Harrison's Neurology in Clinical Medicine, 3rd Edition

REVIEW AND SELF-ASSESSMENTa

Charles Wiener image Cynthia D. Brown image Anna R. Hemnes

QUESTIONS


DIRECTIONS: Choose the one best response to each question.

1. During a neurologic examination, you ask a patient to stand with both arms fully extended and parallel to the ground with his eyes closed for 10 seconds. What is the name of this test?

A. Babinski sign

B. Dysdiadochokinesis

C. Lhermitte symptom

D. Pronator drift

E. Romberg sign

2. This sign is considered positive if there is flexion at the elbows or forearms, or if there is pronation of the forearms. A positive test is a sign of:

A. Abnormal sensation

B. Early dementia

C. Localized brainstem disease

D. Potential weakness

E. Underlying cerebellar dysfunction

3. A 55-year-old woman with known metastatic breast cancer presents to the emergency department complaining of new-onset weakness and numbness. The symptoms involve both arms and legs. She also has developed urinary incontinence over the past 24 hours. On physical examination, strength is 3/5 in the lower extremities and 4/5 in the upper extremities. Anal sphincter tone is decreased. Babinski sign is positive. Sensation is decreased in the extremities, but not in the face. Cranial nerves are symmetric and intact, and mental status is normal. Based on this information, what is the most likely site of the lesion causing the patient’s symptoms?

A. Brainstem

B. Cerebrum

C. Cervical spinal cord

D. Lumbar spinal cord

E. Neuromuscular junction

4. A 54-year-old woman presents to the emergency department complaining of the abrupt onset of what she describes as the worst headache of her life. You are concerned about the possibility of subarachnoid hemorrhage. What is the most appropriate initial test for diagnosis?

A. Cerebral angiography

B. CT of the head with IV contrast

C. CT of the head without IV contrast

D. Lumbar puncture

E. Transcranial Doppler ultrasound

5. A 74-year-old woman has a recent diagnosis of small cell lung cancer. She is now complaining of headaches, and her family has noticed confusion as well. Metastatic disease to the brain is suspected. A mass lesion on magnetic resonance imaging (MRI) is demonstrated in the right parietal lobe. Which MRI technique would best identify the extent of the edema surrounding the lesion?

A. MR angiography

B. FLAIR

C. T1-weighted

D. T2-weighted

E. B and D

6. Which of the following is a possible complication of administration of gadolinium to a patient with chronic kidney disease?

A. Acute renal failure

B. Hyperthyroidism

C. Hypocalcemia

D. Lactic acidosis

E. Nephrogenic systemic sclerosis

7. In a patient with coma, an EEG showing triphasic waves is most suggestive of which of the following clinical disorders?

A. Brain abscess

B. Herpes simplex encephalitis

C. Locked-in syndrome

D. Metabolic encephalopathy

E. Nonconvulsive status epilepticus

8. A 25-year-old woman becomes lightheaded and experiences a syncopal event while having her blood drawn during a cholesterol screening. She has no medical history and takes no medications. She experiences a brief loss of consciousness for about 20 seconds. She has no seizure-like activity and immediately returns to her usual level of functioning. She is diagnosed with vasovagal syncope, and no follow-up testing is recommended. Which of the following statements regarding neurally mediated syncope is TRUE?

A. Neurally mediated syncope occurs when there are abnormalities of the autonomic nervous system.

B. Proximal and distal myoclonus do not occur during neurally mediated syncope and should increase the likelihood of a seizure.

C. The final pathway of neurally mediated syncope results in a surge of the sympathetic nervous system with inhibition of the parasympathetic nervous system.

D. The primary therapy for neurally mediated syncope is reassurance, avoidance of triggers, and plasma volume expansion.

E. The usual finding with cardiovascular monitoring is hypotension and tachycardia.

9. A 76-year-old woman is brought to the emergency department after a syncopal event that occurred while she was singing in her church choir. She has a history of hypertension, diabetes mellitus, and chronic kidney disease (stage III). She does recall at least two prior episodes of syncope similar to this one. Her medications include insulin glargine 40 units daily, lispro insulin sliding scale, lisinopril 20 mg daily, and hydrochlorothiazide 25 mg daily. By the time she arrived in the emergency department, she reports feeling back to her usual self. She does recall feeling somewhat lightheaded before the syncopal events but does not recall the event itself. Witnesses report some jerking of her upper extremities. She regained full consciousness in less than 2 minutes. Her current vital signs include blood pressure of 110/62 mmHg, heart rate of 84 beats/min, respiratory rate of 16 breaths/min, and oxygen saturation of 95% on room air. She is afebrile. Her physical examination is unremarkable and includes a normal neurologic examination. Which of the following would be least helpful in determining the etiology of the patient’s syncope?

A. CT scan of the head

B. Electrocardiogram

C. Fingerstick glucose measurement

D. Orthostatic blood pressure measurement

E. Tilt table testing

10. A 48-year-old man presents to the emergency department complaining of dizziness. He describes it as a sensation that the room is spinning. All of the following would be consistent with a central cause of vertigo EXCEPT:

A. Absence of tinnitus

B. Gaze-evoked nystagmus

C. Hiccups

D. Inhibition of nystagmus by visual fixation

E. Purely vertical nystagmus

11. A 62-year-old woman presents complaining of severe dizziness. She notes it especially when she turns over in bed and immediately upon standing. Her initial physical examination findings are normal. Upon further testing, you ask the patient to sit with her head turned 45 degrees to the right. You lower the patient to the supine position and extend the head backward 20 degrees. This maneuver immediately reproduces the patient’s symptoms, and you note torsional nystagmus. What is the most appropriate next step in evaluation and treatment of this patient?

A. MRI of the brainstem

B. Methylprednisolone taper beginning at 100 mg daily

C. Repositioning (Epley) maneuvers

D. Rizatriptan 10 mg orally once

E. Valacyclovir 1000 mg three times daily for 7 days

12. A 42-year-old man presents complaining of progressive weakness over a period of several months. He reports tripping over his toes while walking and has dropped a cup of hot coffee on one occasion because he felt too weak to continue to hold it. A disorder affecting lower motor neurons is suspected. All of the following findings would be found in an individual with a disease primarily affecting lower motor neurons EXCEPT:

A. Decreased muscle tone

B. Distal greater than proximal weakness

C. Fasciculations

D. Hyperactive tendon reflexes

E. Severe muscle atrophy

13. A 78-year-old man is seen in clinic because of recent falls. He reports gait difficulties with a sensation of being off balance at times. One recent fall caused a shoulder injury requiring surgery to repair a torn rotation cuff. In epidemiologic case series, what is the most common cause of gait disorders?

A. Cerebellar degeneration

B. Cerebrovascular disease with multiple infarcts

C. Cervical myelopathy

D. Parkinson’s disease

E. Sensory deficits

14. A 65-year-old man presents complaining of frequent falls and gait abnormalities. He first noticed the difficulty about 6 months ago. He has a history of hypertension and hypothyroidism and hyperlipidemia. His current medications include amlodipine 10 mg daily, simvastatin 20 mg daily, and levothyroxine 75 μg daily. On neurologic examination, you observe his gait to be wide based with short, shuffling steps. He has difficulty rising from his chair and initiating his gait. Upon turning, he takes multiple steps and appears unsteady. However, cerebellar testing results are normal, including heel-to-shin and Romberg testing. He has no evidence of sensory deficits in the lower extremities, and strength is 5/5 throughout all tested muscle groups. He shows no evidence of muscle spasticity on passive movement. His neurologic examination is consistent with which of the following causes?

A. Alcoholic cerebellar degeneration

B. Communicating hydrocephalus

C. Neurosyphilis

D. Multiple system atrophy

E. Lumbar myelopathy

15. A 74-year-old woman is admitted to the medical intensive care unit with confusion and sepsis from a urinary origin. Her initial blood pressure was 70/40 mmHg with a heart rate of 130 beats/min. She is volume resuscitated but requires dopamine to maintain an adequate blood pressure. Her mental status improved initially, but now she is agitated and pulling at her IV catheters. She is screaming that she is trapped, and she is not oriented to place or year. All of the following statements regarding the patient’s condition are true EXCEPT:

A. An episode of delirium is associated with an in-hospital mortality rate of 25% to 33%.

B. A patient who has an episode of delirium in the hospital is more likely to be discharged to a nursing home.

C. Delirium is associated with an increased risk of all-cause mortality for at least 1 year after hospital discharge.

D. Delirium is typically short-lived and does not persist longer than several days.

E. Individuals who experience delirium have longer lengths of stay in the hospital.

16. You are covering the night shift at a local hospital and are called acutely to the bedside of a 62-year-old man to evaluate a change in his mental status. He was admitted 36 hours previously for treatment of community-acquired pneumonia. He received treatment with levofloxacin 500 mg daily and required oxygen 2 L/min. He has a medical history of tobacco abuse, diabetes mellitus, and hypertension. He reports alcohol intake of 2–4 beers daily. His vital signs at 10 pm were blood pressure of 138/85 mmHg, heart rate of 92 beats/min, respiratory rate of 20 breaths/min, temperature of 37.4°C (99.3°F), and SaO2of 92% on oxygen 2 L/min. Currently, the patient is agitated and pacing his room. He is reporting that he needs to leave the “meeting” immediately and go home. He states that if he does not do this, someone is going to take his house and car away. He has removed his IV and oxygen tubing from his nose. His last vital signs taken 30 minutes previously were blood pressure of 156/92 mmHg, heart rate of 118 beats/min, respiratory rate of 26 breaths/min, temperature of 38.3°C (100.9°F), and oxygen saturation of 87% on room air. He is noted to be somewhat tremulous and diaphoretic. All of the following should be considered as part of the patient’s diagnostic work-up EXCEPT:

A. Arterial blood gas testing

B. Brain imaging with MRI or head CT

C. Fingerstick glucose testing

D. More thorough review of the patient’s alcohol intake with his wife

E. Review of the recent medications received by the patient

17. Delirium, an acute confusional state, is a common disorder that remains a major cause of morbidity and mortality in the United States. Which of the following patients is at the highest risk for developing delirium?

A. A 36-year-old man admitted to the medical ward with a deep venous thrombosis

B. A 55-year-old man postoperative day 2 from a total colectomy

C. A 68-year-old woman admitted to the intensive care unit (ICU) with esophageal rupture

D. A 74-year-old woman in the preoperative clinic before hip surgery

E. An 84-year-old man living in an assisted living facility

18. A 28-year-old woman has severe head trauma after a motor vehicle accident. One year after the accident, she is noted to have spontaneous eye opening and is able to track an object visually at times. She does not speak or follow any commands. She breathes independently but is fed through a gastrostomy tube. She can move all extremities spontaneously but without purposeful movement. What term best describes this patient’s condition?

A. Coma

B. Locked-in

C. Minimally conscious state

D. Persistent vegetative state

E. Vegetative state

19. A 52-year-old man is evaluated after a large subarachnoid hemorrhage (SAH) from a ruptured cerebral aneurysm. There is concern that the patient has brain death. What test is most commonly used to diagnose brain death in this situation?

A. Apnea testing

B. Cerebral angiography

C. Demonstration of absent cranial nerve reflexes

D. Demonstration of fixed and dilated pupils

E. Performance of transcranial Doppler ultrasonography

20. Which of the following neurologic phenomena is classically associated with herniation of the brain through the foramen magnum?

A. Third-nerve compression and ipsilateral papillary dilation

B. Catatonia

C. “Locked-in” state

D. Miotic pupils

E. Respiratory arrest

21. Which of the following is the most common finding in aphasic patients?

A. Alexia

B. Anomia

C. Comprehension

D. Fluency

E. Repetition

22. A 65-year-old man experiences an ischemic cerebrovascular accident affecting the territory of the right anterior cerebral artery. After the stroke, an assessment reveals the findings shown in Figure 22. What diagnosis does this figure suggest?

A. Construction apraxia

B. Hemianopia

C. Hemineglect

D. Object agnosia

E. Simultanagnosia

image

FIGURE 22

23. A 42-year-old man is evaluated for excessive sleepiness that is interfering with his ability to work. He works at a glass factory that requires him to work rotating shifts. He typically cycles across day (7 am–3 pm), evening (3 pm–11 pm), and night (11 pm–7 am) shifts over the course of 4 weeks. He notes the problem to be most severe when he is on the night shift. Twice he has fallen asleep on the job. Although no accidents have occurred, he has been threatened with loss of his job if he falls asleep again. His preferred sleep schedule is 10 pm until 6 am, but even when he is working day shifts, he typically only sleeps from about 10:30 pm until 5:30 am. However, he feels fully functional at work on day and evening shifts. After his night shifts, he states that he finds it difficult to sleep when he first gets home, frequently not falling asleep until 10 am or later. He is up by about 3 pm when his children arrive home from school. He drinks about 2 cups of coffee daily but tries to avoid drinking more than this. He does not snore and has a body mass index of 21.3 kg/m2. All of the following are reasonable approaches to treatment in this man EXCEPT:

A. Avoidance of bright light in the morning after his shifts

B. Exercise in the early evening before going to work

C. Melatonin 3 mg taken at bedtime on the morning after a night shift

D. Modafinil 200 mg taken 30–60 minutes before starting a shift

E. Strategic napping of no more than 20 minutes during breaks at work

24. A 45-year-old woman presents for evaluation of abnormal sensations in her legs that keep her from sleeping at night. She first notices the symptoms around 8 pm when she is sitting quietly watching television. She describes the symptoms as “ants crawling in my veins.” Although the symptoms are not painful, they are very uncomfortable and worsen when she lies down at night. They interfere with her ability to fall asleep about four times weekly. If she gets out of bed to walk or rubs her legs, the symptoms disappear almost immediately only to recur as soon as she is still. She also sometimes takes a very hot bath to alleviate the symptoms. During sleep, her husband complains that she kicks him throughout the night. She has no history of neurologic or renal disease. She currently is perimenopausal and has been experiencing very heavy and prolonged menstrual cycles over the past several months. The physical examination findings, including thorough neurologic examination, are normal. Her hemoglobin is 9.8 g/dL and hematocrit is 30.1%. The mean corpuscular volume is 68 fL. Serum ferritin is 12 ng/mL. Which is the most appropriate initial therapy for this patient?

A. Carbidopa/levodopa

B. Hormone replacement therapy

C. Iron supplementation

D. Oxycodone

E. Pramipexole

25. A 20-year-old man presents for evaluation of excessive daytime somnolence. He is finding it increasingly difficult to stay awake during his classes. Recently, his grades have fallen because whenever he tries to read, he finds himself drifting off. He finds that his alertness is best after exercising or brief naps of 10–30 minutes. Because of this, he states that he takes 5 or 10 “catnaps” daily. The sleepiness persists despite averaging 9 hours of sleep nightly. In addition to excessive somnolence, he reports occasional hallucinations that occur as he is falling asleep. He describes these occurrences as a voice calling his name as he drifts off. Perhaps once weekly, he awakens from sleep but is unable to move for a period of about 30 seconds. He has never had apparent loss of consciousness but states that whenever he is laughing, he feels heaviness in his neck and arms. Once he had to lean against a wall to keep from falling down. He undergoes an overnight sleep study and multiple sleep latency test. There is no sleep apnea. His mean sleep latency on five naps is 2.3 minutes. In three of the five naps, rapid eye movement sleep is present. Which of the following findings of this patient is most specific for the diagnosis of narcolepsy?

A. Cataplexy

B. Excessive daytime somnolence

C. Hypnagogic hallucinations

D. Rapid eye movement sleep in more than two naps on a multiple sleep latency test

E. Sleep paralysis

26. Which of the following is the most common sleep disorder in the U.S. population?

A. Delayed sleep phase syndrome

B. Insomnia

C. Obstructive sleep apnea

D. Narcolepsy

E. Restless legs syndrome

27. In which stage of sleep are the parasomnias somnambulism and night terrors most likely to occur?

A. Stage 1

B. Stage 2

C. Slow-wave sleep

D. Rapid eye movement sleep

28. A 44-year-old man is seen in the emergency department after a motor vehicle accident. The patient says, “I never saw that car coming from the right side.” On physical examination, his pupils are equal and reactive to light. His visual acuity is normal; however, there are visual field defects in both eyes laterally (bitemporal hemianopia). Which of the following is most likely to be found on further evaluation?

A. Retinal detachment

B. Occipital lobe glioma

C. Optic nerve injury

D. Parietal lobe infarction

E. Pituitary adenoma

29. A 42-year-old construction worker complains of waking up with a red, painful left eye. She often works without goggles at her construction site. Her history is notable for hypertension, inflammatory bowel disease, diabetes, and prior IV drug use. Her only current medication is lisinopril. On examination, the left eye is diffusely red and sensitive to light. The eyelids are normal. In dim light, visual acuity is normal in both eyes. All of the following diagnoses will explain her findings EXCEPT:

A. Acute angle-closure glaucoma

B. Anterior uveitis

C. Corneal abrasion

D. Posterior uveitis

E. Transient ischemic attack

30. A 75-year-old triathlete complains of gradually worsening vision over the past year. It seems to be involving near and far vision. The patient has never required corrective lenses and has no significant medical history other than diet-controlled hypertension. He takes no regular medications. Physical examination is normal except for bilateral visual acuity of 20/100. There are no focal visual field defects and no redness of the eyes or eyelids. Which of the following is the most likely diagnosis?

A. Age-related macular degeneration

B. Blepharitis

C. Diabetic retinopathy

D. Episcleritis

E. Retinal detachment

31. All of the following statements regarding olfaction are true EXCEPT:

A. Decrements in olfaction may lead to nutritional deficiency.

B. More than 40% of patients with traumatic anosmia will regain normal function over time.

C. Significant decrements in olfaction are present in more than 50% of the population 80 years and older.

D. The most common identifiable cause of long-lasting or permanent loss of olfaction in outpatients is severe respiratory infection.

E. Women identify odorants better than men at all ages.

32. A 64-year-old man is evaluated for hearing loss that he thinks is worse in his left ear. His wife and children have told him for years that he does not listen to them. Recently, he has failed to hear the chime of the alarm on his digital watch, and he admits to focusing on the lips of individuals speaking to him because he sometimes has difficulties in word recognition. In addition, he reports a continuous buzzing that is louder in his left ear. He denies any sensation of vertigo, headaches, or balance difficulties. He has worked in a factory for many years that makes parts for airplanes, and the machinery that he works with sits to his left primarily. He has no family history of deafness, although his father had hearing loss as he aged. He has a medical history of hypertension, hyperlipidemia, and coronary artery disease. You suspect sensorineural hearing loss related to exposure to the intense noise in the factory for many decades. Which of the following findings would you expect on physical examination?

A. A deep tympanic retraction pocket seen above the pars flaccida on the tympanic membrane.

B. Cerumen impaction in the external auditory canal.

C. Hearing loss that is greater at lower frequencies on pure tone audiometry.

D. Increased intensity of sound when a tuning fork is placed on the mastoid process when compared with placement near the auditory canal.

E. Increased intensity of sound in the right ear when a tuning fork is placed in the midline of the forehead.

33. All of the following neurologic conditions have a mechanistic association with abnormalities of ion channel function EXCEPT:

A. Epilepsy

B. Lambert-Eaton syndrome

C. Migraine

D. Parkinson’s disease

E. Spinocerebellar ataxia

34. All of the following neurologic diseases are matched correctly with the neurotransmitter system that is dysfunctional EXCEPT:

A. Lambert-Eaton syndrome: acetylcholine

B. Myasthenia gravis: acetylcholine

C. Orthostatic tachycardia syndrome: serotonin

D. Parkinson’s disease: dopamine

E. Stiff-person syndrome: GABA

35. An 18-year-old man seeks evaluation at his university health center for increasing episodes of sudden-onset smelling of burning kerosene. These episodes had occurred every few months during high school and he never told anyone. However, since starting college, he notes an increasing frequency, often when sleep deprived. The episodes typically start without warning and he’ll smell a distinct kerosene smell no matter the environment. The episodes last about 3–5 minutes and stop spontaneously. He has never lost consciousness. During the episodes, he can communicate with friends. An EEG during an episode shows abnormal discharges distinctly localized to an area of the frontal lobe. Which of the following is the most accurate classification of his seizure disorder?

A. Focal seizures with dyscognitive features

B. Focal seizures without dyscognitive features

C. Generalized seizure

D. Myoclonic seizures

E. Typical absence seizure

36. On the neurologic consultation service, you are asked to evaluate a patient with mesial temporal lobe epilepsy syndrome. The patient has a history of intractable focal seizures that rarely generalize. Her seizures often begin with an aura and commonly manifest as behavioral arrests, complex automatisms, and unilateral posturing. MRI findings include small temporal lobes and a small hippocampus with increased signal on T2-weighted sequences. Which of these additional historic factors is also likely to be present in this patient?

A. History of febrile seizures

B. Hypothyroidism

C. Neurofibromas

D. Recurring genital ulcers

E. Type 2 diabetes mellitus

37. You have just admitted a young man with a prior history of seizure disorder who was witnessed to have a seizure. His family’s description suggests a focal seizure involving the left hand that spread to involve the entire arm. He did not lose consciousness. He was brought in 2 hours after symptom onset and is currently awake, alert, and oriented. He has not had any further seizures but has been unable to move his left hand since his seizure. His electrolytes and complete blood count are within normal limits. A noncontrast CT scan of his head is unremarkable. On examination, sensation is intact in the affected limb, but his strength is 0 out of 5 in the musculature of the left hand. What is the best course of action at this time?

A. Cerebral angiogram

B. Lumbar puncture

C. Magnetic resonance angiogram

D. Psychiatric evaluation

E. Reassess in a few hours

38. A 37-year-old man is witnessed by his family to have a generalized tonic-clonic seizure at a party. He does not have a known seizure disorder. There is no history of head trauma, stroke, or tumor. The patient is unemployed, married, and takes no medication. Physical examination shows no skin abnormalities and no stigmata of chronic liver or renal disease. The patient is postictal. His neck is difficult to maneuver due to stiffness. His white blood cell count is 19,000/μL, hematocrit 36%, and platelets 200,000/μL. Glucose is 102 mg/dL, sodium 136 meq/dL, calcium 9.5 mg/dL, magnesium 2.2 mg/dL, SGOT 18 U/L, blood urea nitrogen 7 mg/dL, and creatinine 0.8 mg/dL. Urine toxicology screen is positive for cocaine metabolites. Which next step is most appropriate in this patient’s management?

A. Electroencephalogram (EEG)

B. IV loading with antiepileptic medication

C. Lumbar puncture

D. Magnetic resonance imaging

E. Substance abuse counseling

39. All of the following statements regarding epilepsy are true EXCEPT:

A. The incidence of suicide is higher in epileptic patients than it is in the general population.

B. Mortality is no different in patients with epilepsy than it is in age-matched controls.

C. A majority of patients with epilepsy that is completely controlled with medication eventually will be able to discontinue therapy and remain seizure-free.

D. Surgery for mesial temporal lobe epilepsy (MTLE) decreases the number of seizures in over 70% of patients.

E. Tricyclic antidepressants lower the seizure threshold and may precipitate seizures.

40. A 20-year-old woman is brought to the emergency department after a witnessed generalized tonic-clonic seizure. She has no identifying information, and her past medical history is unknown. What is the most likely cause of her seizure?

A. Amyloid angiopathy

B. Fever

C. Genetic disorder

D. Illicit drug use

E. Uremia

41. A 36-year-old man is brought to the emergency department because of a seizure. His family reports he has a history of seizure disorder but stopped his medications a month ago due to financial issues. He had a brief seizure at home that stopped within a few minutes. However, 15 minutes later he began seizing again and the tonic-clonic activity has persisted for 30 minutes. On physical examination he is afebrile, hypertensive, and actively seizing. All of the following are potential therapies for his condition EXCEPT:

A. Carbamazepine

B. Fosphenytoin

C. Lorazepam

D. Phenobarbital

E. Valproate

42. The most common cause of a cerebral embolism is:

A. Atrial fibrillation

B. Cardiac prosthetic valves

C. Dilated cardiomyopathy

D. Endocarditis

E. Rheumatic heart disease

43. A 54-year-old male is referred to your clinic for evaluation of atrial fibrillation. He first noted the irregular heartbeat 2 weeks ago and presented to his primary care physician. He denies chest pain, shortness of breath, nausea, or gastrointestinal symptoms. Past medical history is unremarkable. There is no history of hypertension, diabetes, or tobacco use. His medications include metoprolol. The examination is notable for a blood pressure of 126/74 mmHg and a pulse of 64 beats/min. The jugular venous pressure is not elevated. His heart is irregularly irregular, with normal S1 and S2. The lungs are clear, and there is no peripheral edema. An echocardiogram shows a left atrial size of 3.6 cm. Left ventricular ejection fraction is 60%. There are no valvular or structural abnormalities. Which of the following statements regarding his atrial fibrillation and stroke risk is true?

A. He requires no antiplatelet therapy or anticoagulation because the risk of embolism is low.

B. Lifetime vitamin K antagonist therapy is indicated for atrial fibrillation in this situation to reduce the risk of stroke.

C. He should be admitted to the hospital for IV heparin and undergo electrical cardioversion; afterward there is no need for anticoagulation.

D. His risk of an embolic stroke is less than 1%, and he should take a daily aspirin.

E. He should be started on SC low-molecular-weight heparin and transitioned to warfarin.

44. All the following have been shown to reduce the risk of atherothrombotic stroke in primary or secondary prevention EXCEPT:

A. Aspirin

B. Blood pressure control

C. Clopidogrel

D. Statin therapy

E. Warfarin

45. A 57-year-old man is brought to the emergency department after falling while playing tennis and developing garbled speech. He has a past history of hypertension and hypercholesterolemia. His medications include atorvastatin and enalapril. On physical examination, his blood pressure is 210/115 mmHg with heart rate 105 beats/min, respirations 28 breaths/min, temperature 37°C (98.6°F), and oxygen saturation 94% on room air. He is alert but aphasic with upper and lower left extremity hemiparesis. He is able to move his right side normally. Based on the results of immediate imaging, all of the following are potential therapeutic considerations for his condition EXCEPT:

A. Anticoagulation

B. Blood pressure lowering

C. Hypothermia protocol

D. Intracerebral stent placement

E. IV thrombolysis

46. A 72-year-old right-handed male with a history of atrial fibrillation and chronic alcoholism is evaluated for dementia. His son gives a history of a stepwise decline in the patient’s function over the last 5 years with the accumulation of mild focal neurologic deficits. On examination he is found to have a pseudobulbar affect, mildly increased muscle tone, and brisk deep-tendon reflexes in the right upper extremity and an extensor plantar response on the left. The history and examination are most consistent with which of the following?

A. Alzheimer’s disease

B. Binswanger’s disease

C. Creutzfeldt-Jakob disease

D. Multi-infarct dementia

E. Vitamin B12 deficiency

47. A 49-year-old woman presents for a second opinion regarding symptoms of tremors, difficulty with ambulation, and periodic flushing. Her symptoms originally began approximately 3 years ago. At that time, she was hospitalized for a syncopal episode, after which she was told to increase her salt intake. Since then, she has had progressive motor difficulties including bilateral tremors and a stiff, slow gait. She also has had several more episodes of syncope. She states that she knows when these syncopal events will occur because she feels faint and weak. She has never had an injury from syncope. A final recent symptom has been periodic flushing and sweating. A neurologist previously diagnosed her with Parkinson’s disease and prescribed therapy with ropinirole. Despite increasing doses, she does not feel improved, but rather has recently noticed uncontrollable movements that she describes as tics of her face. Her only other medical history is recent recurrent urinary tract infections. Her medications are ropinirole 24 mg daily and nitrofurantoin 100 mg daily. She reports no history of drug use. On physical examination, her blood pressure is 130/70 mmHg with a heart rate of 78 beats/min while sitting. Upon standing, her blood pressure drops to 90/50 mmHg with a heart rate of 110 beats/min. Her ocular movements are full and intact. She has recurrent motor movements of the right side of her face. Her neurologic examination shows increased muscle tone in the lower extremities with bilateral 4-Hz tremor. Deep tendon reflexes are brisk and 3+ in upper and lower extremities. Three beats of myoclonus are present at the ankles bilaterally. She walks with a spastic gait. Strength is normal. What is the most likely diagnosis?

A. Corticobasal degeneration

B. Diffuse Lewy body dementia

C. Drug-induced Parkinson’s disease

D. Multiple system atrophy with parkinsonian features

E. Parkinson’s disease with inadequate treatment

48. A 65-year-old man presents to your office complaining of a tremor and progressive gait abnormalities. He states that he first noticed a slowing of his gait approximately 6 months ago. He has difficulty rising to a standing position and states that he shuffles when he walks. In addition, he states that his right hand shakes more so than his left, and he is right handed. He believes it to be worse when not moving but states there are times when he spills his morning coffee because of the tremors. He has retired but states he is not able to play tennis and golf any longer because of his motor symptoms. He denies syncope or presyncope, difficulty swallowing, changes to his voice, or memory difficulties. His past medical history is significant for hypertension and hypercholesterolemia. His medications are hydrochlorothiazide 25 mg daily, ezetimibe 10 mg daily, and lovastatin 40 mg daily. He drinks a glass of wine with dinner daily and is a lifelong non-smoker. On physical examination, he has masked facies. His gait shows decreased arm swing with slow shuffling steps. He turns en bloc. A pill-rolling tremor is present on the right side. There is cogwheel rigidity bilaterally. Eye movements are full and intact. There is no orthostatic hypotension. A brain MRI with gadolinium shows no evidence of mass lesions, hydrocephalus, or vascular disease. You diagnose the patient with Parkinson’s disease. The patient asks about his prognosis and likelihood of disability. Which of the following is correct about the clinical course and treatment of Parkinson’s disease?

A. Early initiation of therapy with levodopa predisposes an individual to a higher likelihood of dyskinesias early in the disease.

B. Early therapy with bilateral deep-brain stimulation of the subthalamic nuclei slows the progression of Parkinson’s disease.

C. Initial treatment with a dopamine agonist such as pramipexole is likely to be effective in controlling his motor symptoms for 1–3 years before the addition of levodopa or another agent is necessary.

D. Levodopa should be started immediately to prevent the development of disabling rigidity.

E. MAO inhibitors are contraindicated once the diagnosis of Parkinson’s disease is established.

49. All of the following statements regarding restless legs syndrome (RLS) are true EXCEPT:

A. Dopamine antagonists are effective therapy.

B. Most patients develop symptoms before the age of 30 years old.

C. RLS may cause sleep disorder and daytime hyper-somnolence.

D. RLS is more common in Asians than in the general U.S. population.

E. Symptoms may involve the upper extremity.

50. Which of the following statements regarding Alzheimer’s disease is true?

A. Delusions are uncommon.

B. It accounts for over half of the cases of significant memory loss in patients over 70 years of age.

C. It typically presents with rapid (<6 months) significant memory loss.

D. Less than 5% of patients present with nonmemory complaints.

E. Pathologically, the most notable abnormalities are in the cerebellar regions.

51. A 63-year-old man seeks medical attention because of progressive weakness of the left foot and lower leg over the last 6 months. The progression has been gradual, and he only noticed it initially because of cramping and tripping while playing squash. He denies back pain. His only medication is atorvastatin. On physical examination, vital signs are normal and the only abnormalities are on neurologic examination. His left leg strength is notably diminished in the hip flexors, hip adductors, quadriceps, and calf muscles. There is atrophy of the quadriceps and calf. His ankle and knee reflexes are increased on the left. He has subtle weakness on the right quadriceps. There are no sensory abnormalities in light touch, pinprick, temperature, or proprioception. There are occasional fasciculations of the abdominal muscles. Before diagnosing the patient with amyotrophic lateral sclerosis (ALS), all of the following alternative diagnoses should be ruled out EXCEPT:

A. Cervical spondylosis

B. Foramen magnum tumor

C. Lead poisoning

D. Multifocal motor neuropathy with conduction block

E. Vitamin C deficiency

52. A 42-year-old woman seeks medical attention for a 5- to 6-week history of marked fatigue that is affecting her work. She reports that she has felt some general fatigue but her symptoms are most notable when she starts moving around during the day. She has taken her pulse and it feels fast to her. She reports no loss of consciousness, but does say that she feels lightheaded and has blurred vision after arising. Sitting or lying down improves the symptoms. She has no notable past medical history and takes no medications other than a calcium/vitamin supplement. On physical examination, her supine heart rate is 90 beats/min with blood pressure of 110/70 mmHg. Upon standing her heart rate increases to 130 beats/min and is regular, and her blood pressure standing is 115/75 mmHg. She reports lightheadedness during the episode. An ECG while symptomatic shows sinus tachycardia without any conduction abnormalities. Which of the following is the most likely diagnosis?

A. Addison’s disease

B. Autoimmune autonomic neuropathy

C. Diabetic neuropathy

D. Multisystem atrophy

E. Postural orthostatic tachycardia syndrome

53. A 45-year-old male complains of severe right arm pain. He gives a history of having slipped on the ice and severely contusing his right shoulder approximately 6 months ago. Soon thereafter, he developed sharp, knifelike pain in the right arm and forearm that lasted for a few months. There was some arm swelling and warmth. He was evaluated in an urgent care setting. There were no radio-graphic abnormalities and he was not treated. Since the injury, the pain and swelling have persisted. Physical examination reveals a right arm that is more moist and hairy than the left arm. There is no specific weakness or sensory change. However, the right arm is clearly more edematous than the left, and the skin appears shiny and cool. The patient’s pain most likely is due to:

A. Acromioclavicular separation

B. Brachial plexus injury

C. Cervical radiculopathy

D. Complex regional pain syndrome

E. Subclavian vein thrombosis

54. Which of the following criteria suggests the diagnosis of trigeminal neuralgia?

A. Deep-seated, steady facial pain

B. Elevated erythrocyte sedimentation rate (ESR)

C. Objective signs of sensory loss on physical examination

D. Response to gabapentin therapy

E. None of the above

55. A 72-year-old woman presents with recurrent episodes of incapacitating facial pain lasting from second to minutes and then dissipating. The episodes occur usually twice per day, usually without warning, but are also occasionally provoked by brushing of her teeth. On physical examination, she appears well with normal vital signs. Detailed cranial nerve examination reveals no sensory or motor abnormalities. The remainder of her neurologic examination is normal. What is the next step in her management?

A. Brain MRI

B. Brain MRI plus carbamazepine therapy

C. Carbamazepine therapy

D. Glucocorticoid therapy

E. Referral to Otolaryngology for surgical cure

56. A 72-year-old female presents with brief, intermittent excruciating episodes of lancinating pain in the lips, gums, and cheek. Touching the lips or moving the tongue can initiate these intense spasms of pain. The results of a physical examination are normal. MRI of the head is also normal. The most likely cause of this patient’s pain is:

A. Acoustic neuroma

B. Amyotrophic lateral sclerosis

C. Meningioma

D. Trigeminal neuralgia

E. Facial nerve palsy

57. A 33-year-old woman presents with rapidly worsening pain at the top of the back over the last 3 days. The pain is not relieved by lying down or by wearing a soft neck collar. She notes that the pain is much worse with movement and has woken her from sleep. The pain is severe and is impeding her daily activities. She denies any arm pain or weakness. There is no history of prior back or neck pain, trauma, or arthritis. She works as a postal delivery agent and her only physical activity is walking. She is monogamous with her husband and has no illicit activities. Her family history is notable for an aunt and mother with breast cancer. Her MRI is shown in Figure 57. Which is the most likely diagnosis?

A. Cervical spondylosis

B. Hematomyelia

C. Metastatic breast cancer

D. Spinal epidural abscess

E. Spinal epidural hematoma

image

FIGURE 57

58. A 34-year-old female complains of lower extremity weakness for the last 3 days. She has noted progressive weakness in the lower extremities with loss of sensation “below the belly button” and incontinence. She had had some low-grade fevers for the last week. She denies recent travel. Past medical history is unremarkable. Physical examination is notable for a sensory level at the level of the umbilicus. The lower extremities show +3/5 strength bilaterally proximally and distally. Reflexes, cerebellar examination, and mental status are normal. All of the following are appropriate steps in evaluating this patient EXCEPT:

A. Antinuclear antibodies

B. Electromyography

C. Lumbar puncture

D. MRI of the spine

E. Viral serologies

59. Which of the following statements about syringomyelia is true?

A. More than half the cases are associated with Chiari malformations.

B. Symptoms typically begin in middle age.

C. Vibration and position sensation are usually diminished.

D. Syrinx cavities are always congenital.

E. Neurosurgical decompression is usually effective in relieving the symptoms.

60. A 17-year-old adolescent is seen in the clinic several weeks after he suffered a concussion during a high-school football game. At the time of the event, paramedics reported that he experienced no loss of consciousness but was confused for a period of about 10 minutes. Head imaging was normal. He describes a generalized headache that is present all the time since his trauma, and he occasionally feels dizzy. His mother is concerned that he is having a hard time concentrating in school and seems depressed to her lately; she describes him as being very energetic prior to his concussion. The patient’s physical examination is entirely normal except for a somewhat flattened affect. Which of the following statements regarding his condition is true?

A. He has an excellent prognosis.

B. He meets the criteria for postconcussive syndrome and should improve over 1–2 months.

C. He should avoid contact sports for 2 weeks.

D. He is most likely malingering.

E. Low-dose narcotics should be started for headache.

61. A 68-year-old man is brought to the clinic by his wife for evaluation. She has noticed that over past 2–3 months her husband has had increasingly slowed thinking and a change in his personality in that he has become very withdrawn. His only complaint is a mild but persistent, diffuse headache. There is no history of head trauma, prior neurologic or psychiatric disease, or family history of dementia. Physical examination is only notable for a moderate cognitive deficit with a mini-mental examination of 19/30. His head CT is shown in Figure 61. What is the most likely diagnosis?

A. Acute epidural hematoma

B. Acute subarachnoid hemorrhage

C. Alzheimer’s disease

D. Chronic subdural hematomas

E. Normal-pressure hydrocephalus

image

FIGURE 61

62. A 76-year-old nursing home resident is brought to the local emergency department after falling out of bed. The fall was not witnessed; however, she was suspected to have hit her head. She is not responsive to verbal or light tactile stimuli. At baseline she is able to converse but is frequently disoriented to place and time. She has a medical history that includes stable coronary disease, mild emphysema, and multi-infarct dementia. Immediately after triage she is taken for a CT scan of the head. Which of the following is true regarding head injury and hematomas?

A. More than 80% of patients with subdural hematomas will experience a lucid interval prior to loss of consciousness.

B. Epidural hematomas generally arise from venous sources.

C. Epidural hematomas are common among the elderly with minor head trauma.

D. Most patients presenting with epidural hematomas are unconscious.

E. Subdural hematomas lead to rapid increases in intracranial pressure and can require arterial ligation.

63. A 49-year-old man is admitted to the hospital with a seizure. He does not have a history of seizures and he currently takes no medications. He has AIDS and is not under any care at this time. His physical examination is most notable for small, shoddy lymphadenopathy in the cervical region. A head CT shows a ring-enhancing lesion in the right temporal lobe, with edema but no mass effect. A lumbar puncture shows no white or red blood cells, and the Gram stain is negative. His serum Toxoplasma IgG is positive. He is treated with pyrimethamine, sulfadiazine, and levetiracetam. After 2 weeks of therapy the central nervous system (CNS) lesion has not changed in size and he has not had any more seizures. All microbiologic cultures and viral studies, including Epstein-Barr virus DNA from the cerebrospinal fluid, are negative. What is the best course of action for this patient at this time?

A. Continue treatment for CNS toxoplasmosis.

B. Dexamethasone.

C. IV acyclovir.

D. Stereotactic brain biopsy.

E. Whole-brain radiation therapy.

64. A young man with a history of a low-grade astrocytoma comes into your office complaining of weight gain and low energy. He is status post resection of his low-grade astrocytoma and had a course of whole-brain radiation therapy (WBRT) 1 year ago. A laboratory workup reveals a decreased morning cortisol level of 1.9 μg/dL. In addition to depressed adrenocorticotropic hormone (ACTH) function, which of the following hormones is most sensitive to damage from whole-brain radiation therapy?

A. Growth hormone

B. Follicle-stimulating hormone

C. Prolactin

D. Thyroid-stimulating hormone

65. A 37-year-old woman with a history of 6 months of worsening headache is admitted to the hospital after a tonic-clonic seizure that occurred at work. The seizure lasted a short time and terminated spontaneously. On examination her vital signs are normal, she is somnolent but awake, and there are no focal abnormalities. Her initial CT scan showed no acute hemorrhage but was abnormal. An MRI is obtained and is shown in Figure 65. What is the most likely diagnosis in this patient?

A. Brain abscess

B. Glioblastoma

C. Low-grade astrocytoma

D. Meningioma

E. Oligodendroglioma

image

FIGURE 65

66. All of the following hormones are produced by the anterior pituitary EXCEPT:

A. Adrenocorticotropic hormone

B. Growth hormone

C. Oxytocin

D. Prolactin

E. Thyroid-stimulating hormone

67. A 22-year-old woman who is otherwise healthy undergoes an uneventful vaginal delivery of a full-term infant. One day postpartum she complains of visual changes and severe headache. Two hours after these complaints, she is found unresponsive and profoundly hypotensive. She is intubated and placed on mechanical ventilation. Her blood pressure is 68/28 mmHg, heart rate is regular at 148 beats/min, and oxygen saturation is 95% on FiO2 0.40. Physical exam is unremarkable. Her laboratories are notable for glucose of 49 mg/dL and normal hematocrit and white blood cell count. Which of the following is most likely to reverse her hypotension?

A. Activated drotrecogin alfa

B. Hydrocortisone

C. Piperacillin/tazobactam

D. T4

E. Transfusion of packed red blood cells

68. A 45-year-old man reports to his primary care physician that his wife has noted coarsening of his facial features over several years. In addition, he reports low libido and decreased energy. Physical examination shows frontal bossing and enlarged hands. An MRI confirms that he has a pituitary mass. Which of the following screening tests should be ordered to diagnose the cause of the mass?

A. 24-hour urinary free cortisol

B. ACTH assay

C. Growth hormone level

D. Serum IGF-1 level

E. Serum prolactin level

69. All of the following are potential causes of hyper-prolactinemia EXCEPT:

A. Cirrhosis

B. Hirsutism

C. Nipple stimulation

D. Opiate abuse

E. Rathke’s cyst

70. A 28-year-old woman presents to her primary care physician’s office with 1 year of amenorrhea. She reports mild galactorrhea and headaches. Although she is sexually active, a urine pregnancy test is negative. Serum prolactin level is elevated and she is subsequently diagnosed with a microscopic prolactinoma. Which of the following represents the primary goal of bromocriptine therapy for her condition?

A. Control of hyperprolactinemia

B. Reduction in tumor size

C. Resolution of galactorrhea

D. Restoration of menses and fertility

E. All of the above

71. A 58-year-old man undergoes severe head trauma and develops pituitary insufficiency. After recovery, he is placed on thyroid hormone, testosterone, glucocorticoids, and vasopressin. On a routine visit he questions his primary care physician regarding potential growth hormone deficiency. All of the following are potential signs or symptoms of growth hormone deficiency EXCEPT:

A. Abnormal lipid profile

B. Atherosclerosis

C. Increased bone mineral density

D. Increased waist:hip ratio

E. Left ventricular dysfunction

72. A 75-year-old man presents with development of abdominal obesity, proximal myopathy, and skin hyperpigmentation. His laboratory evaluation shows a hypokalemic metabolic alkalosis. Cushing’s syndrome is suspected. Which of the following statements regarding this syndrome is true?

A. Basal ACTH level is likely to be low.

B. Circulating corticotropin-releasing hormone is likely to be elevated.

C. Pituitary MRI will visualize all ACTH-secreting tumors.

D. Referral for urgent performance of inferior petrosal venous sampling is indicated.

E. Serum potassium level below 3.3 mmol/L is suggestive of ectopic ACTH production.

73. A 23-year-old college student is followed in the student health center for medical management of panhypopituitarism after resection of craniopharyngioma as a child. She reports moderate compliance with her medications but feels generally well. A TSH is checked and is below the limits of detection of the assay. Which of the following is the next most appropriate action?

A. Decrease levothyroxine dose to half of current dose.

B. Do nothing.

C. Order free T4 level.

D. Order MRI of her brain.

E. Order thyroid uptake scan.

74. A 23-year-old woman presents to the clinic complaining of months of weight gain, fatigue, amenorrhea, and worsening acne. She cannot precisely identify when her symptoms began, but she reports that without a change in her diet she has noted a 12.3-kg weight gain over the past 6 months. She has been amenorrheic for several months. On examination she is noted to have truncal obesity with bilateral purplish striae across both flanks. Cushing’s syndrome is suspected. Which of the following tests should be used to make the diagnosis?

A. 24-hour urine free cortisol

B. Basal adrenocorticotropic hormone (ACTH)

C. Corticotropin-releasing hormone (CRH) level at 8 am

D. Inferior petrosal venous sampling

E. Overnight 1-mg dexamethasone suppression test

75. A patient visited a local emergency room 1 week ago with a headache. She received a head MRI, which did not reveal a cause for her symptoms, but the final report states, “An empty sella is noted. Advise clinical correlation.” The patient was discharged from the emergency department with instructions to follow up with her primary care physician as soon as possible. Her headache has resolved, and the patient has no complaints; however, she comes to your office 1 day later very concerned about this unexpected MRI finding. What should be the next step in her management?

A. Diagnose her with subclinical panhypopituitarism, and initiate low-dose hormone replacement.

B. Reassure her and follow laboratory results closely.

C. Reassure her and repeat MRI in 6 months.

D. This may represent early endocrine malignancy—whole-body positron emission tomography/CT is indicated.

E. This MRI finding likely represents the presence of a benign adenoma—refer to neurosurgery for resection.

76. All of the following are frequent initial symptoms of multiple sclerosis EXCEPT:

A. Optic neuritis

B. Paresthesias

C. Sensory loss

D. Visual loss

E. Weakness

77. Which of the following is the most common clinical classification of multiple sclerosis?

A. Autoimmune autonomic neuropathy

B. Primary progressive

C. Progressive relapsing

D. Relapsing/remitting

E. Secondary progressive

78. Lumbar puncture should be preceded by CT or MRI in all of the following subsets of patients suspected of having meningitis EXCEPT those with:

A. Depressed consciousness

B. Focal neurologic abnormality

C. Known central nervous system (CNS) mass lesion

D. Positive Kernig’s sign

E. Recent head trauma

79. A 78-year-old man with diabetes mellitus presents with fever, headache, and altered sensorium. On physical exam his temperature is 40.2°C (104.4°F), heart rate is 103 beats/min, and blood pressure is 84/52 mmHg. His neck is stiff and he has photophobia. His cerebrospinal fluid (CSF) examination shows 2100 cells/μL, with 100% neutrophils, glucose 10 mg/dL, and protein 78 mg/dL. CSF Gram stain is negative. In addition to empiric antibacterial antibiotics, initial therapy should include which of the following?

A. Acyclovir

B. Dexamethasone after antibiotics

C. Dexamethasone prior to antibiotics

D. IV γ globulin

E. Valacyclovir

80. Which of the following groups of patients should receive empirical antibiotic therapy that includes coverage of Listeria monocytogenes in cases of presumed meningitis?

A. Immunocompromised patients

B. Elderly patients

C. Infants

D. All of the above

81. Which of the following medicines has been most commonly implicated in the development of non-infectious chronic meningitis?

A. Acetaminophen

B. Acyclovir

C. β-lactam antibiotics

D. Ibuprofen

E. Phenobarbital

82. Variant Creutzfeldt-Jakob disease (vCJD) has been diagnosed in which of the following populations?

A. Family members with well-defined germ-line mutations leading to autosomal dominant inheritance of a fatal neurodegenerative disease

B. New Guinea natives practicing cannibalism

C. Patients accidentally inoculated with infected material during surgical procedures

D. Worldwide, in sporadic cases, mostly during the fifth and sixth decades of life

E. Young adults in Europe thought to have been exposed to tainted beef products

83. The presence of startle myoclonus in a 60-year-old man with rapidly progressive deficits in cortical dysfunction is which of the following?

A. Neither sensitive nor specific for Creutzfeldt-Jacob disease (CJD) but does represent grounds to explore further for this condition with an electroencephalogram (EEG)

B. Neither sensitive nor specific for CJD but does represent grounds to explore further for this condition with an EEG and brain MRI

C. Sensitive but not specific for CJD and is not enough to prompt a further workup for this condition unless other clinical criteria are met

D. Specific but not sensitive for CJD and should therefore prompt immediate referral for brain biopsy to confirm the diagnosis

E. Virtually diagnostic for CJD, and further workup including EEG, brain MRI, and perhaps brain biopsy serves only a prognostic purpose

84. A 55-year-old woman presents with progressive incoordination. Physical examination is remarkable for nystagmus, mild dysarthria, and past pointing on finger-to-nose testing. She also has an unsteady gait. MRI reveals atrophy of both lobes of the cerebellum. Serologic evaluation reveals the presence of anti-Yo antibody. Which of the following is the most likely cause of this clinical syndrome?

A. Non–small cell cancer of the lung

B. Small cell cancer of the lung

C. Breast cancer

D. Non-Hodgkin’s lymphoma

E. Colon cancer

85. A 24-year-old man presents for evaluation of foot-drop. He has noted that for the last several months, he has had difficulty picking his feet up to walk up stairs and over thresholds. His right leg is more affected than his left leg. He has not noted any sensory changes. He has several family members with similar complaints. His exam is notable for distal leg weakness with reduced sensation to light touch in both lower extremities. Knee and ankle jerk reflexes are unobtainable. Calves are reduced in size bilaterally. Upper extremity examination is normal. Which of the following is the most likely diagnosis?

A. Charcot-Marie-Tooth syndrome

B. Fabry disease

C. Guillain-Barré syndrome

D. Hereditary neuralgic amyotrophy

E. Hereditary sensory and autonomic neuropathy

86. A 57-year-old immigrant from Vietnam is evaluated by his primary caregiver for dysesthesias that have been present in his hands and feet for the past several weeks. He also reports some difficulty walking. His past medical history is notable for hypertriglyceridemia, tobacco abuse, and a recently discovered positive PPD with sputum that is smear-negative for Mycobacterium tuberculosis. His medications include niacin, aspirin, and isoniazid. Which of the following is likely to reverse his symptoms?

A. Cobalamin

B. Levothyroxine

C. Neurontin

D. Pregabalin

E. Pyridoxine

87. A 52-year-old woman with long-standing, poorly controlled type 2 diabetes mellitus is evaluated for a sensation of numbness in her fingers and toes, as if she is wearing gloves and socks all the time. She also reports tingling and burning in the same location, but no weakness. Her symptoms have been intermittently present for the last several months. After a thorough evaluation, nerve biopsy is obtained and demonstrates axonal degeneration, endothelial hyperplasia, and perivascular inflammation. Which of the following statements regarding this condition is true?

A. Autonomic neuropathy is rarely seen in combination with sensory neuropathy.

B. The presence of retinopathy or nephropathy does not portend increased risk for diabetic neuropathy.

C. This is the most common cause of peripheral neuropathy in developed countries.

D. Tight glucose control from now on will reverse her neuropathy.

E. None of the above is true.

88. All the following cause primarily a sensory neuropathy EXCEPT:

A. Acromegaly

B. Critical illness

C. HIV infection

D. Hypothyroidism

E. Vitamin B12 deficiency

89. A 50-year-old male complains of weakness and numbness in the hands for the last month. He describes paresthesias in the thumb and the index and middle fingers. The symptoms are worse at night. He also describes decreased grip strength bilaterally. He works as a mechanical engineer. The patient denies fevers, chills, or weight loss. The examination is notable for atrophy of the thenar eminences bilaterally and decreased sensation in a median nerve distribution. You consider the diagnosis of carpal tunnel syndrome. All the following are causes of carpal tunnel syndrome EXCEPT:

A. Amyloidosis

B. Chronic lymphocytic leukemia

C. Diabetes mellitus

D. Hypothyroidism

E. Rheumatoid arthritis

90. A 27-year-old woman is diagnosed with Guillain-Barré syndrome after presenting with flaccid paralysis and sensory disturbance several weeks after a diarrheal illness. Which of the following bacteria have been implicated in cases of Guillain-Barré syndrome?

A. Bartonella henselae

B. Campylobacter jejuni

C. Escherichia coli

D. Proteus mirabilis

E. Tropheryma whippelii

91. A 34-year-old female complains of weakness and double vision for the last 3 weeks. She has also noted a change in her speech, and her friends tell her that she is “more nasal.” She has noticed decreased exercise tolerance and difficulty lifting objects and getting out of a chair. The patient denies pain. The symptoms are worse at the end of the day and with repeated muscle use. You suspect myasthenia gravis. All the following are useful in the diagnosis of myasthenia gravis EXCEPT:

A. Acetylcholine receptor (AChR) antibodies

B. Edrophonium

C. Electrodiagnostic testing

D. Muscle-specific kinase (MuSK) antibodies

E. Voltage-gated calcium channel antibodies

92. A 38-year-old female patient with facial and ocular weakness has just been diagnosed with myasthenia gravis. You intend to initiate therapy with anticholinesterase medications and glucocorticoids. All of the following tests are necessary before instituting this therapy EXCEPT:

A. MRI of mediastinum

B. Purified protein derivative skin test

C. Lumbar puncture

D. Pulmonary function tests

E. Thyroid-stimulating hormone

93. All of the following lipid-lowering agents are associated with muscle toxicity EXCEPT:

A. Atorvastatin.

B. Ezetimibe.

C. Gemfibrozil.

D. Niacin.

E. All of the above are associated with muscle toxicity.

94. All of the following endocrine conditions are associated with myopathy EXCEPT:

A. Hypothyroidism.

B. Hyperparathyroidism.

C. Hyperthyroidism.

D. Acromegaly.

E. All of the above are associated with myopathy.

95. A 34-year-old woman seeks evaluation for weakness. She has noted tripping when walking, particularly in her left foot, for the past 2 years. She recently also began to drop things, once allowing a full cup of coffee to spill onto her legs. In this setting, she also feels as if the appearance of her face has changed over the course of many years, stating that she feels as if her face is becoming more hollow and elongated, although she hasn’t lost any weight recently. She has not seen a physician in many years and has no past medical history. Her only medications are a multivitamin and calcium with vitamin D. Her family history is significant for similar symptoms of weakness in her brother who is 2 years older. Her mother, who is 58 years old, was diagnosed with mild weakness after her brother was evaluated, but is not symptomatic. On physical examination, the patient’s face appears long and narrow with wasting of the temporalis and masseter muscles. Her speech is mildly dysarthric, and the palate is high and arched. Strength is 4/5 in the intrinsic muscles of the hand, wrist extensors, and ankle dorsiflexors. After testing handgrip strength, you notice that there is a delayed relaxation of the muscles of the hand. What is the most likely diagnosis?

A. Acid maltase deficiency (Pompe’s disease)

B. Becker muscular dystrophy

C. Duchenne muscular dystrophy

D. Myotonic dystrophy

E. Nemaline myopathy

96. An elevation in which of the following serum enzymes is the most sensitive indicator of myositis?

A. Aldolase

B. Creatinine kinase

C. Glutamic-oxaloacetic transaminase

D. Glutamate pyruvate transaminase

E. Lactate dehydrogenase

97. A 64-year-old woman is evaluated for weakness. For several weeks she has had difficulty brushing her teeth and combing her hair. She has also noted a rash on her face. Examination is notable for a heliotrope rash and proximal muscle weakness. Serum creatine kinase (CK) is elevated and she is diagnosed with dermatomyositis. After evaluation by a rheumatologist, she is found to have anti-Jo-1 antibodies. She is also likely to have which of the following findings?

A. Ankylosing spondylitis

B. Inflammatory bowel disease

C. Interstitial lung disease

D. Primary biliary cirrhosis

E. Psoriasis

98. A 63-year-old woman is evaluated for a rash on her eyes and fatigue for 1 month. She reports difficulty with arm and leg strength and constant fatigue, but no fevers or sweats. She also notes that she has a red discoloration around her eyes. She has hypothyroidism but is otherwise well. On examination she has a heliotrope rash and proximal muscle weakness. A diagnosis of dermatomyositis is made after demonstration of elevated serum creatinine kinase and confirmatory EMGs. Which of the following studies should be performed as well to look for associated conditions?

A. Mammogram

B. Serum antinuclear antibody measurement

C. Stool examination for ova and parasites

D. Thyroid-stimulating immunoglobulins

E. Titers of antibodies to varicella zoster

99. You are seeing your patient with polymyositis for follow-up. He has been taking prednisone at high doses for 2 months, and you initiated mycophenolate mofetil at the last clinic visit for a steroid-sparing effect. He began a steroid taper 2 weeks ago. His symptoms were predominantly in the lower extremities and face, and he has improved considerably. He no longer needs a cane and his voice has returned to normal. Laboratory data show a creatine kinase (CK) of 1300 U/L, which is unchanged from 2 months ago. What is the most appropriate next step in this patient’s management?

A. Continue current management.

B. Continue high-dose steroids with no taper.

C. Switch mycophenolate to methotrexate.

D. Repeat muscle biopsy.

100. A 45-year-old woman who is 6 months post–liver transplant is admitted to the hospital after two grand mal seizures in the last 45 minutes. For the last day she has complained about headache and confusion. Her medications include diltiazem, cyclosporine, prednisone, and mycophenolate mofetil. She is now awake but somnolent. Her vital signs are normal except a blood pressure of 150/90 mmHg. There is bilateral afferent pupillary defect, and she reports she cannot see out of either eye. Hearing is intact. There is no nuchal rigidity. Her cyclosporine level is therapeutic. The FLAIR image of her MRI is shown in Figure 100. Which of the following is the most likely diagnosis?

A. Acoustic neuroma

B. Calcineurin-inhibitor toxicity

C. Panhypopituitarism

D. Streptococcal meningitis

E. Tuberculous meningitis

image

FIGURE 100

101. A 77-year-old man undergoes coronary artery bypass grafting for refractory angina and three-vessel disease. Prior to surgery he still worked as a classics professor at a university teaching a renowned course on Dante’s “Inferno.” One month after surgery, his cardiac status is normal and his exercise tolerance is better than presurgery. However, his wife reports that he seems depressed and is often confused. His short-term memory is poor and he exhibits no enthusiasm for teaching. He has no fever or night sweats. Current medications include lovastatin and lisinopril. His physical examination is normal except for poor performance on serial 7 subtraction and only recalling 1 or 3 objects at 15 minutes. Which of the following is the most likely diagnosis?

A. Multiple sclerosis

B. Post–cardiac bypass brain injury

C. Streptococcal meningitis

D. Variant Creutzfeldt-Jacob disease

E. West Nile virus encephalitis

102. A 24-year-old man is recovering from ARDS due to severe influenza A infection. During his complicated 3-week course of respiratory failure, he was placed on high-frequency ventilation and prone positioning necessitating paralysis and heavy sedation. Passive splints were placed on his upper and lower extremities. He is now extubated and awake, requiring only nasal oxygen. While starting his physical therapy, it is noted that he has right foot-drop and numbness on the lateral leg. Additional examination reveals a unilateral right motor defect in foot dorsiflexion with intact inversion. There is sensory loss of the lateral aspect of the leg below the knee extending to the dorsum of the foot. The rest of the neurologic examination of the right leg and foot appears normal. Which of the following is the most likely etiology of his defects?

A. Cauda equina syndrome

B. Femoral nerve injury

C. L4 radiculopathy

D. L5 radiculopathy

E. Peroneal nerve injury

103. In the CDC diagnostic criteria for chronic fatigue syndrome, in addition to clearly delineated findings of fatigue, all of the following symptoms or findings must be concurrently present for at least 6 months EXCEPT:

A. Delusional disorder

B. Impaired memory or concentration

C. Muscle pain

D. Sore throat

E. Tender cervical or axillary lymph nodes

104. Which of the following is a beneficial therapy for chronic fatigue syndrome?

A. Bupropion

B. Cognitive behavioral therapy

C. Doxycycline

D. Fluoxetine

E. Olanzapine

105. A 26-year-old woman presents to the emergency department complaining of shortness of breath and chest pain. These symptoms began abruptly and became progressively worse over 10 minutes, prompting her to call 911. Over this same period, the patient describes feeling her heart pounding and states that she felt like she was dying. She feels lightheaded and dizzy. It is currently about 20 minutes since the onset of symptoms and the severity has abated, although she continues to feel not back to her baseline. She denies any immediate precipitating cause, although she has been under increased stress as her mother has been hospitalized recently with advanced breast cancer. She does not take any medications and has no medical history. She denies tobacco, alcohol, or drug use. On initial examination, she appears somewhat anxious and diaphoretic. Her initial vital signs show a heart rate of 108 beats/min, blood pressure 122/68 mmHg, and respiratory rate 20 breaths/min. She is afebrile. Her examination is normal. Her arterial blood gas shows a pH of 7.52, Paco2 of 28 mmHg, and Pao2 of 116 mmHg. The ECG is normal as is a chest radiograph. What is the next best step in the management of this patient?

A. Initiate therapy with alprazolam 0.5 mg four times daily.

B. Initiate therapy with fluoxetine 20 mg daily.

C. Perform a CT pulmonary angiogram.

D. Reassure the patient and suggest medical and/or psychological therapy if symptoms recur on a frequent basis.

E. Refer for cognitive behavioral therapy.

106. All of the following antidepressant medications are correctly paired with their class of medication EXCEPT:

A. Duloxetine—Selective serotonin reuptake inhibitor

B. Fluoxetine—Selective serotonin reuptake inhibitor

C. Nortriptyline—Tricyclic antidepressant

D. Phenelzine—Monoamine oxidase inhibitor

E. Venlafaxine—Mixed norepinephrine/serotonin reuptake inhibitor and receptor blocker

107. A 42-year-old woman seeks your advice regarding symptoms concerning for post-traumatic stress disorder. She was the victim of a home invasion 6 months previously where she was robbed and beaten by a man at gunpoint. She thought she was going to die and was hospitalized with multiple blunt force injuries including a broken nose and zygomatic arch. She now states that she is unable to be alone in her home and frequently awakens with dreams of the event. She is irritable with her husband and children and cries frequently. She has worsening insomnia and often stays awake most of the night watching out her window because she is afraid her assailant will return. She has begun drinking a bottle of wine nightly to help her fall asleep, although she notes that this has worsened her nightmares in the early morning hours. You concur that post-traumatic stress disorder is likely. What treatment do you recommend for this patient?

A. Avoidance of alcohol

B. Cognitive behavioral therapy

C. Paroxetine 20 mg daily

D. Trazodone 50 mg nightly

E. All of the above

108. A 36-year-old man is being treated with venlafaxine 150 mg twice daily for major depression. He has currently been on the medication for 4 months. After 2 months, his symptoms were inadequately controlled, necessitating an increase in the dose of venlafaxine from 75 mg twice daily. He has had one prior episode of major depression when he was 25. At that time, he was treated with fluoxetine 80 mg daily for 12 months, but found the sexual side effects difficult to tolerate. He asks when he can safely discontinue his medication. What is your advice to the patient?

A. He should continue on the medication indefinitely as his depression is likely to recur.

B. The current medication should be continued for a minimum of 6–9 months following control of his symptoms.

C. The medication can be discontinued safely if he establishes a relationship with a psychotherapist who will monitor his progress and symptoms.

D. The medication can be discontinued safely now as his symptoms are well controlled.

E. The medication should be switched to fluoxetine to complete 12 months of therapy, as this was previously effective for him.

109. Which of the following will lead to a faster rate of absorption of alcohol from the gut into the blood?

A. Coadministration with a carbonated beverage

B. Concentration of alcohol of more than 20% by volume

C. Concurrent intake of a high-carbohydrate meal

D. Concurrent intake of a high-fat meal

E. Concurrent intake of a high-protein meal

110. Which of the following best reflects the effect of alcohol on neurotransmitters in the brain?

A. Decreases dopamine activity

B. Decreases serotonin activity

C. Increases γ-aminobutyric acid activity

D. Stimulates muscarinic acetylcholine receptors

E. Stimulates N-methyl-D-aspartate excitatory glutamate receptors

111. In an individual without any prior history of alcohol intake, what serum concentration of ethanol (in grams per deciliter) would likely result in death?

A. 0.02

B. 0.08

C. 0.28

D. 0.40

E. 0.60

112. All of the following statements regarding the epidemiology and genetics of alcoholism are true EXCEPT:

A. Among individuals who have demonstrated alcohol abuse, about 10% will develop true alcohol dependence.

B. Approximately 60% of the risk for alcohol abuse disorders is attributed to genetics.

C. Children of alcoholics have a 10-fold higher risk of alcohol abuse and dependence.

D. The presence of a mutation of aldehyde dehydrogenase that results in intense flushing with alcohol consumption confers a decreased risk of alcohol dependence.

E. The lifetime risk of alcohol dependence in most Western countries is about 10–15% for men and 5–8% for women.

113. A 42-year-old man with alcohol dependence is admitted to the hospital for acute pancreatitis. Upon admission, he has an abdominal CT scan that shows edema without necrosis or hemorrhage of the pancreas. He is treated with IV fluids with dextrose, multivitamins, thiamine 50 mg daily, pain control, and bowel rest. He typically drinks 24 12-ounce beers daily. Forty-eight hours after admission, you are called because the patient is febrile and combative with the nursing staff. His vital signs demonstrate a heart rate of 132 beats/min, blood pressure of 184/96 mmHg, respiratory rate of 32 breaths/min, temperature of 38.7°C (101.7°F), and oxygen saturation of 94% on room air. He is agitated, diaphoretic, and pacing his room. He is oriented to person only. His neurologic examination appears nonfocal, although he does not cooperate. He is tremulous. What is the next step in the management of this patient?

A. Administer a bolus of 1 L of normal saline and thiamine 100 mg IV.

B. Administer diazepam 10–20 mg IV followed by bolus doses of 5–10 mg as needed until the patient is calm but able to be aroused.

C. Perform an emergent head CT.

D. Perform two peripheral blood cultures and begin treatment with imipenem 1 g IV every 8 hours.

E. Place the patient in four-point restraints and treat with haloperidol 5 mg IV.

114. A 48-year-old woman is recovering from alcohol dependence and requests medication to help prevent relapse. She has a medical history of stroke occurring during a hypertensive crisis. Which of the following medications could be considered?

A. Acamprosate

B. Disulfiram

C. Naltrexone

D. A and C

E. All of the above

115. What is the most common initial illicit drug of abuse among U.S. adolescents?

A. Benzodiazepines

B. Heroin

C. Marijuana

D. Methamphetamines

E. Prescription narcotics

116. A 32-year-old woman is admitted to the hospital for drainage and treatment of a soft tissue abscess of her left forearm. She uses IV heroin on a daily basis, often spending $100 or more per day on drugs. Upon admission, she has a 4 × 2-cm fluctuant mass in the left forearm associated with fevers to 39.3°C (102.7°F) and tachycardia. The abscess is drained and packed, and the patient is initiated on therapy with IV clindamycin. About 10 hours after admission, you are called to the patient’s bedside for a change in the patient’s condition. You are suspecting narcotic withdrawal. All of the following symptoms are consistent with this diagnosis EXCEPT:

A. Hyperthermia

B. Hypotension

C. Piloerection

D. Sweating

E. Vomiting

117. A 24-year-old man is brought to the emergency department by emergency medical services (EMS) about 2 hours after an intentional overdose of sustained-release oxycodone that was taken in conjunction with alcohol. Upon arrival at the scene, emergency medical technicians found an empty bottle of sustained-release oxycodone tablets with a dose of 20 mg. It is unknown how many pills the patient ingested, but the prescription was written for 60 tablets. The patient was unresponsive with a respiratory rate of 4 breaths/min, blood pressure of 80/56 mmHg, heart rate of 65 beats/min, and oxygen saturation of 86% on room air. The patient was intubated in the field and naloxone 2 mg IM was administered. He is currently intubated and unresponsive without spontaneous respiration above the set ventilator rate. His blood pressure is 82/50 mmHg and heart rate is 70 beats/min. Which of the following is most appropriate at the present time in the evaluation and treatment of this patient?

A. Activated charcoal

B. IV saline bolus 1 L followed by repeated 500–1000 mL boluses to maintain adequate blood pressure

C. Naloxone continuous infusion at a rate of 0.4 mg/h

D. Urine drug screen, acetaminophen levels, and blood alcohol content

E. All of the above

118. Which of the following statements is TRUE with regard to the chronic effects of marijuana use?

A. Chronic use of marijuana is associated with low testosterone levels.

B. Chronic use of marijuana is the primary cause of amotivational syndrome.

C. Marijuana use is associated with an increased risk of psychotic symptoms in individuals with a past history of schizophrenia.

D. Physical and psychological tolerance does not develop in chronic users of marijuana.

E. There is no withdrawal syndrome associated with cessation of marijuana use.

ANSWERS


1 and 2. The answers are D and D, respectively.

(Chap. 1) The ability to perform a thorough neurologic examination is an important skill for all internists to master. A careful neurologic examination can localize the site of the lesion and is important in directing further workup. The components of the neurologic examination include mental status, cranial nerves, motor, sensory, gait, and coordination. The motor examination is further characterized by appearance, tone, strength, and reflexes. Pronator drift is a useful tool for determining if upper extremity weakness is present. In this test, an individual is asked to stand with both arms fully extended and parallel to the floor while closing his or her eyes. If the arms flex at the elbows or fingers or there is pronation of the forearm, this is considered a positive test. Other tests of motor strength include tests of maximal effort in a specific muscle or muscle group. Most commonly this type of strength testing is graded from 0 (no movement) to 5 (full power) with varying degrees of weakness noted against resistance. However, many individuals find it more practical to use qualitative grading of strength, such as paralysis, severe weakness, moderate weakness, mild weakness, or full strength.

  Babinski sign is a sign of upper motor neuron disease above the level of the S1 vertebra and is characterized by paradoxical extension of the great toe with fanning and extension of the other toes as well. Dysdiadochokinesis refers to the inability to perform rapid alternating movements and is a sign of cerebellar disease. Lhermitte symptom causes electric shock–like sensations in the extremities associated with neck flexion. It has many causes including cervical spondylosis and multiple sclerosis. Romberg sign is performed with an individual standing with feet together and arms at the side. The individual is then asked to close his or her eyes. If the individual begins to sway or fall, this is considered a positive test and is a sign of abnormal proprioception.

3. The answer is C.

(Chap. 1) This patient likely has metastatic disease to the cervical spinal cord. The patient’s symptoms are bilateral with sparing of the cranial nerves and normal mental status, localizing the lesion below the level of the brainstem and cerebrum. The patient demonstrates mixed upper and lower motor neuron signs with decreased sphincter tone and a positive Babinski sign, placing the lesion at the level of the spinal cord. As the weakness is involving both the arms and legs, this would indicate a lesion in the lower cervical or upper thoracic spine. Symptoms of abnormalities at the level of the neuromuscular junction include bilateral weakness that can include the face having normal sensation.

4. The answer is C.

(Chap. 4) Appropriate and timely evaluation is needed to determine if a subarachnoid hemorrhage is present as it can be rapidly fatal if undetected. The procedure of choice for initial diagnosis is a CT of the head without IV contrast. On the CT, blood in the subarachnoid space would appear whiter compared to the surrounding brain tissue. The CT of the head is most sensitive when it is performed shortly after the onset of symptoms, but declines over several hours. It can also demonstrate the presence of mass effect and midline shift, factors that increase the severity of the underlying hemorrhage. In the situation where the CT head is negative but clinical suspicion is high, a lumbar puncture can be performed. This may demonstrate increased numbers of red blood cells that do not clear with successive aliquots of cerebrospinal fluid. If the lumbar puncture is performed more than 12 hours after a small subarachnoid hemorrhage, then the red blood cells may begin to decompose, leading to xanthochromia—a yellow to pink coloration of cerebrospinal fluid that can be measured spectrographically. A basic CT of the head with IV contrast is rarely useful in subarachnoid hemorrhage, as the brightness of the contrast material may make it difficult to identify blood in the subarachnoid space. However, a CT angiography that is performed with IV contrast can be useful in identifying the aneurismal vessel leading to the bleeding. Classic angiography is a more direct way to visualize the anatomy of the cranial vasculature and is now often combined with interventional procedures to coiling a bleeding vessel. Transcranial Doppler ultrasound is a test that measures the velocity of blood flow through the cranial vasculature. It is used in some centers following subarachnoid hemorrhage to assess for the development of vasospasm, which can worsen ischemia leading to increased damage to brain tissue following subarachnoid hemorrhage.

5. The answer is E.

(Chap. 4) Magnetic resonance imaging (MRI) is generated from the interaction between the hydrogen protons in biologic tissues, the magnetic field, and the radiofrequency (Rf) of waves generated by the coil placed next to the body part of interest. The Rf pulses transiently excite the protons of the body with a subsequent return to the equilibrium energy state, a process known as relaxation. During relaxation, the protons release Rf energy creating an echo that is then transformed via Fourier analysis to generate the MR image. The two relaxation rates that influence the signal intensity of the image are T1 and T2. T1 refers to the time in milliseconds that it takes for 63% of protons to return to their baseline state. T2 relaxation is the time for 63% of protons to become dephased owing to interactions among nearby protons. The intensity of the signal is also influenced by the interval between Rf pulses (TR) and the time between the Rf pulse and the signal reception (TE). T1-weighted images are produced by keeping both TR and TE relatively short, while T2-weighted images require long TR and TE times. Fat and subacute hemorrhages have relatively shorted TR and TE times and thus appear more brightly on T1-weighted images. Structures with more water such as cerebrospinal fluid or edema conversely have long T1 and T2 relaxation times, resulting in higher signal intensity on T2-weighted images. T2 images are also more sensitive for detecting demyelination, infarction, or chronic hemorrhage.

  FLAIR stands for fluid-attenuated inversion recovery and is a type of T2-weighted image that suppresses the high-intensity signal of CSF. Because of this, images created by the FLAIR technique are more sensitive to detecting water-containing lesions or edema than the standard spin images.

  MR angiography refers to several different techniques that are useful for assessing vascular structures, but does not provide details of the underlying brain parenchyma.

6. The answer is E.

(Chap. 4) For many years, MRI imaging was considered the modality of choice for patients with renal insufficiency because it does not lead to acute renal failure. However, gadolinium was recently linked to a rare disorder called nephrogenic systemic fibrosis. This newly described disorder results in widespread fibrosis in skin, skeletal muscle, bone, lungs, pleura, pericardium, myocardium, and many other tissues. Histologically, thickened collagen bundles are seen in the deep dermis of the skin with increased numbers of fibrocytes and elastic fibers. There is no known medical treatment for nephrogenic systemic fibrosis (NSF), although improvement may be seen following kidney transplantation. It has only recently been linked to the receipt of gadolinium-containing contrast agents with a typical onset between 5 and 75 days following administration of the contrast. The incidence of NSF following administration of gadolinium in individuals with a glomerular filtration rate of less than 30 mL/min may be as high as 4% and is thus considered absolutely contraindicated in individuals with severe renal dysfunction.

  Pseudohypocalcemia can occur following administration of gadolinium in individuals with renal dysfunction, but not true hypocalcemia. This occurs because of an interaction of the contrast dye with standard colorimetric assays for serum calcium that are commonly used. If ionized calcium is measured it would be normal, often in the face of very low levels of serum calcium.

  The other reported complications can be seen following administration of iodinated contrast that is used for CT imaging. The most common complication of CT imaging outside of allergic reactions is the development of worsening renal function or acute renal failure. The risk of this can be minimized if the patient is adequately hydrated. Lactic acidosis is a rare but dreaded side effect of iodinated contrast that has been linked to the coadministration of metformin in diabetic patients. Typically a patient is asked to hold metformin for 48 hours before and after a CT scan. The reason for the development of lactic acidosis is actually related to the development of renal insufficiency and a subsequent buildup of lactic acid. In very rare instances, administration of iodinated contrast can unmask hyperthyroidism.

7. The answer is D.

(Chap. 5) While seldom diagnostic, the EEG can often provide clinically useful information in comatose patients. In patients with an altered mental state or some degree of obtundation, the EEG tends to become slower as consciousness is depressed, regardless of the underlying cause. The EEG generally slows in metabolic encephalopathies, and triphasic waves may be present. The findings do not permit differentiation of the underlying metabolic disturbance but help to exclude other encephalopathic processes by indicating the diffuse extent of cerebral dysfunction. As the depth of coma increases, the EEG becomes non-reactive and may show a burst-suppression pattern, with bursts of mixed-frequency activity separated by intervals of relative cerebral inactivity. The EEG is usually normal in patients with locked-in syndrome and helps in distinguishing this disorder from the comatose state with which it is sometimes confused clinically. Epileptiform activity characterized by bursts of abnormal discharges containing spikes or sharp waves may be useful to diagnose and treat nonconvulsive status in a presumed comatose patient. Patients with herpes simplex encephalitis may show a characteristic pattern of focal (often in the temporal regions) or lateralized periodic slow-wave complexes. Periodic lateralizing epileptiform discharges (PLEDs) are commonly found with acute hemispheric pathology such as a hematoma, abscess, or rapidly expanding tumor.

8. The answer is D.

(Chap. 10) Syncope is a common medical complaint that occurs when there is global cerebral hypoperfusion. Syncope accounts for 3% of all emergency department visits and 1% of all hospitalizations. Additionally, it is estimated that 35% of all individuals will experience at least one syncopal event in their lifetimes. The most common cause of syncope in young adults is neurally mediated syncope. The incidence of neurally mediated syncope is higher in females and has a familial predisposition. Neurally mediated syncope represents a complex reflex arc of the autonomic nervous system and inherently requires an intact autonomic nervous system to occur. The final pathway of neurally mediated syncope is a surge of parasympathetic activity with inhibition of the sympathetic nervous system. This results in hypotension with accompanying bradycardia. Syncope occurs when blood flow to the brain drops abruptly. Triggers of the reflex pathway are varied. Vasovagal syncope is one category without a clearly defined trigger but can occur with intense emotions, strong odors, or orthostatic stress. Individuals who faint at the sight of blood experience vasovagal syncope. Neurally mediated syncope can also be brought about by specific situations such as cough, micturition, swallowing, or carotid sensitivity. The primary symptoms of neurally mediated syncope include premonitory symptoms such as lightheadedness and dizziness as well as parasympathetic symptoms such as diaphoresis, pallor, hyperventilation, pallor, and palpitation. Myoclonic jerks of the extremities can occur and be difficult to distinguish from seizure activity. On rare occasions, an individual may experience urinary incontinence, but fecal incontinence does not occur. Individuals usually recover very quickly from neurally mediated syncope with a rapid return to consciousness and previous level of alertness. Reassurance and avoidance of triggers are the primary treatments. Liberal intake of fluids and salt expand plasma volume and are protective against syncopal events. In randomized controlled trials, isometric counterpressure maneuvers (leg crossing or handgrip) are also protective. In patients with refractory syncope, fludrocortisone, beta-blockers, or vasoconstricting agents have been used with clinical success, although there are no clinical trial data to support their use.

9. The answer is A.

(Chap. 10) The cornerstone of the evaluation of syncope is to perform an thorough history and examination. Clues to the cause of syncope include the presence of prodromal symptoms, presence of injury, and eyewitness accounts of the event. Neurally mediated syncope is one of the most common causes of syncope and often has preceding lightheadedness or dizziness. Ortho-static hypotension is also frequently preceded by symptoms of lightheadedness and is more common in older individuals. Likewise, older individuals are at greater risk of cardiac syncope. Cardiac syncope needs to be considered as cardiac syncope caused by structural heart disease or primary arrhythmia is associated with an increased risk of sudden cardiac death. Cardiac syncope is more likely to occur without warning symptoms and is more likely to have associated serious injury. Hypoglycemia can present with syncope as well and needs to be considered in this case. Neurologic causes of syncope include seizures and vertebrobasilar insufficiency. A cerebrovascular accident does not commonly cause syncope because bihemispheric disruption of cerebral blood flow is necessary to cause loss of consciousness.

  In this individual, evaluation should include fingerstick glucose measurement, orthostatic blood pressures, and an electrocardiogram. Tilt table testing can be considered, particularly because the patient has had recurrent episodes of syncope in the past. A head CT scan, however, should not be a routine part of the evaluation of syncope unless there is concern about a head injury that occurred as a result of the syncope.

10. The answer is D.

(Chap. 11) Dizziness is a common complaint affecting approximately 20% of the population over the course of the year. Most dizziness is benign, self-limited, and must be distinguished from vertigo. Although dizziness is often described as a sensation of lightheadedness, vertigo is more often described as a sensation that the room is spinning. Vertigo is most commonly from peripheral causes affecting labyrinths of the inner ear or the vestibular nerve. However, central lesions of the brainstem and cerebellum can also lead to vertigo. Features of the history and physical examination can be useful in determining central versus peripheral causes of vertigo. By history, deafness or tinnitus is typically absent with central lesions. On physical examination, spontaneous nystagmus is most often a sign of central vertigo, although it can be seen with acute vestibular neuritis. Specific patterns of vertigo that are characteristic of lesions in the cerebellar pathways are vertical nystagmus with a downward fast phase (downbeat nystagmus) and horizontal nystagmus that changes direction with gaze (gaze-evoked nystagmus). Alternatively, in peripheral vertigo, nystagmus typically is provoked by positional maneuvers and can be inhibited by visual fixation. Visual fixation does not, however, inhibit nystagmus in central lesions. Finally, central causes of nystagmus are more likely to be associated with other symptoms that would lead one to suspect a central cause. These include hiccups, diplopia, cranial neuropathies, and dysarthria.

11. The answer is C.

(Chap. 11) The symptoms and physical examination of this patient are typical of benign paroxysmal positional vertigo (BPPV). Episodes of BPPV are typically quite brief, lasting no more than 1 minute, and are brought about by changes in position relative to gravity. Typical movements that elicit the vertigo are lying down, rolling over in bed, rising from the supine position, and tilting the head to look upward. The labyrinth of the inner ear is responsible for process information with regards to position and movement. It consists of three semicircular canals: the superior canal, the posterior canal, and the horizontal canal. BPPV results when calcium carbonate crystals called otoconia migrate from the utricle of the inner ear into the semicircular canals. By far, the most commonly affected canal is the posterior one. When this occurs, vertigo is accompanied by nystagmus that beats upward and torsionally toward the affected ear. This can be brought about by the Dix-Hallpike maneuver, which is described in the clinical scenario. Less commonly, the horizontal canal is affected, leading to horizontal nystagmus. The primary treatment of BPPV is repositioning therapy that uses gravity to remove the otoconia from the affected canal. The Epley maneuver is the most common repositioning procedure.

  The history and physical examination are not consistent with a central cause of vertigo; therefore, a brain MRI is not indicated. Methylprednisolone is the primary treatment of acute vestibular neuritis if used within the first 3 days of symptoms. Acute vestibular neuritis often presents with more prolonged symptoms that persist even when there is no movement of the head. Most patients recover spontaneously, but when used early, methylprednisolone will decrease the duration of symptoms. There is no indication for the use of antiviral therapy unless there is obvious herpes zoster infection. Likewise, the symptoms are not consistent with migrainous vertigo, which would be persistent for hours and not be affected by positional changes. Thus, the use of rizatriptan would not be helpful.

12. The answer is D.

(Chap. 12) Complaints of weakness in a patient have a multitude of causes, and it is important to perform a thorough history and physical examination to help localize the site of weakness. Lower motor neuron diseases occur when there is destruction of the cell bodies of the lower motor neurons in the brainstem or the anterior horn of the spinal cord. Lower motor neuron diseases can also occur because of direct axonal dysfunction and demyelination. The primary presenting symptoms are those of distal muscle weakness such as tripping or decreased hand grip strength. When a motor neuron becomes diseased, it may discharge spontaneously, leading to muscle fasciculations that are not seen in disease of the upper motor neurons or myopathies. Additionally, on physical examination, lower motor neuron disease leads to decreases in muscle tone and decreased or absent deep tendon reflexes. Over time, severe muscle atrophy can occur. A Babinski sign should not be present. If there is evidence of a Babinski sign in the presence of lower motor neuron disease, this should raise the suspicion of a disorder affecting both upper and lower motor neurons such as amyotrophic lateral sclerosis.

13. The answer is E.

(Chap. 13) Approximately 15% of individuals older than 65 years have an identifiable gait disorder. By age 80 years, 25% of individuals require a mechanical aid to assist ambulation. Proper maintenance of gait requires a complex interaction between central nervous system centers to integrate postural control and locomotion. The cerebellum, brainstem, and motor cortex simultaneously process information regarding the environment and purpose of the motion to allow for proper gait and avoidance of falls. Any disorder affecting either sensory input regarding the environment or central nervous system output has the potential to affect gait. In most case series, the most common cause of gait disorders is a sensory deficit. The causes of sensory deficits can quite broad and include peripheral sensory neuropathy from a variety of causes, including diabetes mellitus, peripheral vascular disease, and vitamin B12deficiency, among many others. Other common causes of gait disorders include myelopathy and multiple cerebrovascular infarcts. Although Parkinson’s disease is almost inevitably marked by gait abnormalities, it occurs less commonly in the general population than the previously discussed disorders. Likewise, cerebellar degeneration is frequently associated with gait disturbance but is a less common disorder in the general population.

14. The answer is B.

(Chap. 13) Characteristics found during the neurologic examination can assist with the localization of disease in gait disorders. In this case, the patient presents with signs of a frontal gait disorder or parkinsonism. The specific characteristics that would be seen with a frontal gait disorder are a wide-based stance with slow and short shuffling steps. The patient may have difficulty rising from a chair and has a slow, hesitating start. Likewise, there is great difficult with turning with multiple steps required to complete a turn. The patient has very significant postural instability. However, cerebellar signs are typically absent. Romberg sign may or may not be positive, and seated cerebellar testing results are normal, including heel-to-shin testing and rapid alternating movements. Additionally, there should otherwise be normal muscle bulk and tone without sensory or strength deficits. The most common cause of frontal gait disorders (sometimes known as gait apraxia) is cerebrovascular disease, especially small vessel subcortical disease. Communicating hydrocephalus also presents with a gait disorder of this type. In some individuals, the gait disorder precedes other typical symptoms such as incontinence or mental status change.

  Alcoholic cerebellar degeneration and multiple system atrophy present with signs of cerebellar ataxia. Characteristics of cerebellar ataxia include a wide-based gait with variable velocity. Gait initiation is normal, but the patient is hesitant during turns. The stride is lurching and irregular. Falls are a late event. The heel-to-shin test is abnormal, and the Romberg test is variably positive.

  Neurosyphilis and lumbar myelopathy are examples of sensory ataxia. Sensory ataxia presents with frequent falls. The gait with sensory ataxia, however, is narrow based. Often the patient is noted to be looking down while walking. The patient tends to walk slowly but have path deviation. Gait is initiated normal, but the patient may have some difficulty with turning. The Romberg test is typically unsteady and may result in falls.

15. The answer is D.

(Chap. 16) Delirium is an acute confusional state that most frequently occurs in the context of an acute medical illness. Fluctuating levels of cognitive function with a particular deficit of attention are the primary clinical features of delirium. All levels of cognitive function, however, are invariably involved, including memory, language, and executive functioning. Other common associated symptoms are sleep–wake disturbances, hallucinations or delusions, affect changes, and changes in heart rate or blood pressure. Delirium remains a clinical diagnosis and is believed to affect as much as 50% of hospitalized patients. For elderly patients in intensive care, the incidence rises to between 70 and 87%. However, it has been estimated the diagnosis is missed in one-third of individuals with delirium. Once thought of as an acute but benign condition, increasing research is demonstrating delirium to have persisting effects on cognition and functioning. Delirium typically is short lived, but some episodes of delirium can last for weeks, months, or even years. When delirium persists for longer periods of time, it is thought to represent inadequate treatment of the cause of delirium or permanent neuronal damage from the episode. Delirium also has significant associated morbidity and mortality. A single episode of delirium in hospitalized patients has been associated with an in-hospital mortality rate as high as 25–33%. However, the increased mortality is not simply limited to the hospital stay. Individuals experiencing delirium in the hospital have increased mortality for the next several months to years. In addition, these individuals experience a longer hospital length of stay and are less likely to return to functional independence. Individuals who experience delirium are more likely to be discharged to nursing home care and are at increased risk of rehospitalization.

16. The answer is B.

(Chap. 16) This patient has features of acute delirium, which can be precipitated by many causes in hospitalized patients. Broad categories of causes of delirium include toxins, medication reactions, metabolic disorders, infections, endocrine disorders, cerebrovascular disorders (especially hypertensive encephalopathy), autoimmune disorders, seizures, neoplastic disorders, and hospitalization. Although the list of causes is broad, the initial history and physical examination are important to establish potential etiologies of delirium and guide further workup. In most patients with delirium, it is difficult to obtain an accurate history; therefore, it is important to seek out a spouse of family member to outline the history further. In this case, there are features that could suggest alcohol withdrawal (hypertension, tachycardia, fevers, tremors), and one should clarify his alcohol intake with his wife. Another primary consideration in determining the etiology of a delirium episode is the time course over which it evolves and the current medications. Particularly in older hospitalized individuals, common medications used as sleep aids, such as diphenhydramine, can have a paradoxical effect with delirium and agitation. It is estimated that as many as one-third of episodes of delirium in hospitalized patients are the result of medications. Worsening infection also needs to be considered because the change in the patient’s vital signs could be indicative of an infectious source, although the elevated blood pressure is not consistent with this. Because the patient has required oxygen during his hospitalization, it is important to check an oxygen saturation or arterial blood gas because acute hypoxemia or hypercarbia can precipitate delirium. Likewise, given the patient’s history of diabetes mellitus, a fingerstick glucose is necessary because hypoglycemia could also lead to alterations in mental status with evidence of tachycardia, tremor, and diaphoresis. Other initial tests to consider in an individual with delirium are electrolytes and basic liver and kidney function. Although commonly ordered, brain imaging is most often not helpful in the evaluation of delirium.

17. The answer is C.

(Chap. 16) Confusion is defined as a mental and behavioral state of reduced comprehension, coherence, and capacity to reason. Delirium is used to describe an acute confusional state. Delirium often goes unrecognized despite clear evidence that it is often a cognitive manifestation of many medical and neurologic illnesses. Delirium is a clinical diagnosis that may be hyperactive (e.g., alcohol withdrawal) or hypoactive (e.g., opiate intoxication). There is often dramatic fluctuation between states. Delirium is associated with a substantial mortality rate with in-hospital mortality estimates ranging from 25–33%. Overall estimates of delirium in hospitalized patients range from 15–55% with higher rates in elderly adults. Patients in the intensive care unit have especially high rates of delirium, ranging from 70–87%. The clinic setting represents the lowest risk. Postoperative patients, especially after hip surgery, have an incidence of delirium that is somewhat higher than patients admitted to the medical wards.

18. The answer is D.

(Chap. 17) Alterations in consciousness are among the most common reasons for admission to the hospital and occur frequently in seriously ill patients. When evaluating a patient with an alteration in consciousness, one must have a framework for understanding the spectrum of arousability one may encounter. Coma is a frequently misunderstood term that refers to a deep sleeplike state from which a patient cannot be aroused. A stuporous patient can be aroused briefly with noxious stimuli, and drowsiness refers to a patient who can be aroused easily with maintenance of attention for brief periods. Other conditions that alter the ability of a patient to respond appropriately to stimuli and are often confused with coma. A vegetative state is an awake but unresponsive condition that can occur in a patient who has emerged from a coma and is associated with extensive bilateral cerebral damage. A patient in a vegetative state can open the eyes spontaneously and often track objects. In addition, the patient has retention of respiratory and autonomic functions as well as spontaneous movement of extremities. However, meaningful responses to stimuli do not occur, and a vegetative state is sometimes referred to as an “awake coma.” This patient would be characterized as being in a persistent vegetative state because the duration of the vegetative state has been 1 year. At this point, the likelihood of meaningful recovery of mental faculties is almost zero. A minimally conscious state is a less severe manifestation of bilateral cerebral injury. A patient in a minimally conscious state may have rudimentary vocal or motor behaviors and minimal responses to external stimuli. Other conditions that may be misinterpreted as a coma include akinetic mutism, catatonia, abulia, and locked-in syndrome.

19. The answer is A.

(Chap. 17) Brain death occurs when all cerebral function has ceased but the patient continues to have cardiac activity while supported by artificial means. If an individual is determined to have brain death, life-sustaining therapies are withdrawn. Although this can occur without the consent of the family, certainly it is important to have open communication with the family to allow the withdrawal of care without conflict. Most hospitals have developed specific protocols to diagnose a patient with brain death. Three essential elements should be demonstrated for the diagnosis of brain death. First, the patient should widespread cortical damage with complete absence of response to all external stimuli. Second, the patient should have no evidence of brainstem function with loss of oculovestibular and corneal reflexes and absent pupillary reaction to light. Finally, there should be no evidence of medullary activity manifested by apnea. When a brain death examination is performed, the patient should not be receiving any medications that could alter consciousness. The bedside examination will confirm absence of responsiveness to stimuli and lack of brainstem function. Apnea testing is the final examination in the performance of the brain death examination. This test is important for documenting the absence of medullary function. For an apnea test result to be accurate, the carbon dioxide must be allowed to rise to a level that would stimulate respiration. When performing the test, the patient is preoxygenated with 100% oxygen, which is sustained throughout the test. At this point, ventilator support is stopped. In the absence of any respiration, carbon dioxide rises by 2–3 mmHg/min, and it is necessary for arterial partial pressure of carbon dioxide to rise to between 50–60 mmHg. If the patient has a normal PaCO2 before beginning the apnea test, the test would typically need to continue for at least 5 minutes to be valid. The patient is observed for respiratory effort, and a PaCO2 level is often measured at the end of the test to document that the rise in carbon dioxide is adequate to stimulate respiration. Some patients may have cardiovascular instability that makes the performance of apnea testing risky because one does not wish for the apnea test to lead to cardiovascular collapse. In this setting, an electroencephalogram demonstrating absence of electrical activity is used as an adjunctive diagnostic test. Newer methods of testing, including radionuclide brain scanning, cerebral angiography, and transcranial Doppler ultrasonography, may be used, but these tests are less well validated. In most cases, clinical evidence of brain death must be sustained for 6–24 hours before withdrawal of care.

20. The answer is E.

(Chap. 17) Foraminal herniation, which forces the cerebellar tonsils into the foramen magnum, leads to compression of the medulla and subsequent respiratory arrest. Central transtentorial herniation occurs when the medial thalamus compresses the midbrain as it moves through the tentorial opening; miotic pupils and drowsiness are the classic clinical signs. A locked-in state is usually caused by infarction or hemorrhage of the ventral pons; other causes include Guillain-Barré syndrome and use of certain neuromuscular blocking agents. Catatonia is a semi-awake state seen most frequently as a manifestation of psychotic disorders such as schizophrenia. Third-nerve palsies arise from an uncal transtentorial herniation in which the anterior medial temporal gyrus herniates into the anterior portion of the tentorial opening anterior to the adjacent midbrain. Coma may occur because of compression of the midbrain.

21. The answer is B.

(Chap. 18) When evaluating someone who reports difficulty with language, it is important to assess speech in several different domains, which are spontaneous speech, comprehension, repetition, naming, reading, and writing. Anomia refers to the inability to name common objects and is the most common finding in patients with aphasia. Indeed, anomia is present in all types of aphasia except pure word deafness or pure alexia. Anomia can present in many fashions, including complete an inability to name, provision of a related word (“pen” for “pencil”), a description of the word (“a thing for writing”), or the wrong word. Fluency is assessed by listening to spontaneous speech. Fluency is decreased in Broca’s or global aphasia but is relatively preserved in other forms of aphasia. Comprehension is assessed by asking patients to follow conversation and provide simple answers (yes/no, pointing to appropriate objects). The most common aphasia presenting with deficits of comprehension is Wernicke’s aphasia in which fluent but nonsensical spontaneous speech (word salad) is present. Repetition asks patients to repeat a string of words, sentences, or a single word and is impaired in many types of aphasia. In addition, repetition of tongue twisters can be useful in the evaluation of dysarthria or palilalia as well. Alexia refers to the inability to read aloud or comprehend written language.

22. The answer is C.

(Chap. 18) The parietofrontal area of the brain is responsible for spatial orientation. The major components of the network include the cingulate cortex, posterior parietal cortex, and the frontal eye fields. In addition, subcortical areas in the striatum and thalamus are also important. Together, these systems integrate information to maintain spatial cognition, and a lesion in any of these areas can lead to hemispatial neglect. In neglect syndromes, three behavioral manifestations are seen: Sensory events in the neglected hemisphere have less overall impact; there is a paucity of conscious acts directed toward the neglected hemisphere; and the patient behaves as if the neglected hemisphere is devalued. In Figure 22, almost all of the A’s (the target) represented on the left half of the figure are missed. This is an example of a target detection task. Hemianopia alone is not sufficient to cause this finding because the individual can turn his or her head left and right to identify the targets.

  Bilateral disorders of the parietofrontal area of the brain can lead to severe spatial disorientation known as Balint’s syndrome. In Balint’s syndrome, there is inability to orderly scan the environment (oculomotor apraxia) and inaccurate manual reaching for objects (optic apraxia). A third finding in Balint’s syndrome is simultanagnosia. Simultanagnosia is the inability to integrate information in the center of the gaze with peripheral information. An example is a target detection test in which only the A’s present in the outer portion of the figure would be indicated. Individuals with this finding also tend to miss the larger objects in a figure and would not be able to accurately identify the target when it was made much larger than the surrounding letters. Construction apraxia refers to the inability to copy a simple line drawing such as a house or star and occurs most commonly in association with parietal lesions. Object agnosia is the inability to name a generic object or describe its use in contrast to anomia when an individual should be able to describe the use of the object even if it cannot be named. The defect in the object agnosia is usually in the territory of the bilateral posterior cerebral arteries.

23. The answer is C.

(Chap. 20) Shift work sleep disorder is a disorder of the circadian rhythm that is common in any individual who has to commonly work at night. At present, an estimated 7 million individuals in the United States work permanently at night or on rotating shifts. Increasing research devoted to sleep disorders in night shift workers has demonstrated that the circadian rhythm never fully shifts to allow one to perform at full alertness at night. The reason for this is likely multifactorial and includes the fact that most individuals who work at night try to abruptly shift their sleep schedules to a more normal pattern on days when they are not working. Consequently, night shift workers often have chronic sleep deprivation, increased length of time awake before starting work, and misalignment of their circadian phase with the intrinsic circadian phase. The results of this lead to decreased alertness and increased errors during night shifts. In an estimated 5–10% of individuals working night shifts, the excessive sleepiness during the night and insomnia during the day are deemed to be clinically significant. Strategies for treating shift work sleep disorder use a combination of behavioral and pharmacologic strategies. Caffeine does promote wakefulness, but the effects are not long lasting, and tolerance develops over time. Brief periods of exercise frequently boost alertness and can be used before starting a night shift or during the shift at times of increased sleepiness. Many sleep experts support strategic napping during shifts for no more than 20 minutes at times of circadian nadirs. Naps longer than 20 minutes can lead to sleep inertia during which an individual may feel very disoriented and groggy and experience a decline in motor skills upon abrupt awakening from sleep. Bright lights before and during night shift work may improve alertness, but one must be careful to avoid bright lights in the morning after a night shift because light entrainment is a powerful stimulus of the internal circadian clock. If an individual is exposed to bright light in the morning, it will interfere with the ability to fall asleep during the day. Night shift workers should be encouraged to wear dark sunglasses in the morning on the way home. Sleep during the day is frequently disrupted in night shift workers. Creating a quiet, dark, and comfortable environment is important, and sleep should be a priority for the individual during the day. The only pharmacologic therapy approved by the Food and Drug Administration for treatment of shift work sleep disorder is modafinil 200 mg taken 20–30 minutes before the start of a night shift. Modafinil has been demonstrated to increase sleep latency and decrease attentional failures during night shifts but does not alleviate the feelings of excessive sleepiness. Melatonin is not one of the recommended therapies for shift work sleep disorder. If used, it should be taken 2–3 hours before bedtime rather than right before bedtime to simulate the normal peaks and troughs of melatonin secretion.

24. The answer is C.

(Chap. 20) This patient complains of symptoms that are consistent with restless legs syndrome (RLS). This disorder affects 1–5% of young to middle-aged individuals and as many as 20% of older individuals. The symptom of RLS is a nonspecific uncomfortable sensation in the legs that begins during periods of quiescence and is associated with the irresistible urge to move. Patients frequently find it difficult to describe their symptoms but usually describe the sensation as deep within the affected limb. Rarely is the sensation described as distinctly painful unless an underlying neuropathy is also present. The severity of the disorder tends to wax and wane over time and tends to worsen with sleep deprivation, caffeine intake, pregnancy, and alcohol. Renal disease, neuropathy, and iron deficiency are known secondary causes of RLS symptoms. In this patient, correcting the iron deficiency is the best choice for initial therapy because this may entirely relieve the symptoms of RLS. For individuals with primary RLS (not related to another medical condition), the dopaminergic agents are the treatment of choice. Pramipexole or ropinirole is recommended as first-line treatment. Although carbidopa/levodopa is highly effective, individuals have a high risk of developing augmented symptoms over time with increasingly higher doses needed to control the symptoms. Other options for treating RLS include narcotics, benzodiazepines, and gabapentin. Hormone replacement therapy has no role in the treatment of RLS.

25. The answer is A.

(Chap. 20) Narcolepsy is a sleep disorder characterized by excessive sleepiness with intrusion of rapid eye movement (REM) sleep into wakefulness. Narcolepsy affects about one in 4000 individuals in the United States with a genetic predisposition. Recent research has demonstrated that narcolepsy with cataplexy is associated with low or undetectable levels of the neurotransmitter hypocretin (orexin) in the CSF. This neurotransmitter is released from a small number of neurons in the hypothalamus. Given the association of narcolepsy with the major histocompatibility antigen human leukocyte antigen DQB1*0602, it is thought that narcolepsy is an autoimmune process that leads to destruction of the hypocretin-secreting neurons in the hypothalamus. The classic symptom tetrad of narcolepsy is (1) cataplexy, (2) hypnagogic or hypnopompic hallucinations, (3) sleep paralysis, and (4) excessive daytime somnolence. Of these symptoms, cataplexy is the most specific for the diagnosis of narcolepsy. Cataplexy refers to the sudden loss of muscle tone in response to strong emotions. It most commonly occurs with laughter or surprise but may be associated with anger as well. Cataplexy can have a wide range of symptoms from mild sagging of the jaw lasting for a few seconds to a complete loss of muscle tone lasting several minutes. During this time, individuals are aware of their surroundings and are not unconscious. This symptom is present in 76% of individuals diagnosed with narcolepsy and is the most specific finding for the diagnosis. Hypnagogic and hypnopompic hallucinations and sleep paralysis can occur from any cause of chronic sleep deprivation, including sleep apnea and chronic insufficient sleep. Excessive daytime somnolence is present in 100% of individuals with narcolepsy but is not specific for the diagnosis because this symptom may be present with any sleep disorder as well as with chronic insufficient sleep. The presence of two or more REM periods occurring during a daytime multiple sleep latency test is suggestive but not diagnostic of narcolepsy. Other disorders that may lead to presence of REM during short daytime nap periods include sleep apnea, sleep phase delay syndrome, and insufficient sleep.

26. The answer is B.

(Chap. 20http://www.sleepfoundation.org/site/c.huIXKjM0IxF/b.2417355/k.143E/2002_Sleep_in_America_Poll.htm, accessed May 12, 2011) Insomnia is the most common sleep disorder in the population. In the 2002 Sleep in America Poll, 58% of respondents reported at least one symptom of insomnia on a weekly basis, and one-third of individuals experience these symptoms on a nightly basis. Insomnia is defined clinically as the inability to fall asleep or stay asleep, which leads to daytime sleepiness or poor daytime function. These symptoms occur despite adequate time and opportunity for sleep. Insomnia can be further characterized as primary or secondary. Primary insomnia occurs in individuals with an identifiable cause of insomnia and is often a long-standing diagnosis for many years. Within the category of primary insomnia is adjustment insomnia, which is typically of short duration with a well-defined stressor. Secondary causes of insomnia include comorbid medical or psychiatric conditions and can be related to caffeine or illegal and prescribed drugs. Obstructive sleep apnea is thought to affect as many as 10–15% of the population and is currently underdiagnosed in the United States. In addition, because of the rising incidence of obesity, obstructive sleep apnea is also expected to increase in incidence over the coming years. Obstructive sleep apnea occurs when there is ongoing effort to inspire against an occluded oropharynx during sleep. It is directly related to obesity and has an increased incidence in men and in older populations. Narcolepsy affects 1 in 4000 people and is caused by deficit of hypocretin (orexin) in the brain. Symptoms of narcolepsy include a sudden loss of tone in response to emotional stimuli (cataplexy), hypersomnia, sleep paralysis, and hallucinations with sleep onset and waking. Physiologically, there is intrusion or persistence of rapid eye movement sleep during wakefulness that accounts for the classic symptoms of narcolepsy. Restless legs syndrome is estimated to affect 1–5% of young to middle-aged adults and as many as 10–20% of elderly adults. Restless legs syndrome is marked by uncomfortable sensations in the legs that are difficult to describe. The symptoms have an onset with quiescence, especially at night, and are relieved with movement. Delayed sleep phase syndrome is a circadian rhythm disorder that commonly presents with a complaint of insomnia and accounts for as much as 10% of individuals referred to the sleep clinic for evaluation of insomnia. In delayed sleep phase syndrome, the intrinsic circadian rhythm is delayed such that sleep onset occurs much later than normal. When allowed to sleep according to the intrinsic circadian rhythm, individuals with delayed sleep phase syndrome sleep normally and do not experience excessive somnolence. This disorder is most common in adolescence and young adulthood.

27. The answer is C.

(Chap. 20) Parasomnias are abnormal behaviors or experiences that arise from slow-wave sleep. Also known as confusional arousals, the electroencephalogram during a parasomnia event frequently shows persistence of slow-wave (delta) sleep into arousal. Non–rapid eye movement (NREM) parasomnias may also include more complex behavior, including eating and sexual activity. Treatment of NREM parasomnias is usually not indicated, and a safe environment should be assured for the patient. When injury is likely to occur, treatment with a drug that decreases slow-wave sleep will treat the parasomnia. Typical treatment is a benzodiazepine. There are no typical parasomnias that arise from stage I or stage II sleep. REM parasomnias include nightmare disorder and REM-behavior disorder. REM-behavior disorder is increasingly recognized as associated with Parkinson’s disease and other parkinsonian syndromes. This disorder is characterized by the absence of decreased muscle tone in REM sleep, which leads to the acting out of dreams, sometimes resulting in violence and injury.

28. The answer is E.

(Chap. 21) (See Figure 21-3.) Bitemporal hemianopia is caused by a lesion at the optic chiasm because fibers there decusate into the contralateral optic tract. Crossed fibers are more damaged by compression than uncrossed fibers. This finding is usually caused by symmetric compression in the sellar region by a pituitary adenoma, meningioma, craniopharyngioma, glioma, or aneurysm. These lesions are often insidious and may be unnoticed by the patient. They will escape detection by the physician unless each eye is tested separately. Lesions anterior to the chiasm (retinal injury, optic nerve injury) will cause unilateral impairment and an abnormal pupillary response. Postchiasmic lesions (temporal, parietal, occipital cortex) cause homonymous lesions (similar field abnormalities in both eyes) that vary with location. Occlusion of the posterior cerebral artery supplying the occipital lobe is a common cause of total homonymous hemianopia.

29. The answer is E.

(Chap. 21) The differential diagnosis of a red, painful eye is broad and includes corneal abrasion, subconjunctival hemorrhage, infective or allergic conjunctivitis (the most common cause of red, painful eye), keratoconjunctivitis sicca (medications, Sjögren’s syndrome, sarcoidosis), keratitis (contact lens injury, trachoma, vitamin A deficiency), herpes infection, episcleritis (autoimmune, idiopathic), scleritis (autoimmune), uveitis, endophthalmitis, or acute angle-closure glaucoma. Uveitis requires slit-lamp examination for diagnosis. Anterior uveitis involving the iris is usually idiopathic but may be associated with sarcoidosis, ankylosing spondylitis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriasis, inflammatory arthritis, Behçet’s disease, and a variety of infections. Posterior uveitis in the vitreous, retina, or choroid is more likely to be associated with a systemic disease or infection than anterior uveitis. Acute angle-closure glaucoma, although rare, is often misdiagnosed unless intraocular pressure is measured. Many physicians avoid dilating patients’ pupils for fear of provoking acute angle-closure glaucoma. The risk is remote and rarely causes permanent vision loss. The value of a complete funduscopic examination outweighs the risk of this rare event. Transient ischemic attack (TIA) caused by temporary interruption of blood flow to the retina for more than a few seconds causes transient visual abnormality (amaurosis fugax). TIA is usually associated with atherosclerosis. If flow is restored quickly vision returns to normal.

30. The answer is A.

(Chap. 21) Age-related macular degeneration is a major cause of painless, gradual bilateral central visual loss. It occurs as nonexudative (dry) or exudative (wet) forms. Recent genetic data have shown an association with the alternative complement pathway gene for complement factor H. The mechanism link for that association is unknown. The nonexudative form is associated with retinal drusen that leads to retinal atrophy. Treatment with vitamin C, vitamin E, beta-carotene, and zinc may retard the visual loss. Exudative macular degeneration, which is less common, is caused by neovascular proliferation and leakage of choroidal blood vessels. Acute visual loss may occur because of bleeding. Exudative macular degeneration may be treated with intraocular injection of a vascular endothelial growth factor antagonist (bevacizumab or ranibizumab). Blepharitis is inflammation of the eyelids usually related to acne rosacea, seborrheic dermatitis, or staphylococcal infection. Diabetic retinopathy, now a leading cause of blindness in the United States, causes gradual bilateral visual loss in patients with long-standing diabetes. Retinal detachment is usually unilateral and causes visual loss and an afferent pupillary defect.

31. The answer is B.

(Chap. 23) A history of severe respiratory infection, including the common cold, influenza, pneumonia, or HIV, is the most common cause of long-lasting loss of smell. The mechanism, along with cases of chronic rhinosinusitis (another common cause) is likely related to permanent damage to the olfactory epithelium. Head trauma, causing shearing and scarring of olfactory fila at the cribriform plate, may cause anosmia. Fewer than 10% of patients with posttraumatic anosmia regain normal function. The severity of disease is associated with the likelihood of olfactory abnormality in trauma and chronic rhinosinusitis. Significant decrements in smell are present in more than 50% of people older than 65 years old. This finding may explain the common finding of loss of food flavor and nutritional deficiencies in elderly adults. Confirming popular wisdom studies have shown that at any age, women have a better ability to identify odorants than men (Figure 23-6).

32. The answer is E.

(Chap. 24) Hearing loss is a common complaint, particularly in older individuals. In this age group, 33% have hearing loss to a degree that requires hearing aids. When evaluating hearing loss, the physician should attempt to determine whether the cause is conductive, sensorineural, or mixed. Sensorineural hearing loss results from injury of the cochlear apparatus or disruption of the neural pathways from the inner ear to the brain. The primary site of damage is the hair cells of the inner ear. Common causes of hair cell injury include prolonged exposure to loud noises, viral infections, ototoxic drugs, cochlear otosclerosis, Ménière’s disease, and aging. In contrast, conductive hearing loss results from impairment of the external ear and auditory canal to transmit and amplify sound through the middle ear to the cochlea. Causes of conductive hearing loss include cerumen impaction, perforations of the tympanic membrane, otosclerosis, cholesteatomas, large middle ear effusions, and tumors of the external auditory canal or middle ear among others. The initial physical examination can often differentiate between conductive or sensorineural hearing loss. Examination of the external auditory canal can identify cerumen or foreign body impaction. On otoscopic examination, it is more important to assess the topography of the tympanic membrane than to look for the presence of a light reflex. Of particular attention is the area in the upper third of the tympanic membrane known as the pars flaccida. This area can develop chronic retraction pockets that are indicative of Eustachian tube dysfunction or a cholesteatoma, a benign tumor composed of keratinized squamous epithelium. Bedside tests with a tuning fork also are useful for differentiating conductive from sensorineural hearing loss. In the Rinne’s test, air conduction is compared with bony conduction of sound. A tuning fork is placed over the mastoid process and then in front of the external ear. In conductive hearing loss, the intensity of sound is louder when placed on the bone, but in sensorineural hearing loss, the intensity is greatest at the external ear. In the Weber test, the tuning fork is placed in the midline of the head. In unilateral conductive hearing loss, the intensity of sound is loudest in the affected ear, but in unilateral sensorineural hearing loss, the intensity of sound is loudest in the unaffected ear. This patient reports left greater than right hearing loss that is suspected to be sensorineural in nature. Thus, the sound is expected to be greatest in the right ear on the Weber test. A more formal evaluation of hearing loss would include pure tone audiometry that plots hearing threshold versus frequency. Pure tone audiometry establishes the severity, type, and laterality of hearing loss. In this patient, high-frequency hearing loss would be expected based on his complaints of inability to hear the alarm tone of his digital watch.

33. The answer is D.

(Chap. 25) Channelopathies, disorders of ion channels that lead to disease, are a growing mechanism to explain a number of neurologic diseases. Most are caused by a mutation in the ion channel gene or by autoimmune alteration of ion channel proteins. Some forms of epilepsy, including benign neonatal familial convulsions and generalized epilepsy with febrile convulsions, are associated with genetic abnormalities of sodium or potassium channels. Familial hemiplegic migraines are associated with genetic abnormalities in sodium and calcium channels. Spinocerebellar ataxia and other ataxias are associated with genetic abnormalities in potassium or calcium channels. Lambert-Eaton syndrome is an example of autoimmune-related abnormalities in calcium channel function. Parkinson’s disease is the classic example of neurotransmitter system–mediated disease.

34. The answer is C.

(Chap. 25) Synaptic neurotransmission is the predominant mechanism for neuronal communication. Therefore, it is not surprising that dysfunction with any step in the presynaptic synthesis, vesicular storage, and synaptic cleft release, and receptor binding in the postsynaptic cell may be associated with disease. Neurotransmitters bind to specific receptors that are either ionotropic or metabotropic. Functions related to ionotropic receptors are generally fast (<1 millisecond) and metabotropic receptors are more prolonged. Antibodies to the acetylcholine receptors or motor neuron calcium channels cause myasthenia gravis and Lambert-Eaton syndrome, respectively. Parkinson’s syndrome is related to selective cell death in the nigrostriatal dopamine pathway. Stiff-person syndrome is related to antibodies to glutamic acid decarboxylase, the biosynthetic pathway for GABA. Orthostatic tachycardia syndrome is related to mutations in the norepinephrine transporter. Abnormalities with serotonin neurotransmitter function are implicated in mood disorders, migraine pain pathways, and somatic pain pathways.

35. The answer is B.

(Chap. 26) The International League against Epilepsy (ILAE) Commission on Classification and Terminology, 2005–2009, has provided an updated approach to the classification of seizures. This system is based on the clinical features of seizures and associated electroencephalographic findings. Seizures are classified as focal or generalized. Focal seizures arise from a neuronal network either discretely localized within one cerebral hemisphere or more broadly distributed but still within the hemisphere. They are frequently associated with a structural lesion. Generalized seizures are thought to arise at some point in the brain but immediately and rapidly engage neuronal networks in both cerebral hemispheres. Focal seizures are subdivided into those with or without dyscognitive features depending on the patient’s ability to interact with the environment during an episode. The terms “simple partial seizure” and “complex partial seizure” have been eliminated. Typical absence seizures are characterized by sudden, brief lapses of consciousness without loss of postural control. The seizure typically lasts for only seconds, consciousness returns as suddenly as it was lost, and there is no postictal confusion. Myoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body. Although the distinction from other forms of myoclonus (e.g., metabolic, degenerative neurologic disease, anoxic encephalopathy) is imprecise, myoclonic seizures are considered to be true epileptic events since they are caused by cortical dysfunction.

36. The answer is A.

(Chap. 26) Mesial temporal lobe epilepsy is the most common epilepsy syndrome associated with focal seizures with dyscognitive features. Patients are unable to respond to verbal or visual commands during the seizure and they often manifest complex automatisms or complex posturing. An aura is common before the seizures. There is postictal memory loss or disorientation. Patients often have a history of febrile seizures or a family history of seizures. MRI will show hippocampal sclerosis, a small temporal lobe, or enlarged temporal horn. Mesial temporal lobe epilepsy is important to recognize as a distinct syndrome because it tends to be refractory to treatment with anticonvulsants but responds extremely well to surgical intervention. Hypothyroidism, herpes virus infection, diabetes, and tuberous sclerosis are not associated with mesial temporal lobe epilepsy.

37. The answer is E.

(Chap. 26) Focal seizures without dyscognitive features cause motor, sensory, autonomic, or psychic symptoms without an obvious alteration in consciousness. The phenomenon of abnormal motor movements beginning in a restricted area then progressing to involve a larger area is termed Jacksonian march. The patient is describing Todd’s paralysis, which may take minutes to many hours to return to normal. Although meningitis is a common cause of seizure in young patients, it is unlikely to be the cause in someone who has a known seizure disorder. If his symptoms were to persist beyond many hours, it would be reasonable to investigate a different etiology of his hand weakness with imaging studies. Overt deficits in strength are not compatible with a primary psychiatric disorder. Magnetic resonance angiogram and cerebral angiogram are useful to evaluate for cerebrovascular disorders, but there is no evidence of subarachnoid bleeding or vasculitis.

38. The answer is C.

(Chap. 26) Nuchal rigidity and an elevated white blood cell count are very concerning for meningitis as the etiology for this patient, and lumbar puncture must be performed to rule this out. In addition, acute cocaine intoxication is a plausible reason for this new-onset seizure. Figure 26-2 illustrates the evaluation of the adult patient with a seizure. MRI would be indicated if the patient had a negative metabolic and toxicologic screening. Substance abuse counseling, while indicated, is not indicated at this point in his workup since he is postictal. The patient is not having seizures, does not have a known seizure disorder, and has not been treated for the underlying metabolic abnormality, making IV loading with an antiepileptic medication premature at this time.

39. The answer is B.

(Chap. 26) Optimal medical therapy for epilepsy depends on the underlying cause, type of seizure, and patient factors. The goal is to prevent seizures and minimize the side effects of therapy. The minimal effective dose is determined by trial and error. In choosing medical therapies, drug interactions are a key consideration. Certain medications, such as tricyclic antidepressants, may lower the seizure threshold and should be avoided. Patients who respond well to medical therapy and have completely controlled seizures are good candidates for the discontinuation of therapy, with about 70% of children and 60% of adults being able to discontinue therapy eventually. Patient factors that aid in this include complete medical control of seizures for 1–5 years, a normal neurologic examination, a normal EEG, and single seizure type. On the other end of the spectrum, about 20% of these patients are completely refractory to medical therapy and should be considered for surgical therapy. In the best examples, such as mesial temporal sclerosis, resection of the temporal lobe may result in about 70% of these patients becoming seizure-free and an additional 15–25% having a significant reduction in the incidence of seizures. In patients with epilepsy other considerations are critical. Psychosocial sequelae such as depression, anxiety, and behavior problems may occur. Approximately 20% of epileptic patients have depression, with their suicide rate being higher than that of age-matched controls. There is an impact on the ability to drive, perform certain jobs, and function in social situations. Furthermore, there is a two- to threefold increase in mortality for patients with epilepsy compared with age-matched controls. Although most of the increased mortality results from the underlying etiology of epilepsy, a significant number of these patients die from accidents, status epilepticus, and a syndrome known as sudden unexpected death in epileptic patients (SUDEP). A recent meta-analysis demonstrated that treatment of patients with refractory seizures with an antiepileptic drug could reduce the frequency of SUDEP (Lancet Neurol 2011;10:961).

40. The answer is D.

(Chap. 26) Adolescence and early adulthood mark the period where idiopathic or genetic epilepsy syndromes become less common and seizures due to acquired central nervous system (CNS) lesions become more common. The most common causes of seizures in the young adults are head trauma, CNS infections, brain tumors, congenital CNS lesions, illicit drug use, or alcohol withdrawal. Fever rarely causes seizure in patients older than 12 years. Amyloid angiopathy and uremia are more common in older adults.

41. The answer is A.

(Chap. 26) Status epilepticus refers to continuous seizures or repetitive, discrete seizures with impaired consciousness in the interictal period. The duration of seizure activity sufficient to meet the definition of status epilepticus has traditionally been specified as 15–30 minutes. Generalized convulsive status epilepticus (GCSE) is typically when seizures last beyond 5 minutes. GCSE is an emergency and must be treated immediately, since cardiorespiratory dysfunction, hyperthermia, and metabolic derangements can develop as a consequence of prolonged seizures, and these can lead to irreversible neuronal injury. Furthermore, CNS injury can occur even when the patient is paralyzed with neuromuscular blockade but continues to have electrographic seizures. The most common causes of GCSE are anticonvulsant withdrawal or noncompliance, metabolic disturbances, drug toxicity, CNS infection, CNS tumors, refractory epilepsy, and head trauma. GCSE is obvious when the patient is having overt convulsions. However, after 30–45 minutes of uninterrupted seizures, the signs may become increasingly subtle. Patients may have mild clonic movements of only the fingers or fine, rapid movements of the eyes. There may be paroxysmal episodes of tachycardia, hypertension, and pupillary dilation. In such cases, the EEG may be the only method of establishing the diagnosis. Thus, if the patient stops having overt seizures yet remains comatose, an EEG should be performed to rule out ongoing status epilepticus. The first steps in the management of a patient in GCSE are to attend to any acute cardiorespiratory problems or hyperthermia, perform a brief medical and neurologic examination, establish venous access, and send samples for laboratory studies to identify metabolic abnormalities. Anticonvulsant therapy should then begin without delay; a treatment approach is shown in Figure 26-3. Carbamazepine is a first-line therapy for focal seizures.

42. The answer is A.

(Chap. 27) Cardioembolism accounts for up to 20% of all ischemic strokes. Stroke caused by heart disease is due to thrombotic material forming on the atrial or ventricular wall or the left heart valves. If the thrombus lyses quickly, only a transient ischemic attack may develop. If the arterial occlusion lasts longer, brain tissue may die and a stroke will occur. Emboli from the heart most often lodge in the middle cerebral artery (MCA), the posterior cerebral artery (PCA), or one of their branches. Atrial fibrillation is the most common cause of cerebral embolism overall. Other significant causes of cardioembolic stroke include myocardial infarction, prosthetic valves, rheumatic heart disease, and dilated cardiomyopathy. Furthermore, paradoxical embolization may occur when an atrial septal defect or a patent foramen ovale exists. This may be detected by bubble-contrast echocardiography. Bacterial endocarditis may cause septic emboli if the vegetation is on the left side of the heart or if there is a paradoxical source.

43. The answer is D.

(Chap. 27) Nonrheumatic atrial fibrillation is the most common cause of cerebral embolism overall. The presumed stroke mechanism is thrombus formation in the fibrillating atrium or atrial appendage. The average annual risk of stroke is around 5%. However, the risk varies with the following factors: age, hypertension, left ventricular function, prior embolism, diabetes, and thyroid function. The risk of stroke can be estimated by calculating the CHADS2 score (see Table 27-3). Patients younger than 60 years of age without structural heart disease or without one of these risk factors have a very low annual risk of cardioembolism of less than 0.5%. Therefore, it is recommended that these patients only take aspirin daily for stroke prevention. Older patients with numerous risk factors may have annual stroke risks of 10–15% and must take a vitamin K antagonist indefinitely. Cardioversion is indicated for symptomatic patients who want an initial opportunity to remain in sinus rhythm. However, studies have shown that there is an increased stroke risk for weeks to months after a successful cardioversion, and these patients must remain on anticoagulation for a long period. Patients who do not respond to cardioversion and do not want catheter ablation have mortality and morbidity with rate control and anticoagulation similar to those of patients who opt for cardioversion. Low-molecular-weight heparin may be used as a bridge to vitamin K–antagonist therapy and may facilitate outpatient anticoagulation in selected patients.

44. The answer is E.

(Chap. 27) Numerous studies have identified key risk factors for ischemic stroke. Old age, family history, diabetes, hypertension, tobacco smoking, and cholesterol are all risk factors for atherosclerosis and therefore stroke. Hypertension is the most significant among these risk factors. All cases of hypertension must be controlled in the setting of stroke prevention. Antiplatelet therapy has been shown to reduce the risk of vascular atherothrombotic events. The overall relative risk reduction of nonfatal stroke is about 25–30% across most large clinical trials. The “true” absolute benefit is dependent on the individual patient’s risk; therefore, patients with a low risk for stroke (e.g., younger patients with minimal cardiovascular risk factors) may have a relative risk reduction with antiplatelet therapy but a meaningless “benefit.” Numerous studies have shown the benefit of statin therapy in the reduction of stroke risk even in the absence of hypercholesterolemia. Anticoagulation is the treatment of choice to prevent stroke in patients with atrial fibrillation and other potential causes of cardiocerebral emboli. However, data do not support the use of long-term vitamin K antagonists for preventing atherothrombotic stroke for either intracranial or extra-cranial cerebrovascular disease. The WARSS study found no benefit of warfarin (INR 1.4–2.8) over aspirin 325 mg for secondary prevention of stroke but did find a slightly higher bleeding rate in the warfarin group. A recent European study confirmed this finding. The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) study demonstrated no benefit of warfarin (INR 2–3) over aspirin in patients with symptomatic intracranial atherosclerosis, and also found higher rates of bleeding complications.

45. The answer is C.

(Chap. 27) Once the diagnosis of stroke is made, a brain imaging study is necessary to determine if the cause of stroke is ischemia or hemorrhage (Figure 27-1). There are no clinical findings that definitively distinguish ischemia from hemorrhage. If the stroke is ischemic, administration of recombinant tissue plasminogen activator (rtPA) or endovascular mechanical thrombectomy may be beneficial in restoring cerebral perfusion. Medical management to reduce the risk of complications becomes the next priority, followed by plans for secondary prevention. For ischemic stroke, several strategies can reduce the risk of subsequent stroke in all patients, while other strategies are effective for patients with specific causes of stroke such as cardiac embolus and carotid atherosclerosis. For hemorrhagic stroke, aneurysmal subarachnoid hemorrhage (SAH) and hypertensive intracranial hemorrhage are two important causes. The National Institute of Neurological Disorders and Stroke (NINDS) recombinant TPA (rtPA) Stroke Study showed a clear benefit for IV rtPA in selected patients with acute stroke. The NINDS study used IV rtPA (0.9 mg/kg to a 90-mg max; 10% as a bolus, then the remainder over 60 minutes) versus placebo in patients with ischemic stroke within 3 hours of onset. Subsequent studies using different dosing and timing ranges have not been as positive. rtPA is being reviewed for approval in the 3- to 4.5-hour window in Europe, but is only approved for 0–3 hours in the United States and Canada. Use of IV rtPA is considered a central component in primary stroke centers as the first treatment proven to improve clinical outcomes in ischemic stroke and is cost-effective and cost saving. Because collateral blood flow within the ischemic brain is blood pressure dependent, there is controversy about whether blood pressure should be lowered acutely. Blood pressure should be lowered if there is malignant hypertension or concomitant myocardial ischemia or if blood pressure is above 185/110 mmHg and thrombolytic therapy is anticipated. When faced with the competing demands of myocardium and brain, lowering the heart rate with a β1-adrenergic blocker (such as esmolol) can be a first step to decreasing cardiac work and maintaining blood pressure. Endovascular mechanical thrombectomy has recently shown promise as an alternative or adjunctive treatment of acute stroke in patients who are ineligible for, or have contraindications to, thrombolytics or in those who have failed to have vascular recanalization with IV thrombolytics. Studies have shown excellent acute and chronic recanalization rates and the FDA has approved some devices for intracerebral use. Hypothermia is a powerful neuroprotective treatment in patients with cardiac arrest and is neuroprotective in animal models of stroke, but it has not been adequately studied in patients with ischemic stroke.

46. The answer is D.

(Chap. 29) All the choices given in the question are causes of or may be associated with dementia. Binswanger’s disease, the cause of which is unknown, often occurs in patients with long-standing hypertension and/or atherosclerosis; it is associated with diffuse subcortical white matter damage and has a subacute insidious course. Alzheimer’s disease, the most common cause of dementia, is also slowly progressive and can be confirmed at autopsy by the presence of amyloid plaques and neurofibrillary tangles. Creutzfeldt-Jakob disease, a prion disease, is associated with a rapidly progressive dementia, myoclonus, rigidity, a characteristic EEG pattern, and death within 1–2 years of onset. Vitamin B12 deficiency, which often is seen in the setting of chronic alcoholism, most commonly produces a myelopathy that results in loss of vibration and joint position sense, and brisk deep tendon reflexes (dorsal column and lateral corticospinal tract dysfunction). This combination of pathologic abnormalities in the setting of vitamin B12 deficiency is also called subacute combined degeneration. Vitamin B12 deficiency may also lead to a subcortical type of dementia. Recent studies have demonstrated that elevated levels of MMA, which is a more sensitive measure of vitamin B12 deficiency, may increase the risk of cognitive decline in elderly patients. The therapeutic implications of this finding are not yet clear but emphasize the importance of adequate vitamin B12 intake. Multi-infarct dementia, as in this case, presents with a history of sudden stepwise declines in function associated with the accumulation of bilateral focal neurologic deficits. Brain imaging demonstrates multiple areas of stroke.

47. The answer is D.

(Chap. 30) The differential diagnosis of Parkinson’s disease is broad, and the disease can be difficult to diagnose, with an estimated misdiagnosis of 10–25% even by experienced physicians. This patient exhibits several atypical features that should alert the physician to search for alternative diagnoses. These include early age of onset, prominent orthostasis, autonomic symptoms of flushing and diaphoresis, and failure to respond to dopaminergic agents. In addition, recurrent urinary tract infections should prompt an evaluation for urinary retention due to autonomic dysfunction in this patient. These symptoms are most consistent with multiple system atrophy with parkinsonian features (MSA-p). The average age of onset is 50 years, and these individuals more frequently present with bilateral, symmetric tremor and more prominent spasticity than those with Parkinson’s disease. Orthostasis and autonomic symptoms are typically prominent. On MRI, one would expect to find volume loss and T2-hyperintensity in the area of the putamen, globus pallidus, and white matter. On pathologic examination, α-synuclein–positive inclusions would be seen in the affected areas. Median survival after diagnosis is 6–9 years. Dopaminergic agents are not helpful in the treatment of this disorder and are usually associated with drug-induced dyskinesias of the face and neck, rather than the limbs and trunk. Corticobasal degeneration is a sporadic tauopathy that presents in the sixth to seventh decades. In contrast to Parkinson’s disease, this disorder is frequently associated with myoclonic jerks and involuntary purposeful movements of a limb. Its progressive nature leads to spastic paraplegia. Diffuse Lewy body disease has prominent dementia with parkinsonian features. Neuropsychiatric complaints including paranoia, delusions, and personality changes are more common than in Parkinson’s disease. Drug-induced Parkinson’s disease is not seen with nitrofurantoin, and the patient has no history of illicit drugs such as MTPT, which could cause Parkinson’s disease. Finally, this is unlikely to be inadequately treated Parkinson’s disease because one would expect at least an initial improvement on dopaminergic agents.

48. The answer is C.

(Chap. 30) Therapy for Parkinson’s disease should be initiated when symptoms interfere with the patient’s quality of life. Choice of initial drug therapy is usually with dopamine agonists, levodopa, or MAO inhibitors. The initial choice in most individuals is a dopamine agonist (pramipexole, ropinirole, rotigotine), and monotherapy with dopamine agonists usually controls motor symptoms for several years before levodopa therapy becomes necessary. Over this period, escalating doses are frequently required, and side effects may be limiting. It is thought that dopamine agonists delay the onset of dyskinesias and on-off motor symptoms such as freezing. By 5 years, over half of individuals will require levodopa to control motor symptoms. Levodopa remains the most effective therapy for the motor symptoms of Parkinson’s disease, but once levodopa is started, dyskinesias and on-off motor fluctuations become more common. MAO inhibitors (selegiline, rasagiline) work by decreasing the postsynaptic breakdown of dopamine. As monotherapy, these agents have only small effects and are most often used as adjuncts to levodopa. Surgical procedures such as pallidotomy and deep-brain stimulation are reserved for advanced Parkinson’s disease with intractable tremor or drug-induced motor fluctuations or dyskinesias. In this setting, deep-brain stimulation can alleviate disabling symptoms.

49. The answer is D.

(Chap. 30) Restless legs syndrome (RLS) is a neurologic disorder that affects approximately 10% of the adult population, causing significant morbidity in some. It is rare in Asians. The four core symptoms required for diagnosis are as follows: an urge to move the legs, usually caused or accompanied by an unpleasant sensation in the legs; symptoms begin or worsen with rest; partial or complete relief by movement; worsening during the evening or night. Symptoms most commonly begin in the legs, but can spread to or even begin in the upper limbs. In about 80% of patients, RLS is associated with periodic leg movements (PLMs) during sleep and occasionally while awake. These involuntary movements are usually brief, lasting no more than a few seconds, and recur every 5–90 seconds. The restlessness and PLMs are a major cause of sleep disturbance in patients, leading to poor-quality sleep and daytime sleepiness. Primary RLS is genetic, and several loci have been found with an autosomal dominant pattern of inheritance, although penetrance may be variable. The mean age of onset in genetic forms is 27 years, although pediatric cases are recognized. The severity of symptoms is variable. Secondary RLS may be associated with pregnancy or a range of underlying disorders, including anemia, ferritin deficiency, renal failure, and peripheral neuropathy. The pathogenesis probably involves disordered dopamine function, which may be peripheral or central, in association with an abnormality of iron metabolism. Diagnosis is made on clinical grounds but can be supported by polysomnography and the demonstration of PLMs. The neurologic examination is normal. Secondary RLS should be excluded, and ferritin levels, glucose, and renal function should be measured. Most RLS sufferers have mild symptoms that do not require specific treatment. If symptoms are intrusive, low doses of dopamine (pramipexole, ropinirole) may be administered before bedtime. Levodopa can be effective but is frequently associated with augmentation (spread and worsening of restlessness and its appearance earlier in the day) or rebound (reappearance sometimes with worsening of symptoms at a time compatible with the drug’s short half-life). Other drugs that can be effective include anticonvulsants, analgesics, and even opiates. Management of secondary RLS should be directed to correcting the underlying disorder.

50. The answer is B.

(Chap. 29) Approximately 10% of all persons over the age of 70 have significant memory loss, and in more than half the cause is Alzheimer’s disease (AD). AD can occur in any decade of adulthood, but it is the most common cause of dementia in the elderly. AD most often presents with an insidious onset of memory loss followed by a slowly progressive dementia over several years. Pathologically, atrophy is distributed throughout the medial temporal lobes, as well as lateral and medial parietal lobes and lateral frontal cortex. Microscopically, there are neurofibrillary tangles composed of hyperphosphorylated tau filaments, and accumulation of amyloid in blood vessel walls in the cortex and leptomeninges. The cognitive changes of AD tend to follow a characteristic pattern beginning with memory impairment and spreading to language and visuospatial deficits. Yet approximately 20% of patients with AD present with nonmemory complaints such as word-finding, organizational, or navigational difficulty. In the early stages of the disease, the memory loss may go unrecognized or be ascribed to benign forgetfulness. Slowly the cognitive problems begin to interfere with daily activities, such as keeping track of finances, following instructions on the job, driving, shopping, and housekeeping. Some patients are unaware of these difficulties (anosognosia), while others remain acutely attuned to their deficits. Social graces, routine behavior, and superficial conversation may be surprisingly intact. Language becomes impaired—first naming, then comprehension, and finally fluency. In some patients, aphasia is an early and prominent feature. Word-finding difficulties and circumlocution may be a problem even when formal testing demonstrates intact naming and fluency. Visuospatial deficits begin to interfere with dressing, eating, or even walking, and patients fail to solve simple puzzles or copy geometric figures. Simple calculations and clock reading become difficult in parallel. Loss of judgment and reasoning is inevitable. Delusions are common and usually simple, with common themes of theft, infidelity, or misidentification. In end-stage AD, patients become rigid, mute, incontinent, and bedridden. Hyperactive tendon reflexes and myoclonic jerks may occur spontaneously or in response to physical or auditory stimulation. Generalized seizures may also occur. Often death results from malnutrition, secondary infections, pulmonary emboli, heart disease, or, most commonly, aspiration. The typical duration of AD is 8–10 years, but the course can range from 1 to 25 years. For unknown reasons, some AD patients show a steady decline in function, while others have prolonged plateaus without major deterioration.

51. The answer is E.

(Chap. 32) The combination of upper and lower motor neuron findings is highly suggestive of ALS. Indolent presentation is typical and many patients receive alternative diagnoses before defining ALS. There is currently no curative therapy for ALS; therefore, treatable causes of motor nerve dysfunction should be ruled out. Compression of the cervical spinal cord or cervicomedullary junction from tumors in the cervical regions or at the foramen magnum or from cervical spondylosis with osteophytes projecting into the vertebral canal can produce weakness, wasting, and fasciculations in the upper limbs and spasticity in the legs, closely resembling ALS. Absence of pain or of sensory changes, normal bowel and bladder function, normal roentgenographic studies of the spine, and normal cerebrospinal fluid (CSF) all favor ALS. Another important entity in the differential diagnosis of ALS is multifocal motor neuropathy with conduction block (MMCB). In this disorder, remarkably focal blocks in conduction regionally and chronically disrupt lower motor neuron function. Many cases have elevated serum titers of mono- and polyclonal antibodies to ganglioside GM1; it is hypothesized that the antibodies produce selective, focal, paranodal demyelination of motor neurons. MMCB is not typically associated with corticospinal signs. In contrast with ALS, MMCB may respond dramatically to therapy such as IV immunoglobulin or chemotherapy; it is thus imperative that MMCB be excluded when considering a diagnosis of ALS. A diffuse, lower motor axonal neuropathy mimicking ALS sometimes evolves in association with hematopoietic disorders such as lymphoma or multiple myeloma. Lyme disease may also cause an axonal, lower motor neuropathy, although typically with intense proximal limb pain and a CSF pleocytosis.

  Other treatable disorders that occasionally mimic ALS are chronic lead poisoning and thyrotoxicosis. Vitamin C deficiency may cause myalgias in addition to fatigue, lethargy, and skin findings, but motor neuron findings are not typical.

52. The answer is E.

(Chap. 33) Postural orthostatic tachycardia syndrome is characterized by symptomatic orthostatic intolerance and either an increase in heart rate to more than 120 beats/min or an increase of 30 beats/min with standing that subsides on sitting or lying down. There is no orthostatic hypotension. Women are affected approximately five times more often than men, and most develop the syndrome between the ages of 15 and 50. Approximately half of affected patients report an antecedent viral infection. Lightheadedness, weakness, and blurred vision combined with symptoms of autonomic over activity (palpitations, tremulousness, nausea) are common. Recurrent, unexplained episodes of dysautonomia and fatigue also occur. The pathogenesis is unclear in most cases; hypovolemia, deconditioning, venous pooling, impaired brainstem regulation, or adrenergic receptor supersensitivity may play a role. Although up to 80% of patients improve, only about 25% eventually resume their usual daily activities (including exercise and sports). Expansion of fluid volume and postural training are initial approaches to treatment. If these approaches are inadequate, then midodrine, fludrocortisone, phenobarbital, beta blockers, or clonidine may provide some benefit. Reconditioning and a sustained exercise program are very important. All of the other listed choices are associated with orthostatic hypotension.

53. The answer is D.

(Chap. 33) Complex regional pain syndrome (CRPS) types I and II are the terms that have replaced reflex sympathetic dystrophy (RSD) or causalgia because of the absence of a proven causative role for the autonomic nervous system. CRPS type I is a regional pain syndrome that usually develops after tissue trauma. Examples of associated trauma include myocardial infarction, minor shoulder or limb injury, and stroke. Allodynia, hyperpathia, and spontaneous pain occur. The symptoms are unrelated to the severity of the initial trauma and are not confined to the distribution of a single peripheral nerve. CRPS type II is a regional pain syndrome that develops after injury to a specific peripheral nerve, usually a major nerve trunk. Spontaneous pain initially develops within the territory of the affected nerve but eventually may spread outside the nerve distribution. Pain is the primary clinical feature of CRPS. Vasomotor dysfunction, sudomotor abnormalities, or focal edema may occur alone or in combination but must be present for diagnosis. Localized sweating and changes in blood flow may produce temperature differences between affected and unaffected limbs. CRPS type I has classically been divided into three clinical phases but is now considered to be more variable. Phase I consists of pain and swelling in the distal extremity occurring within weeks to 3 months after the precipitating event. The pain is diffuse, spontaneous, and either burning, throbbing, or aching in quality. The involved extremity is warm and edematous, and the joints are tender. Increased sweating and hair growth develop. In phase II (3–6 months after onset), thin, shiny, cool skin appears. After an additional 3–6 months (phase III), atrophy of the skin and subcutaneous tissue plus flexion contractures complete the clinical picture. A variety of surgical and medical treatments have been developed for CRPS, with conflicting reports of efficacy. Clinical trials suggest that early mobilization with physical therapy or a brief course of glucocorticoids may be helpful for CRPS type I. Other medical treatments include the use of adrenergic blockers, nonsteroidal anti-inflammatory drugs, calcium channel blockers, phenytoin, opioids, and calcitonin. Stellate ganglion blockade is a commonly used invasive technique that often provides temporary pain relief, but the efficacy of repetitive blocks is uncertain.

54. The answer is A.

(Chap. 34) Trigeminal neuralgia is a clinical diagnosis based entirely on patient history. The disorder is characterized by paroxysms of excruciating pain in the lips, gums, cheeks, and chin that resolves over seconds to minutes. It is caused by ectopic action potentials in afferent pain fibers of the fifth cranial nerve, due either to nerve compression or other causes of demyelination. Symptoms are often, but not always, elicited by tactile stimuli on the face, tongue, or lips. An elevated ESR is not part of the clinical syndrome. Elevated ESR is associated with temporal arteritis, a vasculitis associated with jaw claudication, unilateral vision loss, and symptoms of polymyalgia rheumatica. Trigeminal neuralgia is specifically notable for a lack of sensory findings on examination, unless the diagnosis is made in conjunction with another disorder such as a midbrain mass lesion or aneurysm. Deep-seated facial and head pain is more commonly a feature of migraine headache, dental pathology, or sinus disease. First-line therapy is with carbamazepine, not gabapentin. It should be started and increased gradually until pain symptoms subside; 50–75% of patients will respond to this therapy. If treatment is effective, it is continued for 1 month then tapered.

55. The answer is C.

(Chap. 34) Trigeminal neuralgia is a clinical diagnosis based entirely on patient history, and as such should be treated once a patient presents with the virtually pathognomonic complaints of paroxysms of excruciating pain in the lips, gums, cheeks, and chin that resolve over seconds to minutes. Carbamazepine is first-line therapy. Oxcarbazepine likely has equivalent efficacy to carbamazepine with less toxicity. Lamotrigine, orphenytoin, and baclofen are other potential therapeutic options. Surgical approaches, such as radiofrequency thermal rhizotomy, gamma-knife radiosurgery, and microvascular decompression, should be considered only when medical options fail. Steroids have no therapeutic role, as trigeminal neuralgia is not an inflammatory condition. Neuroimaging is not indicated, unless other clinical features or a focal neurologic deficit elicited on history or physical examination suggest another possible diagnosis such as intracranial mass or multiple sclerosis.

56. The answer is D.

(Chap. 34) Brief paroxysms of severe, sharp pains in the face without demonstrable lesions in the jaw, teeth, or sinuses are called tic douloureux, or trigeminal neuralgia. The pain may be brought on by stimuli applied to the face, lips, or tongue or by certain movements of those structures. Aneurysms, neurofibromas, and meningiomas impinging on the fifth cranial nerve at any point during its course typically present with trigeminal neuropathy, which will cause sensory loss on the face, weakness of the jaw muscles, or both; neither symptom is demonstrable in this patient. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that may present with bulbar motor findings but sensory findings (in the absence of muscle spasms) are uncommon.

57. The answer is C.

(Chap. 35) The MRI shows an infiltrated and collapsed second thoracic vertebral body with posterior displacement and compression of the upper thoracic spinal cord due to metastatic breast cancer. The low-intensity bone marrow signal in panel A of Figure 57 signifies replacement by tumor. When a patient presents with possible myelopathy, the first priority is to distinguish between a compressive or noncompressive etiology. The common causes of compressive myelopathy are tumor, epidural abscess or hematoma, herniated disk, or vertebral pathology. Epidural compression due to malignancy or abscess often causes warning signs of neck or back pain, bladder disturbances, and sensory symptoms that precede the development of paralysis. MRI is the optimal diagnostic modality to image the spinal cord. In adults, most neoplasms are epidural in origin, resulting from metastases to the adjacent spinal bones. The propensity of solid tumors to metastasize to the vertebral column probably reflects the high proportion of bone marrow located in the axial skeleton. Almost any malignant tumor can metastasize to the spinal column, with breast, lung, prostate, kidney, lymphoma, and plasma cell dyscrasia occurring particularly frequently. The thoracic spinal column is most commonly involved; exceptions are metastases from prostate and ovarian cancer, which occur disproportionately in the sacral and lumbar vertebrae, probably resulting from spread through Batson’s plexus, a network of veins along the anterior epidural space. Retroperitoneal neoplasms (especially lymphomas or sarcomas) enter the spinal canal through the intervertebral foramens and produce radicular pain with signs of root weakness prior to cord compression. Pain is usually the initial symptom of spinal metastasis and characteristically awakens patients at night. A recent onset of persistent back pain, particularly if in the thoracic spine (which is uncommonly involved by spondylosis), should prompt consideration of vertebral metastasis. Infections of the spinal column (osteomyelitis and related disorders) are distinctive in that, unlike tumor, they may cross the disk space to involve the adjacent vertebral body. Management of cord compression includes glucocorticoids to reduce cord edema, local radiotherapy (initiated as early as possible) to the symptomatic lesion, and specific therapy for the underlying tumor type. Spinal epidural abscess presents as a clinical triad of midline dorsal pain, fever, and progressive limb weakness. Risk factors include an impaired immune status (diabetes mellitus, renal failure, alcoholism, malignancy), IV drug abuse, and infections of the skin or other tissues. Two-thirds of epidural infections result from hematogenous spread of bacteria from the skin (furunculosis), soft tissue (pharyngeal or dental abscesses), or deep viscera (bacterial endocarditis). Hemorrhage into the epidural (or subdural) space causes acute focal or radicular pain followed by variable signs of a spinal cord or conus medullaris disorder. Therapeutic anticoagulation, trauma, tumor, or blood dyscrasias are predisposing conditions. Hemorrhage into the substance of the spinal cord is a rare result of trauma, intraparenchymal vascular malformation, vasculitis due to polyarteritis nodosa or systemic lupus erythematosus (SLE), bleeding disorders, or a spinal cord neoplasm. Hematomyelia presents as an acute, painful transverse myelopathy.

58. The answer is B.

(Chap. 35) This patient has a history and examination consistent with a myelopathy. The rapidity of onset and the lack of other antecedent symptoms (e.g., pain) make a noncompressive etiology most likely. An MRI is the initial test of choice and will easily identify a structural lesion such as a neoplasm or subluxation. Noncompressive myelopathies result from five basic causes: spinal cord infarction; systemic disorders such as vasculitis, systemic lupus erythematosus (SLE), and sarcoidosis; infections (particularly viral); demyelinating disease such as multiple sclerosis; and idiopathic. Therefore, serologies for antinuclear antibodies, viral serologies such as HIV and HTLV-I, and lumbar puncture are all indicated. Because the clinical scenario is consistent with a myelopathy, an electromyogram is not indicated.

59. The answer is A.

(Chap. 35) Syringomyelia is a developmental, slowly enlarging cavitary expansion of the cervical cord that produces a progressive myelopathy. Symptoms typically begin in adolescence or early adulthood. They may undergo spontaneous arrest after several years. More than half are associated with Chiari malformations. Acquired cavitations of the spinal cord are referred to as syrinx cavities. They may result from trauma, myelitis, infection, or tumor. The classic presentation is that of a central cord syndrome with sensory loss of pain and temperature sensation, and weakness of the upper extremities. Vibration and position sensation are typically preserved. Muscle wasting in the lower neck, shoulders, arms, and hands with asymmetric or absent reflexes reflects extension of the cavity to the anterior horns. With progression, spasticity and weakness of the lower extremities, and bladder and bowel dysfunction may occur. MRI scans are the diagnostic modality of choice. Surgical therapy is generally unsatisfactory. Syringomyelia associated with Chiari malformations may require extensive decompressions of the posterior fossa. Direct decompression of the cavity is of debatable benefit. Syringomyelia secondary to trauma or infection is treated with decompression and a drainage procedure, with a shunt often inserted that drains into the subarachnoid space. Although relief may occur, recurrence is common.

60. The answer is A.

(Chap. 36) Concussions result from blunt head trauma that causes anterior-posterior movement of the brain within the skull. Transient loss of consciousness is common, as are confusion and amnesia. Many patients do not lose consciousness but feel dazed, stunned, or confused. A brief period of both retrograde and anterograde amnesia is characteristic of concussion and it recedes rapidly in alert patients. Head imaging is typically normal. Postconcussive syndrome is a constellation of symptoms including fatigue, headache, dizziness, and difficulty concentrating that follows a concussion. The patient described fits this diagnosis; strict diagnostic criteria do not exist. Typically patients will improve over a 6- to 12-month period. Patients who were energetic and highly functioning prior to their trauma have an excellent prognosis. Treatment is aimed at reassurance and relieving prominent symptoms. Dizziness can be treated with Phenergan, which acts as a vestibular suppressant. He should avoid contact sports at least until his symptoms resolve.

61. The answer is D.

(Chap. 36) The head CT (Figure 61) shows chronic bilateral subdural hematomas of varying age. The collections began as acute hematomas and have become hypodense in comparison to the adjacent brain. Some areas of resolving blood are contained in the more recently formed collection on the left. Acute hematomas (which would be as bright as the resolving blood shown in arrows) become hypodense in comparison with adjacent brain after approximately 2 months. During the isodense phase (2–6 weeks after injury), they may be difficult to discern. Chronic subdural hematoma may present without a history of trauma or injury in 20–30% of patients. Headache is common. Other symptoms may be vague, as in this case, or there may be focal signs including hemiparesis mimicking stroke. Underlying cortical damage may serve as a seizure focus. In relatively asymptomatic patients with small hematomas, observation and serial imaging may be reasonable; however, surgical evacuation is often necessary for large or symptomatic chronic hematomas.

62. The answer is D.

(Chap. 36) Hemorrhages beneath the dural layer (subdural) or between the skull and the dura (epidural) are common sequelae of head trauma. They can be life-threatening, and prompt evaluation and management are imperative. Several clinical features allow these conditions to be distinguished from one another. Acute subdural hematomas typically arise from venous sources, often the bridging veins located immediately under the dura mater. As the brain volume decreases with age, traction on these venous structures increases and even minor head trauma in the elderly can lead to a subdural hematoma. A “lucid interval” of several minutes to hours before coma supervenes is most characteristic of epidural hemorrhage, but it is still uncommon, and epidural hemorrhage is not the only cause of this temporal sequence. Subdural bleeding is typically slower than epidural bleeding due to their different sources. Small subdural bleeds are asymptomatic and often do not require evacuation. Epidural hematomas, on the other hand, can arise quickly and typically represent arterial bleeding. A lacerated middle meningeal artery from an overlying skull fracture often causes these. A rapid increase in intracranial pressure from these bleeds can necessitate arterial ligation or emergent craniotomy. Most patients with epidural bleeding are unconscious when first evaluated; a “lucid interval” can occasionally be seen.

63. The answer is D.

(Chap. 37) Distinguishing CNS toxoplasmosis from primary CNS lymphoma in a patient with HIV infection is often difficult. The standard approach in a neurologically stable patient is to treat the patient for toxoplasmosis for 2–3 weeks then repeat neuroimaging. If the imaging shows clear improvement, continue antibiotics. If there is no response to therapy after 2 weeks, therapy does not need to be continued and a stereotactic brain biopsy is indicated. In this immunocompromised patient who has not responded to treatment for CNS toxoplasmosis, a positive CNS EBV DNA would be diagnostic of CNS lymphoma. Whole-brain radiation therapy is part of the treatment for CNS lymphoma, which is not yet diagnosed in this patient, and should not be instituted empirically. Treatments directed at viral infections of the CNS or CNS lymphomas are not indicated at this time since a diagnosis is still yet to be made. In the absence of a change in neurologic status or evidence of mass effect on CT, there is no indication for dexamethasone. Of note, the incidence of primary CNS lymphoma appears to be increasing in immunocompetent individuals for unclear reasons.

64. The answer is A.

(Chap. 37) Endocrine dysfunction resulting in hypopituitarism frequently follows exposure of the hypothalamus or pituitary gland to therapeutic radiation. Growth hormone is the most sensitive to the damaging effects of WBRT, and thyroid-stimulating hormone is the least sensitive. ACTH, prolactin, and gonadotropins have an intermediate sensitivity. Other complications of radiation therapy to the brain include acute radiation injury manifest by headache, sleepiness, and worsening of preexisting neurologic defects. Early delayed radiation injury occurs within the first 4 months after therapy. It is associated with increased white matter signal on MRI and is steroid responsive. Late delayed radiation injury occurs more than 4 months after therapy, typically 8–24 months. There may be dementia, gait apraxia, focal necrosis (after focal irradiation), or the development of secondary malignancies.

65. The answer is D.

(Chap. 37) The postgadolinium MRI shows multiple meningiomas along the falx and left parietal cortex. Meningiomas derive from the cells that give rise to the arachnoid granulations. They are now the most common primary brain tumor, accounting for approximately 32% of the total, and occur more commonly in women than men. They are usually benign (WHO classification grade 1) and attached to the dura. They rarely invade the brain. Meningiomas are diagnosed with increasing frequency as more people undergo neuroimaging studies for various indications. Their incidence increases with age, and they are more common in patients with a history of cranial irradiation. They are most commonly located over the cerebral convexities, especially adjacent to the sagittal sinus, but can also occur in the skull base and along the dorsum of the spinal cord. Many meningiomas are found incidentally following neuroimaging for unrelated reasons. They can also present with headaches, seizures, or focal neurologic deficits. On imaging studies they have a characteristic appearance usually consisting of a partially calcified, densely enhancing extra-axial tumor arising from the dura. The main differential diagnosis of meningioma is a dural metastasis. Total surgical resection of a meningioma is curative. Low-grade astrocytoma and high-grade astrocytoma (glioblastoma) often infiltrate into adjacent brain and rarely have the clear margins seen in Figure 65. Oligodendroma comprise approximately 15% of all gliomas and show calcification in roughly 30% of cases. They have a more benign course and are more responsive than other gliomas to cytotoxic therapy. For low-grade oligodendromas, the median survival is 7–8 years. Brain abscess will have distinctive ring-enhancing features with a capsule, will often have mass effect, and will have evidence of inflammation on MRI scanning.

66. The answer is C.

(Chap. 38) Hormones produced by the anterior pituitary include adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, prolactin, and growth hormone. The posterior pituitary produces vasopressin and oxytocin. The anterior and posterior pituitary has a separate vascular supply, and the posterior pituitary is directly innervated by the hypothalamic neurons via the pituitary stalk, thus making it susceptible to shear stress–associated dysfunction. Hypothalamic control of anterior pituitary function is through secreted hormones; thus it is less susceptible to traumatic injury.

67. The answer is B.

(Chap. 38) The patient has evidence of Sheehan’s syndrome postpartum. In this syndrome, the hyperplastic pituitary postpartum is at increased risk for hemorrhage and/or infarction. This leads to bilateral visual changes, headache, and meningeal signs. Ophthalmoplegia may be observed. In severe cases, cardiovascular collapse and altered levels of consciousness may be observed. Laboratory evaluation commonly shows hypoglycemia. Pituitary CT or MRI may show signs of sellar hemorrhage if present. Involvement of all pituitary hormones may be seen, though the most acute finding is often hypoglycemia and hypotension from the failure of adrenocorticotropic hormone. The hypoglycemia and hypotension present in this case suggest failure of the glucocorticoid system; thus treatment with a corticosteroid is indicated. There is no evidence of sepsis; thus antibiotics and drotrecogin alfa are not indicated. With a normal hematocrit and no reported evidence of massive hemorrhage, packed red cell transfusion is unlikely to be helpful. Although thyroid-stimulating hormone production is undoubtedly low in this patient, the most immediate concern is replacement of glucocorticoid.

68. The answer is D.

(Chap. 38) Functional pituitary adenoma presentations include acromegaly, as in this patient, prolactinomas, and Cushing’s syndrome. Hypersecretion of growth hormone underlies this syndrome in patients with pituitary masses, though ectopic production of growth hormone, particularly by tumors, has been reported. Because growth hormone is secreted in a highly pulsatile fashion, obtaining random serum levels is not reliable. Thus, the downstream mediator of systemic effects of growth hormone, IGF-1, is measured to screen for growth hormone excess. IGF-1 is made by the liver in response to growth hormone stimulation. An oral glucose tolerance test with growth hormone obtained at 0, 30, and 60 minutes may also be used to screen for acromegaly, as normal persons should suppress growth hormone to this challenge. Serum prolactin level is useful to screen for prolactinomas; 24-hour urinary free cortisol and ACTH assay are useful screens for Cushing’s disease.

69. The answer is B.

(Chap. 38) Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Although pituitary adenoma is a frequent cause, there are several physiologic, medication-related, and potentially reversible etiologies. Prolactin is normally elevated during pregnancy and lactation, though levels should fall to normal within 6 months of cessation of breastfeeding. Nipple stimulation, sleep, and stress may all increase prolactin levels. Systemic disorders such as chronic renal failure and cirrhosis may also cause elevated prolactin levels. Prolactin levels are also typically elevated after generalized seizures, which may be useful in the evaluation of pseudoseizures. Drug-induced hypersecretion is associated with dopamine receptor blockers, dopamine synthesis inhibitors, opiates, H2 antagonists, imipramines, selective serotonin reuptake inhibitors, and calcium channel blockers. Hypothalamic-pituitary stalk damage may also cause hyperprolactinemia. Rathke’s cysts, which are benign intrasellar lesions, may produce endocrinologic abnormalities similar to pituitary adenomas.

70. The answer is E.

(Chap. 38) Tumors arising from the lactotrope cells of the pituitary account for half of all functioning pituitary tumors and most commonly affect women. The most common presentations are amenorrhea, infertility, and/or galactorrhea. Microadenomas rarely progress to become macroadenomas. For symptomatic disease, the primary goals of therapy are control of hyperprolactinemia, reduction of tumor size, restoration of menses and fertility, and resolution of galactorrhea. Usually oral dopamine agonists, such as cabergoline and bromocriptine, are used for this purpose.

71. The answer is C.

(Chap. 38) Adult growth hormone deficiency is usually caused by hypothalamic or pituitary damage. Because growth hormone is no longer important for achieving stature, the presentation is different from childhood growth hormone deficiency. Although growth hormone has direct tissue effects, it primarily acts through increasing secretion of IGF-1, which in turn stimulates lipolysis, increases circulating fatty acids, reduces omental fat mass, and enhances lean body mass. Thus, deficiency of growth hormone causes the opposite effects. In addition, hypertension, left ventricular dysfunction, and increased plasma fibrinogen levels may also be present with deficient growth hormone. Reduced, not increased, bone mineral density may also occur in adults with growth hormone deficiency.

72. The answer is E.

(Chap. 38) The patient has a clinical presentation consistent with Cushing’s syndrome. Although many cases of inappropriate elevation of ACTH are due to pituitary tumors, a substantial proportion are due to ectopic ACTH secretion. Clues to this diagnosis include a rapid onset of hypercortisolism features associated with skin hyperpigmentation and severe myopathy. Additionally, hypertension, hypokalemic metabolic alkalosis, glucose intolerance, and edema are more prominent in ectopic ACTH secretion than in pituitary tumors. Serum potassium below 3.3 mmol/L is present in 70% of ectopic ACTH cases, but in less than 10% of pituitary-dependent Cushing’s syndrome. ACTH levels will be high, as this is the underlying cause of both types of Cushing’s syndrome. Corticotropin-releasing hormone is rarely the cause of Cushing’s syndrome. Unfortunately, MRI of the pituitary gland will not visualize lesions less than 2 mm; thus occasional sampling of the inferior petrosal veins is required, but this is not indicated in the case presented at this time in the evaluation.

73. The answer is C.

(Chap. 38) The patient has panhypopituitarism and is unable to make TSH; thus her plasma TSH level will always be low, regardless of the adequacy of her T4 replacement. A free T4 level will allow the determination of whether her plasma level is in the normal range of thyroid hormone. This, coupled with her symptoms, will aid in the determination of proper levothyroxine dosing. There is no evidence of recurrent disease clinically; thus MRI is not useful. She is unlikely to have primary thyroid disease, and T4 level is unknown presently, so thyroid uptake scan is not indicated at this time.

74. The answer is A.

(Chap. 38) The diagnosis of Cushing’s syndrome relies on documentation of endogenous hypercortisolism. Of the list of choices, the most cost-effective and precise test is the 24-hour urine free cortisol. Failure to suppress plasma morning cortisol after overnight suppression with 1 mg dexamethasone is an alternative. Most ACTH-secreting pituitary adenomas are less than 5 mm in diameter, and approximately half are not detected even with sensitive MRI. Further, because incidental microadenomas are common in the pituitary, the presence of a small pituitary abnormality on MRI may not establish the source of ACTH production. Basal plasma ACTH levels are used to distinguish between ACTH-independent (adrenal or exogenous glucocorticoid) and ACTH-dependent (pituitary, ectopic ACTH) sources of hypercortisolism. Mean basal ACTH levels are higher in patients with ectopic ACTH production than in patients with pituitary ACTH adenomas. There is significant overlap in ACTH levels, however, and this test should not be used as an initial diagnostic test. Rarely, patients have Cushing’s syndrome and elevated ACTH due to a CRH-releasing tumor. In this case, CRH levels are elevated. Inferior petrosal venous sampling can be used to identify a pituitary source of ACTH secretion when imaging modalities do not reveal a source.

75. The answer is B.

(Chap. 38) The identification of an empty sella is often the result of an incidental MRI finding. Typically these patients will have normal pituitary function and should be reassured. It is likely that the surrounding rim of pituitary tissue is functioning normally. An empty sella may signal the insidious onset of hypopituitarism, and laboratory results should be followed closely. Unless her clinical situation changes, repeat MRI is not indicated. Endocrine malignancy is unlikely, and surgery is not part of the management of an empty sella.

76. The answer is D.

(Chap. 39) The onset of multiple sclerosis (MS) may be abrupt or insidious. Symptoms may be severe or seem so trivial that a patient may not seek medical attention for months or years. Indeed, at autopsy, approximately 0.1% of individuals who were asymptomatic during life will be found, unexpectedly, to have pathologic evidence of MS. Similarly, in the modern era, an MRI scan obtained for an unrelated reason may show evidence of asymptomatic MS. Symptoms of MS are extremely varied and depend on the location and severity of lesions within the CNS (see Table 39-2). Examination often reveals evidence of neurologic dysfunction, often in asymptomatic locations. For example, a patient may present with symptoms in one leg but signs in both.

77. The answer is D.

(Chap. 39) The four clinical types of multiple sclerosis (MS) include relapsing/remitting, secondary progressive, primary progressive, and progressive relapsing. Relapsing/remitting MS (RRMS) accounts for 85% of MS cases at onset and is characterized by discrete attacks that generally evolve over days to weeks (rarely over hours). There is often complete recovery over the ensuing weeks to months. However, when ambulation is severely impaired during an attack, approximately half will fail to improve. Between attacks, patients are neurologically stable. Secondary progressive MS (SPMS) always begins as RRMS. At some point, however, the clinical course changes so that the patient experiences a steady deterioration in function unassociated with acute attacks (which may continue or cease during the progressive phase). SPMS produces a greater amount of fixed neurologic disability than RRMS. For a patient with RRMS, the risk of developing SPMS is approximately 2% each year, meaning that the great majority of RRMS ultimately evolves into SPMS. SPMS appears to represent a late stage of the same underlying illness as RRMS. Primary progressive MS (PPMS) accounts for approximately 15% of cases. These patients do not experience attacks but only a steady functional decline from disease onset. Compared to RRMS, the sex distribution is more even, the disease begins later in life (mean age approximately 40 years), and disability develops faster (at least relative to the onset of the first clinical symptom). Despite these differences, PPMS appears to represent the same underlying illness as RRMS. Progressive/relapsing MS (PRMS) overlaps PPMS and SPMS and accounts for about 5% of MS patients. Like patients with PPMS, these patients experience a steady deterioration in their condition from disease onset. However, like SPMS patients, they experience occasional attacks superimposed upon their progressive course. Autoimmune autonomic neuropathy is a distinct clinical syndrome not related to MS. It presents with the subacute development of autonomic disturbances with orthostatic hypotension, enteric neuropathy (gastroparesis, ileus, constipation/diarrhea), and cholinergic failure; the latter consists of loss of sweating, sicca complex, and a tonic pupil. Autoantibodies against the ganglionic ACh receptor (A3 AChR) are present in the serum of many patients and are now considered to be diagnostic of this syndrome.

78. The answer is D.

(Chap. 40) In a patient with suspected bacterial meningitis empirical therapy should be administered promptly to reduce mortality and morbidity. The decision to obtain an imaging study prior to lumbar puncture (LP) is based on the concern of precipitating herniation in a patient with elevated intracranial pressure or focal CNS lesions. Therefore, patients with the presence of papilledema on physical examination, history of recent head trauma, known or suspected intracranial lesions (immunosuppressed, known malignancy), focal neurologic findings, or depressed level of consciousness should have a head CT or MRI prior to LP. In an immunocompetent patient with no known history of recent head trauma, a normal level of consciousness, and no evidence of papilledema or focal neurologic deficits, it is considered safe to perform LP without prior neuroimaging studies. Kernig’s sign is elicited in a supine patient by flexing the thigh and knee. A positive sign occurs when the patient has head/neck pain when passively straightening the knee. The sensitivity and specificity of this sign (also Brudzinski’s) for bacterial meningitis are unknown, but they imply meningeal irritation, not an intracranial lesion or elevated intracranial pressure. While cerebrospinal fluid cultures may be impacted by administration of antibiotics prior to LP, stains, antigen tests, and polymerase chain reaction tests will not be affected.

79. The answer is B.

(Chap. 40) The release of bacterial cell wall components after killing by antibiotics may evoke a marked inflammatory cytokine response in the subarachnoid space. This inflammation may lead to increased damage of the blood-brain barrier and central nervous system damage. Glucocorticoids can blunt this response by inhibiting tumor necrosis factor and interleukin-1. They work best if administered before antibiotics. Clinical trials have demonstrated that dexamethasone, 10 mg IV administered 20 minutes before antibiotics, reduced unfavorable outcomes, including death. The dexamethasone was continued for 4 days. The benefits were most striking in pneumococcal meningitis. Because this is the most common cause of meningitis in the elderly, empirical coverage should include this intervention as well. The efficacy of dexamethasone therapy in preventing neurologic sequelae is different between high- and low-income countries. Randomized trials in low-income countries (sub-Saharan Africa, Southeast Asia) failed to show benefit in subgroups of patients. The lack of efficacy of dexamethasone in these trials has been attributed to late presentation to the hospital with more advanced disease, antibiotic pretreatment, malnutrition, infection with HIV, and treatment of patients with probable, but not microbiologically proven, bacterial meningitis. The results of these clinical trials suggest that patients in sub-Saharan Africa and those in low-income countries with negative CSF Gram stain and culture should not be treated with dexamethasone. Empirical antibiotics in this case should include a third-generation cephalosporin, vancomycin, and ampicillin. However, dexamethasone may decrease vancomycin penetration into the CSF, so its use should be considered carefully in cases where the most likely organism requires vancomycin coverage. Acyclovir or valacyclovir may be used as initial empiric treatment in cases of suspected herpes CNS infection. However, in this case the LP is highly suggestive of acute bacterial infection. Intravenous gamma globulin is used as adjunctive therapy in children with known immunoglobulin deficiency who are at risk of viral meningitis/encephalitis.

80. The answer is D.

(Chap. 40) Listeria has become an increasingly important cause of bacterial meningitis in neonates (<1 month of age), pregnant women, individuals more than 60 years old, and immunocompromised individuals. Infection is acquired by eating contaminated foods such as unpasteurized dairy products, coleslaw, milk, soft cheeses, delicatessen meats, and uncooked hot dogs. Ampicillin is the agent most often added to the initial empirical regimen to cover L. monocytogenes.

81. The answer is D.

(Chap. 41) Ibuprofen, isoniazid, ciprofloxacin, tolmetin, sulfa-containing medicines, and phenazopyridine have been implicated in drug hypersensitivity leading to meningitis. The cerebrospinal fluid (CSF) will typically show neutrophils, but mononuclear cells or eosinophils are occasionally present. Most causes of chronic (not recurrent) meningitis cause a predominance of mononuclear cells. The differential for chronic meningitis is broad and a diagnosis is often difficult to make. The treating physician needs to consider a diverse array of viral, fungal, bacterial, mycobacterial, helminthic, and protozoal pathogens, both common and exotic, and therefore should obtain a detailed social history and consult an expert in the field. Recurrent meningitis is often due to herpes simplex virus type 2 infection and this should be ruled out, particularly if active genital ulcers develop concurrently. Malignancy, sarcoidosis, and vasculitis are all potential causes, and history, physical examination, and appropriate further testing should dictate the degree to which these possibilities are explored. Medications are often overlooked as a cause of chronic meningitis and should always be carefully considered. When CSF neutrophils predominate after 3 weeks of illness, NocardiaActinomycesBrucella, tuberculosis (<10% of cases), and fungal and noninfectious causes of chronic meningitis should be considered.

82. The answer is E.

(Chap. 43) Prions are infectious particles that cause central nervous system degeneration. The human prion diseases described to date include Creutzfeldt-Jacob disease (CJD), kuru, Gerstmann-Straüssler-Scheinker disease, and fatal insomnia. The most common prion disease is sporadic CJD (sCJD), which occurs in a seemingly random pattern in adults in their fifth and sixth decades of life. sCJD accounts for about 85% of cases of CJD and occurs in approximately 1 per 1 million population. Variant CJD (vCJD) results from infection from bovine exposure to tainted beef from cattle with bovine spongiform encephalopathy (BSE). There has been a steady decline of cases of vCJD in Europe over the past decade. Infectious CJD (iCJD) has resulted from injection of tainted human growth hormone, as well as transplant of infected dura mater grafts into humans. Familial CJD (fCJD) is due to germ-line mutations that follow an autosomal dominant inheritance. Kuru is due to infection through ritualistic cannibalism. Gerstmann-Straüssler-Scheinker disease and familial fatal insomnia (FFI) occur as dominantly inherited prion diseases. Sporadic cases of fatal insomnia (sFI) have been described.

83. The answer is B.

(Chap. 43) Startle myoclonus is a worrisome sign but is neither sensitive nor specific for CJD, though it is more worrisome if it occurs during sleep. The constellation of dementia, myoclonus, and periodic electrical bursts in an afebrile 60-year-old patient generally indicates CJD. Clinical abnormalities in CJD are confined to the CNS. Lewy body dementia, Alzheimer’s disease, central nervous system infections, and myoclonic epilepsy can all cause myoclonus. Both EEG and MRI can help differentiate CJD from these disorders. The MRI finding of cortical ribboning and intensity in the basal ganglia on fluid-attenuated inversion recovery sequences is characteristic of CJD. EEG is useful if stereotypical periodic bursts every 1–2 seconds are present, but this is seen in only 60% of cases, and other findings may be less specific. Demonstration of specific immunoassays for proteolytic products of disease-causing prion proteins (PrPSc) at brain biopsy may be necessary to confirm diagnosis in some cases. However, these proteins are not uniformly distributed throughout the brain and false-negative biopsies occur. Both surgeons and pathologists must be warned to use standard precautions under these circumstances. These proteins cannot be measured from cerebrospinal fluid (CSF). CSF in CJD is usually normal except for a minimally elevated protein. Many patients with CJD have elevated CSF stress protein 14-3-3. This test alone is neither sensitive nor specific, as patients with herpes simplex virus encephalitis, multi-infarct dementia, and stroke may have similar elevations.

84. The answer is C.

(Chap. 44) One of the better characterized paraneoplastic neurologic syndromes is cerebellar ataxia caused by Purkinje cell drop-out in the cerebellum; it is manifested by dysarthria, limb and gait ataxia, and nystagmus. Radiologic imaging reveals cerebellar atrophy. Many antibodies have been associated with this syndrome, including anti-Yo, anti-Tr, and antibodies to the glutamate receptor. Although lung cancer, particularly small cell cancer, accounts for a large number of patients with neoplasm-associated cerebellar ataxia, those with the syndrome who display anti-Yo antibodies in the serum typically have breast or ovarian cancer. Cerebellar ataxia may also be seen in Hodgkin’s lymphoma in association with anti-Tr antibodies.

85. The answer is A.

(Chap. 45) Charcot-Marie-Tooth (CMT) syndrome is the most common type of hereditary neuropathy. CMT is comprised of several similar but genetically distinct conditions with different associated mutations. CMT1 is the most common and is an inherited demyelinating sensorimotor neuropathy. CMT1 affects patients in the first to third decades of life with distal leg weakness, i.e., footdrop. Although patients generally do not complain of sensory symptoms, these can often be elicited on physical examination. Muscle stretch reflexes are unobtainable or reduced throughout and calves are often atrophied, which makes legs appear to have a so-called inverted champagne bottle appearance. Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder characterized by recurrent attacks of pain, weakness, and sensory loss in the distribution of the brachial plexus that often begins in childhood. Hereditary sensory and autonomic neuropathy (HSAN) is a very rare group of hereditary neuropathies in which sensory and autonomic dysfunction predominates over muscle weakness. This would not fit the clinical pattern described here. Guillain-Barré syndrome presents generally acutely with involvement of both proximal and distal weakness and sensory loss. The prolonged symptom period and distribution described here is not typical for Guillain-Barré syndrome. Fabry disease is an X-linked disorder in which men are more commonly affected than women. Patients have angiokeratomas, which are reddish-purple lesions usually found around the umbilicus, scrotum, and inguinal region. Burning pain in the hands and feet often is found in late childhood or early adult life. Patients also have premature atheroscloerosis from the underlying mutation in the alpha-galactosidase gene with accumulation of ceramide in nerves and blood vessels.

86. The answer is E.

(Chap. 45) One of the most common side effects of isoniazid treatment is peripheral neuropathy. The elderly, malnourished, and “slow acetylators” are at increased risk for developing the neuropathy. INH inhibits pyridoxal phosphokinase, resulting in pyridoxine (vitamin B6) deficiency and the neuropathy. Prophylactic administration of pyridoxine can prevent the neuropathy from developing. Symptoms are generally dysesthesias and sensory ataxia. Impaired large-fiber sensory modalities are found on examination. Cobalamin (B12) is not reduced in this condition and is unaffected by isoniazid. Neurontin and pregabalin may alleviate symptoms but will not reverse the neuropathy. There is no indication that hypothyroidism is present.

87. The answer is C.

(Chap. 45) Diabetes mellitus (DM) is the most common cause of peripheral neuropathy in developed countries and is associated with several different types of polyneuropathy including distal symmetric sensory or sensorimotor polyneuropathy, autonomic neuropathy, diabetic neuropathic cachexia, polyradiculoneuropathies, cranial neuropathies, and other mononeuropathies. Risk factors for the development of neuropathy include long-standing and poorly controlled diabetes and the presence of retinopathy or nephropathy. The patient here appears to have diabetic distal symmetric sensory and sensorimotor polyneuropathy (DSPN), which is the most common form of diabetic neuropathy and presents with sensory loss beginning in the toes and gradually progresses over time up the legs and into the fingers and arms. Symptoms also may include tingling, burning, and deep, aching pains. Nerve biopsy, though rarely indicated, often shows axonal degeneration, endothelial hyperplasia, and occasionally perivascular inflammation. Tight glucose control prevents the development of disease but does not reverse established disease. Diabetic autonomic neuropathy is often seen in combination with DSPN and manifests by abnormal sweating, dysfunctional thermoregulation, dry eyes and mouth, postural hypotension, gastrointestinal abnormalities including gastroparesis, and genitourinary dysfunction.

88. The answer is B.

(Chap. 45) Peripheral neuropathy is a general term indicating peripheral nerve disorders of any cause. The causes are legion, but peripheral neuropathy can be classified by a number of means: axonal versus demyelinating, mononeuropathy versus polyneuropathy versus mononeuritis multiplex, sensory versus motor, and by the tempo of the onset of symptoms. Mononeuropathy typically results from local compression, trauma, or entrapment of a nerve. Polyneuropathy often results from a more systemic process. The distinction between axonal and demyelinating can often be made only with nerve conduction studies. HIV infection causes a common, distal, symmetric, mainly sensory polyneuropathy. Vitamin B12 deficiency typically causes a sensory neuropathy that predominantly involves the dorsal columns. Hypothyroidism and acromegaly may both cause compression and swelling of nerve fibers, resulting first in sensory symptoms and later in disease with motor symptoms. Critical illness polyneuropathy is predominantly motor in presentation. Patients typically present with weakness that can be profound. These patients may recover over the course of weeks to months. The etiology is unknown, but an association may exist with prolonged immobilization, severity of illness, neuromuscular blockade, and corticosteroids.

89. The answer is B.

(Chap. 45) Carpal tunnel syndrome is caused by the entrapment of the median nerve at the wrist. Symptoms begin with paresthesias in the median nerve distribution. With worsening, atrophy and weakness may develop. This condition is most commonly caused by excessive use of the wrist and situations involving repetitive motion. Most cases are idiopathic other than those related to occupational or environmental associations. Less commonly, systemic disease may result in carpal tunnel syndrome related to nerve compression or infiltrative disease. This may be suspected when bilateral disease is apparent. Tenosynovitis with arthritis, as in the case of rheumatoid arthritis, and thickening of the connective tissue, as in the case of amyloid or acromegaly, may cause carpal tunnel syndrome. Other systemic diseases, such as hypothyroidism and diabetes mellitus, are also possible etiologies. Acute or chronic leukemia is not typically associated with carpal tunnel syndrome.

90. The answer is B.

(Chap. 46) Guillain-Barré syndrome (GBS) is an acute, severe polyradiculoneuropathy that is autoimmune in nature. GBS manifests as rapidly evolving, areflexic motor paralysis with or without sensory disturbance, usually with ascending paralysis developing over several days. Approximately 70% of GBS cases occur 1–3 weeks after an acute infectious process, usually respiratory or gastrointestinal. Twenty to thirty percent of cases in North America, Europe, and Australia are preceded by infection or reinfection with Campylobacter jejuni. Other implicated infections include Epstein-Barr virus, CMV, and Mycoplasma pneumoniaeT. whippelii is the etiologic agent of Whipple’s disease and B. henselae is implicated in cat-scratch fever.

91. The answer is E.

(Chap. 47) Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. The primary defect is a decrease in the number of acetylcholine receptors at the neuromuscular junction secondary to autoimmune antibodies. MG is not rare, affecting at least 1 in 7500 individuals. Women are affected more frequently than men. Women typically present in the second and third decades of life, and men present in the fifth and sixth decades. The key features of MG are weakness and fatigability. Clinical features include weakness of the cranial muscles, particularly the eyelids and extraocular muscles. Diplopia and ptosis are common initial complaints. Weakness in chewing is noticeable after prolonged effort. Speech may be affected secondary to weakness of the palate or tongue. Swallowing may result from weakness of the palate, tongue, or pharynx. In the majority of patients the weakness becomes generalized. The diagnosis is suspected after the appearance of the characteristic symptoms and signs. Edrophonium is an acetylcholinesterase inhibitor that allows ACh to interact repeatedly with the limited number of AChRs, producing improvement in the strength of myasthenic muscles. False-positive tests may occur in patients with other neurologic diseases. Electrodiagnostic testing may show evidence of reduction in the amplitude of the evoked muscle action potentials with repeated stimulation. Testing for the specific antibodies to AChR are diagnostic. In addition to anti-AChR antibodies, antibodies to MuSK have been found in some patients with clinical MG. Antibodies to voltage-gated calcium channels are found in patients with the Lambert-Eaton syndrome.

92. The answer is C.

(Chap. 47) Except for lumbar puncture, all of the options listed are indicated at this time. Thymic abnormalities are present in 75% of patients with myasthenia gravis. A CT or MRI of the mediastinum may show enlargement or neoplastic changes in the thymus and is recommended upon diagnosis. Hyperthyroidism occurs in 3–8% of patients with myasthenia gravis and may aggravate weakness. Testing for rheumatoid factor and antinuclear antibodies should also be obtained because of the association of myasthenia gravis to other autoimmune diseases. Due to side effects of immunosuppressive therapy, a thorough evaluation should be undertaken to rule out latent or chronic infections such as tuberculosis. Measurements of ventilatory function are valuable as a baseline because of the frequency and seriousness of respiratory impairment in myasthenic patients, and they can be used as an objective measure of response to therapy.

93. The answer is E.

(Chap. 48) All classes of lipid-lowering agents have been implicated in muscle toxicity including fibrates, HMG-CoA reductase inhibitors, niacin, and ezetimibe. Myalgia, malaise, and muscle tenderness are the most common manifestations, and muscle pain may be exacerbated by exercise. Proximal weakness may be found on examination. In severe cases, rhabdomyolysis and myoglobinuria may occur, though most cases are mild. Concomitant use of statins with fibrates and cyclosporine are more likely to cause adverse muscle reactions. Elevated serum CK is often identified, and muscle weakness is evidenced by myopathic EMG studies and myonecrosis on muscle biopsy. Severe myalgias, muscle weakness, and significant elevations in CK (>3 × upper limit of normal) and myoglobinuria are indications for stopping. After cessation, improvement generally occurs after several weeks.

94. The answer is E.

(Chap. 48) A number of endocrinologic conditions are associated with myopathy. Both hypo- and hyperthyroidism are associated with proximal muscle weakness. Hypothyroidism is frequently associated with an elevated CK, even with minimal clinical evidence of muscle disease. Thyrotoxic patients may have fasciculations in addition to proximal myopathy, but in contrast to hypothyroid patients, CK is not generally elevated. Hyperparathyroidism is associated with muscle weakness that is generally proximal. Muscle wasting and brisk reflexes are also generally present. Serum CK levels may be normal or slightly elevated. Serum calcium and phosphate levels show no correlation with clinical weakness. Hypoparathyroid patients also often have myopathy due to hypocalcemia. Patients with acromegaly usually have mild proximal weakness without atrophy. The duration of acromegaly, not the serum growth hormone levels, correlate with the degree of myopathy. Diabetes mellitus is a very rare cause of myopathy, generally due to ischemic infarction of muscle and not a primary myopathy. Finally, vitamin D deficiency is associated with muscle weakness, as are glucocorticoid excess states, e.g., Cushing’s disease.

95. The answer is D.

(Chap. 48) There are two recognized clinical forms of myotonic dystrophy, both of which are characterized by autosomal dominant inheritance. Myotonic dystrophy 1 (DM1) is the most common form and the most likely disorder in this patient. Characteristic clinical features of this disorder include a “hatchet-faced” appearance, due to wasting of the facial muscles, and weakness of the neck muscles. In contrast to the muscular dystrophies (Becker and Duchenne), distal limb muscle weakness is more common in DM1. Palatal, pharyngeal, and tongue involvement are also common and produce the dysarthric voice that is frequently heard. The failure of relaxation after a forced hand-grip is characteristic of myotonia. Percussion of the thenar eminence can also elicit myotonia. In most individuals, myotonia is present by age 5, but clinical symptoms of weakness that lead to diagnosis may not be present until adulthood. Cardiac conduction abnormalities and heart failure are also common in myotonic dystrophy. Diagnosis can often be made from clinical features alone in an individual with classic symptoms and a positive family history. An electromyogram would confirm myotonia. Genetic testing for DM1 would show a characteristic trinucleotide repeat on chromosome 19. Genetic anticipation occurs with an increasing number of repeats and worsening clinical disease over successive generations. Myotonic dystrophy 2 (DM2) causes primarily proximal muscle weakness and is also known by the name proximal myotonic myopathy (PROMM). Other features of the disease overlap with DM1. Acid maltase deficiency (glucosidase deficiency, or Pompe’s disease) has three recognized forms, only one of which has onset in adulthood. In the adult-onset form, respiratory muscle weakness is prominent and often is the presenting symptom. As stated previously, Becker and Duchenne muscular dystrophies present with primarily proximal muscle weakness and are X-linked recessive disorders. Becker muscular dystrophy presents at a later age than Duchenne muscular dystrophy and has a more prolonged course. Otherwise, their features are similar. Nemaline myopathy is a heterogeneous disorder marked by the threadlike appearance of muscle fibers on biopsy. Nemaline myopathy usually presents in childhood and includes a striking facial appearance similar to that in myotonic dystrophy with a long, narrow face. This disease is inherited in an autosomal dominant fashion.

96. The answer is B.

(Chap. 49) When patients present with proximal muscle weakness and myositis, whether polymyositis, dermatomyositis, or inclusion body myositis, the diagnosis is confirmed by analysis of serum muscle enzymes, EMG findings, and muscle biopsy. The most sensitive serum enzyme is creatinine kinase (CK), which can be elevated as much as 50-fold in active disease. CK levels usually parallel disease activity, but can be normal in some patients with inclusion body myositis or dermatomyositis. CK is always elevated in active polymyositis and thus is considered most sensitive. Other enzymes may be elevated as well including glutamic-oxaloacetic transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, and aldolase.

97. The answer is B.

(Chap. 49) Various autoantibodies against nuclear antigens, e.g., ANAs, and cytoplasmic antigens are found in up to 20% of patients with inflammatory myopathies. The antibodies to cytoplasmic antigens are directed against ribonucleoproteins involved in protein synthesis (antisynthetases) or translational transport (anti–signal-recognition particles). The antibody directed against the histidyl-transfer RNA synthetase, called anti-Jo-1, accounts for 75% of all the antisynthetases and is clinically useful because up to 80% of patients with this autoantibody will have interstitial lung disease. Patients with anti-Jo-1 may also have Raynaud’s phenomenon, nonerosive arthritis, and the MHC molecules DR3 and DRw52. Interstitial lung disease associated with anti-Jo-1 is often rapidly progressive and fatal, even if treated aggressively with cyclophosphamide or other immunosuppressants.

98. The answer is A.

(Chap. 49) Dermatomyositis is associated with malignancy in up to 15% of cases, thus age-appropriate cancer screening is indicated when this diagnosis is made. Exhaustive cancer searches are not recommended, however. Dermatomyositis may be associated occasionally with scleroderma and mixed connective tissue disease, but less frequently with systemic lupus erythematosus, rheumatoid arthritis, or Sjögren’s syndrome, which are more closely associated with polymyositis or inclusion body myositis (IBM). Viruses may be associated with IBM and polymyositis, but are not proven to be associated with dermatomyositis. Parasites and bacteria such as cestodes and nematodes are associated with polymyositis, but not other forms of inflammatory myopathy. Finally, thyroid-stimulating immunoglobulins are not known to be associated with dermatomyositis.

99. The answer is A.

(Chap. 49) A common mistake in the management of patients with inflammatory myopathy is to “chase the CK” instead of adjusting therapy based on the clinical response. The goal of therapy is to improve strength. If that goal is being achieved, no augmentation of therapy is necessary. In this case, the plan to switch to long-term maintenance with steroid-sparing immunosuppressants should still be pursued. There have been no controlled studies comparing mycophenolate to methotrexate for long-term use in polymyositis, and in the absence of an adverse reaction to mycophenolate, therapy should not be changed. Despite an elevated CK, patients with polymyositis who are responding to therapy do not need a repeat muscle biopsy.

100. The answer is B.

(Chap. 50) The FLAIR MRI shows increased signal bilaterally in the occipital lobes predominantly involving the white matter. This pattern is typical of a hyperperfusion state, in this case secondary to calcineurin-inhibitor toxicity. This clinical-radiographic abnormality was previously described as reversible posterior leukoencephalopathy. However, this characterization is no longer utilized because the syndrome may not be reversible, the territory may not be confined posteriorly, and gray matter may be involved. Hyperperfusion syndrome may be due to a hydrostatic elevation in cerebral capillary pressure or disorders with endothelial dysfunction and capillary leakage. Hydrostatic causes include hypertensive encephalopathy, post–carotid endarterectomy syndrome, (pre)eclampsia, and high-altitude cerebral edema. Endothelial dysfunction causes include calcineurin-inhibitor toxicity, other chemotherapeutic agent toxicity, HELLP syndrome, TTP, SLE, or granulomatosis with polyangiitis (Wegener’s). The diagnosis is clinical and radiographic. CSF findings are nonspecific. In the case of cyclosporine the syndrome may occur with therapeutic serum levels and sporadically after years of treatment. Acoustic neuroma would present on MRI with a discrete mass. The radiologic and clinical appearance is not consistent with pituitary apoplexy. Post–liver transplant patients are at risk of acute (streptococcal) and chronic (tuberculous) meningitis, but the clinical and radiologic findings in this case would not be typical.

101. The answer is B.

(Chap. 50) Acute neurologic events, such as encephalopathy or stroke (often related to intraoperative hypotension or embolism), are common after open heart surgery or coronary artery bypass graft (CABG). Additionally, a chronic syndrome of cognitive impairment is now increasingly recognized after surgery. Small or microemboli during surgery are thought to be the etiology of a hyper- or hypoactive confusional state in the postoperative period. A smaller burden of microemboli may be responsible for the more subtle post–cardiac surgery syndrome characterized by confusion and depressive symptoms as described in this case. Cardiac surgery may also unmask the early manifestations of vascular dementia or Alzheimer’s disease. Off-pump CABG patients have a shorter length of hospital stay and fewer perioperative complications. Recent studies do not confirm the hypothesis that off-pump surgery results in less cognitive impairment than on-pump surgery. Ongoing studies are testing the efficacy of microfilters to capture emboli and reduce CNS complications. Given the temporal relation to CABG surgery and the lack of temporal variability, multiple sclerosis is not likely in this case. Similarly, in the absence of meningitis or encephalitis signs or symptoms, streptococcal or West Nile virus disease is unlikely. vCJD is associated with ingestion of prion-contaminated product. It is characterized by rapidly developing delirium and dementia, often associated with myoclonic jerks.

102. The answer is E.

(Chap. 50) The peroneal nerve winds around the head of the fibula below the lateral aspect of the knee. This superficial location makes it vulnerable to trauma. Poorly applied leg braces, fibular fracture, tight-fitting stockings, or casts may cause peroneal nerve injury and neuropathy. Patients may present with footdrop (dorsiflexion defect) with weakness of foot eversion. Intact foot inversion at the ankle distinguishes peroneal nerve injury from L5 radiculopathy, which involves the muscles innervated by the tibial nerve. Sensory loss due to peroneal nerve injury involves the lateral aspect of the leg below the knee and the dorsum of the foot. Cauda equina syndrome is caused by compression of the spinal nerve roots of the lumbar plexus usually due to tumor, trauma, or spinal stenosis. It typically presents with weakness of the muscles innervated by the involved nerves, incontinence, and decreased anal sphincter tone. Cauda equina syndrome is usually a medical emergency to avoid permanent functional loss. The femoral nerve branches into anterior and posterior portions in the leg. Injury of the anterior branches may lead to sensory findings in the thigh and muscular findings in the sartorius and the quadriceps. L4 radiculopathy causes symptoms in the anterior thigh and knee extensors (including the patellar reflex).

103. The answer is A.

(Chap. 52) Chronic fatigue syndrome (CFS) is a disorder characterized by persistent and unexplained fatigue resulting in severe impairment in daily functioning. Besides intense fatigue, most patients with CFS report concomitant symptoms such as pain, cognitive dysfunction, and unrefreshing sleep. Additional symptoms can include headache, sore throat, tender lymph nodes, muscle aches, joint aches, feverishness, difficulty sleeping, psychiatric problems, allergies, and abdominal cramps. Criteria for the diagnosis of CFS have been developed by the U.S. Centers for Disease Control and Prevention (see Table 52-1). CFS is seen worldwide, with adult prevalence rates varying between 0.2% and 0.4%. In the United States, the prevalence is higher in women, members of minority groups (African and Native Americans), and individuals with lower levels of education and occupational status. Approximately 75% of all CFS patients are women. The mean age of onset is between 29 and 35 years. It is probable that many patients go undiagnosed and/or do not seek help.

104. The answer is B.

(Chap. 52) Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) have been found to be the only beneficial interventions in chronic fatigue syndrome (CFS). CBT is a psychotherapeutic approach directed at changing condition-related cognitions and behaviors. CBT for CFS aims at changing a patient’s perpetuating factors by exploiting various techniques and components. The intervention, which typically consists of 12–14 sessions spread over 6 months, helps CFS patients gain control over their symptoms. GET is based on the model of deconditioning and exercise intolerance and usually involves a home exercise program that continues for 3–5 months. Walking or cycling is systematically increased, with set target heart rates. Evidence that deconditioning is the basis for symptoms in CFS is lacking, however. The primary component of CBT and GET that results in a reduction in fatigue is a change in the patient’s perception of fatigue and focus on symptoms. CBT is generally the more complex treatment, which might explain why CBT studies tend to yield better improvement rates than GET trials. Not all patients benefit from CBT or GET. Predictors of poor outcome are somatic comorbidity, current disability claims, and severe pain. CBT offered in an early stage of the illness reduces the burden of CFS for the patient as well as society in terms of decreased medical and disability-related costs. Full recovery from untreated CFS is rare: the median annual recovery rate is 5% (range 0–31%) and the improvement rate 39% (range 8–63%). Major depressive disorder, bipolar disorder, eating disorder, and schizophrenia are exclusion criteria for the diagnosis of chronic fatigue syndrome.

105. The answer is D.

(Chap. 54) This patient is experiencing her first episode of a panic attack and does not meet the criteria for panic disorder. In this situation, no specific treatment is required. The patient should be reassured in a manner that is empathetic and supportive that she does not have any evidence of a serious medical disorder. Panic attacks are common, with about 1–3% of the population experiencing at least one panic attack. Panic attacks begin abruptly, most commonly without an immediate precipitating cause, and peak in severity over 10 minutes. The symptoms usually subside spontaneously over the course of an hour. Diagnostic criteria for a panic attack include a minimum of four of the following criteria: palpitations or racing heart, sweating, trembling, shortness of breath, feeling of choking, chest pain, nausea or GI distress, dizziness, derealization, fear of losing control, fear of dying, paresthesias, or chills/hot flushes. If a patient subsequently develops panic disorder, a variety of treatment options can be pursued. Panic disorder is marked by at least 1 month of recurrent panic attacks associated with excessive worry about or change in behavior as a result of the attacks. The goals of therapy for panic attacks are to decrease the frequency of attacks and the severity of symptoms during the attack. Antidepressant medications are the cornerstone of therapy with selective serotonin reuptake inhibitors being the most frequently used class of medication. The dose of medication for panic disorder is typically lower than the antidepressant dose. For fluoxetine, this would be 5–10 mg daily. As these medications take 2–6 weeks to become effective, they are often combined with benzodiazepines to be used on an as-needed basis for immediate relief of attacks. Alprazolam and clonazepam are common agents used for panic disorder, although alprazolam may have more associated dependence with the need for escalating doses of medications. In combination with pharmacologic therapy, psychotherapy and education are also useful for the treatment of panic disorder. The therapy often includes breathing techniques, cognitive behavioral therapy, and even homework assignments.

106. The answer is A.

(Chap. 54) There are increasing numbers of antidepressant medications available in a variety of classes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used antidepressant drugs. This class of medications includes fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram. These medications are taken once daily and have side effects including sexual dysfunction, headache, and insomnia. Tricyclic antidepressants were commonly used in past decades for the treatment of depression. However, overdoses can be lethal, and anticholinergic side effects including dry mouth, constipation, and urinary retention can limit the dose. Medications in the tricyclic class of antidepressants include amitriptyline, nortriptyline, imipramine, desipramine, doxepin, and clomipramine. Mixed norepinephrine/serotonin reuptake inhibitors and receptor blockers are a newer class of medications. These medications are increasing in use as they are quite effective and do not have the same frequency of sexual dysfunction. Medications in this class include venlafaxine, desvenlafaxine, duloxetine, and mirtazapine. Monoamine oxidase inhibitors were once a common antidepressant class of medication, but these medications are now only rare used. There is a wide range of drug and food interactions that can lead to hypertensive crises. Examples of medication in this class include phenelzine, tranylcypromine, and isocarboxazid. A final class of antidepressants is called simply mixed action drugs and includes trazodone, bupropion, and nefazodone.

107. The answer is E.

(Chap. 54) Post-traumatic stress disorder (PTSD) was only added as a discrete disorder in 1980. The diagnostic criteria for PTSD are long and require that an individual experiences an event where there was an actual or perceived threat of death or serious injury and that the individual’s reaction included intense fear or helplessness. Following the event, the individual continues to re-experience the event and avoids stimuli associated with the trauma. In association with this, there is also often a generalized withdrawal and decrease in responsiveness. At the same time, the patient exhibits an increase in arousal that is often exhibited by insomnia, irritability, hypervigilance, and difficulty concentrating. Treatment of PTSD is almost always multifactorial, including both pharmacotherapy and psychotherapy. It is not uncommon for an individual with PTSD to develop a dependence on drugs or alcohol as an attempt to control the symptoms, and any substance abuse issues need to be treated simultaneously as well. This patient’s treatment would include avoidance of alcohol and intensive substance abuse treatment as needed. Treatment with antidepressant medications can decrease anxiety and avoidance behaviors. Trazodone is often given at night for its sedating properties. Psychotherapeutic strategies include cognitive behavioral therapy to overcome avoidance behaviors as well.

108. The answer is B.

(Chap. 54) Fifteen percent of the population will experience at least one episode of major depression over the course of a lifetime, and most episodes of major depression are treated by primary care practitioners. Treatment can be any of a number of medications across a variety of classes. Despite the popularity of newer antidepressants, there is no evidence that these medications are more efficacious than older drugs like tricyclic antidepressants. Indeed, 60–70% of patients will respond to any drug chosen if given in a sufficient dose for 6–8 weeks. Once a patient has been on treatment for about 2 months, the response should be evaluated, and if there has been an insufficient response, a dosage increase should be considered. In this patient, a dosage increase yielded control of depressive symptoms at 4 months. Once control of symptoms has been achieved, the drug should be continued for an additional 6–9 months to prevent relapse. If a patient experiences any additional episodes of major depression, he or she will likely require indefinite maintenance treatment.

109. The answer is A.

(Chap. 56) Alcohol is primarily absorbed through the proximal small intestine, but small to moderate amounts can also be absorbed in the mouth, esophagus, stomach, and large intestines. Several factors can increase the rate of absorption. One factor that increases absorption is rapid gastric emptying, which can be induced by concurrent consumption of carbonated beverages. Another factor that increases absorption from the gut to the blood is the ingestion of alcohol in the absence of other calorie sources such as proteins, fat, or carbohydrates. A final factor that can increase absorption is to drink alcohol that is diluted to a modest concentration (~20% or less). At high alcohol concentrations absorption is decreased, although high blood levels may be achieved because the amount of alcohol ingested is high.

110. The answer is C.

(Chap. 56) Alcohol has effects on many neurotransmitters in the brain. The predominant effect of alcohol lies in its ability to cause the release of γ-aminobutyric acid (GABA) and acts primarily at the GABAAreceptors. GABA is the primary inhibitory neurotransmitter in the brain and is associated with the sedative effects of alcohol. Many other drugs affect the GABA system including benzodiazepines, nonbenzodiazepine sleep aids such as zolpidem, anticonvulsants, and muscle relaxants. The euphoric effects of alcohol consumption are related to increases in dopamine, which is common to all pleasurable activities. The effects on dopamine are thought to be important in alcohol craving and relapse. In addition, alcohol alters opioid receptors and can lead to a release of beta endorphins during acute ingestion. In addition to these effects, alcohol also inhibits postsynaptic N-methyl-D-aspartate excitatory glutamate receptors. Glutamate is the primary excitatory neurotransmitter of the brain, and its inhibition further contributes to the sedative effects of alcohol. Additional important effects on neurotransmitters include increased serotonin activity and decreased nicotinic acetylcholine receptors.

111. The answer is D.

(Chap. 56) The acute effects of any drug depend on many factors including amount consumed and absorbed, presence of other drugs, and past experience with the drug. In an individual who is naïve to alcohol, drug levels as low as 0.02 g/dL can lead to a decrease in inhibitions and a slight feeling of intoxication. In the United States, “legal” intoxication occurs at a blood alcohol level of 0.08 g/dL in most states. At this level, decreases in cognitive and motor abilities are seen. Once an alcohol level of 0.20 g/dL is achieved, an individual is obviously impaired with slurred speech, poor judgment, and impaired coordination. Light coma and depression of respiratory rate, blood pressure, and pulse occur at levels of around 0.30 g/dL, and death is likely to occur at levels of 0.40 g/dL. However, in individuals who drink heavily, tolerance begins to develop to alcohol. After a period of 1–2 weeks of daily alcohol consumption, liver metabolism of alcohol increases by as much as 30%, but disappears quite quickly with abstinence. Cellular or pharmacodynamic tolerance also occurs and refers to the neurochemical changes that allow an individual to maintain more normal physiologic functioning despite the presence of alcohol.

112. The answer is C.

(Chap. 56) Alcohol abuse is defined as repetitive problems in any one of four life areas that can be attributed to alcohol. The four life areas that can be affected by alcohol include social, interpersonal, legal, or occupational. In addition, an individual who repetitively engages in hazardous behaviors while under the influence of alcohol would be considered to suffer from alcohol abuse. However, this is to be differentiated from alcohol dependence. Alcohol dependence is defined in the DSM-IV as repeated alcohol-related difficulties in three of seven life areas and includes the development of tolerance and dependence. If tolerance or dependence is present, this predicts a more severe clinical course, and the presence of alcohol dependence decreases overall life span by about a decade. Only about 50% of individuals with alcohol abuse will continue to experience similar alcohol-related problems 3–5 years later, and only 10% will go on to develop alcohol dependence. The lifetime risk of alcohol dependence in most Western countries is about 10–15% in men and 5–8% in women. However, there may be higher rates in Ireland, France, and Scandinavian countries. In addition, native cultures appear to be especially susceptible to problems with alcohol dependence. This has been seen in Native Americans, Maoris, and the aboriginal tribes of Australia.

  About 60% of the risk for alcohol use disorders is attributed to genetic influences. Children of alcoholics do have a higher risk of alcohol abuse and dependence; however, this risk is about 4 times higher, not 10. Identical twins also exhibit a higher risk of concurrent alcohol abuse and dependence when compared to fraternal twins. The genetic factors that appear to be most strongly linked to alcohol use disorders include genes that are linked to impulsivity, schizophrenia, and bipolar disorder. In addition, genes that affect alcohol metabolism or sensitivity to alcohol also contribute to the genetics of alcoholism. A mutation in aldehyde dehydrogenase that is more common in individuals of Asian descent results in intense flushing when alcohol is consumed and confers a decreased risk of alcohol dependence. Conversely, genetic variants that lead to a low sensitivity to alcohol increase the risk of subsequent alcohol abuse and dependence, as higher and higher doses of alcohol are required to achieve the same effects.

113. The answer is B.

(Chap. 56) Individuals with alcohol dependence are susceptible to alcohol withdrawal when alcohol intake is stopped abruptly. The individual in this case scenario is likely alcohol dependent given his large amount of alcohol intake on a daily basis. Symptoms of alcohol withdrawal can range from mild tremulousness to hallucinations, seizures, or the development of delirium tremens. Other clinical features of alcohol withdrawal include anxiety, insomnia, and autonomic nervous system over-activity manifested as tachycardia, tachypnea, elevated blood pressure, and fever. This patient exhibits symptoms of the more severe delirium tremens, with mental confusion, agitation, and fluctuating levels of consciousness. While minor symptoms of alcohol withdrawal may begin as soon as 5–10 hours after cessation of alcohol intake, the symptoms do not peak for 48–72 hours, putting this patient in the appropriate time frame for alcohol withdrawal.

  The best approach for the alcohol-dependent patient who abruptly stops all alcohol intake is to take a prophylactic approach and screen early for symptoms of alcohol withdrawal. Tools such as the Revised Clinical Institute for Withdrawal Assessment for Alcohol (CIWA-Ar) may help clinicians and nurses screen for the early development of symptoms and allow intervention before symptoms escalate. In this setting, most experts recommend the use of oral long-acting benzodiazepines such as chlordiazepoxide or diazepam beginning on the first day. However, in this case, the patient received no such treatment and is now experiencing severe alcohol withdrawal and delirium tremens. Intravenous medications that have a rapid onset of action and can be titrated for more aggressive symptom management are often employed in this setting. Thus, the use of IV lorazepam or diazepam is preferred in this patient. Following an initial bolus, repeated doses can be used in short intervals until the patient is calm but arousable. In some instances a continuous infusion may be required, although bolus dosing is preferred. In the most severe cases, propofol or barbiturates may be required, although the patient would most likely need to be intubated for airway protection with use of these medications.

  The other options listed are not appropriate for initial management of this patient. Intravenous fluids and thiamine had been administered since hospital admission. Administration of glucose-containing fluids without thiamine in the alcohol-dependent patient can precipitate Wernicke’s encephalopathy, which would present with ophthalmoparesis, ataxia, and encephalopathy. Given the patient’s fever, an infectious etiology can be considered, and it would be appropriate to perform blood cultures in this patient. However, given the clear symptoms of alcohol withdrawal and lack of necrotizing pancreatitis on CT abdomen, empiric treatment with antibiotics is not required. Likewise, without focal neurologic findings, a head CT would be a low-yield diagnostic procedure that would be difficult to perform in the patient’s current agitated condition and would only delay appropriate therapy. Finally, restraints are best avoided if the patient’s safety can be ensured through the appropriate use of benzodiazepines, as restraints are only likely to make the patient’s agitation worse and may lead to iatrogenic harm. Haloperidol may have some sedative effect on the patient, but could lead to torsades de pointe arrhythmia as this patient is at risk for electrolyte deficiencies from his alcoholism and pancreatitis.

114. The answer is D.

(Chap. 56) In individuals recovering from alcoholism several medications may have a modest benefit in increasing abstinence rates. The two medications with the best risk-benefit ratio are acamprosate and naltrexone. Acamprosate inhibits NMDA receptors, decreasing symptoms of prolonged alcohol withdrawal. Naltrexone is an opioid antagonist than can be administered orally or as a monthly injection. It is thought to act by decreasing activity in the dopamine-rich ventral tegmental area of the brainstem and subsequently decreasing the pleasurable feelings associated with alcohol consumption. There is some research to suggest that the use of these medications in combination may be more effective than either one alone. Disulfiram is an aldehyde dehydrogenase inhibitor that has been used for many years in the treatment of alcoholism. However, it is no longer a commonly used drug due to its many side effects and risks associated with treatment. The primary mechanism by which it acts is to create negative effects of vomiting and autonomic nervous system hyperactivity when alcohol is consumed concurrently with use of the medication. As it inhibits an enzyme that is part of the normal metabolism of alcohol, it allows the buildup of acetaldehyde, which creates these symptoms. Because of the autonomic side effects, it is contraindicated in individuals with hypertension, a history of stroke, heart disease, or diabetes mellitus.

115. The answer is E.

(Chap. 57) Prescription drug abuse has increased dramatically among all age groups and is strikingly common in teenagers. Since 2007, prescription opiates have passed marijuana as the most common illicit drugs that adolescents initially abuse. This has occurred at the same time as rates of prescription narcotic abuse have increased across all age groups. The annual prevalence of heroin abuse is approximately 0.14% of the population. In contrast, this prevalence is only one-third the rate of prescription opiate abuse. Among prescription narcotics, oxycodone is the single most commonly abused drug. Other common prescription narcotics that are abused include morphine and hydrocodone. Among health care professionals, meperidine and fentanyl are more frequently abused.

116. The answer is B.

(Chap. 57) Tolerance and withdrawal begin within 6–8 weeks of chronic daily opioid use. Tolerance develops not because of increased metabolism, but through a change in the pharmacodynamics of the drugs, requiring increasing doses to achieve the euphoric effects and prevent withdrawal. With the abrupt cessation of narcotics, acute withdrawal symptoms begin within 8–10 hours after the last dose. While the symptoms of narcotic withdrawal are noxious, they are not life threatening, as is the case with benzodiazepine or barbiturate withdrawal. The primary symptoms of opiate withdrawal are related to over activity of the autonomic nervous system. This manifests as increased lacrimation, rhinorrhea, and sweating. In addition, patients frequently will have diffuse piloerection (chill bumps), giving rise to the term “cold turkey.” As withdrawal symptoms progress, patients appear restless with myalgias, nausea, vomiting, and diarrhea. Hypertension, hyperthermia, and tachypnea can occur as well. Hypotension is not a symptom of opioid withdrawal. A patient with known infection and new-onset hypotension should be evaluated for systemic infection, not withdrawal.

117. The answer is E.

(Chap. 57) The patient is presenting with an acute overdose of an unknown quantity of extended-release opioid medications taken with alcohol. When evaluating and treating a patient with an intention overdose, the first priority is to stabilize the patient’s condition. The patient was appropriately given the opiate antagonist naloxone by emergency responders as the patient was near-apneic. In addition, the patient was also appropriately intubated and stabilized for transport to the hospital. In the emergency room, however, the patient remained hypotensive and unresponsive. At this point, the next step in stabilizing the patient is to support the blood pressure with bolus fluid resuscitation, and if the patient fails to respond, IV vasopressors would be required. Given his ongoing unresponsive state and the expected long duration of effect with a sustained-release preparation, it is appropriate to initiate a continuous infusion of naloxone. After a bolus dose, the expected onset of action is 1–2 minutes, but the duration of effect is only a few hours. Some care must be taken when giving naloxone as one only wants to reverse the respiratory and cardiovascular depression associated with the overdose. Particularly in chronic drug abusers, high doses of naloxone can precipitate the distressing symptoms of narcotic withdrawal. When long-acting preparations of opioids are taken, activated charcoal and gastric lavage are appropriate considerations to decrease the absorption of any undigested pills. While the patient is being stabilized from a cardiovascular and respiratory standpoint, it is important that the clinician consider if any other concurrent ingestion may have occurred that would affect the patient’s outcome. As the patient is unable to provide any history and the overdose was not witnessed, one must not focus solely on the opioids. The appropriate approach is to perform a comprehensive toxicology evaluation that should include a urine drug screen, blood alcohol level, and acetaminophen levels, at a minimum. One could also consider sending for levels of aspirin or tricyclic antidepressants.

118. The answer is C.

(Chap. 58) Marijuana is the most commonly used illegal drug in the United States with over 6% of all individuals reporting current usage in 2009 (http://www.whitehousedrugpolicy.gov/publications/pdf/nsduh.pdf, accessed July 25, 2011). In part, the prevalence of marijuana use is related to the widespread belief that marijuana is thought to have few negative health effects. Acutely, marijuana causes a sense of relaxation and mild euphoria, not unlike that of alcohol intoxication. In addition, impaired judgment, cognition, and psychomotor performance are seen. Occasionally, acute intoxication can lead to negative emotional responses as well. A consensus about the chronic effects of marijuana usage is not clearly defined. Traditionally, marijuana usage has been linked with an “amotivational syndrome.” While it is true that chronic users of marijuana may lose interest in day-to-day activities and spend more time using the drug, this is certainly not specific for marijuana uses, and a specific “amotivational syndrome” is not defined with chronic marijuana use. Other symptoms that have been attributed to chronic marijuana use that lack good evidence for causation include depression and maturational dysfunction. In individuals with a history of schizophrenia, however, chronic marijuana use has been associated with an increased risk of psychotic symptoms.

  The physical effects of chronic marijuana use are also not clearly known. Acutely, marijuana causes increased heart rate, but tolerance for this effect occurs rapidly. Acute ingestion can also precipitate angina. The chronic effects on lung function are not known, as tobacco products are frequent confounders. Acute decreases in vital capacity and diffusion capacity are seen, but whether this translates into an increased risk of emphysema has not yet been determined. Most studies have not found an association with emphysema. A variety of other adverse physical effects have been described but not confirmed in a systematic fashion. This includes reports of low testosterone levels, decreased sperm count, impaired fetal growth, and chromosomal abnormalities.

  Contrary to popular belief, chronic use of marijuana is associated with the development of tolerance as well as a withdrawal syndrome. Signs of physical tolerance include tolerance to the development of tachycardia and conjunctival injection. The psychological tolerance that develops is more prominent and predictable. This occurs rapidly, with individuals often seeking more potent compounds or smoking the drug more frequently. With cessation of marijuana use, a withdrawal syndrome can be demonstrated with irritability, anorexia, and sleep disturbance.

aQuestions and answers were taken from Wiener C et al (eds): Harrison’s Principles of Internal Medicine Self-Assessment and Board Review, 18th ed. New York: McGraw-Hill, 2012.

 


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