerve glioma

• Six or more café au lait spots 1.5 cm or larger in postpubertal individuals and 0.5 cm or larger in prepubertal children

• A first-degree relative with NF1

• Two or more Lisch nodules

• Axillary or inguinal freckling

• A distinctive osseous lesion (dysplasia of the sphenoid bone or thinning of long bone cortex)

13. (A) The most common CNS tumors in NF1 are lowgrade astrocytomas, mostly occurring in the optic pathway. Meningiomas, medulloblastomas, ependymomas, and primitive neuroectodermal tumors also occur but are much less common.

14. (C) Six or more café au lait spots are required to make the diagnosis. See diagnostic criteria listed for answer 12.

15. (C) To make a diagnosis of NF2, bilateral eighth nerve masses must be seen upon neuroimaging. Alternatively, the patient must have a first-degree relative with NF2 and either a unilateral eighth nerve mass or 2 of the following: meningioma, glioma, neurofibroma, schwannoma, and juvenile posterior subcapsular lenticular opacity.

16. (E) Periungual fibromas are seen in TSC. Ungual fibromas are pathologically similar to the facial angiofibromas.

17. (B) A rare disorder, transmitted as an autosomal dominant trait, Von Hippel-Lindau disease is characterized by retinal and cerebellar hemangioblastomas. Spinal cord angiomas and cystic tumors of the pancreas, epididymis, and kidney are also observed.

18. (D) See explanation for question 10.

19. (A) See diagnostic criteria for NF1 listed in answer 12.


SUGGESTED READING

Kandt RS. Tuberous sclerosis complex and neurofibromatosis type 1: the two most common neurocutaneous diseases. Neurol Clin North Am. 2002;20:941-964.

Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms. Neurology. 2004;62:1668-1681.

Thiele EA, Korf BR. Phakomatoses and allied conditions. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:771.

CASE 133: A 2-YEAR-OLD GIRL WITH HEADACHE AND FEVER

You are called to the emergency department (ED) to evaluate a 2-year-old girl who presents with headache and confusion. In the ED her temperature is 102°F. The patient was in good health until 6 days before presentation when she developed malaise and low-grade fevers. Shortly after, her mother states she complained of headaches, which have increased in severity. She states her daughter is usually very pleasant but recently has become agitated and increasingly irritable. In the last few days, she has become more somnolent. Immunizations are up to date. The ED staff has ordered a head CT, which is reportedly within normal limits. A lumbar puncture, performed by the ED physician, revealed 340 white blood cells/mmwith a predominance of polymorphonuclear cells, a glucose of 35 mg/dL, and a protein of 55 mg/dL. Although the patient knew her name on arousal, she has become stuporous and cannot abduct her left eye.

On your physical examination, the girl is obtunded but withdraws appropriately to pain. She is unable to abduct her left eye and her pupils are sluggish. The remainder of her cranial nerve examination is normal including a funduscopic examination. The deep tendon reflexes are mildly hyperactive and she has bilateral upgoing toes. Her skin examination is unremarkable.

SELECT THE ONE BEST ANSWER

1. A Gram stain of the patient’s cerebrospinal fluid (CSF) would most likely reveal which of the following?

(A) gram-positive or gram-negative diplococci

(B) gram-negative rods

(C) mixed bacterial morphology

(D) gram-variable cocci in tetrads

(E) gram-positive bacillus

2. Which of the following antibiotics is the treatment of choice for meningitis of unknown etiology in a patient without known drug allergies?

(A) penicillin

(B) ceftriaxone

(C) vancomycin

(D) rifampin

(E) B and C

3. Important causes of bacterial meningitis in this age group include

(A) Streptococcus pneumoniae

(B) Haemophilus influenzae, type b

(C) Listeria monocytogenes

(D) Neisseria meningitidis

(E) A and D

4. The differential diagnosis of bacterial meningitis includes which of the following diseases?

(A) head trauma

(B) brain abscess

(C) intracranial hemorrhage

(D) neoplastic meningitis

(E) all of the above

5. Which of the following are complications of bacterial meningitis?

(A) sensorineural deafness

(B) hydrocephalus

(C) syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

(D) extra-axial fluid collections

(E) all of the above

6. Before discharge, children treated for pneumococcal meningitis routinely require which of the following tests?

(A) neuropsychological evaluations

(B) repeat lumbar puncture

(C) MRI of the brain

(D) hearing evaluation

(E) EEG

7. Which of the following organisms is the most common cause of acute bacterial meningitis in the neonatal period?

(A) group B streptococcus

(B) Streptococcus pneumoniae

(C) H influenzae, type b

(D) L monocytogenes

(E) coagulase-negative staphylococci

8. L monocytogenes is treated with which of the following antibiotics?

(A) gentamicin

(B) ampicillin

(C) vancomycin

(D) cefotaxime

(E) A and B

9. You are called to the ED to evaluate a 21/2-week-old full-term infant who experienced a focal tonic seizure witnessed by the nurse. The infant was initially described as irritable but now appears lethargic. The child has a slight fever. On careful history taking, you learn that the infant’s mother has a history of sexual transmitted diseases (STDs). She denies any history of vaginal vesicular lesions before delivery. Laboratory evaluation reveals a lymphocytic pleocytosis and elevated protein in the CSF. The Gram stain is negative. A head CT was normal. An EEG performed earlier revealed left temporal sharp waves. The most likely cause of this child’s symptoms is which of the following?

(A) herpes simplex virus (HSV)1

(B) HSV2

(C) cytomegalovirus (CMV)

(D) human immunodeficiency virus (HIV)

(E) human herpes virus type 6

10. The action most likely to support your diagnosis for the case presented in question 9 is which of the following?

(A) assay for HSV DNA by polymerase chain reaction (PCR)

(B) viral culture

(C) MRI of the brain with and without contrast

(D) urine for CMV culture

(E) noninfused head CT

11. The most appropriate antimicrobial therapy for this infant is which of the following drugs?

(A) ganciclovir

(B) methylprednisolone

(C) acyclovir

(D) zidovudine

(E) no effective therapy known

12. In utero herpes simplex viral infection can cause which of the following clinical features?

(A) intrauterine growth retardation

(B) microcephaly

(C) intracranial calcifications

(D) cataracts

(E) all of the above

13. All of the following are causes of arthropodtransmitted encephalitis except

(A) lymphocytic choriomeningitis virus

(B) West Nile virus

(C) Japanese encephalitis virus

(D) St. Louis encephalitis virus

(E) eastern equine encephalitis virus

14. A 6-year-old boy presents to your clinic with the chief complaint of new-onset headache, fever, and neck stiffness on returning from a camping trip. He has also had a sore throat for 3 days. On physical examination, he has an erythematous rash over the palms of his hands and vesicular lesions and ulcers over the oropharynx. The most likely cause of this child’s symptoms is which of the following?

(A) echovirus

(B) HSV type 1

(C) HIV

(D) Chikungunya virus

(E) West Nile virus

15. Which of the following parasites is responsible for cysticercosis?

(A) Diphyllobothrium latum

(B) Taenia multiceps

(C) Taenia solium

(D) Angiostrongylus cantonensis

(E) Plasmodium falciparum

16. Which of the following anaerobic organisms have been isolated from brain abscesses?

(A) Actinomyces

(B) Bacteroides

(C) Peptostreptococcus

(D) Propionibacterium

(E) all of the above

MATCH EACH OF THE FOLLOWING BACTERIA WITH THE CORRESPONDING NEUROLOGIC DISEASE

17. Treponema pallidum (A) Cat-scratch disease

18. Borrelia burgdorferi  (B) Lyme disease

19. Bartonella henselae   (C) Syphilis

20. Mycoplasma pneumoniae (D) Acute disseminated encephalomyelitis

ANSWERS

1. (A) This patient most likely has S pneumoniae or N meningitidis. H influenzae type b disease has virtually disappeared with the advent of effective immunization, and pneumococcal meningitis has become less frequent as well. The recent introduction of a 13-valent pneumococcal conjugate vaccine should further decrease the prevalence of pneumococcal meningitis. S pneumoniae is a gram-positive diplococci. Group B streptococci (Streptococcus agalactiae) are also gram-positive cocci usually configured in chains. N meningitidis is a gram-negative diplococcus. Escherichia coli is a gram-negative rod; L monocytogenes is a gram-positive bacillus. Staphylococci are gram-positive cocci appearing in “grape-like” clusters. Mixed bacterial flora rarely cause meningitis.

2. (E) Recent concern has been raised regarding the increased prevalence of penicillin-resistant S pneumoniae. As a result, children older than 1 month of age who are suspected of having bacterial meningitis should be treated with vancomycin and ceftriaxone or cefotaxime. The therapy is especially indicated if the Gram stain reveals gram-positive diplococci (see answer 1). Of course, susceptibility testing should be performed, and the antimicrobial therapy should be altered based on that laboratory testing.

3. (E) As a result of H influenzae and now S pneumoniae vaccination programs, the epidemiology of meningitis has changed with H influenzae, type b disease virtually absent in the United States and the incidence of pneumococcal meningitis drastically reduced. Importantly, these vaccines are not yet in the routine immunization programs of many nations.

4. (E) The differential diagnosis includes all of the diseases listed. Other possibilities include febrile seizures, encephalitis, and other unusual infectious agents, such as fungi or tuberculosis.

5. (E) Sensorineural hearing loss, hydrocephalus, SIADH, and extra-axial fluid collections are all complications of bacterial meningitis. In addition, seizures, cranial nerve involvement (as seen in this case), infarction, and disseminated intravascular coagulation can also occur.

6. (D) Bacterial meningitis is an important cause of acquired sensorineural deafness that can be caused by the infectious agent, especially S pneumoniae, or the use of ototoxic antibiotics. Before discharge, each child should have audiometry or brainstem auditory-evoked potentials in a younger child. If total deafness is observed, cochlear implants should be considered.

7. (A) Group B streptococcus and L monocytogenes can both cause bacterial meningitis in the neonate. L monocytogenes, however, although often considered, does so quite rarely.

8. (E) Listeria monocytogenes is best treated with ampicillin and gentamicin. The gentamicin is added to provide synergy.

9. (B) This infant most likely has a neonatal HSV2 infection acquired during passage through an infected birth canal. Although the mother denied a history of vaginal or vesicular lesions, in most cases, infection occurs in children of asymptomatic mothers. Outside the neonatal period, HSV2 is a relatively rare cause of viral encephalitis. In older individuals, HSV1 is more likely to cause encephalitis with an estimated annual occurrence of 1 in 250,000-500,000 individuals. Most individuals acquire HSV1 from oral transmission.

HSV2 infection in neonates can be classified into 3 categories.

1. Encephalitis (localized CNS disease)

2. Skin, eye, mouth disease

3. Disseminated disease

In the case of localized disease, symptoms typically occur 2-3 weeks after birth. HSV2 seems to have a predilection for the insula, temporal cortex, and cingulate gyrus; however, focal abnormalities may be seen in other cortical regions. Unilateral and bilateral lesions can be observed on neuroimaging. In the past, HSV2 infection was more commonly thought of as a hemorrhagic encephalitis. This perception was based on postmortem studies before the widespread use of PCR as a diagnostic tool. As a result, it is now known that HSV encephalitis can occur without the presence of red blood cells in the CSF. In severe cases (those that resulted in the postmortem studies), red blood cells in the CSF are observed. CMV is the most frequent cause of intrauterine viral infection. Affected infants may be asymptomatic or have a petechial skin rash, intrauterine growth retardation, sensorineural hearing loss, hepatosplenomegaly, microcephaly, seizures, and/or retinitis. Periventricular calcifications can be observed on head CT. Although the clinical manifestations of HIV are highly variable, infants who acquire HIV vertically typically become symptomatic around 3 months of age. These children may present with failure to thrive, lymphadenopathy, neurologic disease, hepatomegaly, or with an opportunistic infection. Some children do not manifest symptoms for several years. Human herpes virus 6 causes roseola in children. It has been linked to encephalitis and myelitis in young children and adults. Incidentally, acyclovir seems to be an ineffective treatment, despite the fact that this virus is a member of the Herpesviridae family.

10. (A) Although HSV can be isolated by culture from CSF, the yield is relatively low (25-35%). As a result of this low yield, the use of PCR to detect HSV DNA has become routine in laboratory investigation. The sensitivity and specificity of this test are greater than 90%. An MRI of the brain or head CT may reveal destruction of the insular and temporal areas but is not specific for HSV. A head CT may be helpful in detecting intracranial calcifications seen following CMV infection, toxoplasmosis, or in utero HSV infection.

11. (C) The dose of acyclovir for treatment of neonatal herpes infection involving the CNS is 60 mg/kg per day in 3 divided doses given for 21 days, assuming normal renal function.

12. (E) HSV is acquired in utero in approximately 5% of cases. Under these circumstances, infants experience intrauterine growth retardation, cataracts, microcephaly, and vesicular rash. Intracranial calcifications are also observed.

13. (A) Lymphocytic choriomeningitis virus (LCMV) is acquired by inhalation of aerosolized virus or by direct contact with contaminated fomites. The natural host and reservoir is the common house mouse. The virus can be transmitted vertically if a pregnant woman acquires the virus and develops viremia. The virus can also be transmitted to the infant during delivery. Although a third of patients are asymptomatic and many develop a self-limited febrile illness, others may experience symptoms of an aseptic meningitis: fever, headache, nuchal rigidity, photophobia, and malaise. Most patients recover fully, although on rare occasions, LCMV can be fatal.

14. (A) This patient has an aseptic meningitis due to enterovirus (non-poliovirus) infection, most likely caused by echovirus. Other members of the enterovirus (non-poliovirus) family include group A coxsackie viruses, group B coxsackie viruses, echoviruses, and other unclassified enteroviruses. The illness is more common in children, and often the patients have a mild pharyngitis or other respiratory symptoms. A rash commonly occurs that varies in distribution. Treatment is primarily supportive.

15. (C) Cysticercosis is caused by Taenia solium, the pork tapeworm. It is the most common parasitic infection of the CNS. Headache, seizures, meningeal signs, neuropsychiatric symptoms, visual loss, and ataxia are common symptoms. D latum is a fish tapeworm, which causes vitamin B12 deficiency. The neurologic symptoms of this parasite are caused by the vitamin deficiency. T multiceps is a canine tapeworm that results in symptoms similar to cysticercosis with more pronounced ophthalmic involvement. This condition is extremely rare. A cantonensis is a nematode responsible for eosinophilic meningitis. Humans are infected by eating snails or shrimp. P falciparum is a parasite responsible for one kind of malaria.

16. (E)All of these anaerobic organisms have been isolated from brain abscesses. In addition, aerobic organisms, such as members of the genera Staphylococcus, Streptococcus, and Haemophilus, have been isolated as have Gram-negative enterics. Brain abscesses frequently contain more than one organism. Fungal brain abscesses can occur, primarily in immunocompromised hosts. The causal organism depends on the underlying condition: head injury, postoperative infection, chronic otitis media, and cardiac disease.

17. (C)

18. (B) (See Figure 133-1.)

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FIGURE 133-1Erythema migrans due to Borrelia burgdorferi (Lyme Disease). (Reproduced, with permission, from McPhee SJ, Papadakis MA. Current Medical Diagnosis and Treatment 2010, 49th ed. New York: McGraw-Hill; 2010: Plate 32.)


19. (A) (See Figure 133-2.)

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FIGURE 133-2. Bartonellosis: cat-scarch disease with a primary lesion. Erythematous nodule of the check of a 9-year-old girl at the site of the cat scratch. The diagnosis was made on the histologic findings of the excised specimen. (Reproduced, with permission, from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 6th ed. New York: McGrawHill; 2009: Fig. 24-55.)


20. (D)


SUGGESTED READING

American Academy of Pediatrics. In: Pickering LK, Baker CJ, Overturf GD, et al, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

Bale JF. Viral infections of the nervous system. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006: 1595.

Bonthius DJ, Karacay B. Meningitis and encephalitis in children—an update. Neurol Clin North Am. 2002;20:1013-1038.

Cochrane DD. Brain abscess. Pediatr Rev. 1999;20:209-215.

Glaser CA, Lewis PF, Schuster FL. Fungal, rickettsial, and parasitic diseases of the nervous system. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1631.

Täuber MG, Schaad UB. Bacterial infections of the nervous system. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1571.

Volpe JJ. Viral, protozoan, and related intracranial infections. In: Volpe JJ, ed. Neurology of the Newborn. 4th ed. Philadelphia, PA: WB Saunders; 2001:717.

Whitley RJ, Kimberlin DW. Viral encephalitis. Pediatr Rev. 1999;20:192-198.

CASE 134: A 17-YEAR-OLD ADOLESCENT GIRL WITH MUSCLE WEAKNESS

A 17-year-old athletic, right-handed adolescent girl comes into your clinic with the chief complaint of lower extremity muscle weakness. She states that she first noted the weakness 1 month ago while playing soccer. At that time, she noted she was unable to keep up with her teammates. She states that she feels fine for the first 10-15 minutes but after that seems to fatigue. In addition, during routine practices, she falls approximately 10-12 times per session. She states that although she can walk well, she has difficulty climbing stairs. She has to rest after 2 flights and cannot climb without holding on to the railing. In addition to soccer, the patient runs competitively, stating she used to be able to run 400 meters in 65 seconds. She can no longer compete. These symptoms were not present before a month ago. She denies any history of muscle pain, myoglobinuria, or previous infectious illness. She denies any history of rash or joint swelling.

On review of her past medical history, she was born at full term without complications. She has a history of bifrontal headaches associated with photophobia and phonophobia. A head CT was reportedly normal. On review of symptoms she has experienced occasional diplopia. She states that her vision is worse in the evening and better in the morning. There is no family history of rheumatologic or neuromuscular disorders. She has a maternal aunt with “thyroid problems.” On physical examination, she is alert and in no apparent distress. Her general examination is unremarkable. Her cranial nerves are intact. However, on prolonged upward gaze, she developed moderate bilateral ptosis after 20 seconds. When asked to abduct her left arm repetitively, she developed left deltoid weakness after 45 attempts. Her strength returned to normal following a 4-minute rest period. The remainder of her neurologic examination was normal.

SELECT THE ONE BEST ANSWER

1. Which of the following tests is most likely to provide you with a diagnosis?

(A) MRI of the brain with and without contrast

(B) lumbar puncture

(C) EEG

(D) MRI of the spine

(E) antibody testing

2. You send blood for a creatine kinase (CK) level and antibodies to the acetylcholine receptor. The CK comes back at 89 (45-230) U/L. The acetylcholine binding, blocking, and modulating antibody titers are 69 (0-0.4) mmol/L, 55% (0-15), and 46% (0-20), respectively. The most likely diagnosis is which of the following?

(A) botulism

(B) congenital myasthenia

(C) Lambert-Eaton myasthenic syndrome

(D) juvenile myasthenia gravis

(E) neonatal myasthenia gravis

3. Which of the following statements regarding juvenile myasthenia gravis is false?

(A) it is more common in boys than in girls

(B) ptosis can be unilateral

(C) the disease is frequently associated with other autoimmune disorders

(D) anti-AchR antibodies can cross the placenta

(E) ptosis is the most common clinical finding

4. An important study to obtain in the management of this patient is which of the following?

(A) muscle biopsy

(B) pulmonary function tests

(C) chest CT

(D) oropharyngeal motility testing

(E) thyroid function tests

5. Treatment of this patient’s condition includes which of the following?

(A) pyridostigmine

(B) corticosteroids

(C) azathioprine

(D) plasmapheresis

(E) all of the above

6. A patient with myasthenia presents to the ED with the chief complaint of dysphagia. The patient is given a dose of pyridostigmine. Shortly after, the patient complains of nausea and abdominal cramps. The patient has a hard time handling her secretions. The patient soon develops respiratory distress. The most likely cause of this patient’s exacerbation is which of the following?

(A) myasthenic crisis

(B) cholinergic crisis

(C) pneumonia

(D) Guillain-Barré syndrome

(E) none of the above

7. In counseling this patient, you warn her that certain common medications may make her condition worse. From the following list of medications, which will potentially exacerbate her condition?

(A) erythromycin

(B) penicillin

(C) lidocaine

(D) phenytoin

(E) all of the above

8. A 4-year-old boy comes to your clinic with the chief complaint of muscle weakness. During the examination, you notice a waddling gait and hypertrophic calves. He has a high serum CK enzyme level. A muscle biopsy demostrates a lack of dystrophin staining. The most likely diagnosis would be which of the following?

(A) Duchenne muscular dystrophy (DMD)

(B) limb-girdle muscular dystrophy

(C) scapuloperoneal muscular dystrophy

(D) congenital muscular dystrophy

(E) myotonic dystrophy

9. Which of the following statements is true regarding the genetics of DMD muscular dystrophy?

(A) it is transmitted as an autosomal recessive trait

(B) it is transmitted as an autosomal dominant trait with variable penetrance

(C) the disorder demonstrates an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) multiple modes of inheritance are possible

10. Which of the following statements is true regarding the genetics of Becker muscular dystrophy?

(A) it is transmitted as an autosomal recessive trait

(B) it is transmitted as an autosomal dominant trait

(C) the disorder demonstrates an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) the disorder is a result of mutations of mitochondrial DNA

11. Which of the following statements is true regarding the genetics of myotonic dystrophy?

(A) it is transmitted as an autosomal recessive trait

(B) little is known regarding the molecular genetics of this disorder

(C) the disorder demonstrates an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) the disorder is a result of mutations of mitochondrial DNA

12. Gower sign indicates which of the following?

(A) proximal muscle weakness

(B) distal muscle weakness

(C) hypotonia

(D) high riding scapulae and facial weakness

(E) none of the above

13. Children with congenital muscular dystrophy are deficient in which of the following proteins?

(A) dystrophin

(B) alpha-sarcoglycan

(C) F-actin

(D) dysferlin

(E) merosin

14. You are called to the intensive care nursery to evaluate a 4-day-old male infant who is reportedly “floppy.” The infant was born at full term with Apgars of 5 and 7. Shortly after birth, he developed respiratory distress requiring mechanical ventilation. A prenatal ultrasound revealed polyhydramnios. On review of his family history, you learn that a previous child died at 36 hours of life. His maternal aunt also had a male child who died shortly after birth. On physical examination, the cranial nerves are intact with the exception of slight ptosis and a weak gag. There are no tongue fasciculations. The infant has decreased tone and absent deep tendon reflexes. There is no arthrogryposis (nonprogressive contracture of the joints). This infant most likely has which of the following disorders?

(A) nemaline myopathy

(B) central core disease

(C) spinal muscular atrophy type I

(D) centronuclear (myotubular) myopathy

(E) congenital muscular dystrophy

15. Tongue fasciculations are most commonly seen with which of the following disorders?

(A) spinal muscular atrophy

(B) DMD muscular dystrophy

(C) nemaline myopathy

(D) centronuclear myopathy

(E) none of the above

MATCH EACH OF THE FOLLOWING DISEASES WITH ITS CORRESPONDING DEFECT OR DEFICIENCY

16. Myoclonus epilepsy with ragged-red fibers (MERRF)

(A) myophosphorylase

(B) acid maltase

17. Pompe disease

(C) tRNA Lys gene

18. McArdle disease

(D) phosphorylase B kinase

 

(E) lactate dehydrogenase

ANSWERS

1. (E) In many cases the clinician can make the diagnosis of myasthenia gravis based on the history and physical examination (see Figure 134-1). The most specific test for myasthenia gravis is the detection of acetylcholine receptor antibodies in the patient’s serum. However, it should be remembered that antibodies are not detectable in all patients with myasthenia gravis. In fact, children with myasthenia gravis often do not have these antibodies. Single-fiber electromyography (EMG), nerve conduction studies with repetitive stimulation, antibody testing, and an edrophonium test can confirm the diagnosis. Edrophonium testing involves the administration of intravenous drug to patients with suspected myasthenia gravis. The drug is a cholinesterase inhibitor. A positive test consists of clinical improvement following administration of the drug, such as resolution of dysarthria or improved ocular motility. Neuroimaging, lumbar puncture, and an EEG are all likely to be normal in this patient given the clinical history.

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FIGURE 134-1Pathogenesis of myasthenia gravis. Acetylcholine released at the nerve ending by the nerve impulse normally binds with acetylcholine receptors. This evokes the action potential in the muscle. In myasthenia gravis, anti-acetylcholine receptor antibody evokes immune-mediated destruction of the end plate. (Reproduced, with permission, from McPhee SJ, Papadakis MA. Current Medical Diagnosis and Treatment 2010, 49th ed. New York: McGraw-Hill; 2010.)


2. (D) Nearly a quarter of patients with myasthenia gravis develop the disease during childhood and adolescence. The condition is characterized by muscles weakness and, importantly, fatigability. Muscles of the eye, oropharynx, and extremities can be involved. In addition, respiration can be affected. Exertion and stress can bring on the symptoms. There are different categories of myasthenia gravis. This patient presents with juvenile myasthenia gravis in which onset is usually after the age of 10 years. It is more common in girls. Typically, most patients present with ocular findings, such as ptosis. However, extremity weakness can be the initial presenting sign and usually principally involves the proximal muscle groups. Neonatal myasthenia gravis is a transient condition resulting from the placental transfer of acetylcholine receptor antibodies to the fetus. Congenital myasthenic syndromes are a collection of rare diseases that are not autoimmune related. In these patients, antibodies are not found and immunosuppressive therapy is ineffective. Most patients develop symptoms in the first few years of life. Symptoms include limb weakness, ocular findings, respiratory dysfunction, and feeding difficulties. Botulism can result in dysarthria, dysphagia, ptosis, and blurred vision. In infantile botulism, hypotonia is commonly observed. This condition is caused by a toxin produced by Clostridium botulinum, which acts on presynaptic nerve terminals to block calcium-dependent acetylcholine release.

3. (A) As stated above, myasthenia gravis is more common in girls than in boys. Ptosis is the most common presenting clinical complaint with a third of patients presenting with a unilateral onset. Myasthenia gravis is frequently associated with rheumatoid arthritis, thyroid disease, diabetes, and systemic lupus erythematosus. Placental transfer of anti-AchR antibodies results in transient symptoms in the neonate.

4. (C) Although some debate exists, it is generally accepted that most pubertal patients with juvenile myasthenia gravis will benefit from a thymectomy with or without thymoma. The presence of a thymoma is an absolute indication for thymectomy in patients with juvenile myasthenia gravis. As a result, it is imperative that all newly diagnosed patients with myasthenia gravis undergo a chest CT to evaluate for thymoma.

5. (E) The main treatment of myasthenia gravis is the use of acetylcholinesterase inhibitors, such as pyridostigmine. Side effects include diarrhea, nausea, and gastrointestinal cramping. In addition, an immunosuppressive agent is usually employed, such as a corticosteroid. Azathioprine, cyclosporine, and cyclophosphamide have also been used. Azathioprine has been used when patients relapse on corticosteroids or as a steroid-sparing agent. Other forms of therapy that have been tried include plasmapheresis and the administration of intravenous immunoglobulin. Thymectomy has been considered above.

6. (B) This patient has developed a cholinergic crisis, with respiratory failure secondary to an overdose of acetylcholinesterase inhibitors. Overstimulation of the muscarinic and nicotinic cholinergic receptors results in nausea, abdominal cramps, excessive secretions, and bronchospasm. The term myasthenic crisis refers to respiratory failure that results from the patient’s disease. Treatment of the patient with cholinergic crisis involves intubation and mechanical ventilation. The patient is admitted to the intensive care unit and acetylcholinesterase inhibitors are discontinued.

7. (E) Patients with myasthenia gravis can have worsening of their disease should they take medications that interfere with neuromuscular transmission. Antibiotics such as sulfonamides, clindamycin, fluoroquinolones, and tetracycline can also exacerbate myasthenia gravis. Aminoglycosides are the most commonly implicated antimicrobial agents.

8. (A) Many patients with Duchenne muscular dystrophy (DMD) will have a small percent of dystrophinpositive “revertant fibers” which are believed to be the result of alternative splicing or secondary mutation events that restore an open reading frame. In this case, it serves as a positive control for the dystrophin staining. A subset of children with congenital muscular dystrophy lack merosin. Boys with DMD typically present with muscle weakness of the hip girdle muscles that produce a waddling gait. Later in the course, shoulder girdle muscles are affected. Smaller children may have a Gower sign (see later) when attempting to stand up from a sitting position on the floor. Calf hypertrophy is also observed. This is best characterized as a pseudohypertrophy as the apparent increase in muscle mass is caused by normal muscle being replaced by collagen and adipose tissue. Limb girdle muscular dystrophies (LGMD) represent a heterogeneous group of muscle disorders that are inherited in an autosomal dominant (LGMD1) or autosomal recessive (LGMD2) fashion. Mutations of calpain 3, alpha-sarcoglycan, and dysferlin, to name a few, result in this phenotype. This condition should be considered if dystrophin mutations have been excluded. Scapuloperoneal muscular dystrophy is a dominantly inherited condition characterized by leg weakness, foot drop (peroneal and anterior tibial muscle wasting), proximal arm weakness, and scapular winging. The calf muscles are usually unaffected. Myotonic dystrophy is inherited in an autosomal dominant fashion and caused by a trinucleotide repeat expansion mutation of a protein kinase gene. Clinically, patients with myotonic dystrophy have a high degree of variability. While some patients can be asymptomatic, others can be profoundly affected by the disease. For example, neonates may have severe hypotonia, swallowing difficulties, and respiratory distress requiring ventilatory support. Classically, patients have elongated facies, myotonia, facial diplegia, ptosis, tented upper lip, and wasting of the temporalis muscles.

9. (C) DMD is transmitted as an X-linked recessive disorder with mutations occurring on the short arm of the chromosome (Xp21). Most males with DMD have an absence of dystrophin.

10. (C) Becker muscular dystrophy is transmitted as an X-linked recessive disorder with mutations occurring on the short arm of the chromosome (Xp21). In contrast to DMD, dystrophin is present in reduced amounts.

11. (D) Myotonic dystrophy is inherited as an autosomal dominant trait (chromosome 19). Expansion of the triplet repeat (CTG) results in decreased expression of a protein kinase gene. This disorder demonstrates the phenomenon of anticipation; the severity of the disease progresses in subsequent generations.

12. (A) Gower sign occurs when a child uses all 4 limbs to push himself up off the floor from a sitting position. The child then braces his hands on his knees and thighs to push himself into an upright position. The maneuver is necessary because patients with DMD have hip muscle weakness, primarily of the gluteus maximus.

13. (E) Congenital muscular dystrophies (CMD) refer to a group of disorders characterized by proximal muscle weakness and hypotonia presenting in early infancy. The diseases can occur with or without major brain malformations. A portion of children with CMD are deficient in merosin (alphachain of laminin). Patients with dysferlin and sarcoglycan mutations have limb girdle muscular dystrophies types 2B and 2D, respectively.

14. (D) This child has one of the congenital myopathies, which represent a diverse group of skeletal muscle disorders. The group of disorders is represented in this question by central core disease, nemaline myopathy, and centronuclear myopathy. Most patients with congenital myopathy have a benign clinical course with some cases occurring in late childhood or adulthood. The congenital myopathies are differentiated from one another based on characteristic pathologic findings of the skeletal muscle, predominantly affecting type 1 myofibers. The congenital myopathies often come to mind in a floppy child without reflexes. The myopathies can have overlapping clinical features with each other, as well as with CMD. As a result, in the absence of a muscle biopsy, it may be difficult to distinguish one from the other. The clinical history presented in this case suggests X-linked recessive transmission. Of the choices listed, only centronuclear (myotubular) myopathy has X-linked recessive transmission. In fact, the X-linked or neonatal form of centronuclear myopathy is particularly severe. Neonatal onset is associated with a rapidly progressive course in which infants often develop respiratory complications leading to death. Other forms of centronuclear myopathy exist with onset occurring in late infancy and childhood (autosomal recessive transmission) or adulthood (autosomal dominant transmission). The name myotubular myopathy is generally used for the severe X-linked form of the disease. As its name implies, centronuclear myopathy is characterized by the presence of centrally located nuclei in small type 1 myofibers on histology. The first congenital myopathy described was central core disease due to palely stained cores within type 1 myofibers on histology. The disease is inherited as an autosomal dominant trait. Nemaline myopathy was the second congenital myopathy to be defined based on its distinctive morphologic feature of myogranules or “rods,” located beneath the sarcolemma, stained reddish/purple on trichrome staining. However, nemaline rods are not entirely specific to nemaline myopathy. Autosomal dominant and recessive inheritance has been observed for this disorder. Spinal muscular atrophy type 1 (Werdnig-Hoffmann disease) is an autosomal recessive disorder characterized by the loss of lower motor neurons in the anterior horn of the spinal cord. It is the most severe of the 3 types, resulting in death by 2 years of age from respiratory failure or infection. Affected infants have severe weakness of the intercostal muscles and limbs, tongue fasciculations, and polyminimyoclonus (a fine tremor) of the hands. Deep tendon reflexes are usually absent.

15. (A) Fasciculation of the tongue, as well as atrophy, occurs with injury to the ipsilateral hypoglossal nucleus or hypoglossal nerve (cranial nerve XII). Fasciculations are commonly seen in spinal muscular atrophy type 1.

16. (C) Many cases of MERRF are caused by mutations to the tRNA Lys gene of mitochondrial DNA. However, there does appear to be genetic heterogeneity because not all patients with MERRF have this mutation. Any patient with seizures, myoclonus, and a myopathy should raise the suspicion of a mitochondrial disorder such as MERRF.

17. (B) As muscle is a highly energy-dependent tissue, any disruption of energy metabolism can result in a myopathy. Pompe disease (type 2 glycogenosis), a disorder of glycogen metabolism, is caused by an acid maltase deficiency and refers to the more severe generalized disease of infancy. A more benign form, with onset in childhood or adulthood, also exists. Patients with Pompe disease present with weakness, hypotonia, macroglossia, hepatomegaly, and cardiomegaly.

18. (A) McArdle disease (type 5 glycogenosis), a cause of recurrent myoglobinuria, is caused by a myophosphorylase deficiency. Patients experience myoglobinuria following exercise. Resting serum creatine kinase levels are increased.


SUGGESTED READING

Escolar DM, Leshner RT, Swaiman KF. Muscular dystrophies. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1969.

Mathews KD. Muscular dystrophy overview: genetics and diagnosis. Neurol Clin North Am. 2003;21:795-816.

Riggs JE, Bodensteiner JB, Schochet SS Jr. Congenital myopathies/dystrophies. Neurol Clin North Am. 2003;21:779-794.

Wolfe GI, Barohn RJ. Diseases of the neuromuscular junction. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric Neurology: Principles & Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1942.

CASE 135: A 7-YEAR-OLD BOY WITH HEAD JERKS

A 7-year-old boy with attention deficit disorder comes to your clinic for a routine follow-up examination. During the examination, you notice occasional eye blinking and right-sided head jerks. His mother states that she has noticed these movements for approximately 6 months. A year ago, the patient would repetitively open his mouth wide open, as if to “stretch his jaw.” The movements seem to come and go but never disappear for more than 2 months. The movements are infrequent, and she always assumed they were behavioral or “part of his allergies.” The child states that the movements are involuntary. On questioning his mother further about the allergies, you learn he has periods of sniffing and throat clearing. Her previous pediatrician stated these were symptoms of seasonal allergies. The movements never occur during sleep and are exacerbated by stress. The patient states that if he tries hard enough, he can suppress the behaviors for brief periods of time. There is no history of seizure-like activity. There is a family history of psychiatric illness on both sides of the family. On review of his past medical history, you note he has not had any history of streptococcal throat infections. His physical examination is normal.

SELECT THE ONE BEST ANSWER

1. In further evaluating this child it is important to ask which of the following questions?

(A) “what medications does your child currently take?”

(B) “does your child suffer from any sleep disorders?”

(C) “are the movements bothersome to the child or do his friends comment on the movements?”

(D) “does your child suffer from any psychiatric conditions, such as obsessive-compulsive disorder, depression, or anxiety?”

(E) all of the above

2. His mother states that he is currently taking an antihistamine for his allergies and denies any history of psychiatric illness. The most likely diagnosis of this child’s medical problem is which of the following?

(A) seizure disorder

(B) Wilson disease

(C) Tourette syndrome

(D) allergic rhinitis

(E) anxiety disorder

3. His mother states that she was given a prescription for methylphenidate to treat his ADHD but that he hasn’t started taking it yet. In counseling the mother regarding the use of this medication, which of the following statements is appropriate?

(A) “methylphenidate is best given before the patient goes to bed”

(B) “methylphenidate will also help control the motor movements”

(C) “there is a chance that the methylphenidate will exacerbate the movements and, as a result, you should consider a medication that treats both the tics and ADHD, such as clonidine”

(D) “an EEG should be obtained before starting the medication”

(E) none of the above

4. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic criteria for Tourette syndrome include all of the following except

(A) onset must have occurred before the age of 18 years

(B) the patient must demonstrate multiple motor tics

(C) the duration of symptoms must be longer than 6 months

(D) vocal tics must be present

(E) the disorder is not the result of another medical condition

5. Which of the following neuropsychological problems are associated with Tourette syndrome?

(A) OCD

(B) ADHD

(C) depression

(D) behavioral problems

(E) all of the above

6. On further questioning, you learn that the patient frequently washes his hands because he believes they are contaminated with harmful germs. He frequently checks to make sure the windows are locked to the point that he cannot leave the house until he has checked each window. The most appropriate treatment for this disorder is which of the following medications?

(A) clonazepam

(B) dextroamphetamine

(C) risperidone

(D) desipramine

(E) fluoxetine

7. Which of the following statements is false regarding Tourette syndrome?

(A) females are more commonly affected than males

(B) the mean age of onset is between 6 and 7 years of age

(C) an MRI of the brain is most often normal in these patients

(D) treatment of tics should be reserved for those patients who have failed nonpharmacologic treatments and in whom the movements are disturbing or functionally disabling

(E) in terms of prognosis, tics will remain stable or increase in approximately a quarter of the patients, whereas most will show at least some improvement into adulthood

8. All of the following have been used in the treatment of tic disorders except

(A) pimozide

(B) clonazepam

(C) haloperidol

(D) baclofen

(E) fluphenazine

9. A 12-year-old girl comes to your office with the chief complaint of writhing movements involving the hands and feet. In addition, the patient experiences random muscle jerks that prevent her from using eating utensils. She was referred to a child psychiatrist because she has had periods of inappropriate laughter mixed with periods of extreme sadness. Her past medical history is significant for a severe pharyngitis she experienced approximately 3 months ago. There is no family history of Huntington disease. On examination, the patient is a thin female who has a hard time sitting still. Her vital signs are normal. She has a new cardiac murmur, which you confirmed with her previous pediatrician. You note the movements described above, but her neurologic examination is otherwise within normal limits. This patient most likely has which of the following diagnoses?

(A) restless legs syndrome

(B) Sydenham chorea

(C) rheumatic heart disease

(D) Wilson disease

(E) B and C are equally likely

10. The next most important action/study in the evaluation of the patient from question 9 is which of the following?

(A) an EEG

(B) MRI of the brain with and without contrast

(C) referral to a pediatric cardiologist for an echocardiogram and ECG

(D) enteroviral titers

(E) ceruloplasmin

11. Opsoclonus myoclonus is associated with which of the following disorders?

(A) Wilms’ tumor

(B) neuroblastoma

(C) epilepsy

(D) benign myoclonus of early infancy

(E) Pelizaeus-Merzbacher disease

12. You are asked to see an 8-year-old girl who recently developed torticollis and dystonic posturing of her upper limb 30 minutes after an oral dose of medication. The medication most likely to cause these symptoms is which of the following?

(A) baclofen

(B) acetaminophen

(C) diphendydramine

(D) prochlorperazine

(E) phenobarbital

13. An almost 18-year-old young woman presents to your clinic for evaluation of bilateral hand tremor. On physical examination you notice a coarse resting tremor that increases with volitional movement. You also note subtle side-to-side head movements. The tremors never occur during sleep. On obtaining a substance abuse history, the patient reluctantly admits to occasional alcohol use. Interestingly, she states that her tremors are better following an alcoholic beverage. Her father, a recovering alcoholic, developed similar symptoms when he was in his early 20s. This patient most likely has which of the following conditions?

(A) juvenile Parkinson disease

(B) delirium tremens

(C) physiologic tremor

(D) essential familial tremor

(E) drug-induced Parkinson disease

14. Kernicterus is caused by which of the following etiologies?

(A) hypoxia

(B) hyperbilirubinemia

(C) infection

(D) maternal drug use

(E) prematurity

15. Brown copper deposits occurring on the iris (Kaiser-Fleischer rings) are seen in which of the following disorders?

(A) TSC

(B) NF type 1

(C) Wilson disease

(D) Tay-Sachs disease

(E) Sturge-Weber syndrome

MATCH EACH OF THE FOLLOWING MOVEMENTS WITH ITS DEFINITION

16. Tremor

(A) violent, flinging movements typically involving the shoulder

17. Dystonia

(B) very rapid, involuntary, repetitive contractions of a muscle or group of muscles

18. Myoclonus

(C) continuous, rhythmic, oscillatory movement of a body part occurring at rest or with movement

19. Chorea

(D) sustained simultaneous contraction of agonist and antagonist muscles

20. Ballismus

(E) smooth, “dance-like” movements of the extremities involving several body parts

ANSWERS

1. (E) This child most likely has a tic disorder, which range in severity from a transient tic disorder to Tourette syndrome. In the evaluation of tic disorders, the physician must determine if the disorder is primary (Tourette syndrome) or secondary (Tourette-like disorder). Certain medications, such as stimulants used in the treatment of ADHD, have been shown to “unmask” tics in patients that may subsequently develop Tourette syndrome. Neuropsychological problems are often seen in patients with Tourette syndrome and include OCD behaviors, anxiety, depression, aggressive behaviors, ADHD, and sleep disturbances. In terms of deciding on a treatment course, it is important to know if the movements are functionally disabling to the child or psychologically bothersome.

2. (C) This child most likely has Tourette syndrome given the presence of multiple motor tics, at least one vocal tic, and symptoms occurring for longer than 1 year with an age of onset before the age of 18 years. In addition, the child has not been symptom free for longer than 3 months, which is a DSM-IV criterion. The differential diagnosis of tic disorders includes seizure disorders, Wilson disease, juvenile Huntington disease, and PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). Many of these disorders can be excluded with an accurate history and physical examination. Ultimately, because there is no specific diagnostic test for Tourette syndrome, and the diagnosis is made clinically.

3. (C) Methylphenidate is a stimulant used in the treatment of ADHD. The use of stimulants in patients with ADHD and tic disorders is controversial because some of the medications used in the treatment of ADHD, such as methylphenidate, can exacerbate the movements. Clonidine has been used to treat ADHD as well as tic disorders and may be tried in this setting. Because methylphenidate is a stimulant, when used, it is best given in the morning. Patients who take it later in the day or evening may have difficulty falling asleep. Motor and vocal tics are not associated with electrographic changes on EEG. Hence the study would not add anything to the decision-making process.

4. (C) The DSM-IV diagnostic criteria for Tourette disorder require that the patient experience symptoms for at least 1 year. The course is gradual, and certain types of tics may come and go. At least one vocal tic must be present. To be considered Tourette disorder, the patient cannot have more than 3 consecutive months without symptoms. The disorder cannot be a side effect of drugs or be caused by another medical condition.

5. (E) Children with Tourette syndrome can have a number of neuropsychological problems including OCD, ADHD, depression, and behavioral problems. Obsessions include intrusive, unwelcome thoughts or ideas. The obsessions (eg, feeling that one’s hands are covered with bacteria) may result in a compulsion, a purposeful repetitive behavior designed to relieve the obsession (eg, hand washing). The incidence of OCD in patients with Tourette’s syndrome ranges from approximately 30-60% depending on the study. ADHD is comorbid in approximately 50% of patients with Tourette syndrome. ADHD may precede the diagnosis of tics by a few years. Although children with Tourette syndrome can have serious difficulties in school, the presence of comorbid ADHD is probably the most important contributing factor. Psychosocial factors, behavioral problems, and depression are also important contributing factors to poor school performance.

6. (E) This patient most likely has an OCD in addition to Tourette syndrome. OCD can be treated with selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, or a serotonin/norepinephrine reuptake inhibitor, such as clomipramine.

7. (A) TS is more common in males than females with a mean age of onset of 6-7 years. Because there is no diagnostic test specific for TS, neuroimaging, as well as routine blood work, is typically normal. Over the course of the illness, most tics change in quality and even severity. The tics are exacerbated by stress, fear, fatigue, and excitement. Treatment is generally reserved for those patients in whom the tics become troublesome, either by causing impairment of function or by harming the child on a psychosocial level. In this circumstance, the child has also failed nonpharmacologic modes of treatment.

8. (D) Pimozide, clonazepam, haloperidol, and fluphenazine have all been used in the treatment of tic disorders. Baclofen has been used in the treatment of chorea and spasticity.

9. (E) This patient is experiencing chorea and emotional lability, 2 of 3 classical characteristics of Sydenham chorea, a condition that occurs after a group A streptococcal infection of the tonsils and pharynx. The third classical characteristic is hypotonia. In addition to these symptoms, the patient now has a new cardiac murmur suggestive of rheumatic myocarditis. The hallmark heart murmur of rheumatic myocarditis is that of mitral regurgitation. As a result of the chorea and carditis, the patient meets the criteria for a diagnosis of rheumatic fever given that she has 2 major manifestations of the Jones criteria. The other 3 major manifestations are polyarthritis, erythema marginatum, and subcutaneous nodules. There are also minor criteria such as fever, arthralgia, elevated acute-phase reactants (erythrocyte sedimentation rate and Creactive protein), and prolonged PR interval on echocardiography. Rheumatic heart disease is seen in approximately a third of patients with Sydenham chorea. Several medications have been tried to control the choreiform movements including diazepam, phenothiazines, valproic acid, and butyrophenones.

10. (C) The severity of rheumatic myocarditis can vary from mild cardiac failure resulting in death. Under the circumstances this patient should be referred to a pediatric cardiologist, who based on the physical examination may obtain an echocardiogram to confirm the type of murmur heard on auscultation. In addition, the cardiologist may order an electrocardiogram as a baseline study or to assess the PR interval. An EEG and MRI of the brain would most likely be normal in patients with Sydenham chorea. Enteroviruses cause protean manifestations in children but not illness similar to this girl’s. Serum concentrations of ceruloplasmin are decreased in Wilson disease.

11. (B) Opsoclonus myoclonus (“dancing eyes”) is a paraneoplastic or postinfectious movement disorder characterized by ataxia, myoclonus, and oscillopsia, which refers to multidirectional, chaotic eye movements. The syndrome typically presents in infancy or early childhood (6-36 months of age). When observed, the clinician should begin an investigation for a neural crest tumor, most commonly neuroblastoma, because 50% of patients with opsoclonus myoclonus have such a tumor. The pathogenesis of this syndrome is poorly understood but is most likely immune mediated. This is supported by the observation that treatment with steroids and other immunotherapies, such as IVIG and azathioprine, are of some benefit.

12. (D) A number of prescription medications can result in neurologic morbidity, including acute dystonia, parkinsonism, tardive dyskinesia, acute akathisia, and neuroleptic malignant syndrome. Some of the more common medications that can cause acute dystonia include phenothiazines, butyrophenones, levothyroxine, and some antiepileptics (carbamazepine and phenytoin). Prochlorperazine is a phenothiazine used commonly as an antiemetic. Patients can develop an acute dystonia following a single dose of a neuroleptic. The acute dystonic reactions are usually self-limited and can be quite diverse in presentation. Some patients may present with oculogyric crisis, torticollis, or opisthotonic posturing. Anticholinergic agents, such as diphenhydramine or benztropine, can provide immediate relief in most patients.

13. (D) Essential familial tremor is a common form of tremor. It is inherited as an autosomal dominant trait with a typical onset in the patient’s teens. The diagnosis is usually evident by the time the patient is in his or her 20s or 30s. Patients typically manifest a coarse resting tremor in the upper extremities that worsens with volitional movement. The tremor is not present during sleep. Head and face may also be involved, often resembling titubation (shaking or tremor of the head due to cerebellar dysfunction). Interestingly, essential tremors get better with alcohol ingestion. The clinical characteristics of Parkinson disease include rigidity, bradykinesia, tremor, and postural instability. The tremor in Parkinson disease is a resting tremor; however, voluntary movement suppresses it. Physiologic tremor occurs when the patient extends the arms forward. Certain drugs such as valproic acid can exacerbate a physiologic tremor.

14. (B) Kernicterus is caused by elevated bilirubin levels in the perinatal period resulting in injury to the globus pallidus. As a result, patients can develop choreoathetosis and dystonia. In addition, patients can develop sensorineural hearing loss. Infection, prematurity, and hypoxia can increase the susceptibility to hyperbilirubinemia. The most effective treatment for this condition is prevention.

15. (C) Wilson disease has the clinical findings of tremor, rigidity, drooling, and Kayser-Fleischer rings (see Figure 135-1) in the setting of liver dysfunction. The disease is caused by an impairment of copper metabolism, which results in the deposition and accumulation of copper in various tissues, including the liver. On ingestion, copper binds to albumin and is transferred to the liver where it will be incorporated into ceruloplasmin. The concentration of this protein is decreased in patients with Wilson disease. Kayser-Fleischer rings are pathognomonic for Wilson disease. The rings form as a result of copper granule deposition in Descemet membrane. The disease is transmitted as an autosomal recessive trait. The disease is treated by restricting copper from the diet and chelation therapy with D-penicillamine.

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FIGURE 135-1Brownish Kaiser-Fleischer ring at the rim of the cornea in a patient with Wilson disease. (Reproduced, with permission, from Fauci AS, Kasper DL, Braunwald E, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008. Fig. 354-1.)


16. (C)

17. (D)

18. (B)

19. (E)

20. (A)


SUGGESTED READING

Pranzatelli MR. Movement disorders in childhood. Pediatr Rev. 1996;17:388-394.

Sanger TD, Mink JW. Movement disorders. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1271.

CASE 136: A 16-YEAR-OLD GIRL WITH HEADACHES AND BLURRED VISION

A 16-year-old girl presents to your clinic with the chief complaint of headaches and blurred vision. The patient was in her usual state of health until approximately 2 months ago when she started to experience headaches over the “top of her head.” The headaches occur daily and are exacerbated by coughing or exercise. The headaches seem to be worse in the morning. She states that she has been treating the headaches with acetaminophen with little, if any, benefit despite taking the medication daily. Recently, she started experiencing blurred vision and vertigo. She denies any history of nausea, vomiting, or photophobia. There is no family history of migraines. Her paternal grandfather died of “brain cancer.”

On physical examination, she is an obese female in mild distress. Her body mass index is 30. She is afebrile and her vital signs are stable. On examination of her fundi, you note bilateral papilledema. Examination of her visual fields at the bedside reveals bilateral enlarged blind spots. Her pupils are round, reactive, and equal to light. Extraocular eye movements are intact without pain on lateral or upward gaze. The remainder of her cranial nerve examination is normal. On motor examination, her muscle tone, bulk, and strength are normal in the upper and lower extremities bilaterally. Her deep tendon reflexes, gait, and sensory examination are normal.

SELECT THE ONE BEST ANSWER

1. The next appropriate action in the evaluation of this patient is which of the following?

(A) neuroimaging with head CT or MRI of the brain

(B) lumbar puncture

(C) visual field testing

(D) tonometry

(E) no further action is necessary for diagnosis

2. Which of the following medical conditions or prescription drugs can cause papilledema?

(A) tetracycline

(B) primary CNS tumors

(C) Guillain-Barré syndrome

(D) lupus erythematosus

(E) all of the above

3. You were able to obtain an MRI of the brain with and without contrast that same day. The radiologist calls you to tell you that the study is completely normal. At this point, the highest yield diagnostic study is which of the following?

(A) static Humphrey perimetry (visual field testing)

(B) vitamin A level

(C) cerebral angiography

(D) lumbar puncture

(E) erythrocyte sedimentation rate

4. Intraocular pressure as measured by tonometry was normal. Assuming the patient has an elevated opening pressure on lumbar puncture (280 mm H2O), which of the following is the most likely diagnosis of this patient’s medical problem?

(A) glaucoma

(B) pseudotumor cerebri

(C) migraine without aura

(D) Arnold-Chiari type I malformation

(E) chronic daily headache

5. In terms of counseling this patient, which of the following statements are especially important in this case?

(A) “you should reduce your intake of nonsteroidal anti-inflammatory drugs to no more than 2-3 times per week because you are at risk for medication overuse headaches”

(B) “a decrease in body weight of at least 15% will help reduce or alleviate your headaches”

(C) “certain drugs and vitamins, such as oral contraceptives and vitamin A, are risk factors for your condition”

(D) “you should not drive”

(E) all of the above are correct

6. Following the spinal tap, the patient’s headaches and visual symptoms dramatically improve. You decide to start the patient on a daily medication to help manage her headaches. Which of the following medications is most likely to benefit the patient?

(A) valproic acid

(B) propranolol

(C) acetazolamide

(D) ibuprofen

(E) dihydroergotamine

7. What is the average head circumference for a fullterm newborn boy?

(A) 40 cm

(B) 38 cm

(C) 35 cm

(D) 30 cm

(E) 20 cm

8. A 10-year-old boy comes to your office for evaluation of headaches. He states he first experienced headaches at the age of 8 years. The pain is localized to the frontal regions bilaterally. He describes a pulsating quality to the headaches and cites that they are extremely severe. The headaches are associated with nausea, photophobia, and phonophobia. They are aggravated by routine physical activity. He has averaged approximately 1 headache per month but states that last summer he did not experience any head pain. His physical examination is normal. A head CT was performed in the ED and is reportedly normal. This patient’s headache is most likely due to which of the following?

(A) migraine headache with aura (classic migraine)

(B) episodic tension-type headaches

(C) migraine headache without aura (common migraine)

(D) complicated migraine

(E) basilar artery migraine

9. An 8-year-old boy complains of unilateral headache, photophobia, nausea, and vomiting. He has had symptoms on and off for approximately 15 months. On occasion, the headaches are so severe he needs to stay home from school. Before many of the headaches, he sees brightly colored lights for approximately 12 minutes. This patient’s headache is most likely due to which of the following disorders?

(A) migraine with aura (classic migraine)

(B) complex partial seizure

(C) basilar artery migraine

(D) ophthalmoplegic migraine

(E) complicated migraine

10. An 18-year-old young man presents to the ED with the chief complaint of headache. He has had occasional headaches before this one but states, “this is the worst headache of my life.” On the way to the ED, the patient complained of nausea and vomited. He now complains of pain on flexing his head forward. The patient is afebrile. The next most appropriate action is which of the following?

(A) order a head CT

(B) perform a lumbar puncture

(C) administer an opiate analgesic agent, such as morphine

(D) order a urine toxicology screen

(E) assure the patient that this is probably a migraine, which will get better

11. The radiology resident for the patient in question 10 calls you to tell you that the head CT is probably normal. With this information, you next decide to perform a spinal tap, which reveals a yellow fluid with occasional red blood cells. This patient most likely has which of the following diagnoses?

(A) complicated migraine

(B) herpes simplex hemorrhagic meningoencephalitis

(C) acute subdural hematoma

(D) subarachnoid hemorrhage

(E) glioblastoma multiforme

12. Which of the following drugs are used as prophylactic agents in the treatment of migraine headaches?

(A) cyproheptadine

(B) valproic acid

(C) amitriptyline

(D) propranolol

(E) all of the above

13. Hemicrania continua is especially responsive to which of the following medications?

(A) ibuprofen

(B) sumatriptan

(C) cyproheptadine

(D) indomethacin

(E) none of the above

14. Sumatriptan is an example of which of the following categories of medications used in the treatment of migraines?

(A) antidepressant

(B) beta-blocker

(C) 5-HT receptor agonist

(D) antiepileptic drug

(E) nonsteroidal anti-inflammatory agent

15. Which of the following are typical triggers of migraine headaches?

(A) menstruation

(B) stress

(C) cheese

(D) fatigue

(E) all of the above

16. Which of the following primary brain tumors is the most common type encountered in children younger than 15 years of age?

(A) meningioma

(B) supratentorial low-grade astrocytoma

(C) medulloblastoma

(D) ependymoma

(E) cerebellar astrocytoma

17. A 3-year-old boy presents to the ED with a 3-month history of headache, nausea, and vomiting. The patient has progressively gotten worse and now is ataxic. Figure 136-1 shows an MRI of his brain. Based on this information, this patient most likely has which of the following posterior fossa brain tumors?

(A) cerebellar astrocytoma

(B) medulloblastoma

(C) ependymoma

(D) brainstem glioma

(E) meningioma

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FIGURE 136-1A brain MRI of a 3-year-old boy presenting with headache, nausea, and vomiting from question 17. (A) Sagittal T1-weighted image following contrast administration. (B) Axial T1-weighted image. (Courtesy of Dr. Daniel Curry, University of Chicago.)


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FIGURE 136-2A brain MRI of a 4-year-old boy presenting with headache, nausea, and vomiting from question 18. (A) Sagittal T1-weighted image following contrast administration. (B) Axial T1-weighted image following contrast administration. (Courtesy of Dr. Daniel Curry, University of Chicago.)


18. On the same night you see a 4-year-old boy who presents to the ED with similar symptoms. He has a 3-month history of progressive headaches, nausea, vomiting, and ataxia. His ataxia is so severe that he no longer is able to walk. He was recently seen by his primary physician who treated him with antibiotics for an otitis media without resolution of his symptoms. His MRI of the brain is shown in Figure 136-2. This patient most likely has which of the following diagnoses?

(A) cerebellar astrocytoma

(B) medulloblastoma

(C) ependymoma

(D) brainstem glioma

(E) meningioma

19. A 2-year-old girl presents to the ED with inconsolable crying and vomiting. An MRI of the brain and a head CT are shown in Figure 136-3. The most likely cause(s) of this patient’s symptoms is which of the following?

(A) choroid plexus papilloma

(B) subependymal giant cell astrocytoma

(C) hydrocephalus

(D) colloid cyst

(E) A and C are correct

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FIGURE 136-3A brain MRI and head CT of a 2-year-old girl presenting with inconsolable crying and vomiting from question 19. (A) Sagittal T1-weighted image following contrast administration. (B) Head CT. (Courtesy of Dr. Daniel Curry, University of Chicago.)


ANSWERS

1. (A) In a patient who presents with headache and papilledema, it is important to rule out hydrocephalus or a mass lesion given the potential of developing a herniation syndrome. In fact, in this case neuroimaging is mandatory before performing a lumbar puncture. Although an MRI of the brain with and without contrast is the preferred study, especially if the practitioner suspects meningeal disease, a head CT with contrast can be useful. In fact, the head CT may be more readily available and the only option if the patient is extremely obese (other than an open MRI). In addition, a head CT would be very helpful in evaluating an intracerebral hemorrhage. For postpartum patients or those on oral contraceptives, MRI has the added advantage of being able to perform a magnetic resonance venogram (MRV) to rule out cerebral venous thrombosis. Once a structural lesion and hydrocephalus are ruled out, a lumbar puncture can be performed. Tonometry is used to measure intraocular pressure as part of an evaluation for glaucoma. Although visual field testing is a sensitive tool in assessing optic nerve involvement, the test would be performed following a neuroimaging study done to define the cause of the papilledema.

2. (E) In evaluating a patient with papilledema, it is important to look for an underlying cause. Several medical conditions are associated with papilledema. These include neurologic conditions, such as CNS tumors (primary and metastatic), infectious conditions, medications and toxins, such as tetracycline, vitamin A, and lead, certain endocrine diseases, autoimmune diseases, such as lupus erythematous, vascular diseases; and hematologic diseases.

3. (D) The study most likely to yield the diagnosis in this patient is the lumbar puncture to measure opening pressure. To accurately assess visual function in patients with papilledema, perimetry, either by Goldmann field testing or by the static Humphrey method, should be performed. In the case of papilledema, an enlargement of the blind spot is typically seen. Although perimetry is the most useful test for evaluating visual function, it does not provide the etiology for the papilledema. Vitamin A toxicity has been associated with diplopia and pseudotumor cerebri. However, one should be able to assess for vitamin A toxicity with good historytaking skills. The erythrocyte sedimentation rate is a nonspecific test for inflammation and may be elevated in patients with autoimmune conditions. If cerebral vasculitis is suspected clinically, a cerebral angiogram should be performed to assess narrowing of the blood vessels. If a venous sinus thrombosis is clinically suspected, conventional cerebral angiography should be performed, especially if noninvasive methods such as magnetic resonance angiography and computed tomography angiography are not available.

4. (B) The normal range of CSF pressure is 100-200 mm H2O. Hence a pressure of 280 mm H2O is elevated. Given the papilledema, normal MRI of the brain, and raised intracranial pressure as measured by lumbar puncture, this patient most likely has pseudotumor cerebri. Glaucoma, an elevation in intraocular pressure, can mimic the visual field deficit seen in pseudotumor cerebri because it can cause optic nerve damage. The normal intraocular pressure measured by tonometry rules out this diagnosis. An Arnold-Chiari type I malformation refers to cerebellum and cerebellar-tonsillar displacement 5 mm or more beyond the foramen magnum line. Patients may also have syringomyelia. Clinically, patients with Arnold-Chiari type 1 malformation complain of recurrent headaches, primarily over the frontal and occipital regions, neck pain, difficulty swallowing, and ataxia. The headaches can be exacerbated by exertion. In patients with syringomyelia, upper limb sensory changes and weakness are sometimes also observed. Arnold-Chiari type 2 malformations are similar to type 1 but are associated with myelomeningocele. A type 3 Arnold-Chiari malformation consists of the cerebellar displacement defined above and an encephalocervical meningocele. Type 4 consists of hypoplasia of the cerebellum and may actually represent a variation of a Dandy-Walker malformation. The normal MRI of the brain ruled out the Arnold-Chiari malformations. Finally, migraines and chronic daily headaches are not associated with abnormal physical findings, such as papilledema or elevated intracranial pressure.

5. (E) Pseudotumor cerebri, or idiopathic intracranial hypertension, is characterized by increased intracranial pressure without evidence of a brain tumor or mass lesion as the cause of elevated pressure. Patients typically present with headaches, papilledema, visual field defects (typically an enlarged blind spot), and, occasionally, diplopia. There is no gender predilection in early childhood. An important risk factor for pseudotumor cerebri is obesity. Other risk factors include various drugs, such as oral contraceptives, high levels of vitamin A, and corticosteroids, which the patient should avoid if possible. Steroid use can also play a role in weight gain. In terms of treatment, weight reduction is strongly recommended in those patients who are obese. A drop in body weight by 15% may even lead to resolution of symptoms, including elevated intracranial pressure. Given this patient’s visual symptoms she should not drive until her vision has been restored. Finally, given the daily use of analgesics, this patient is at risk for developing a medication overuse headache, formerly known as rebound headaches. Patients with medication overuse headaches usually see their primary headache disorder (eg, migraines or pseudotumor cerebri) transformed into chronic daily headaches. Once medication overuse headaches develop, they can be very difficult to treat, and patients may also develop a comorbid depression. Patients usually need to be detoxified for approximately 2 weeks. Because the headaches may be severe, some patients may require hospitalization. Other treatment strategies have been reported.

6. (C) Each of the drugs listed in this question have been used in the treatment of migraines. However, acetazolamide has been shown to decrease the formation of CSF. Acetazolamide is a sulfonamide drug. Thus, for those patients who are allergic to sulfonamides, furosemide may be used for a similar purpose. Other side effects of acetazolamide include drowsiness, numbness, renal calculi, and anorexia. Incidentally, patients with pseudotumor cerebri and obesity should avoid valproic acid (if clinically possible) because this medication may also cause weight gain.

7. (C) The mean head circumference for a full-term newborn boy at birth is approximately 35 cm; it is 34 cm for girls.

8. (C) Migraines without aura are the most common type of migraine in children and adolescents. When evaluating a patient with headaches it is important to note the temporal pattern to the headache. The examiner should ascertain whether the headache is acute versus chronic, single versus recurrent, or progressive versus nonprogressive. At times, the physician may observe a mixed pattern. This question gives an example of an acute recurrent headache. Typically, acute recurrent headaches, separated by pain-free intervals and associated with nausea, vomiting, photophobia, or phonophobia, are a result of migraines. Because this patient does not have an aura before the headache it would be classified as migraine without aura. Patients with complicated migraine typically have a transient neurologic deficit associated with their headache. This deficit could include weakness or sensory loss. However, complicated migraine is a diagnosis of exclusion, and, as a result, a structural lesion should be ruled out by neuroimaging. Basilar migraines typically present with symptoms referable to the brainstem, cerebellar, or other posterior circulation territories. These symptoms include blurred vision, vertigo, ataxia, dizziness, paresis, dysarthria, nausea, and vomiting. It is more common among adolescent females.

9. (A) This is an example of classic migraines or migraines with aura. The headaches are acute and recurrent with pain-free intervals. The patient can describe the aura as brightly colored lights and does not appear to lose consciousness during the episode, thus ruling out complex partial seizures. Patients with ophthalmoplegic migraines complain of severe pain located behind the eye. They also present with a complete or incomplete third cranial nerve palsy (eg, ptosis, diplopia, lateral eye deviation, and mydriasis), which may persist for several days even after the headache has subsided.

10. (A) When a patient without a history of severe headaches complains of the “worst headache of his or her life” in the setting of meningismus and emesis, the clinician should consider a diagnosis of subarachnoid hemorrhage (see Figure 136-4). In this case, a head CT can be performed relatively quickly to evaluate this possibility. Certainly, a neuroimaging study would be performed before lumbar puncture. Intracranial hemorrhage, stroke, and seizures have been reported following cocaine use. As a result, a urine toxicology screen may be an appropriate study in the evaluation of this patient. In terms of the next appropriate action, a neuroimaging study would enable the physician not only to confirm the diagnosis but also to assist in further managing the patient should he or she need a neurosurgical consultation or neuro-intensive care.

11. (D) Subarachnoid hemorrhages may be difficult to appreciate on head CT (see Figure 136-5). A more definitive test may be the lumbar puncture. In patients with subarachnoid hemorrhage, the CSF may contain red blood cells that do not clear in serially collected samples. In addition, xanthochromia may be seen as early as 4 hours after the bleed. Subarachnoid hemorrhages can be seen following head trauma, meningitis, birth trauma, and coagulopathies. However, the most likely etiology is a vascular malformation, although these are exceedingly rare in very young children. Patients with complicated migraine should not have red blood cells or xanthochromia on lumbar puncture. Subdural hematoma, hemorrhagic herpes meningoencephalitis, and glioblastoma multiforme are typically suggested by abnormalities observed with head CT.

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FIGURE 136-4A non-contrast head CT demonstrating diffuse subarachnoid blood. (Reproduced, with permission, from Stone CK, Humphries RL. Current Diagnosis & Treatment: Emergency Medicine, 6th ed. New York: McGraw-Hill; 2008: Fig. 35-1.)


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FIGURE 136-5Classic appearance of a large subarachnoid hemorrhage. Notice the hemorrhage pattern fills the cerebrospinal fluid spaces at the base of the brain and around the brain stem. (Reproduced, with permission, from Doherty G. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill; 2010: Fig. 36-22.)


12. (E) Treatment of migraines involves both pharmacologic and nonpharmacologic methods. The patient first needs to be assured that he or she does not have a serious or life-threatening condition. The clinician should always start with nonpharmacologic methods in the treatment of migraines. This includes recognition and elimination of triggering factors, such as relaxation methods to reduce stress, adequate sleep, and a regular diet. In terms of pharmacologic therapy, prophylactic agents can be used should nonpharmacologic methods fail and the patient continue to experience frequent headaches. Typically, this type of patient has severe headaches and misses several days of school. Some commonly used prophylactic drugs include amitriptyline, valproic acid, propranolol, and cyproheptadine.

13. (D) Hemicrania continua is an example of an indomethacin-responsive headache. This headache consists of severe, steady pain localized to one side of the head. The patients are usually female without a family history of such headaches.

14. (C) This question highlights several of the classes of medications used in the prophylactic treatment of migraine headaches. Sumatriptan is an example of a 5-HT receptor agonist.

15. (E) Menstruation, certain foods, fatigue, and stress are common triggers of migraines. Other triggers include oral contraceptive pills, anxiety, physical exertion, alcohol, sleep deprivation, and weather changes.

16. (B) The 3 most common primary brain tumors in children are, in order of decreasing frequency, supratentorial low-grade astrocytoma, medulloblastoma, and cerebellar astrocytoma.

17. (B) Medulloblastomas are posterior fossa tumors typically occurring in the midline. They tend to be well-demarcated tumors. Cyst formation, hemorrhage, and calcifications are rare in comparison with cerebellar astrocytomas. Some studies have suggested that the presence of the c-myc oncogene is associated with a poorer prognosis. Brainstem gliomas tend to occupy the region of the brainstem near the fourth ventricle and aqueduct of Sylvius. Thickening of the pons is often observed. Ependymomas can occur anywhere along the ventricular system. Most of the tumors (two-thirds) are infratentorial. Ependymomas are well defined and can be very cystic. Meningiomas are relatively uncommon tumors in children. When they are observed, they tend to occur in the posterior fossa or in the ventricular system, often causing obstructive hydrocephalus. This question highlights the importance of recognizing chronic progressive headaches, which usually imply some pathologic process, such as brain tumor, pseudotumor cerebri, subdural hematoma, or hydrocephalus, to name a few. In general, migraine headaches are rare in patients younger than 5 years.

18. (A) In contrast to medulloblastomas, cerebellar astrocytomas can occur anywhere in the cerebellum. Most of these tumors are cystic, as shown in this example. In some cases, a solid mural nodule is associated with a large cyst. Calcifications are seen in a quarter of the patients. Cerebellar astrocytomas can be separated into 2 groups: diffuse astrocytoma and juvenile cerebellar astrocytoma. Most of the astrocytomas fall into the latter category. Juvenile cerebellar astrocytoma, shown in this example, is cystic and associated with better survival rates than the diffuse type.

19. (E) Choroid plexus tumors, colloid cysts, giant cell astrocytomas, and meningiomas are all examples of ventricular tumors. This figure (Figure 136-2) shows a choroid plexus papilloma involving the lateral ventricle, a typical site for this tumor in older children. These tumors are usually found in the fourth ventricle in very young children and adults. Unlike colloid cysts, which are found in the third ventricle, choroid plexus tumors are rarely seen in the third ventricle. Patients with choroid plexus tumors often present with signs of increased intracranial pressure, such as vomiting and headache. Subependymal giant cell astrocytomas occur in the region of the ventricles and are often associated with TSC. They are commonly seen in the area around the foramen of Monro.


SUGGESTED READING

Cohen ME, Duffner PK. Tumors of the brain and spinal cord including leukemic involvement. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1688.

Evans RW, ed. Secondary headache disorders. Neurol Clin North Am. 2004;22(1), 237-249.

Mathews MK, Sergott RC, Savino PJ. Pseudotumor cerebri. Curr Opin Ophthalmol. 2003;14:364-370.

Winner P, Rothner AD. Headache in Children and Adolescents. Hamilton, Ontario, Canada: BC Decker; 2001.

CASE 137: AN 8-YEAR-OLD BOY WITH DIFFICULTY IN SCHOOL

An 8-year-old boy is referred to your clinic for evaluation of a learning disability. His mother states that her son was born at full term and met all of the developmental milestones at the appropriate ages. A week ago, she attended a meeting with his school teacher who expressed concerns about his grades and inability to pay attention in class. When asked about his behavior at home, she describes her son as very active. She admits it is probably beyond what most would consider “normal boy behavior.” For example, he recently took a set of markers and scribbled all over the kitchen walls. She states that she has to keep an eye on him every minute of the day to ensure he doesn’t get into any mischief. He has a hard time sitting still and jumps from task to task. As a result, very few of the neighborhood children will play with him because he never seems to complete any of the games and is very disruptive. When she tries to talk to him, he doesn’t seem to want to listen.

During the examination, the child has a hard time sitting still. He empties all the equipment from the drawers, despite his mother’s objections. When asked to write the alphabet, he gets to the letter “E” before running out the door. His mother has an exasperated look on her face as she chases him into the waiting room. While she is gone, his father states that he had similar problems in school. On the child returning to the examination room, you manage to complete the physical examination with difficulty and find it is within normal limits.

SELECT THE ONE BEST ANSWER

1. To make a diagnosis and begin therapy, you will need which of the following pieces of information?

(A) a letter from the school teacher delineating some of the observed behaviors and academic difficulties

(B) an MRI of the brain looking for frontal lobe injury

(C) completion of behavior rating scales by the parents and school teachers

(D) psychiatric evaluation

(E) A and C

2. You obtain the appropriate information and it confirms your initial hypothesis. The most likely diagnosis in this patient is which of the following?

(A) conduct disorder

(B) ADHD

(C) mental retardation

(D) bipolar disorder

(E) oppositional defiant disorder

3. His father asks if he could have passed on these symptoms to his son. In fact, he has wondered about treatment for himself. Which of the following is the most appropriate response?

(A) “the likelihood is small because ADHD is probably not a genetic disorder”

(B) “probably not, because ADHD is an X-linked disorder”

(C) “possibly, however, environmental factors, such as upbringing and maternal drug use, are much more important”

(D) “ADHD is probably a genetic disorder; a child born to a parent with ADHD has a greater than 50% risk of developing symptoms”

(E) “not much is known about the genetics of ADHD because concordance for monozygotic twins is low”

4. Which of the following is not a DSM-IV diagnostic criteria for ADHD?

(A) symptoms of hyperactivity and/or inattention are present for at least 6 months

(B) impairment from the symptoms occurs in 2 or more settings

(C) hyperactive or inattentive symptoms must be present after the age of 7 years

(D) the patient must have at least 6 symptoms of either inattention or hyperactivity-impulsivity to be considered for that specific type of ADHD or 6 from each category to be considered for the combined type

(E) the symptoms cannot be due to another condition, such as pervasive developmental delay or a psychotic disorder

5. You decide to start the patient on therapy. Which of the following treatment options could be considered in patients with ADHD?

(A) behavioral therapy

(B) dextroamphetamine

(C) methylphenidate

(D) A, B, and C

(E) only B and C are correct

6. You decide to start the patient on a stimulant. You inform his parents that you will need to see him in the clinic every 1-3 months to assess for which of the following?

(A) growth progress

(B) academic progress

(C) cardiovascular side effects

(D) psychological well-being

(E) all of the above

7. Although the patient demonstrates significant improvement following initiation of therapy, he continues to have some academic difficulty despite several medication adjustments. At this point, the most appropriate action would be which of the following choices?

(A) a second opinion

(B) request for a child psychiatry consultation

(C) neuropsychologic or psychoeducational testing

(D) an EEG

(E) treatment with nonstimulant medications, such as bupropion or tricyclic antidepressants

8. Which of the following medications used in the treatment of ADHD is associated with chemical hepatitis and, rarely, fulminant liver failure?

(A) methylphenidate

(B) dextroamphetamine

(C) pemoline

(D) clonidine

(E) bupropion

9. Which of the following is the most frequently observed learning disorder?

(A) mathematics disorder

(B) disorder of written expression

(C) reading disorder

(D) atypical learning disorder

(E) none of the above

10. A child in the third grade presents to your clinic for evaluation of a learning disorder. His mother states that although he has a good memory and does well with rote learning, he has problems with comprehension, organization of information, and concept formation. He initially did well in math but now struggles to finish his homework, despite a significant amount of effort. She states that he doesn’t seem to have good reasoning skills. Which of the following learning disorders is most likely in this child?

(A) dyslexia

(B) mental retardation

(C) mathematics disorder

(D) nonverbal learning disability

(E) disorder of written expression

11. A 7-year-old girl comes to your clinic with a letter from her teacher. The letter states that the child is having problems with reading, especially with phonologic processing. In particular, she has a problem identifying phonemes. Her father states that he had reading difficulties as a child. You ask the child to read a short paragraph and she has a hard time associating sounds with letters and often mispronounces words. When asked to write the alphabet, she demonstrates a tendency to reverse certain letters. She has a hard time spelling simple words. Her physical examination is unremarkable. This patient most likely has which of the following diagnoses?

(A) mental retardation

(B) reading disorder

(C) ADHD

(D) disorder of written expression

(E) nonverbal learning disability

12. In terms of evaluating the patient from question 11 further, which of the following would be helpful in making the diagnosis?

(A) chromosome karyotyping

(B) MRI of the brain pre- and postcontrast

(C) EEG

(D) behavior rating scales

(E) no further studies

13. In the DSM-IV, the category “Pervasive Developmental Disorders” has 5 subgroups. Which of the following is not a subgroup of this category?

(A) autistic disorder

(B) Asperger syndrome

(C) childhood disintegrative disorder

(D) Angelman syndrome

(E) Rett syndrome

14. A 3-year-old girl presents to your clinic for an evaluation of profound language delay. Although the child is capable of vocalizing, mostly in the form of screaming, she has no words and cannot communicate her needs. Her mother states that her verbal development has never been normal. She does not make eye contact and seems oblivious to your presence. Her mother states that she is not very affectionate and has been unable to make friends with the child next door who is the same age. During the examination, the child repetitively opens and closes a drawer containing medical supplies without removing them. A hearing test was reportedly normal. You try to perform your physical examination, but the child cries and furiously flaps her arms. Her head circumference has been stable at the 97th percentile for the last year. The most likely diagnosis is which of the following?

(A) childhood disintegrative disorder

(B) autism

(C) Rett syndrome

(D) Asperger syndrome

(E) Landau-Kleffner syndrome

15. Which of the following statements is (are) true regarding the association of autism and seizures?

(A) approximately a third of patients with autism develop epilepsy by adulthood

(B) studies have suggested that up to 80% of patients with autism can have abnormal EEGs

(C) a family history of seizures is a risk factor for the development of seizures in a patient with autism

(D) patients with autism and seizures are more likely to have complex partial seizures, although all seizure types can occur

(E) all of the above statements are true

16. In evaluating a child with speech and language disorders, the only test considered “a must” in the evaluation is which of the following?

(A) EEG

(B) MRI of the brain

(C) audiometry

(D) chromosome analysis

(E) serum amino acids

17. An 18-month-old girl presents to your clinic for evaluation of language delay and poor social skills. The patient was born at full term and developed normally until a couple of months ago. Recently, she has developed frequent bouts of screaming fits. Her mother states there has been a regression in speech and language skills. She has lost the ability to use her hands purposefully. On examination, she has truncal ataxia and an apraxic gait. She has stereotyped hand movements in the form of handwringing. This patient most likely has which of the following?

(A) Angelman syndrome

(B) autism

(C) pervasive developmental delay

(D) Rett syndrome

(E) childhood disintegrative disorder

18. A 7-year-old boy presents to your clinic for an evaluation of behavior problems. The patient gets very angry when he does not “get his way.” His mother states that her son has a hard time making friends, even though he has a strong desire to be with other children. She states that the other children often refuse to play with him because he “only wants to play by his rules.” He is not very empathetic. He has recently started collecting bottle caps. He exhibits hand-flapping behavior. His language development was normal. This patient most likely has which of the following diagnoses?

(A) autism

(B) Asperger syndrome

(C) childhood disintegrative disorder

(D) oppositional defiant disorder

(E) pervasive developmental delay

ANSWERS

1. (E) This child most likely has ADHD, the combined type. However, to make the diagnosis, DSM-IV criteria require that the patient have symptoms that occur in at least 2 different settings, such as home and school. Hence the diagnosis is based on information obtained from both parents and school reports. Several behavioral rating scales have been created to allow for a systematic approach to documenting the symptoms of inattention, hyperactivity, and impulsivity. Although the diagnosis of ADHD can be made based on the compilation of findings from the clinical history, school reports, and physical examination, behavior rating scales are useful adjuncts not only in the diagnosis but also in serving as baseline measures of ADHD symptoms, which can then be used to monitor therapy efficacy. Laboratory studies in the diagnosis of ADHD are typically not very helpful, and routine neuroimaging in the setting of a normal physical examination is not indicated. Laboratory studies, such as EEG or blood work looking for systemic disease (eg, thyroid function tests) should be performed only if clinically indicated. Because patients with ADHD can develop symptoms of depression and low self-esteem, it is important to monitor for these symptoms. However, in the absence of these symptoms a psychiatric evaluation is not necessary to make the diagnosis. It should be stressed, however, that clinically depressed patients can have symptoms consistent with a diagnosis of ADHD. As a result, a DSM-IV diagnostic criterion for ADHD is that the symptoms cannot be better accounted for by another mental disorder, such as a mood disorder. One can have devastating consequences should a diagnosis of major depression be attributed to ADHD.

2. (B) This child has ADHD, combined type, which is approximately 2-4 times more common in males than females. To be diagnosed with ADHD, combined type, patients must have at least 6 symptoms of inattention plus 6 or more symptoms of hyperactivity and impulsivity. The symptoms should be present for at least 6 months and present before the age of 7 years. Symptoms of inattention include difficulty paying attention, making frequent careless mistakes in schoolwork, reluctance to engage in tasks, forgetfulness, distractibility, difficulty organizing activities, inability to listen while others are speaking, and a tendency to lose objects. Symptoms of hyperactivity and impulsivity include talking excessively, difficulty playing quietly, fidgeting, abruptly leaving the classroom seat, difficulty waiting one’s turn, blurting out answers before being called on, and interrupting others during conversations or games. If patients meet criteria for only the inattentive symptoms, a diagnosis of ADHD, predominantly inattentive type is given. This type is more common in girls. If the patient only has symptoms of hyperactivity, then the diagnosis of ADHD, predominantly hyperactive-impulsive type, is given. This type of ADHD is rare. The differential diagnosis of ADHD includes disruptive behavioral disorders, such as conduct disorder and oppositional defiant disorder, mental retardation, bipolar disorder, schizophrenia, anxiety disorder, and certain drugs, such as phenobarbital in the older child.

3. (D) Assuming the patient’s father truly had ADHD, children born to a parent with ADHD have an almost 60% chance of developing symptoms. In addition, concordance for monozygotic twins is high. Having a sibling with ADHD imposes a 30% risk. Given the mechanism of action of the pharmacologic agents used to treat ADHD and recent research, the dopamine receptor and transporter have been implicated in the pathogenesis. However, it is likely that several genes are involved.

4. (C) Some symptoms of hyperactivity/impulsivity or inattention should be present before the age of 7 years.

5. (D) Treatment of ADHD includes nonpharmacologic and pharmacologic approaches. Nonpharmacologic approaches include educational counseling and cognitive-behavioral therapies. Educational counseling may include providing one-on-one tutoring in the classroom, minimizing distractions by rearranging the classroom seating arrangement, and teaching organizational skills. Educational counseling can be provided by a number of individuals, including pediatricians, nurses, social workers, psychologists, and mental health professionals. The counseling can occur on an individual basis or in groups. Cognitive-behavioral therapies employ techniques such as positive and negative reinforcement to modify self-control problems and encourage active participation in learning activities. Parents of a child with ADHD often experience feelings of incompetence or social isolation. Indeed, the difficulties in raising a child with ADHD can lead to problems in the marriage. As a result, parents may benefit from a consultation with a mental health professional or social worker. Some families have benefited from family therapy to assess for family dysfunction and help with behavior management. In addition, support groups are available to further assist parents.

6. (E) Once a decision is made to start a child on medication, follow-up is arranged to assess for patient growth (height and weight), academic progress, cardiovascular side effects, and psychological wellbeing. Studies have shown that stimulants have significant short-term benefits in most children (up to 80%) with ADHD. With dose adjustments and perhaps trials with other stimulant medications, response rates can be nearly 90%. Hence it is important to monitor the child for dose adequacy and academic progress. It may be helpful to have the parents and schoolteachers repeat behavior rating scales to quantitate improvement. Stimulant medications have side effects, most of which are transient and manageable with close monitoring. The more common side effects include anorexia, insomnia, irritability, and headaches. It is important to monitor the patient’s weight and height because stimulants can cause weight loss and reduced height velocity. Exacerbation of tics with concurrent stimulant use is observed in some children. Stimulants may cause slight elevations in heart rate and blood pressure, and, as a result, these parameters should be monitored. Finally, children with ADHD are at risk for developing psychiatric comorbidity. They can have feelings of low self-esteem and depression. In addition, approximately a third of children with ADHD experience an anxiety disorder during the course of their life. Hence it is important to monitor for psychiatric symptoms.

7. (C) If a child continues to have academic difficulties, despite pharmacologic and nonpharmacologic interventions, it is important to perform psychoeducational or neuropsychological testing, if not already done, to evaluate for a learning disability. The association of learning disabilities, especially reading disorders (dyslexia), and ADHD is probably quite common. Some studies have found that up to 90% of children with ADHD may also have a reading disorder. Other studies have not documented as dramatic an association.

8. (C) Pemoline has been associated with chemical hepatitis and, rarely, fulminant liver failure. Although the onset of hepatitis is unpredictable, many clinicians will monitor liver function at least every 6 months following baseline liver function tests before initiating the drug.

9. (C) Learning disorders are seen in approximately 10% of the population. Roughly half of the patients with learning disorders have a reading disorder (dyslexia). The remaining half are due to mathematics disorder, atypical learning disorders, and disorder of written expression. Most children with learning disorders are diagnosed before the second grade when it becomes clear that the child is not keeping up with peers or grades start to fall. Boys are 2-4 times as likely as girls to have a learning disorder.

10. (D) This patient most likely has a nonverbal learning disability (NVLD). Patients with NVLD tend to do well with rote learning. They have simple verbal skills and strengths in nonvisual memory. Weaknesses include problems with motor skills, problem solving, concept formation, and comprehension. Initially, these children tend to do well in math, given the rote nature of beginning lessons. However, as the child with NVLD progresses through school, he or she struggles with nonverbal reasoning and more advanced math concepts. Social difficulty develops as social skills depend on the child’s ability to perform nonverbal processing. Written expression and reading comprehension are often problematic. In mathematics disorder, patients have a hard time performing calculations. At times, patients with NVLD may appear to have a mathematics disorder, but the weaknesses listed often give an indication that the mathematics disability is part of the larger learning disability that is NVLD. Patients with disorder of written expression have a decreased ability to present information in writing compared with verbal expression.

11. (B) This patient has a reading disorder (dyslexia), the most common type of learning disorder. Patients with a reading disorder have a hard time processing sound units and sound-symbol relationships. They often have difficulty with phonologic processing. Although dyslexia has been characterized by frequent letter reversals in the lay literature, this feature is not required to make the diagnosis. Another myth is that dyslexia is primarily a disorder of males. More recent population-based studies did not demonstrate a difference in prevalence rates between males and females.

12. (E) This patient most likely has a reading disorder (dyslexia). In patients with reading disorders, a thorough history and physical examination, including an assessment of reading skills, are sufficient to make the diagnosis. Laboratory evaluations, such as chromosome karyotyping, electroencephalography, and neuroimaging studies, are performed when clinically indicated. Behavior rating scales are helpful adjuncts in the evaluation for ADHD. Although patients with ADHD can have underlying learning disabilities, dyslexia and ADHD are separate conditions. Should a patient with a reading disorder manifest signs and symptoms of ADHD, an evaluation would be warranted.

13. (D) Autism and pervasive developmental disorders (PDDs) represent a spectrum of disorders associated with cognitive and neurobehavioral problems. Patients demonstrate impairments in verbal and nonverbal communication and social interaction. In addition, they can demonstrate repetitive and restricted patterns of behavior. The 5 subgroups listed under the pervasive developmental (autistic spectrum) disorders category in the DSM-IV are autistic disorder, Asperger syndrome, PDD not otherwise specified, childhood disintegrative disorder, and Rett syndrome. Angelman syndrome is not listed as a subtype of the autistic spectrum disorders, although there seems to be substantial overlap between this disorder and autism.

14. (B) This patient probably has autism. Patients with autism often have impairment in social interactions manifested by decreased eye contact, failure to develop peer relationships, lack of awareness of others, and failure to participate in groups. These patients are often described as not being very affectionate. Patients with autism also demonstrate impairment in communication that can be quite variable. Some patients have no spoken language, whereas others have immature forms of language, such as echolalia. There may be a stereotyped or repetitive use of language. Those with adequate speech may be unable to sustain a conversation. Finally, patients with autism typically demonstrate restrictive, repetitive and stereotypic behaviors, such as hand-flapping. They may be fascinated with parts and movements of an object, such as the opening and closing of drawers. Children with autism are usually inflexible in their adherence to certain routines. Onset is before the age of 3 years. Patients with childhood disintegrative disorder have significant regression in 2 or more areas of functioning after at least 24 months of normal early development. It is a relatively rare disorder that usually occurs between 3 and 4 years of age but can occur up to approximately 10 years of age.

15. (E) Depending on the study, approximately 80% of the children with autistic spectrum disorder have an abnormal EEG. The abnormalities can range from slowing of the background activity to overt epileptiform activity. As children with autism approach adulthood, the cumulative prevalence of developing a seizure disorder is approximately 35%. Although patients with autism can experience all types of seizures, the type most frequently encountered seems to be complex partial seizures. Patients with autism can have unusual behaviors, and, as a result, it may be difficult to determine if a behavior is truly epileptiform. Home monitoring video EEG has been useful in assessing if a behavior is associated with epileptiform activity. A family history of seizures and mental retardation are significant risk factors for the development of seizures.

16. (C) Routine testing with neuroimaging, chromosome analysis, serum amino acids, or other metabolic tests are usually not helpful in the absence of historical or physical findings warranting these tests. Likewise, EEG should be performed if the clinical suspicion of seizures is high. If a patient demonstrates regression of language skills, a prolonged EEG capturing sleep should be performed to rule out disorders such as Landau-Kleffner syndrome.

17. (D) This patient most likely has Rett syndrome, a neurodegenerative disorder. This disorder mainly occurs in females who develop symptoms following a period of normal development. The birth history is typically normal. Patients have normal head circumferences. At some point between 6 and 18 months of age, patients start to manifest symptoms characterized by deterioration of behavior, regression of speech and language skills, truncal ataxia, loss of purposeful hand movements, stereotyped hand movements (hand-wringing), autistic behavior, seizures, and acquired microcephaly. The key features in this case are the regression of skills, loss of purposeful hand movements, stereotyped hand movements, and ataxia. Patients with Angelman syndrome can also have developmental delay, seizures, ataxia, and acquired microcephaly. Patients with Angelman syndrome typically do not have the stereotyped hand movements. They have characteristic facial features such as prognathism, a protruding tongue, and wide mouth. Most cases of Angelman syndrome are due to deletions of chromosome 15q11-q13.

18. (B) Patients with Asperger syndrome have sustained impairments in social interaction, especially among their peers. Similar to autism, patients with Asperger syndrome have repetitive, restricted, and stereotypic behaviors. In contrast to patients with autism, language development is typically normal, although they may have pragmatic abnormalities in language. IQ tends to be in the normal or borderline range. Boys tend to be affected more than girls. Some clinicians believe Asperger syndrome is a mild form of autism.


SUGGESTED READING

Dunn DW, Kronenberger WG. Attention-deficit/hyper-activity disorder in children and adolescents. Neurol Clin North Am. 2003;21:933-940.

Hirtz DG, Wagner A, Filipek PA. Autistic spectrum disorders. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice. 4th ed. Philadelphia, PA: Mosby; 2006:905.

Kronenberger WG, Dunn DW. Learning disorders. Neurol Clin North Am. 2003;21:941-952.

Mandelbaum DE. Attention-deficit hyperactivity disorder. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice, 4th ed. Philadelphia, PA: Mosby; 2006:871.

Miller KJ, Castellanos FX. Attention deficit/hyperactivity disorders. Pediatr Rev. 1998;19:373-384.

Tuchman R. Autism. Neurol Clin North Am. 2003;21:915-932.

CASE 138: A 2-YEAR-OLD BOY WITH DEVELOPMENTAL DELAY AND SPASTICITY

A 2-year-old boy presents to your clinic with the chief complaint of developmental delay. His mother states he was born at 34 weeks’ gestation. The pregnancy was complicated by premature rupture of membranes 5 weeks before delivery. His mother was hospitalized and received a 7-day course of ampicillin and 2 doses of betamethasone. At the time of delivery, she developed a fever of 102°F. The baby was delivered by cesarean secondary to fetal tachycardia and arrest of descent. Because the baby was found to have a poor heart rate and respiratory effort, CPR was initiated. His Apgar scores were 1, 2, and 5 at 1, 5, and 10 minutes, respectively. He was admitted to the neonatal intensive care unit (NICU) for management of possible sepsis. A head ultrasound revealed a “hemorrhage” according to his mother.

At 7 months of age, his mother states she became concerned because her son was not able to sit without support. By 15 months of age, he was still not walking. His language development is normal. She presented to her primary pediatrician who referred her to an Early Intervention program. As a result of occupational and physical therapies, he is now able to use a spoon and a sippy cup. He developed the ability to crawl and in fact is now able to cruise around furniture. Although his mother is pleased by his developmental progress, she notes that he still has a tendency to use his left hand more than his right.

On physical examination, he is a very happy and active child. His head circumference is at the 50th percentile. His cranial nerve examination is normal. On motor examination, he is able to reach for a block but clearly favors his left hand. His right thumb is persistently adducted. He is unable to perform a pincer grasp with his right hand. His muscle tone is increased on the right side of his body. His heel cord on the right is tight. His deep tendon reflexes are asymmetric with the right side of his body slightly brisker than the left side. He is able to bear weight on his legs but stands on his tiptoe on the right. Examination of his skin reveals a small café au lait spot on his back.

SELECT THE ONE BEST ANSWER

1. Intraventricular hemorrhages (IVH) are most likely to affect which of the following brain structures in the premature infant?

(A) cortex

(B) middle cerebral artery

(C) germinal matrix

(D) basal ganglia

(E) lenticulostriate arteries

2. You were able to review the patient’s head ultrasound, which demonstrated blood within the ventricular system. The ventricle was not distended. What grade IVH did this patient have based on the head ultrasound?

(A) grade 1

(B) grade 2

(C) grade 3

(D) grade 4

(E) none of the above

3. This child most likely has which of the following diagnoses?

(A) mental retardation

(B) spastic hemiplegic cerebral palsy

(C) ataxic cerebral palsy

(D) spastic diplegic cerebral palsy

(E) mixed cerebral palsy

4. Which of the following are risk factors for the development of cerebral palsy?

(A) low birthweight

(B) hyperbilirubinemia

(C) maternal antenatal methyl mercury ingestion

(D) preterm delivery

(E) all of the above

5. Which of the following are classifications of cerebral palsy?

(A) spastic

(B) choreoathetotic

(C) ballismic

(D) A and C

(E) A, B, and C

6. A 4-year-old boy born to immigrant parents comes to your clinic. He presents with sensorineural hearing loss, supernuclear ophthalmoplegia, enamel hypoplasia, and choreoathetosis. The most likely cause of his symptoms is which of the following?

(A) stroke

(B) congenital infection with CMV

(C) congenital infection with rubella

(D) kernicterus

(E) lissencephaly

7. A preterm infant is most likely to have which form of cerebral palsy?

(A) spastic diplegia

(B) spastic quadriplegia

(C) spastic hemiplegia

(D) choreoathetotic

(E) atonic or hypotonic

8. Which of the following statements regarding the spastic hemiplegic form of cerebral palsy is false?

(A) for unknown reasons, the left hemisphere is more often affected than the right hemisphere

(B) the arm is usually more affected than the leg

(C) facial involvement is typical

(D) provided the child has no other major problems, he or she will most likely walk by 2 years of age

(E) all of the above statements are false

9. Which form of cerebral palsy is most often associated with birth asphyxia?

(A) spastic diplegia

(B) spastic quadriplegia

(C) spastic hemiplegia

(D) choreoathetotic

(E) atonic or hypotonic

10. The patient’s mother asks you what treatment options are available for her son should his spasticity get worse. Which of the following interventions have been used in the treatment of cerebral palsy?

(A) selective dorsal rhizotomy

(B) botulinum toxin injections

(C) physical therapy

(D) baclofen

(E) all of the above

11. A 7-year-old boy presents to your clinic for an evaluation of behavioral problems and new-onset seizures. During the last 3 months, he has received poor grades, especially in writing. His mother states that until recently he was a completely normal child. She is concerned because her estranged sister had a male child with similar symptoms before he died. In the next couple of months, the patient rapidly deteriorates. He now has a spastic paraparesis and visual loss. The study most likely to help make the diagnosis is which of the following?

(A) EEG

(B) galactocerebroside beta-galactosidase levels

(C) MRI of the brain

(D) plasma very long chain fatty acids

(E) C and D

12. An MRI of the brain demonstrates bilateral parietooccipital white matter lesions. The most likely diagnosis in this patient is which of the following?

(A) Alexander disease

(B) X-linked adrenoleukodystrophy

(C) metachromatic leukodystrophy

(D) Canavan disease

(E) Pelizaeus-Merzbacher disease

13. All of the following are considered lipidoses except

(A) Niemann-Pick disease

(B) Krabbe disease

(C) Tay-Sachs disease

(D) X-linked adrenoleukodystrophy

(E) Gaucher disease

14. Which of the following statements is true regarding the genetics of Niemann-Pick disease?

(A) it is transmitted as an autosomal recessive trait

(B) it is transmitted as an autosomal dominant trait

(C) the disorder has an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) the disorder is the result of mutations of mitochondrial DNA

MATCH EACH OF THE FOLLOWING DISEASES WITH ITS CORRESPONDING DEFECT OR DEFICIENCY

15. Gaucher disease

(A) beta-glucocerebrosidase

16. Tay-Sachs disease

(B) methyl-CpG-binding protein (MECP)

17. Metachromatic leukodystrophy

(C) galactocerebroside beta-galactosidase

18. Rett syndrome

(D) arylsulfatase A

19. Krabbe disease

(E) hexosaminidase A

ANSWERS

1. (C) IVHs occur within the germinal matrix, which, along with the germinal ventricular zone, is the site of neuronal and glial precursor cell proliferation. This structure remains relatively intact until approximately 34 weeks’ gestational age, after which it starts to involute, a process completed by term. Preterm infants are most likely to experience IVHs within the first 3-4 days following birth.

2. (B) There are 4 grades of IVH. A grade 1 IVH consists of bleeding within the germinal matrix. In a grade 2 IVH, blood is found within the ventricular system and there is no associated distension. If there is bleeding within the ventricle with concomitant distension, the IVH is considered grade 3. In a grade 4 IVH, there is parenchymal involvement by the hemorrhage.

3. (B) This case is an example of a nonprogressive encephalopathy. This child most likely has the spastic hemiplegic form of cerebral palsy given that the right side of his body is weak and spastic with increased reflexes (signs of upper motor neuron involvement). Cerebral palsy is a nonspecific term that describes a disability of motor function seen in early infancy. The patients usually have problems with muscle tone (typically spasticity), ataxia, or involuntary movements. Although cognitive, behavioral, and sensory problems can be observed in children with cerebral palsy, these features are not necessary to make the diagnosis. Patients with spastic hemiplegia can have difficulties with gross and fine motor coordination. The child is usually unable to perform a pincer grasp with the affected hand, as was the case with this child. Facial involvement is unusual in the spastic hemiplegic form of cerebral palsy. Over time the affected limbs usually undergo growth retardation. This is often best demonstrated by comparing the affected limb with the opposite normal limb. This needs to be monitored closely because a growth discrepancy of the leg may cause problems with ambulation and lead to further orthopedic difficulties. An older study looking at patients with spastic hemiplegia suggested that up to a third might have mental retardation and/or seizures. A wide range of medical conditions may lead to the spastic hemiplegic form of cerebral palsy including infarction and hemorrhage.

4. (E) Low birthweight and preterm delivery are significant risk factors for the development of cerebral palsy. Twin gestation also may predispose to cerebral palsy because the infants are at risk for low birthweight. Marked hyperbilirubinemia was once a common cause of choreoathetotic cerebral palsy in the setting of kernicterus. Finally, ingestion of certain toxins, such as methyl mercury, during pregnancy is associated with the subsequent development of cerebral palsy. Intrauterine and neonatal infections can also lead to the development of cerebral palsy. It should be noted that although birth trauma and asphyxia can result in cerebral palsy, they are not the leading causes.

5. (E) Cerebral palsy is classified according to certain neurologic signs and symptoms. These include the following: spastic, choreoathetotic, dystonic, ballismic, ataxic, and mixed. Based on the limb involvement, the classes can be further subdivided. Hence a patient with spasticity and bilateral lower extremity involvement would have spastic diplegia, whereas an individual with 4-extremity involvement would have spastic quadriplegia.

6. (D) This patient presents with the classical clinical tetrad observed in kernicterus: sensorineural hearing loss, supernuclear ophthalmoplegia, enamel hypoplasia, and choreoathetosis. However, rarely does one observe all 4 symptoms in a single affected patient. Kernicterus is caused by the deposition of bile pigments in various nuclei of the brain (brainstem, cerebellum, and basal ganglia) and spinal cord. Infants with marked hyperbilirubinemia may manifest symptoms as early as the second or third day of life. Sensorineural hearing loss is common and results from degeneration of the cochlear nuclei.

7. (A) Approximately 80% of preterm infants with the spastic form of cerebral palsy have the diplegic form. These patients have periventricular leukomalacia at the germinal matrix. Porencephalic cysts may also be observed.

8. (C) As stated above, facial involvement is rare in patients with spastic hemiplegia. Approximately two-thirds of patients have left hemispheric involvement for unclear reasons. The arm is usually more affected than the leg. Most children with spastic hemiplegia walk by the age of 2 years compared with spastic diplegia where a little more than half walk by 3 years of age. Spastic hemiplegic patients who learn to walk may have a circumductive gait.

9. (B) Birth asphyxia typically leads to the spastic quadriplegic form of cerebral palsy. In this form of cerebral palsy the legs are more involved than the arms. Approximately half of the children with spastic quadriplegia have seizures of the generalized tonic-clonic type.

10. (E) A major goal in the treatment of cerebral palsy is to maximize function so the patient will be able to satisfy daily needs. To that extent, all of the interventions listed in this question have been used in the treatment of cerebral palsy. Because every patient’s needs are different, the treatment is tailored to the individual patient. Physical and occupational therapy programs are almost always employed in the overall treatment plan of cerebral palsy. These therapies help increase range of motion and prevent contractures. In addition, patients are taught normal movement patterns and methods of compensation. Orthotic devices, such as braces, are employed to prevent contractures. Surgical techniques, such as selective dorsal rhizotomy, which involves cutting half of the dorsal roots, can be employed with the goal of decreasing muscle tone in the affected limb. A number of medications have been tried to reduce hypertonicity. These medications include diazepam, baclofen, and dantrolene. Baclofen can be given orally or intrathecally via an infusion pump. These medications are especially useful if the spasticity is generalized. Botulinum toxin injections offer the advantage of isolating specific muscles. The toxin inhibits the release of acetylcholine from the presynaptic terminal. The benefits of the injection typically last around 3 months.

11. (E) Based on the clinical history, this child has a progressive neurologic disorder as evident by the regression of skills and rapid clinical deterioration. Although the EEG would be helpful in confirming the clinical suspicion of seizures and in fact may help classify the seizure type, it is unlikely in this case to yield the diagnosis. An MRI of the brain would be helpful given the rapid development of spastic paraparesis and clinical seizures. The MRI would be able to determine whether the underlying disease process affects primarily gray matter, as would be suspected given the history of seizures, white matter, or both. A primarily white matter process would suggest a leukodystrophy; gray and white matter lesions would be suggestive of a mitochondrial process. Two disorders, globoid cell leukodystrophy (Krabbe disease) and X-linked adrenoleukodystrophy, can present with visual loss. Given the possibility that the mother’s nephew died of the same condition, an X-linked disorder should be suspected. In the early stages, involvement of the parieto-occipital white matter is seen in Krabbe disease, possibly resembling X-linked adrenoleukodystrophy. Because the latter is a peroxisomal disorder, plasma very long chain fatty acids will be increased.

12. (B) Given the clinical history and MRI findings, this patient most likely has X-linked adrenoleukodystrophy (see Figure 138-1). Male children are usually normal until 4-8 years of age when symptoms begin. This disorder is rapidly progressive. In approximately 85% of the cases, the MRI of the brain demonstrates hyperintensity of the parietooccipital white matter. Alexander and Canavan disease are 2 leukodystrophies associated with macrocephaly. Alexander disease has a predilection for the frontal white matter, whereas the MRI findings in Canavan disease show diffuse white matter involvement with prominent involvement of the subcortical U fibers. The MRI of a patient with Pelizaeus-Merzbacher disease demonstrates heterogeneous hyperintense lesions in the white matter with scattered small foci of normal areas, lending the name “tigroid” pattern .

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FIGURE 138-1Adrenal leukodystrophy in a 7-year-old male. Confluent areas of increased signal involving the frontal, occipital, and parietal white matter (thick arrows) and of the anterior and posterior portions of the corpus callosum (long stemmed arrows). (Reproduced, with permission, from Bisese JH. Cranial MRI. New York: McGraw-Hill; 1991.)


13. (D) The term lipidoses refers to a group of inherited disorders in which lipid metabolism is abnormal. Lysosomal enzymes are affected. Niemann-Pick disease (sphingomyelin lipidosis), Krabbe disease (galactosylceramide lipidosis), Tay-Sachs disease (GMgangliosidosis), and Gaucher disease (glucosylceramide lipidosis) are all examples of lipidoses. X-linked adrenoleukodystrophy is an example of a peroxisomal disorder.

14. (A) All types of Niemann-Pick disease (A-D) are transmitted in an autosomal recessive inheritance pattern.

15. (A) Gaucher disease is most common among Ashkenazi Jews and is one of the most frequent lysosomal disorders. The deficient enzyme is betaglucocerebrosidase. Glucosylceramide accumulates in various tissues: brain, spleen, bone marrow, and liver.

16. (E) Children with Tay-Sachs disease present with hyperacusis and a propensity to startle with noise. Patients can have myoclonic seizures and a “cherry red spot” (see Figure 138-2) on fundoscopic examination. The disorder is transmitted in an autosomal recessive fashion, especially among those of Ashkenazi Jewish descent. The deficient enzyme is hexosaminidase A.

17. (D) Approximately 80% of patients with metachromatic leukodystrophy develop symptoms in the first 2 years of life. Symptoms include ataxia, neuropathy, optic atrophy, seizures, and spasticity. Loss of speech, intellect, and coordination are also observed. The enzyme deficiency is arylsulfatase A.

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FIGURE 138-2Retinal cherry-red spot in a patient with Tay-Sachs disease. The whitish ring surrounds the dark macula. (Reproduced, with permission, from Lichtman MA, Beutler E, Kipps TJ, et al. Williams Hematology, 7th ed. New York: McGraw-Hill; 2006: Fig. 73-4.)


18. (B) Methyl-CpG-binding protein 2 (MeCP2) most likely regulates gene expression and chromatin structure by binding to methylated DNA. This gene is mutated in most cases of sporadic Rett syndrome.

19. (C) Krabbe disease or globoid cell leukodystrophy is caused by a deficiency of the lysosomal hydrolase, galactocerebroside beta-galactosidase.


SUGGESTED READING

Crumrine PK. Degenerative disorders of the central nervous system. Pediatr Rev. 2001;22:370-379.

Neul JL, Zoghbi HY. Rett syndrome: a prototypical neurodevelopmental disorder. Neuroscientist. 2004;10:118-128.

Osborn AG. Inherited metabolic, white matter and degenerative diseases of the brain. In: Osborn AG, ed. Diagnostic Neuroradiology. St. Louis, MO: Mosby; 1994:716.

Swaiman KF, Wu Y. Cerebral palsy. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice. 4th ed. Philadelphia, PA: Mosby; 2006:491.

CASE 139: A 17-YEAR-OLD BOY WITH WEAKNESS AND PARESTHESIAS

You are called to the ED to evaluate a 17-year-old young man who presents with upper and lower extremity weakness and back pain. The patient states that he was in his usual state of health until approximately 21/weeks ago when he developed an upper respiratory tract infection. His primary doctor thought the infection was most likely due to a virus. Yesterday the patient states he experienced tingling over the soles of his feet. His gait became unsteady and his legs “felt weak.” On awakening this morning, the patient states the weakness had spread to his arms. His lower extremities are also weaker compared with the previous day, and he cannot walk 5 meters without support. There is no history of trauma. The patient states he has had a hard time urinating.

On physical examination, the patient is an athleticappearing young man in mild distress. He is afebrile with a heart rate of 124 bpm. His blood pressure seems to fluctuate. His mental status and cranial nerve examination are normal. On motor examination, he has normal tone and bulk. He is barely able to lift his legs from the bed and cannot move his toes. He is barely able to move his arms against gravity. His deep tendon reflexes are absent bilaterally in the lower extremities and 1/4+ in the upper extremities. Sensation to vibration and pinprick are slightly diminished in the lower extremities.

SELECT THE ONE BEST ANSWER

1. In evaluating this patient further, which of the following studies could help in confirming the diagnosis?

(A) MRI of the spine

(B) lumbar puncture

(C) nerve conduction velocities

(D) EMG

(E) all of the above

2. An MRI of the spine is performed with and without contrast. The study is unremarkable. CSF examination in this patient is most likely to reveal which of the following?

(A) elevated opening pressure, elevated protein, normal glucose, and a cell count of about 300 lymphocytes/mm3

(B) normal opening pressure, normal protein and glucose, and a cell count of about 10 leukocytes/mm3

(C) normal opening pressure, elevated protein, normal glucose, and a cell count of about 10 mononuclear cells/mm3

(D) elevated opening pressure, elevated protein, decreased glucose, and about 1000 polymorphonuclear cells/mm3

(E) no abnormal CSF findings

3. Clinical features of Guillain-Barré syndrome (GBS) include all of the following except

(A) fever at onset

(B) weakness involving more than 1 limb

(C) areflexia

(D) nearly symmetric physical signs

(E) cranial nerve involvement

4. The Moro reflex should disappear by what age?

(A) 1 month

(B) 2 months

(C) 6 months

(D) 12 months

(E) 15 months

5. The tonic neck reflex should disappear by what age?

(A) 1 month

(B) 6 months

(C) 12 months

(D) 15 months

(E) 18 months

6. The palmar grasp reflex should disappear by what age?

(A) 1-2 months

(B) 3-6 months

(C) 6-9 months

(D) 9-12 months

(E) the palmar reflex disappears at the same time as the plantar grasp reflex

7. On average, by what age will a child mimic housework according to the Denver Developmental Screening Test (Denver II)?

(A) 15 months

(B) 2 years

(C) 3 years

(D) 4 years

(E) 6 years

8. Which of the following therapies are used in the treatment of GBS?

(A) plasmapheresis

(B) IVIG

(C) high-dose corticosteroids

(D) A and B

(E) A, B, and C

9. The differential diagnosis of GBS includes all of the following diagnoses except

(A) porphyria

(B) botulism

(C) HIV infection

(D) hysteria

(E) no exception; all of the above are in the differential

10. Which of the following statements regarding GBS is false?

(A) in children, acquired inflammatory neuropathy (GBS) is the most frequent cause of peripheral nerve disease

(B) for the most part, males and females are equally affected

(C) surgery has been shown to be a cause of GBS

(D) sensory symptoms are more common than weakness

(E) GBS occurs in all parts of the world

11. Which of the following is (are) a complication(s) of plasmapheresis?

(A) hypocalcemia

(B) hemorrhage

(C) transfusion reaction

(D) septicemia

(E) all of the above

12. Which of the following heavy metals is associated with neuropathy, alopecia, and GI symptoms?

(A) lead

(B) mercury

(C) thallium

(D) arsenic

(E) none of the above

13. A 15-year-old girl comes to your clinic with the chief complaint of right facial weakness. The patient is unable to close her right eye. She was healthy until a couple of weeks ago when she developed an upper respiratory tract infection. She is otherwise fine. On physical examination, there is no other sign of weakness. She does not demonstrate fatigue on sustained motor testing. Her deep tendon reflexes are normal. A head CT performed in the ED is reportedly normal. Which of the following is the most likely cause of her symptoms?

(A) Möbius syndrome

(B) GBS

(C) Bell palsy

(D) myasthenia gravis

(E) cerebellar tumor

14. Which of the following cervical nerves are injured in an Erb palsy?

(A) C5, C6

(B) C6, C7

(C) C7, C8

(D) C8, T1

(E) C5, C6, C7

15. Which of the following cervical nerves are injured in a Klumpke paralysis?

(A) C5, C6

(B) C6, C7

(C) C7, C8

(D) C8, T1

(E) C5, C6, C7

16. Which of the following are signs and symptoms of acute lead poisoning?

(A) seizures

(B) cerebral edema

(C) drowsiness

(D) irritability

(E) all of the above

17. Which of the following vitamins can result in a sensory neuropathy if taken in large doses?

(A) vitamin A

(B) pyridoxine

(C) cobalamin

(D) vitamin C

(E) vitamin E

18. Friedreich ataxia is transmitted by which mode of inheritance?

(A) as an autosomal recessive trait

(B) as an autosomal dominant trait

(C) by an X-linked mode of inheritance

(D) the disorder is the result of mutations of mitochondrial DNA

(E) not much is known about the genetics of Friedreich ataxia

ANSWERS

1. (E) This patient most likely has GBS, the diagnosis of which can be made by the history and physical examination. However, a number of confirmatory studies can be performed to support the diagnosis. These include MRI of the spine, lumbar puncture, and electrophysiologic studies, such as nerve conduction velocities and EMG. Enhancement of the cauda equina and lumbar roots following contrast administration is sometimes observed in GBS, indicating that an inflammatory process is indeed involved. An additional reason to perform an MRI of the spine with and without contrast is to exclude or confirm a transverse myelitis, which is in the differential diagnosis.

2. (C) The characteristic CSF finding in GBS is elevation of protein without significant pleocytosis (albuminocytologic dissociation). Approximately 10% of patients have 10-50 cells/mm3. Most of these cells are lymphocytes. A cell count greater than 50 cells/mmshould cause consideration of an alternative diagnosis. The protein level may be normal in the first few days but subsequently increases and peaks in 4-6 weeks. Opening pressure and glucose are usually normal.

3. (B) GBS or acute inflammatory demyelinating polyradiculoneuropathy is a disorder in which patients experience progressive motor weakness, areflexia, paresthesias, and elevated CSF protein typically following an upper respiratory tract infection. In 1990, Asbury and Cornblath proposed a set of diagnostic criteria. The criteria are:

Features required for diagnosis:

Progressive weakness of both arms and legs or more than 1 limb

Areflexia

Clinical features supportive of diagnosis:

Progression up to 4 weeks

Relative symmetry of signs

Cranial nerve involvement

Autonomic dysfunction

Recovery usually beginning 2-4 weeks after progression ceases

Absence of fever at onset

Laboratory features supportive of diagnosis:

Elevated CSF protein with less than 10 cells/μL

Electrodiagnostic features of conduction block or nerve conduction slowing

Autonomic dysfunction consists of sinus tachycardia, SVT, bradycardia, fluctuations in blood pressure, sphincter dysfunction, anhidrosis, and postural hypotension. Patients can experience respiratory difficulty requiring mechanical ventilation. Weakness usually starts in the lower extremities and ascends in a distal to proximal fashion. Cranial nerves can be affected with facial diplegia as the most common presentation. Paresthesias are a frequent early symptom and involve mild sensory loss and pain. Low back pain and myalgias are common. The pathogenesis of GBS involves immune-mediated segmental demyelination of peripheral nerves. By definition, the progression of symptoms ends by 4 weeks into the illness. If the progression lasts 4-10 weeks, then the term subacute inflammatory demyelinating polyradiculoneuropathy is used. If the progression is chronic or the patient experiences multiple relapses, the condition is termed chronic inflammatory demyelinating polyradiculoneuropathy.

4. (C) The Moro reflex can be present in children up to 5-6 months of age.

5. (B) The tonic neck reflex reaches a peak at approximately 2 months of age and should be absent by 6 months of age.

6. (B) The palmar grasp reflex disappears by 3-6 months of age. At this point, voluntary grasping should be evident. The plantar grasp reflex disappears much later by 15 months of age.

7. (A) Approximately 60% of children can mimic housework by 15 months of age with 100% of the normal children accomplishing this milestone by 17-18 months of age.

8. (D) Plasmapheresis and IVIG appear to be equally effective in the treatment of GBS or acute inflammatory demyelinating polyneuropathy. Corticosteroids are not effective. But they have been shown to be effective in the treatment of chronic inflammatory demyelinating polyneuropathy.

9. (E) The differential diagnosis of GBS is broad. The differential includes porphyria, transverse myelitis, acute myasthenia gravis, diphtheria, botulism, tick paralysis, hexane inhalation, Lyme disease, HIV infection, poliomyelitis, and hysteria. A good history and physical examination can help exclude some of these possibilities.

10. (D) GBS is regarded as a predominantly motor neuropathy with occasional sensory symptoms. Approximately three-fourths of the patients present with weakness. Pain and paresthesias are observed but to a lesser degree than the motor symptoms.

11. (E) Although plasmapheresis appears to be safe in children, there are a number of potential complications, including hypocalcemia, hemorrhage, hypotension, transfusion reactions, arrhythmias, and infection.

12. (C) Ingestion of certain heavy metals can result in a neurotoxic neuropathy. The heavy metals include lead, mercury, and thallium. Certain rat poisons and insecticides contain thallium. Ingestion may cause a sensory and motor peripheral neuropathy, nausea, vomiting, abdominal pain, and alopecia. Alopecia typically occurs 2-3 weeks after intoxication.

13. (C) This patient most likely has a Bell palsy or facial nerve paralysis. Bell palsy often follows an upper respiratory tract infection. Patients are unable to close the eyelid. Facial weakness develops over several hours to a few days. Lacrimation and taste may also be affected. Males and females are equally affected. Although approximately two-thirds of children recover fully without therapy, steroids have been used in the treatment of Bell palsy. Supportive eye care, including placement of an eye patch for protection and eye drops to prevent corneal dryness, is usually needed. The prognosis for recovery is good.

14. (A) Erb palsy is the most common brachial plexus injury in newborns. Damage to the upper trunk of the brachial plexus (C5 and C6 nerves) results in weakness of the upper arm. The patient presents with the humerus internally rotated and adducted. The elbow is extended and the wrist flexed.

15. (D) Klumpke palsy is a rare cause of brachial plexus injury in newborns. It results from damage to the lower brachial plexus (C8 and T1 nerves). Patients have weakness of the forearm extensors, wrist flexors, finger flexors, and intrinsic hand muscles. Horner syndrome can be present.

16. (E) Acute lead poisoning is now rare because the use of lead-based paints were banned in the United States in 1978. Acute lead encephalopathy initially presents with irritability and drowsiness followed by seizures and signs of increased intracranial pressure. Severe cerebral edema develops and can lead to irreversible neurologic injury.

17. (B) Large doses of pyridoxine can result in a sensory neuropathy with intact muscle strength. Paresthesias, autonomic dysfunction, diffuse sensory loss, and sensory ataxia can be observed.

18. (A) Friedreich ataxia is transmitted as an autosomal recessive trait. It is also one of the triplet repeat disorders. Patients with Friedreich ataxia develop a slowly progressive ataxia, cardiomyopathy, and sensory neuropathy. Deformities such as pes cavus and hammer toes are also observed (see Figure 139-1).

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FIGURE 139-1Cavus foot: clinical appearance and radiographic appearance. (Reproduced, with permission, from Skinner HB. Current Diagnosis & Treatment in Orthopedics, 4th ed. New York: McGraw-Hill; 2006: Fig. 11-19.)



SUGGESTED READING

Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol. 1990;27:S21-S24.

Sladky JT, Ashwal S. Inflammatory neuropathies. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1919.

Smith SA, Ouvrier R. Peripheral neuropathies. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice. 4th ed. Philadelphia, PA: Mosby; 2006:1887.

Swaiman KF. Neurologic examination after the newborn period until 2 years of age. In: Swaiman KF, Ashwal S, Ferriero DM, eds. Pediatric NeurologyPrinciples Practice., 4th ed. Philadelphia, PA: Mosby; 2006:37.