SECTION XI
Neurologic Disorders
QUESTIONS
DIRECTIONS: Choose the one best response to each question.
XI-1. A 78-year-old man with a history of prostate cancer presents to the emergency department with
weakness affecting his right arm and leg and left face. The weakness began abruptly earlier during
the day and is associated with numbness and paresthesias. On physical examination, strength is 4/5
in the right leg and arm. The upper and lower facial muscles fail to move on the left. Babinski sign is
positive. Sensation is decreased in the right extremities and on the left face. Based on this
information, what is the most likely site of the lesion causing the patient’s symptoms?
A.
B.
C.
D.
E.
Brainstem
Cerebrum
Cervical spinal cord
Multiple spinal cord levels
Neuromuscular junction
XI-2. 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.
B.
C.
D.
E.
Babinski sign
Dysdiadochokinesis
Lhermitte symptom
Pronator drift
Romberg sign
XI-3. The test described in Question XI-2 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 which of the following?
A.
B.
C.
D.
E.
Abnormal sensation
Early dementia
Localized brainstem disease
Potential weakness
Underlying cerebellar dysfunction
XI-4 through XI-8. For each of the following clinical findings on neurologic examination, identify the
most likely anatomic location:
4. Anal sphincter dysfunction
5. Bilateral ptosis and diplopia
6. Diminished sensation bilaterally at the ankles and feet in a patient with diabetes
7. Left homonymous hemianopia
8. Right lateral extraocular muscle paresis
A.
B.
C.
D.
E.
Brainstem
Cerebrum
Neuromuscular junction
Peripheral nerve
Spinal cord
XI-9. 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.
B.
C.
D.
E.
Cerebral angiography
Computed tomography (CT) of the head with intravenous contrast
CT of the head without intravenous contrast
Lumbar puncture
Transcranial Doppler ultrasound
XI-10. 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.
B.
C.
D.
E.
Magnetic resonance angiography
Fluid-attenuated inversion recovery (FLAIR)
T1-weighted
T2-weighted
B and D
XI-11. Which of the following is a possible complication of administration of gadolinium to a patient
with chronic kidney disease?
A.
B.
C.
D.
E.
Acute renal failure
Hyperthyroidism
Hypocalcemia
Lactic acidosis
Nephrogenic systemic sclerosis
XI-12. A 45-year-old woman is admitted to the emergency department after a first episode of witnessed
generalized tonic-clonic seizure. She is administered lorazepam 2 mg with cessation of seizure
activity. All of the following are likely possible causes of her seizure EXCEPT:
A.
B.
C.
D.
E.
Alcohol withdrawal
Autoantibodies
Brain tumor
Genetic disorder
Hyperglycemia
XI-13. A 48-year-old woman is evaluated for seizure-like episodes. She has a history of major depression
and borderline personality disorder. She is currently taking escitalopram 10 mg daily. She smokes
one pack of cigarettes daily and drinks one to two glasses of wine daily. You are called to the bedside
during an episode. You observe her head turning vigorously side to side with large-amplitude limb
shaking and upward thrusting of the pelvis. You are concerned about psychogenic seizures. Which of
the following findings could assist in this diagnosis?
A. A normal creatine kinase level within 30 minutes of the episode
B.
C.
D.
E.
A normal prolactin level within 30 minutes of the episode
An elevated creatine kinase within 30 minutes of the episode
An elevated prolactin level within 30 minutes of the episode
Decreased arousability in the period immediately following the episode
XI-14. A 56-year-old man with glioblastoma multiforme in the right parietal lobe experiences his first
generalized tonic-clonic seizure. What is the best course of action for this patient?
A.
B.
C.
D.
E.
Initiate therapy with ethosuximide
Initiate therapy with lamotrigine
Initiate therapy with phenytoin
Observe for additional seizures and initiate therapy only if additional seizures occur
Refer for electroencephalogram (EEG) and treat only if an epileptogenic focus is identified
XI-15. A 24-year-old man presents to your office requesting to be taken off of his antiepileptic drugs. He
was in an automobile accident at the age of 12, resulting in significant head trauma. He was in a
medically induced coma for 6 weeks and had intracranial edema with generalized tonic-clonic
seizures at that time. These persisted for several years afterward. His last seizure that he is aware of
occurred at the age of 18 and was generalized. He continues to take valproic acid 1000 mg bid. On
physical examination, he demonstrates normal cognition and affect. He has ongoing focal weakness
involving his left lower extremity with spasticity. You refer him for a sleep-deprived EEG, which
shows no evidence of focal abnormalities. Which of the following factors is of greatest concern
regarding his risk of recurrent seizures?
A.
B.
C.
D.
Focal defect on neurologic examination
Generalized seizure disorder
Head trauma
Seizure within the past 7 years
XI-16. A 38-year-old man with a history of seizure disorder presents with generalized convulsive status
epilepticus. He had been having persistent seizure activity for 20 minutes when emergency medical
services were activated. He was given paralytic agents in the field to allow for intubation as well as
lorazepam 8 mg intravenously (IV). Upon arrival in the emergency department 20 minutes later, the
neuromuscular blockade has worn off and generalized seizure activity is again apparent. His initial
temperature is 39.2°C with blood pressure of 182/92 mmHg, heart rate of 158 bpm, respiratory rate
of 38 breaths/min, and SaO2 of 95% on mechanical ventilation with an assist control mode with a set
rate of 15, tidal volume of 420 mL, positive end-expiratory pressure of 5 cmH2O, and FiO2 of 0.6.
What is the next step in the management of this patient?
A.
B.
C.
D.
E.
Additional dosing of neuromuscular blockers
Isoflurane anesthesia
Fosphenytoin 20 mg/kg IV
Pentobarbital 5 mg/kg bolus followed by an infusion at 1 mg/kg/hr
Propofol 2 mg/kg bolus followed by an infusion at 2 mg/kg/hr
XI-17. A 68-year-old man presents to the emergency department with right-sided face, arm, and leg
weakness that began abruptly 1 hour prior to arrival. The patient is accompanied by his wife. He
exhibits Broca aphasia and dysarthria. Physical examination confirms a dense hemiparesis of the right
face, arm, and leg with decreased sensation. In addition, there is a gaze preference to the left. The
patient’s initial blood pressure on presentation to the emergency department is 195/115 mmHg.
Multiple follow-up blood pressures have been sustained between 160–170/100– 110 mmHg without
treatment. An emergent noncontrast head CT shows no evidence of intracranial hemorrhage or edema
with only mild loss of gray-white matter differentiation. On further review of the patient’s medical
history, he had a prior embolic stroke affecting the posterior circulation 12 months ago. He also has a
history of colon cancer that was diagnosed 3 months ago when he presented with a lower
gastrointestinal (GI) bleed requiring transfusion of 4 units of packed red blood cells. He successfully
underwent left hemicolectomy of a stage I adenocarcinoma. In the postoperative period, he
developed a deep venous thrombosis of the superficial femoral vein on the right. He is currently
being treated with warfarin at 5 mg daily. His last international normalized ratio (INR) was
therapeutic at 2.2. It was checked 4 days ago. Which of the following factors is a contraindication to
use of IV recombinant tissue plasminogen activator in this patient?
A.
B.
C.
D.
E.
GI bleeding within the past 3 months
Initial blood pressure elevation >180/110 mmHg
Major surgery within the past 3 months
Prior embolic stroke
Use of warfarin with elevated INR
XI-18. A 54-year-old woman is seen in your office for a new patient visit. She is very concerned about
her risk of stroke and wants to do whatever she can to prevent it. Her mother died following a stroke
related to untreated hypertension at the age of 62. The patient has hypertension and diabetes
mellitus. She currently is taking hydrochlorothiazide 25 mg daily and metformin 500 mg twice daily.
She smokes one pack of cigarettes daily. Her blood pressure today is 158/92 mmHg. Fasting lipids
show a total cholesterol of 232 mg/dL, triglyceride level of 168 mg/dL, high-density lipoprotein of 32
mg/dL, and low-density lipoprotein of 166 mg/dL. The hemoglobin A1C is 7.5%. What advice is
LEAST helpful in primary prevention of stroke in this individual?
A. Add aspirin 81 mg daily as an antiplatelet agent
B. Add atorvastatin 10 mg daily to lower cholesterol
C. Add lisinopril 20 mg daily to decrease blood pressure to a target blood pressure of 130/80 mmHg
D. Increase metformin to 1000 mg twice daily and change diet to obtain a goal hemoglobin A1C
level of less than 7%
E. Recommend smoking cessation and offer counseling and nicotine replacement
XI-19. A 76-year-old man was seen in the emergency department for left-sided arm weakness that
rapidly improved over the course of 4 hours. He has a past medical history positive for hypertension,
dyslipidemia, and coronary artery disease. He previously has undergone coronary angioplasty with
stenting to both his left anterior descending artery and right coronary artery on two occasions. He is
currently being treated with aspirin 81 mg daily, metoprolol 100 mg bid, benazepril 20 mg daily,
rosuvastatin 10 mg daily, and clopidogrel 75 mg daily. Evaluation demonstrates a 75% occlusion of
the right internal carotid artery. The patient is considering whether he would like to undergo carotid
endarterectomy. What information is needed for him to make an informed decision about the risks
and benefits of the surgery for him?
A.
B.
C.
D.
E.
Perioperative mortality rate for the surgeon performing his surgery
Perioperative stroke rate for the surgeon performing his surgery
Risk of stroke in the next 90 days
Risk of stroke in the next year
The surgeon cannot schedule his surgery for 6 weeks
XI-20. A 48-year-old man presents to the emergency department with stupor. He was feeling well until
30 minutes ago when he complained of headache and right-sided weakness. He has a history of
hypertension and cocaine use. He is prescribed hydrochlorothiazide 25 mg daily, but it is unknown
whether he is taking his medication. On presentation, he is drowsy and minimally responsive to
questioning. His blood pressure is 242/148 mmHg, heart rate is 124 bpm, respiratory rate is 24
breaths/min, SaO2 is 98% on room air, and temperature is 37.0°C. He is not moving his right arm
and leg. He does withdraw to pain. His noncontrast head CT is shown in Figure XI-20. What is the
diagnosis?
FIGURE XI-20
A.
B.
C.
D.
E.
Brain mass
Epidural hematoma
Intracranial hemorrhage
Ischemic stroke in the left middle cerebral artery territory
Subdural hematoma
XI-21. A 26-year-old woman has throbbing right-sided headaches that are centered around her right eye.
They are worse with movement and aggravated by loud noises. There are no premonitory warning
features. Triggers for the headaches include lack of sleep, stress, and red wine. A mild attack can be
treated by ibuprofen, but nonsteroidal anti-inflammatory drugs have no effect on more severe pain.
Which of the following best characterizes what is understood about the pathogenesis of the patient’s
headache syndrome?
A.
B.
C.
D.
E.
Diffuse muscular contraction of the neck and scalp
Disinhibition of the central pacemaker neurons in the posterior hypothalamic region
Dysfunction of monoaminergic sensory control systems in brainstem and hypothalamus
Focal cerebral vasodilation in the region of the brain that is the focus of the pain
Vascular compression of the trigeminal nerve as it enters the pons
XI-22. A 34-year-old woman is evaluated for migraine headaches. She has had migraines since her early
20s, and they are worse with recovery from sleep loss, menstrual cycles, stress, and certain foods that
she tries to avoid. She describes the pain as left occipital in nature, throbbing, and severe. She has
photophobia with episodes and occasionally vomits. With an acute episode, she takes rizatriptan 10
mg. It works within 1–2 hours in about 75% of attacks. However, recently, she has been having about
six episodes per month. She has missed some days of work due to attacks. She would like to escalate
her therapy and is asking for your advice. What is your advice about medications for migraine
prevention?
A. Methysergide and phenelzine are first-line medications for this indication.
B. No drugs have a Food and Drug Administration–approved indication for migraine prevention.
C. Preventive therapy would not be recommended unless she has more than seven attacks per
month.
D. The probability of success with use of a preventive medication is 90%.
E. There is a lag of 2–12 weeks after starting a new medication before an effect is seen.
XI-23. A 42-year-old man is evaluated for severe headaches that have occurred several times over the
past 5–7 years. He describes the headaches as occurring behind his left eye and coming on suddenly.
The headaches have a stabbing quality and are associated tearing of his eye and nasal congestion. He
says the pain is a “12” out of 10 when it occurs, and he finds that he can’t even sit still due to pain.
The headaches last about 20 minutes and then subside. He says that the headaches seem to occur at
the same time every day, around 5 AM, but he can go months without having any headache at all. He
has a difficult time identifying a trigger for the headaches. What is the most likely cause of his
headaches?
A.
B.
C.
D.
E.
Cluster headache
Migraine
Paroxysmal hemicrania
Short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing (SUNCT)
Tension headache
XI-24. A 72-year-old woman is evaluated for memory problems. She and her husband first noticed some
mild problems about 2 or 3 years ago, but attributed her symptoms to “old age.” They decided to
seek an evaluation when she became lost while returning home from the grocery store last week. She
had driven back and forth from this same store weekly for the past 20 years, and this incident
frightened them both. She does not know what happened and had to call her husband for help. She
has shown no changes to her personality. Her medical history is significant for hypertension and
stage II breast cancer treated 10 years ago. She is taking ramipril 5 mg bid. She smoked one pack of
tobacco daily from the age of 20 until she was 64. She drinks a glass of wine nightly. She retired from
her position as an accountant at the age of 60. On examination, she appears well-groomed and
pleasant. Her blood pressure is 158/90 mmHg, and heart rate is 82 bpm. Her neurologic examination
is normal without focal defect. Gait is normal. No rigidity is present. Neuropsychological testing
shows impairment 1.5 standard deviations below the norm. What would be the most likely pathologic
finding in the brain?
A. Deposition of amyloid within cerebral blood vessels
B.
Loss of cortical serotonergic innervation with atrophy of the frontal, insular, and/or temporal
cortex
C. Neuritic plaques and neurofibrillary tangles in the medial temporal lobes
D.
Presence of intraneuronal cytoplasmic inclusions that stain with periodic acid–Schiff and
ubiquitin in the substantia nigra, amygdala, cingulate gyrus, and neocortex
XI-25. A 78-year-old man has been diagnosed with mild cognitive impairment after complaining of
decreased memory. He asks you to prescribe something that will decrease his likelihood to progress
to Alzheimer disease. What treatment do you recommend?
A.
B.
C.
D.
E.
Brain training exercises
Donepezil
Gingko biloba
Memantine
No treatment at this time has been demonstrated to delay the progression of mild cognitive
impairment to Alzheimer disease.
XI-26. A 62-year-old man presents with memory and behavior problems. Until 1 year ago, he had
worked as a senior account manager at a local bank, but he had to retire after he had an angry
outburst with a client and was inappropriate with a female colleague in a departmental meeting. His
family reports that this behavior was entirely out of character for him, and since then, he is
increasingly brusque and easily angered. He also has been overly sexual and has said many
inappropriate things within the hearing of his teenaged grandchildren. At the same time, it has been
noted that his memory has been worsening. He has an MBA degree, but his wife has recently began
managing the money after he could no longer be relied on to do this. The financial records were
highly disorganized when she began to look into them. The patient also recently had a near-miss
accident while driving the wrong way down a one-way street. On examination, he is gruff and says
that he doesn’t want to do “this damn thing.” He needs to “get the hell out of here.” He is quite rude
and insults his wife several times. He has a positive glabellar reflex. Mini Mental State Examination
score is 20/30. There is no rigidity. Gait is normal. Deep tendon reflexes are 3+ and symmetric.
Strength is 5/5 throughout, and there are no sensory deficits. Cerebellar function is normal. What is
the most likely diagnosis?
A.
B.
C.
D.
E.
Alzheimer disease
Dementia with Lewy bodies
Frontotemporal dementia
Progressive supranuclear palsy
Vascular dementia
XI-27. Which of the following statements regarding Parkinson disease is true?
A. Cigarette smoking reduces the risk of developing the disease.
B. Older age at presentation is more likely to be associated to genetic predisposition.
C. Parkinson disease has been identified as a monogenetic disorder related to mutations in the αsynuclein protein.
D. The typical age of onset of symptoms is about 70 years.
E. The hallmark pathologic feature of Parkinson disease is presence of neurofibrillary tangle and tau
protein in the substantia nigra pars compacta.
XI-28. A 64-year-old man presents with symptoms of tremor and a generalized feeling of slowing down.
His tremor bothers him most on his left side. His past medical history is significant for depression,
hypertension, and hyperlipidemia. He is taking fluoxetine 40 mg daily, lisinopril 40 mg daily, and
atorvastatin 20 mg daily. On physical examination, he has a resting tremor with presence of
cogwheel rigidity. When observing his gait, you note slow, shuffling steps with difficulty
maneuvering to turn around. His facial features show decreased range of emotion and appear
somewhat flat. Eye movements are full. Mental status examination shows normal mentation. You
suspect Parkinson disease. What is your first choice of therapy?
A.
B.
C.
D.
E.
F.
Defer therapy until further diagnostic studies are performed
Levodopa-carbidopa
Rotigotine
Selegiline
Either B or C can be used
Any of the above can be used
XI-29. Which of the following patients with Parkinson disease is the best candidate for deep brain
stimulation?
A.
B.
C.
D.
E.
A 64-year-old woman on levodopa-carbidopa who continues to experience episodes of freezing
while walking
A 68-year-old man with recurrent falls due to orthostatic hypotension
A 70-year-old woman with severe tremor unresponsive to dopaminergic therapy
A 71-year-old man with worsening symptoms of dementia
All of the above patients will respond to deep brain stimulation.
XI-30. A 54-year-old man presents complaining of weakness. He has a difficult time pinpointing an
onset. He believes he first noticed weakness in his right foot and leg about 6 months ago. He reports
that he frequently trips over his toes and drags his foot. He also gets frequent cramps when he
stretches in bed in the mornings. The weakness is progressing to involve both legs now. On
examination, you note tongue fasciculations. Deep tendon reflexes are 3+ at the knees and ankles.
Strength is 4– at the extensors and flexors of the right foot and 4+ at the left foot. Hand grip strength
is also 4+. Which of the following is the suspected pathologic cause of this patient’s symptoms?
A.
B.
C.
D.
E.
F.
Degeneration of the corticospinal tracts
Demyelinating plaques
Loss of anterior horn cells in the spinal cord
Loss of large pyramidal cells in the precentral gyrus
Lymphocytic infiltrate of spinal roots and nerves
A and C
XI-31. A 62-year-old woman is evaluated for symptoms of “slowing down.” She used to be very active
and ran 2– 4 miles at least 3 days per week. For the past 6 months, she has not been able to complete
even 1 mile, and her husband feels she has been moving more slowly and with a shuffling gait. She
reports no tremor. She frequently feels lightheaded upon standing and has been evaluated in the
emergency department twice for falls that occurred soon after standing. After one fall, she did require
sutures for a scalp laceration. She has also been experiencing significant constipation requiring daily
treatment with polyethylene glycol and bisacodyl suppositories. On physical examination, she has a
blood pressure of 122/78 mmHg and a heart rate of 72 bpm while seated. Upon standing, her blood
pressure falls to 92/60 mmHg with a heart rate of 102 bpm. She does report dizziness with the
maneuver. She has bradykinesia and walks with a shuffling gait. Cranial nerves are intact with full
eye movements. Deep tendon reflexes are 2+ and symmetric. There is rigidity with passive motion of
the forearms. She has no tremor. Mental status examination is normal. What is the most likely
diagnosis?
A.
B.
C.
D.
E.
Diffuse Lewy body disease
Multiple system atrophy
Parkinson disease
Postural orthostatic tachycardia syndrome
Progressive supranuclear palsy
XI-32. A 58-year-old woman is seen for complaints of very sharp pain lasting about 1 minute over her
right cheek and lips. These pain episodes occur in clusters with intense pain during the episode.
When an episode occurs, it is present both day and night and can recur over a period of about a
week. Paroxysms of pain can be elicited by washing her face. On physical examination, there is no
sensory or motor loss in the right face. There are no masses. Touching the right face does bring about
an episode of pain for the patient. What is the next best step in management of this patient?
A.
B.
C.
D.
E.
Initiate treatment with carbamazepine 100 mg with a goal dose of 200 mg qid
Perform an MRI/magnetic resonance angiography (MRA) of the brain
Refer patient for a temporal artery biopsy
Refer patient for electromyography and nerve conduction study
Refer patient for microvascular decompression surgery
XI-33. A 65-year-old woman with a prior history of stage IIB carcinoma of the right breast presents with
a 1-week history of sharp mid-back pain. She reports that it becomes worse with movement and
coughing. She has not slept well because the pain awakens her. On the day of presentation, she
developed weakness in her lower extremities such that she is not able to bear weight. She has had
incontinence of the bladder. On examination, the patient has tenderness to palpation over the lower
thoracic spine. The strength in the lower extremities is 3 out of 5 with decreased deep tendons
reflexes. Anal sphincter tone is decreased. Sensation to light touch and pinprick also demonstrates a
decrease in perception to the level of T8. Metastatic disease to the spine is demonstrated in multiple
thoracic and lumbar vertebral bodies with cord compression at T8 on T1-weighted MRI. What is the
next best step in the management of this patient?
A.
B.
C.
D.
E.
F.
G.
Administer dexamethasone 10 mg IV every 6 hours
Consult neurosurgery for surgical decompression
Consult medical oncology for additional chemotherapy
Consult radiation oncology for urgent radiotherapy
A and D
A, C, and D
A, B, C, and D
XI-34. A 32-year-old African American man presents to the emergency department with progressive
lower extremity weakness that has been present for the past month. It has now progressed to the
point that he is unable to bear weight. He also has been experiencing loss of sensation and aching
pains in his mid-back and a sensation of incomplete voiding with mild urinary incontinence. Today,
he also had incontinence of stool. His past medical history is significant for a stab wound to the left
chest 9 months prior. He required surgical repair. A CT scan was negative at that time for any lymph
node abnormalities. He is on no medications and does not smoke or drink alcohol. Physical
examination confirms lower extremity paresis with strength of only 3/5 and decreased deep tendon
reflexes. Sensation to light tough and pinprick is absent in the lower extremities. He develops sensory
perception at the umbilicus. An MRI shows multilevel enhancement of the spinal cord consistent with
edema. It has a predominance in the mid-thoracic spinal cord. Gadolinium administration shows
enhancement in a nodular fashion of the surface of the cord. Lumbar puncture is performed. There
are 32 white blood cells (WBC)/µL in the first tube and 24 WBC/µL in the fourth tube. These are 90%
lymphocytes. The cerebrospinal fluid protein level is 75 mg/dL. The glucose level is normal. A chest
radiograph demonstrates enlargement of the hilar lymph nodes without pulmonary infiltrates. On
chest CT, bilateral hilar, subcarinal, and precarinal lymphadenopathy is observed with the largest
lymph node measuring 2 × 1.8 cm. Serum calcium is 12.5 mg/dL. A biopsy of the hilar lymph nodes
is planned. What is the most likely finding on biopsy?
A.
B.
C.
D.
E.
Abundant atypical lymphocytes that demonstrate clonality on flow cytometry
Caseating granulomatous inflammation
Noncaseating granulomatous inflammation
Nonspecific chronic inflammatory changes
Sheets of small, round cells with dark nuclei, scant cytoplasm, and salt-and-pepper chromatin
with indistinct nucleoli; frequent mitotic figures are also seen
XI-35. A 32-year-old woman presents for neurologic evaluation after experiencing a severe burn on the
palm of her right hand. She had placed her hand onto the hot surface of a smooth electric range. She
did not feel the burn when it occurred, and only when she picked her hand up did she notice the
burn. After that, it was discovered that the patient unknowingly has bilateral loss of pain and
temperature sensation in both hands. However, she does have touch and vibratory sense. Mapping of
her loss of sensation shows decreased pain sensation in the nape of her neck, shoulders, and upper
arms as well in a cape-like distribution. Deep tendon reflexes are absent at the biceps and triceps, and
there is visible muscle wasting of the right biceps and shoulder musculature. What is the most likely
diagnosis?
A.
B.
C.
D.
E.
Arteriovenous malformation of the spine
Neoplastic spinal cord compression
Subacute combined degeneration
Syringomyelia
Transverse myelitis
XI-36. A 31-year-old white woman is evaluated for symptoms of blurred vision and weakness. She is not
really sure how long the symptoms have been occurring. She has had intermittent blurring of her
vision for the past 2 months, although it has been more persistent for the past 2 weeks. She states
that she also notes that colors seem less vivid and that her symptoms are worse in the right eye.
Three months ago, she did notice some sharp pains in the right eye that were worse when she looked
around. They subsided after about a week, and since then, her vision has worsened. At the same time,
she feels as though she is stiff in her legs and also feels that her left leg is weak. She sometimes feels
as if her left leg will give out on her if she stands on it for a prolonged period. Her past medical
history is significant for type 1 diabetes mellitus for which she uses an insulin pump. She has smoked
one pack of cigarettes daily since the age of 18. On physical examination, there is spasticity in both of
her lower extremities with passive motion. Deep tendon reflexes are 3+ bilaterally with strength at
the quadriceps on the right at 4/5. All other strength in the lower extremity is 5/5 bilaterally.
Sensation to light touch and pinprick is decreased in the lower extremities. A dilated funduscopic
examination shows swelling of the optic disc. Which of the following findings is most likely to be
demonstrated?
A. Elevated protein levels in the cerebrospinal fluid to more than 100 mg/dL
B. Hyperintensity on T1-weight images consistent with a mass lesion in the occipital lobe with
hydrocephalus
C. Hyperintensity on T2-weighted MRI images in multiple areas of the brain, brainstem, and spinal
cord
D. Marked increased in transmission of somatosensory evoked potentials of lower limbs
E. Presence of 15 polymorphonuclear cells/µL in the cerebrospinal fluid
XI-37. In the patient in Question XI-36, the expected finding is demonstrated on testing. On further
historical review, the patient reports that she had one prior episode of blurred vision that resolved
spontaneously about 8 months ago. She never sought treatment for it, although it lasted for about 2
weeks. You make the correct diagnosis. All of the following are epidemiologic risks factors for her
disease EXCEPT:
A.
B.
C.
D.
E.
Age between 20 and 40
Cigarette smoking
Female sex
History of an autoimmune disorder (type 1 diabetes mellitus)
White race
XI-38. A 38-year-old woman has relapsing/remitting multiple sclerosis. She has experienced two attacks
of disease previously that have left her with residual lower extremity weakness. She was initially
treated with glucocorticoids with some improvement in her symptoms. However, she is currently
only able to walk with a rolling walker about 100 m. A prior antibody test shows that she is positive
for reactivity to the JC virus. You are planning to start a disease-modifying therapy. Which of the
following is LEAST appropriate for this individual?
A. Dimethyl fumarate (DMF)
B. Interferon-β-1a
C. Fingolimod
D. Natalizumab
E. Teriflunomide
XI-39. You are evaluating a 42-year-old woman for complaints of muscle weakness and tingling in her
lower extremities. You suspect a peripheral neuropathy. All of the following questions are important
for the history and physical examination EXCEPT:
A.
B.
C.
D.
E.
Are there any important comorbid conditions?
Is there evidence of upper motor neuron involvement?
What does the electromyogram and nerve conduction study demonstrate?
What is the distribution of the weakness?
Which systems are involved—motor, sensory, autonomic, or combination?
XI-40. 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. His father and paternal aunt
each have had some weakness in their lower extremities. However, his father is currently 50 years of
age and only began to develop some weakness in the past 2 years. His paternal aunt has always had a
limp for as long as he can recall. He does not remember his grandparents having any symptoms,
although his paternal grandfather died in a car accident at the age of 46 prior to his birth. The
patient’s examination 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.
B.
C.
D.
E.
Charcot-Marie-Tooth syndrome
Fabry disease
Guillain-Barré syndrome
Hereditary neuralgic amyotrophy
Hereditary sensory and autonomic neuropathy
XI-41. A 57-year-old immigrant from Vietnam is evaluated by his primary care giver 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 purified protein derivative (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.
B.
C.
D.
E.
Cobalamin
Levothyroxine
Neurontin
Pregabalin
Pyridoxine
XI-42. 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 will reverse her neuropathy.
E. None of the above is true.
XI-43. A 52-year-old man presents to the emergency department complaining of weakness that has
developed over the past 2 days. He first noticed that he had generalized fatigue and felt like he was
having a hard time moving his feet. Over the past 24 hours, the weakness has progressed to the point
that he can barely stand with assistance. He was brought into the emergency department in a
wheelchair. He is beginning to feel that it is difficult to lift his arms. He also complains of a sharp
pain in his shoulders and along his spine. Both his hands and feet are tingling. On physical
examination, his initial blood pressure is 138/82 mmHg. On repeat 1 hour later, it is 92/50 mmHg.
His heart rate is 108 bpm, respiratory rate is 24 breaths/min, temperature is 37.0°C, and SaO2 is 96%
on room air. He appears anxious and weak. Deep tendon reflexes are absent at the knee, ankle, and
wrist. The brachioradialis reflex is 1+. Strength throughout the lower extremities is diminished as
the patient is unable to lift either leg against gravity. In the arms, strength is 4/5 in the deltoids,
biceps, and triceps. However, he is unable to maintain a grip, and wrist flexion and extension are
3/5. Which of the following features would most commonly accompany this patient’s history?
A.
B.
C.
D.
E.
A diagnosis of “walking pneumonia” that was treated with azithromycin 2 weeks prior to
presentation
An acute diarrheal illness 2 weeks prior to presentation
Presence of a massive mediastinal lymphadenopathy on chest radiograph
Presence of a monoclonal gammopathy of unknown significance on laboratory testing
Recent immunization with the H1N1 vaccine
XI-44. You make the correct diagnosis for the patient in Question XI-43 and transfer him to the intensive
care unit for close monitoring. Forced vital capacity on admission is 1.5 L (20 mL/kg), and maximum
negative inspiratory force is 30 cmH2O. You are very concerned about impending respiratory failure.
Cerebrospinal fluid analysis shows a protein level of 100 mg/dL. There is 1 WBC in the first tube and
none in the fourth tube. What is the next step in the management of this patient?
A.
B.
C.
D.
E.
Azithromycin
IV immunoglobulin
Oseltamivir
Prednisone
Pyridostigmine
XI-45. A 34-year-old woman is seen for complaints of weakness for the past month. She notes this to be
particularly worse in the late afternoon and evening. Initially, she attributed the weakness to stress
from her job, but she feels that the weakness is worsening despite taking several days off work. She
also is now noticing some occasional double vision, and her husband has noticed that her voice
sounds weak. The patient denies pain. On physical examination, you note the appearance of mild
ptosis and a nasal, breathy tone to her voice. Which of the following tests would be most sensitive
and specific for making a diagnosis in this patient?
A.
B.
C.
D.
E.
Acetylcholine receptor (AChR) antibodies
Edrophonium test
Muscle-specific kinase (MuSK) antibodies
Repetitive nerve stimulation test
Voltage-gated calcium channel antibodies
XI-46. A 26-year-old woman is diagnosed with myasthenia gravis in the setting of complaints of
diplopia, dysphagia, and weakness with fatigability. Acetylcholine receptor antibodies are positive.
She is initially treated with pyridostigmine 60 mg three times daily with improvement. She is further
evaluated for concomitant conditions. A CT scan of the neck reveals a “thymic shadow” but no
evidence of thymoma. She is not found to have hyperthyroidism or any other autoimmune disorder.
Her forced vital capacity after treatment with pyridostigmine is 2.9 L (73% predicted). What is the
next best approach for treatment of this patient?
A.
B.
C.
D.
E.
Continue pyridostigmine at current dose only
Continue pyridostigmine at current dose and add mycophenolate mofetil 1 g twice daily
Continue pyridostigmine at current dose and add prednisone 20 mg daily
Refer for treatment with plasmapheresis
Refer for thymectomy
XI-47. A 56-year-old man with facial and ocular weakness has just been diagnosed with myasthenia
gravis. All of the following tests are necessary before instituting therapy EXCEPT:
A.
B.
C.
D.
E.
CT of mediastinum
Lumbar puncture
Pulmonary function tests
Purified protein derivative skin test
Thyroid-stimulating hormone
XI-48. All of the following lipid-lowering agents are associated with muscle toxicity EXCEPT:
A.
B.
C.
D.
E.
Atorvastatin
Ezetimibe
Gemfibrozil
Niacin
All of the above are associated with muscle toxicity.
XI-49. All of the following endocrine conditions are associated with myopathy EXCEPT:
A.
B.
C.
D.
E.
Hypothyroidism
Hyperparathyroidism
Hyperthyroidism
Acromegaly
All of the above are associated with myopathy.
XI-50. 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 also has recently begun to drop things, once
allowing a full cup of coffee to spill onto her legs. The patient 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.
B.
C.
D.
E.
Acid maltase deficiency (Pompe disease)
Becker muscular dystrophy
Duchenne muscular dystrophy
Myotonic dystrophy
Nemaline myopathy
XI-51. A 33-year-old woman seeks an additional medical opinion after seeing multiple physicians in the
past 3 years. She describes unrelenting fatigue that has lasted for approximately 2 years to the point
where she no longer exercises and is in danger of losing her job as a copy editor. Her sleep is
typically unsettled, and no matter how much she sleeps, she reports never feeling refreshed. She dates
the onset of the fatigue to an episode of serologically confirmed mononucleosis 3 years prior. Her
husband agrees that “she has never recovered from that episode.” She has tried antidepressants and
various supplements with no benefit. Her past medical history is unremarkable other than having
anorexia and depression as a teenager. She says she is fully recovered from that since college. Her
physical examination is unremarkable other than a resting heart rate of 95 bpm. She has a normal
body mass index (BMI). Which of the following is an exclusion to the diagnosis of chronic fatigue
syndrome?
A.
B.
C.
D.
E.
History of anorexia and depression
History of mononucleosis
Normal BMI
Resting heart rate >90 bpm
None of the above
XI-52. In the patient described in Question XI-51, which of the following has been shown to improve
symptoms?
A.
B.
C.
D.
E.
Acyclovir
Cognitive behavioral therapy
Gabapentin
Psychoanalysis
Venlafaxine
XI-53. A 34-year-old woman seeks evaluation because of insomnia. She reports difficulty both falling
and staying asleep because she cannot calm her mind. When questioned, she says she has always
been a worrier. You are considering a diagnosis of generalized anxiety disorder. All of the following
characteristics are common in this disorder EXCEPT:
A.
B.
C.
D.
E.
She has episodic palpitations and shortness of breath lasting 10–30 minutes associated with
feelings of impending doom.
She particularly worries about her job as a data analyst at a major telecommunications company,
and she frequently avoids social outings because she “freezes” in social situations.
She reports concomitant feelings of hopelessness and sadness and worries about death.
She reports drinking four glasses of wine or more nightly to calm herself prior to bed.
Symptoms began during her teenage years.
XI-54. You are paged by the clinic staff covering the sleep laboratory. A 24-year-old man has walked
into the sleep laboratory asking if a sleep study will help him understand where the voices in his
head are coming from. The staff says he appears somewhat agitated and is talking to himself. You
arrive at the sleep laboratory to find a disheveled-appearing young man pacing in the lobby. When
you attempt to speak with him, he says that he has been hearing an angry voice telling him that he is
a worthless pig. It gets loudest whenever he is lying in bed. Sometimes it tells him he is a demon and
to hurt himself. He says these voices are being sent into his brain by an alien satellite and thinks a
sleep study will help show the abnormal brain waves that are not his since the voices are worse at
night. His speech is pressured, and he speaks rapidly, pacing the entire time. He refuses to go to the
emergency department for help. You call 911 because it is obvious that the patient is having active
hallucinations. The man is unwilling to provide any medical history or even his last name. He is
admitted involuntarily to a psychiatric facility and diagnosed with acute psychosis and eventually
schizophrenia, as this was his first episode of psychosis. He is treated appropriately with
antipsychotics. Which of the following statements regarding his prognosis is true?
A.
B.
C.
D.
E.
Antipsychotics are effective in treating 95% of patients with a first episode of psychosis.
Full remission from an episode of psychosis typically takes 3–6 months.
If medications are discontinued, the relapse rate is 60% at 6 months.
More than 25% of schizophrenia patients commit suicide.
Prognosis depends on severity of symptoms at initial presentation.
XI-55. A 26-year-old woman presents to the emergency department complaining of shortness of breath
and chest pain. These symptoms began abruptly while at a shopping mall and became progressively
worse over 10 minutes, prompting her to call 911. Over this same period, the patient describes
feeling her heart pounding, and she 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 is not back to her baseline. She denies any immediate precipitating cause, although she
has been under increased stress because her mother has been hospitalized recently with advanced
breast cancer. She has never had any episode like this previously. 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 bpm,
blood pressure of 122/68 mmHg, and respiratory rate of 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 electrocardiogram (ECG) shows sinus tachycardia. A D-dimer is normal. What is the
next best step in the management of this patient?
A. Initiate therapy with alprazolam 0.5 mg as needed
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
XI-56. All of the following antidepressant medications are correctly paired with their class of medication
EXCEPT:
A.
B.
C.
D.
E.
Duloxetine—Selective serotonin reuptake inhibitor
Fluoxetine—Selective serotonin reuptake inhibitor
Nortriptyline—Tricyclic antidepressant
Phenelzine—Monoamine oxidase inhibitor
Venlafaxine—Mixed norepinephrine/serotonin reuptake inhibitor and receptor blocker
XI-57. A 42-year-old woman seeks your advice regarding symptoms concerning for posttraumatic 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 posttraumatic stress disorder is likely. What
treatment do you recommend for this patient?
A.
B.
C.
D.
E.
Avoidance of alcohol
Cognitive behavioral therapy
Paroxetine 20 mg daily
Trazodone 50 mg nightly
All of the above
XI-58. 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 because 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 because his symptoms are well controlled.
E. The medication should be switched to fluoxetine to complete 12 months of therapy because this
was previously effective for him.
XI-59. You are seeing a 28-year-old man in your primary care clinic. He reports drinking alcohol on
most days. Typically, he drinks 3–4 beers daily, but on weekends, he will drink as many as 8–12
beers per night. He has not missed work due to his drinking, although he does state that he has been
hungover at work at least twice in the past month. He also has blacked out from binge drinking at
least once in the past 6 months. However, he does not feel that he has any problem with alcohol. He
states he never drinks and drives and has not ever felt guilt related to his drinking. You suspect he
may be minimizing his level of alcohol consumption. Which of the following laboratory tests has the
greatest sensitivity and specificity in identifying heavy alcohol consumption?
A. Aspartate aminotransferase (AST) elevated >2× alanine aminotransferase (ALT)
B. Carbohydrate-deficient transferrin (CDT) >20 U/L or >2.6%
C. γ-Glutamyl transferase >35 U/L
D. Mean corpuscular volume (MCV) >91 µm3
E. A and D
F. B and C
XI-60. Which of the following will lead to a faster rate of absorption of alcohol from the gut into the
blood?
A.
B.
C.
D.
E.
Coadministration with a carbonated beverage
Concentration of alcohol of more than 20% by volume
Concurrent intake of a high-carbohydrate meal
Concurrent intake of a high-fat meal
Concurrent intake of a high-protein meal
XI-61. Which of the following statements best reflects the effect of alcohol on neurotransmitters in the
brain?
A.
B.
C.
D.
E.
Decreases dopamine activity
Decreases serotonin activity
Increases γ-aminobutyric acid activity
Stimulates muscarinic acetylcholine receptors
Stimulates N-methyl-D-aspartate excitatory glutamate receptors
XI-62. In an individual without any prior history of alcohol intake, what serum concentration of ethanol
(in g/dL) would likely result in death?
A.
B.
C.
D.
E.
0.02
0.08
0.28
0.40
0.60
XI-63. All of the following statements regarding the epidemiology and genetics of alcoholism are true
EXCEPT:
A. Approximately 60% of the risk for alcohol abuse disorders is attributed to genetics.
B. At least 20% of all patients seen in primary care offices have an alcohol use disorder.
C.
Children of alcoholics have a 10-fold higher risk of alcohol abuse and dependence even if
adopted early in life and raised by nonalcoholics.
D. 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.
XI-64. A 42-year-old man with alcohol dependence is admitted to the hospital for acute pancreatitis.
Upon admission, he has an abdominal CT that shows pancreatic edema without necrosis or
hemorrhage. He is treated with IV dextrose-containing fluids, 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 bpm, blood pressure of 184/96 mmHg, respiratory rate of 32
breaths/min, temperature of 38.7°C, 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. Administration of a bolus of 1 L of normal saline and thiamine 100 mg IV
B. Administration of diazepam 10–20 mg IV followed by bolus doses of 5–10 mg as needed until the
patient is calm but arousable
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
XI-65. 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.
B.
C.
D.
E.
Acamprosate
Disulfiram
Naltrexone
A and C
A, B, or C
XI-66. Which of the following statements about cigarette smoking is true?
A.
B.
C.
D.
E.
Approximately 75% of cigarette smokers will die prematurely due to cigarette smoking unless
they are able to quit.
Approximately 90% of peripheral vascular disease in nondiabetic individuals is attributable to
cigarette smoking.
Cigarette smoking causes small airway inflammation and alveolar destruction sufficient to cause
clinical symptoms in about 40% of smokers.
More than one-half of smokers have attempted to quit in the past year, and of these, 25% remain
quit for 6 months or more.
Two of every five deaths in the United States can be attributed to cigarette use.
XI-67. A 42-year-old woman presents for a yearly office visit. She is in general good health and takes no
medications. Her BMI is 32 kg/m2. She was previously treated for depression with sertraline 100 mg
daily for 12 months. She last took the medication 6 months ago. She is feeling mentally healthy now.
She has smoked since the age of 21 and smokes one pack of cigarettes daily. You advise her to quit
smoking. She tells you she has been thinking about this a lot lately since her father died at the age of
74 from complications of lung cancer and was a smoker. He died 2 years ago this month. She
previously has tried on her own, both “cold turkey” and using nicotine patches. She was unable to
sustain abstinence longer than 1 month. The only time she had sustained abstinence was when she
was pregnant 18 years ago, but she quickly started again after delivery. What do you recommend for
this patient?
A. Close follow-up with ongoing counseling
B. Nicotine replacement therapy with patches or nasal inhaler
C. Varenicline orally
D. A and B only
E. A combined with either B or C is an acceptable option.
XI-68. A 32-year-old man is seen in your office to discuss smoking cessation. He has been smoking since
the age of 16 years. He typically smokes 1.5 to 2 packs of cigarettes each day. At the age of 21, he
was hospitalized in a psychiatric facility for severe depression with psychotic features. He was
originally treated with venlafaxine and quetiapine. After 6 months, the quetiapine was tapered off
without recurrence of the psychosis. His depression has waxed and waned over time, but generally
has been well controlled. He has had no suicide attempts and denies suicidal ideations. He has had
multiple quit attempts in the past with nicotine replacement therapy but has failed each attempt. He
says he would like to try varenicline and asks your opinion about its safety given his psychiatric
history. What advice do you give him?
A.
Varenicline has been recommended by the U.S. Food and Drug Administration for further
monitoring and supervision because it is unclear how frequently severe psychiatric responses
occur.
B.
A recent publication did not demonstrate an increased risk of suicide or psychosis with
varenicline use even though varenicline was used more frequently in individuals with a
preexisting psychiatric diagnosis.
C.
Alternative therapies such as bupropion and/or nicotine replacement therapy should be
considered.
D. All of the above
XI-69. You are counseling your patient on the need to quit smoking cigarettes. She has been smoking for
over two decades and wants to quit in order to avoid the harmful physical effects of smoking.
Wanting to take “baby steps,” she has switched to low-tar, low-nicotine cigarettes. Which of the
following statements is true about the potential benefit of switching to these low-yield cigarettes?
A. Fewer smoking–drug interactions are found among smokers of low-yield cigarettes.
B.
Most smokers inhale the same amount of nicotine and tar even if they switch to low-yield
cigarettes.
C. Smokers of low-yield cigarettes tend to inhale less deeply and smoker fewer cigarettes daily.
D. Smoking low-yield cigarettes decreases the harmful cardiovascular effects of cigarette smoking.
E.
Smoking low-yield cigarettes is a reasonable alternative to complete smoking cessation for
chronic smokers.
ANSWERS
XI-1.
The answer is A. (Chap. 437) This patient is presenting with symptoms of metastatic
neurologic disease, and a careful neurologic examination can localize the site of disease in most
patients. The patient has “crossed” weakness and sensory abnormalities, which localizes the
lesion to the brainstem. In this setting, the limbs exhibit weakness and sensory symptoms
opposite from the facial symptoms. Moreover, the facial weakness localizes to lower motor
neuron as it involves both the upper and lower facial muscles. If the upper facial muscles had
preserved movement, this might suggest multiple areas of metastatic disease in both the
cerebrum and spinal cord.
XI-2 and XI-3. The answers are D and D, respectively. (Chap. 437) 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 function, sensory function, 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 degree 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. An 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.
XI-4, XI-5, XI-6, XI-7 and XI-8 The answers are E, C, D, B, and A, respectively. The clinical data
obtained from the history and examination are interpreted to arrive at a possible anatomic
localization that best explains the clinical findings, helps to narrow the list of diagnostic
possibilities, and helps to select the laboratory tests most likely to be informative (Table XI-8).
TALBLE XI-8 Global Disability-Adjusted Life-Years (DALYs) and Number of Annual Deaths for
Selected Neurologic Disorders in 2010
XI-9.
The answer is C. (Chap. 440e) Appropriate and timely evaluation is needed to determine
whether a subarachnoid hemorrhage is present because it can be rapidly fatal if undetected. The
procedure of choice for initial diagnosis is a computed tomography (CT) of the head without
intravenous (IV) contrast. On the CT, blood in the subarachnoid space would appear whiter
compared to the surrounding brain tissue. The head CT is most sensitive when it is performed
shortly after the onset of symptoms, but sensitivity declines over several hours. It can also
demonstrate significant mass effect and midline shift, factors that increase the severity of the
underlying hemorrhage. In the situation where the head CT 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 (CSF). 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
CSF that can be measure spectrographically. A basic head CT with IV contrast is rarely useful in
subarachnoid hemorrhage because 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 coil 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.
XI-10.
The answer is E. (Chap. 440e) 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 MRI. 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 due 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, whereas T2-weighted images require long TR and
TE times. Fat and subacute hemorrhage have relatively short TR and TE times and thus appear
more bright on T1-weighted images. Conversely, structures with more water such as CSF or
edema 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, and chronic
hemorrhage.
Fluid-attenuated inversion recovery (FLAIR) is a type of T2-weighted image that suppresses
the high-intensity signal of CSF. As a result, images created by the FLAIR technique are more
sensitive to detecting water-containing lesions or edema than the standard spin images.
Magnetic resonance angiography refers to several different techniques that are useful for
assessing vascular structures but does not provide details of the underlying brain parenchyma.
XI-11. The answer is E. (Chap. 440e) For many years, MRI 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 skins with increased numbers of fibrocytes and elastic
fibers. There is no known medical treatment for nephrogenic systemic fibrosis, 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 nephrogenic systemic fibrosis
following administration of gadolinium in individuals with a glomerular filtration rate of <30
mL/min may be as high as 4%, and thus, gadolinium is 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. This risk 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 development of renal
insufficiency and a subsequent buildup of lactic acid. In very rare instances, administration of
iodinated contrast can unmask hyperthyroidism.
XI-12.
The answer is D. (Chap. 445) Age of presentation is an important consideration when an
individual presents with a new onset of seizure because certain causes of seizures are more
likely to present within certain age ranges (Table XI-12), ranging from the neonatal period
throughout older adulthood (age >35 years). In individuals >35 years old, the most likely
causes of new-onset seizures include alcohol withdrawal, cerebrovascular disease, brain tumor,
autoantibodies, Alzheimer disease or other neurodegenerative disease, and a range of metabolic
disorders. These disorders can include either hyper- or hypoglycemia, uremia, hepatic failure,
and a host of electrolyte abnormalities or acid-base disorders. Inherited disorders of ion
channels have been implicated in a variety of rare epilepsy syndromes. These genetic disorders
typically present in childhood and rarely after the age of 18.
TALBLE XI-12 Causes of Seizures
XI-13.
The answer is B. (Chap. 445) Psychogenic seizures are nonepileptic behaviors that resemble
seizures and may be conversion reactions that occur under psychological distress. Psychogenic
seizures may occur in individuals with underlying seizure disorder and may be difficult to
distinguish. Clinical features prominent in psychogenic seizures include side-to-side turning of
the head, asymmetric and large-amplitude movements of the limbs, twitching of all four
extremities without loss of consciousness, and pelvic thrusting. Psychogenic seizures also often
last longer than epileptic seizures and may wax and wane over minutes to hours. Video
electroencephalogram (EEG) monitoring can be quite helpful in this situation as EEG monitoring
during the episode is normal. In addition, there is no postictal period. Measurement of prolactin
levels may also help to distinguish generalized and some focal seizures from psychogenic
seizures because prolactin levels rise in these disorders but remain normal in psychogenic
seizures. Serum creatine kinase may rise following a seizure, but this is not sensitive for
detection of seizure disorder.
XI-14.
The answer is B. (Chap. 445) Determination of when to initiate epileptic drug therapy can be
difficult in clinical practice given the variability in presentation of seizure disorders and the
large number of antiepileptic drugs available. In general, antiepileptic drugs should be initiated
when an individual presents with either recurrent seizures of unknown etiology or known cause
that cannot be reversed. In individuals with a single seizure and a clear cause such as a brain
tumor, infection, or trauma, these individuals should also be treated. Currently, lamotrigine and
valproic acid are considered the best initial therapies for individuals with generalized seizures.
Although used with good efficacy for many years, phenytoin is no longer first-line therapy for
generalized seizures due to its long-term side effect profile including gingival hyperplasia.
Ethosuximide is generally only used for absence seizures.
XI-15.
The answer is A. (Chap. 445) Overall, 70% of children and 60% of adults will be able to
successfully discontinue antiepileptic drugs without recurrence of seizures. However, the data
regarding the time frame to attempt weaning of antiepileptic drugs are scarce. Once the
determination to discontinue antiepileptic drugs has been made, the dosage of medication is
typically decreased over a 2–3 month period, gradually weaning to off. If a recurrence of seizure
were to happen, it is most likely during the first 3 months after discontinuation of therapy. Four
factors predict the greatest likelihood of remaining seizure-free upon discontinuation of
antiepileptic drugs: (1) complete control of seizures for 1–5 years; (2) single seizure type—focal
or generalized; (3) normal EEG; and (4) normal neurologic examination, including intelligence.
Given that this patient continues to have an abnormal neurologic examination following closed
head trauma, he would have a greater likelihood to have a poorer outcome after withdrawal of
his seizure medication.
XI-16.
The answer is C. (Chap. 445) Status epilepticus is a medical emergency that can result in
severe metabolic derangements, hyperthermia, cardiorespiratory collapse, and irreversible
neuronal injury. Prompt recognition and appropriate treatment are necessary to prevent longterm sequelae of this neuronal injury. Status epilepticus is defined as continuous seizures or
repetitive discrete seizures with impaired consciousness in the interictal period. Status
epilepticus has many subtypes, with the most common subtype leading to presentation and
critical care admission being generalized convulsive status epilepticus (GCSE). The duration of
seizure activity that leads to a diagnosis of GCSE is typically defined as 15–30 minutes, but
practically, if intervention with anticonvulsant medication is required to stop the seizure
activity, then one must be concerned about GCSE. Likewise, if a seizure is of sufficient duration
to cause significant metabolic or cardiorespiratory consequence, GCSE must be considered. Once
GCSE is diagnosed, initial treatment should include basic cardiopulmonary support, including
maintaining an appropriate airway, establishing venous access, and obtaining samples of
laboratory analysis to identify contributing laboratory abnormalities. It is important to
understand that suppression of convulsive activity through the use of paralytic agents does not
suppress the epileptic activity in the central nervous system and does not prevent ongoing
neuronal injury and death. Thus, when these agents are used for rapid-sequence intubation, the
treating team should also continue treatment for GCSE through appropriate use of IV
benzodiazepines initially followed by loading doses of either IV phenytoin or fosphenytoin,
valproic acid, or levetiracetam. In many cases, continuous EEG monitoring may be required to
determine when the seizure activity has ceased. If the seizure activity fails to break with these
agents, further therapy with propofol or pentobarbital may be required. In more severe cases,
inhaled anesthetics may be required. In addition, it is important to treat any underlying
infection or metabolic derangements.
XI-17.
The answer is E. (Chap. 446) This patient is presenting with symptoms of an acute ischemic
stroke affecting the middle cerebral artery territory. All patients older than age 18 should be
evaluated promptly upon arrival to determine if they are candidates for administration of
recombinant tissue plasminogen activator (rtPA). A large trial showed a significant improvement
in patients with only minimal disability (32% on placebo vs. 44% on rtPA) and a nonsignificant
reduction in mortality (21% on placebo vs. 17% on rtPA) when IV rtPA was administered within
3 hours of the onset of symptoms. However, rtPA was associated with a significant increase in
the risk of symptomatic intracranial hemorrhage (6.4% on rtPA vs. 0.6% on placebo). A more
recent trial has confirmed this benefit and that rtPA is both cost-effective and cost-saving.
Carefully choosing the correct patients for administration of rtPA is key to best achieve benefits
while minimizing risk of adverse events. Thrombolytic administration should be considered in
all patients ≥18 years old with a clinical diagnosis of stroke presenting with symptom onset of
≤4.5 hours. A noncontrast head CT should be performed promptly to ensure there is no
intracranial hemorrhage or edema of more than one-third of the middle cerebral artery territory.
If a patient meets these criteria, then a careful assessment for possible contraindications should
be undertaken. Hypertension is common in acute stroke. A sustained blood pressure >185/110
mmHg despite treatment is a contraindication to administration of rtPA. However, a single
blood pressure reading higher than this value would not prevent treatment with thrombolytics.
Individuals with rapidly improving symptoms more indicative of a transient ischemic attack or
mild cerebrovascular accident should not be treated with rtPA because the risk outweighs the
potential benefits. At the opposite end of the spectrum, individuals presenting with stupor or
coma should not be treated with thrombolytics. Findings on past medical history that would be
contraindications to the use of rTPA include prior stroke or head injury within 3 months, any
prior history of intracranial hemorrhage, major surgery in the preceding 14 days,
gastrointestinal (GI) bleeding in the preceding 21 days, and recent myocardial infarction.
Individuals with platelets <100,000, hematocrit <25%, use of heparin within 48 hours,
prolonged activated partial thromboplastin time, or elevated international normalized ratio
should also not receive rtPA.
XI-18.
The answer is D. (Chap. 446) Multiple atherosclerotic risk factors contribute to the risk for
stroke. Among these are hypertension, diabetes mellitus, dyslipidemia, cigarette smoking, and
atrial fibrillation. Primary prevention of stroke is largely targeted at these modifiable risk
factors. Untreated or undertreated hypertension is the most significant risk factor for stroke. All
hypertension should be treated to a goal blood pressure of <140–150/90 mmHg. Data are
strongest for thiazide diuretics and angiotensin-converting enzyme inhibitors for secondary
prevention of stroke. This patient also has an elevated total cholesterol, elevated triglycerides,
low high-density lipoprotein (HDL), and high low-density lipoprotein (LDL). Therefore, she
should be treated with a statin for primary stroke prevention. However, even in the absence of
elevated LDL or low HDL, there is evidence that statins can be useful for stroke prevention,
decreasing the incidence of stroke by 51%. Tobacco smoking should be discouraged in all
patients, and the patient should be given assistance in quitting smoking. The use of antiplatelet
agents for primary prevention of stroke is somewhat controversial. The most recent guidelines
for primary stroke prevention recommend aspirin for individuals who are at high risk for stroke.
In those with diabetes, additional risk factors for stroke must also be present. This patient also
has the risk factors of hypertension, smoking, and dyslipidemia. Although diabetes is a risk
factor for stroke, no trial has ever demonstrated that improving glucose control decreases stroke
risk.
XI-19.
The answer is B. (Chap. 446) The choice to perform a carotid endarterectomy for a carotid
stenosis depends on many factors, including the degree of stenosis and whether the patient is
symptomatic. In general, carotid endarterectomy has been demonstrated to have the greatest
benefit in those who are symptomatic and have stenosis of ≥70%. In individuals with
asymptomatic carotid artery stenosis, the risk of stroke is ~2% per year, and the potential
benefits of the procedure may be outweighed by the risks. A more measured approached with
risk factor modification may be more prudent. In symptomatic individuals such as the patient in
this case, several trials have attempted to address the value of carotid endarterectomy. There is
a significant absolute risk reduction favoring surgery of 17%. In the symptomatic patient, the
annual risk of stroke is ~13%. A recent meta-analysis showed that carotid endarterectomy is
most beneficial when performed within 2 weeks of symptoms onset and has greater benefits in
men and those ≥75 years old. However, the procedure should be performed only in institutions
familiar with the procedure. The benefit of the procedure is questionable for any surgeon whose
perioperative stroke rate is ≥6%.
XI-20. The answer is C. (Chap. 446) The noncontrast head CT shows blood within the left putamen in
this patient presenting with marked hypertension and abrupt onset of right hemiparesis. This is
consistent with intracranial hemorrhage. On a noncontrast head CT, blood is demonstrated as a
hyperdense white area, and this is an emergent finding. Most patients have symptoms that begin
abruptly and acutely worsen over the first 30–90 minutes. Diminished level of consciousness is
common, and signs of increased intracranial pressure may occur. Intracranial hemorrhage is
associated with a 40% mortality rate. The patient should be admitted to a neurologic intensive
care unit, if available, and monitored. Any coagulopathy should be corrected. The goal for blood
pressure management at this level of blood pressure is unclear. A recent clinical trial enrolled
patients with blood pressure between 150 and 220 mmHg and demonstrated improved
outcomes with lowering of blood pressure to 140 mmHg over 6 hours. However, it is not known
how individuals with higher blood pressures would respond. The patient should be carefully
monitored for development of increased intracranial pressure and treated appropriately.
Intracranial pressure monitoring is sometimes required with a goal cerebral perfusion pressure
of >60 mmHg.
XI-21.
The answer is C. (Chap. 447) The patient describes a typical history for migraine headaches,
the second most common cause of headache and most common cause of headache-related
disability worldwide. Migraine affects approximately 15% of women and 6% of men in any
given year. Diagnostic criteria for migraine have been simplified recently. To diagnose migraine,
an individual should complain of repeated attacks of headache lasting from 4–72 hours, with a
normal physical examination, and no other clear cause. The headache should be associated with
two of the following four features: unilateral pain, throbbing pain, aggravation by movement,
and moderate to severe intensity. In addition, the individual should complain of either
nausea/vomiting or phonophobia and photophobia. Most individuals with migraine headaches
can identify triggers associated with an attack. Common triggers include lack of sleep or
excessive sleep, stress, hormonal fluctuations, alcohol, and barometric pressures changes. The
pathophysiology that underlies migraine is increasingly understood as a dysfunction of the
monoaminergic sensory control systems located in the brainstem and hypothalamus. Activation
of cells in the trigeminal nucleus leads to release of vasoactive neuropeptides at vascular
terminations of the trigeminal nerve and within the trigeminal nucleus. These neurons also
project centrally, crossing the midline, to project to ventrobasal and posterior nuclei of the
posterior thalamus. The primary vasoactive peptide that has been implicated is calcitonin generelated peptide (CGRP). A new class of medication called gepants is being developed to act as an
antagonist at the CGRP receptor and has been demonstrated to be effective against migraine in
early clinical trials. The most common medications used for acute relief of severe migraine pain
are the triptans, potent agonists of the 5-hydroxytryptamine (serotonin) receptor, implicating
serotonin in pathogenesis of migraine as well. It is thought that serotonin is necessary for
nociceptive signaling in the trigeminovascular system and that triptans arrest this pathway.
Finally, dopamine may also play a role in pathogenesis of migraine because migraine symptoms
can be induced by dopamine stimulation, and individuals with migraine have been
demonstrated to have hypersensitivity to dopamine agonists at doses that do not affect non–
migraine-affected persons. In the past, the “vascular theory” of migraine was frequently
espoused, with the cause of migraine thought to be related to abnormal cerebral vasodilation.
This theory has been discounted as the pathogenesis has become more widely understood.
XI-22.
The answer is E. (Chap. 447) Patients who have increasing frequency of migraines or attacks
that are poorly responsive to abortive treatment should be considered for preventive therapy.
The typical patient considered for preventive therapy has four or more attacks per month. The
U.S. Food and Drug Administration (FDA)-approved medications for migraine prevention
include propranolol, timolol, sodium valproate, topiramate, and methysergide (not currently
available). In addition, many medications are commonly used for migraine prevention off-label
including amitriptyline, nortriptyline, flunarizine, phenelzine, gabapentin, and cyproheptadine.
When considering which medication to choose in a particular patient, one must carefully
consider the potential side effects that may limit use. The appropriate dose for migraine
prevention may also be unclear as the dosing for these drugs was determined for an indication
other than migraine. Patients should be started on a low dose and titrated upward to limit side
effects. The efficacy in decreasing migraine attacks is 50%–75%. However, the treatment effect
is delayed 2–12 weeks. Once efficacy is achieved, the drug is continued for 6 months before
tapering downward. Many patients exhibit fewer and milder attacks after cessation of
medications, indicating that these drugs may potentially alter the natural history of migraine.
XI-23.
The answer is A. (Chap. 447) Cluster headache is a rare disorder affecting only about 0.1% of
the population. This episodic headache disorder is characterized by severe unilateral headache
of relatively short duration that occurs over 8–10 weeks a year, followed by prolonged pain-free
intervals that average a little less than a year. As opposed to migraine, men are more likely to
have cluster headache, but cluster headache does share some features common to migraine
including the unilateral nature of the pain and the stabbing or throbbing characteristics of the
pain. In addition, a patient with cluster headache may also complain of nausea, photophobia, or
phonophobia during the attack. In contrast, however, patients with cluster headache tend to
move about during at attack. A cluster headache is accompanied by ipsilateral symptoms of
cranial parasympathetic activation including lacrimation, rhinorrhea or nasal congestion, and
ptosis. The headache in cluster headache is explosive in onset and associated with intense pain.
During a cluster attack, the headaches can occur as infrequently as every other day to several
times daily. The duration of pain is variable, between 15 and 180 minutes. Cluster headache
falls within a category of trigeminal autonomic cephalgias, along with paroxysmal hemicranias,
short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing
(SUNCT), and short-lasting unilateral neuralgiform headaches with cranial autonomic symptoms
(SUNA). It can be differentiated from these based on historical factors. In paroxysmal
hemicrania, the attacks are more frequent, occurring between 1 and 20 times per day, and last
2–30 minutes. Males and females are equally affected. In contrast to cluster headache,
indomethacin provides very effective prophylactic treatment. SUNCT and SUNA are rare
disorders that are easily distinguished from cluster headache. A patient with one of these
disorders will have 3–200 episodes of unilateral pain daily, but the duration is less than 5
minutes. Migraine headache is a unilateral throbbing headache associated with phonophobia,
photophobia, and nausea and vomiting. It is more common in women than men and is not
associated with the symptoms of tearing or nasal congestion. Tension headache is the most
common cause of headache and does not typically cause debilitating pain. The pain of a tension
headache is described as band-like.
XI-24.
The answer is C. (Chap. 448) Significant memory loss affects about 10% of all individuals
greater than 70 years of age, and in more than half, the cause is Alzheimer disease (AD). AD is
the leading cause of dementia and typically presents as slowly progressive memory loss that
develops over many years. Early in the disease, the memory loss often goes unrecognized or is
attributed to the effects of aging. Memory deficits are typically not noticeable to the patient or
spouse until the deficits fall to 1.5 standard deviations below normal on standardized memory
tests. When this occurs, the term mild cognitive impairment (MCI) is applied. Among those
diagnosed with MCI, about 50% progress to AD over 4 years. Many neurologists have begun to
replace MCI with the term “early symptomatic AD.” As the cognitive disease progresses, patients
will lose their ability to maintain their higher order daily activities such as driving, shopping,
housekeeping, and maintaining finances. Most patients are aware of the loss of these abilities in
early stages of the disease. In middle stages of the disease, the patient loses the ability to work
and is easily lost and confused. Language is increasingly impaired in both comprehension and
fluency. Motor apraxia also becomes noticeable. In advanced stages of the disease, patients may
remain ambulatory but often wander aimlessly. There is a loss of judgment and reasoning. The
patient may have delusions and may not recognize caregivers. The pathologic hallmark of AD is
the presence of neuritic plaques containing amyloid beta and neurofibrillary tangles (option C)
containing hyperphosphorylated tau filament. The earliest and most severe degeneration is seen
in the medial temporal lobe, lateral temporal cortex, and nuclear basalis of Meynert. Amyloid
deposition in cerebral blood vessels (option A) can be seen in AD but is not the pathologic
hallmark of AD. It is also seen in a condition called cerebral amyloid angiopathy, which
predisposes individuals to cerebral hemorrhage. Frontotemporal lobar degeneration spectrum
disorders are a heterogeneous group of disorders including Pick disease, progressive
supranuclear palsy, and corticobasal syndrome that share a common gross pathologic hallmark
of focal atrophy of the frontal, insular, and/or temporal cortex (option B) with a concomitant
loss of serotonergic innervation in many patients. Lewy bodies are intracytoplasmic inclusions
that stain positive with periodic acid–Schiff (PAS) and ubiquitin (option D) that are found
throughout specific brainstem nuclei, substantia nigra, amygdala, cingulate gyrus, and
neocortex. Lewy bodies are seen in dementia syndromes with parkinsonian features.
XI-25.
The answer is E. (Chap. 448) MCI refers to a condition of impaired memory that is 1.5
standard deviations below normal on standardized memory tests. Over 4 years, about 50% of
individuals with MCI will progress to AD. However, no treatment currently has been
demonstrated to slow the decline in memory or delay the progression to AD. Donepezil,
rivastigmine, and galantamine are anticholinesterase inhibitors that are FDA approved for use in
patients diagnosed with AD. Memantine is also approved for use in moderate to severe AD and
blocks N-methyl-D-aspartate (NMDA)–glutamate receptors. These medications have modest
effects on caregiver ratings of patient functioning and slight decrease in rate of decline in
cognitive test scores over periods of up to 3 years. However, these medications have significant
side effects including nausea, diarrhea, altered sleep with vivid dreams, and muscle cramps.
Interventions that have been attempted and failed to show benefit have included hormone
replacement therapy in postmenopausal women and gingko biloba. Many potential therapies are
being investigated to ascertain benefit including vaccination against amyloid beta and statin use
in early AD. Despite the popularity in the media, “brain training” has not been shown to slow
decline in cognitive function.
XI-26.
The answer is C. (Chap. 448) Frontotemporal dementia (FTD) refers to a group of clinical
syndromes that demonstrate frontotemporal lobe degeneration (FTLD) on pathologic
examination. FTD typically presents in the fifth to seventh decades of life and is nearly as
predominant as Alzheimer disease in this age group. Three distinct clinical syndromes are
described: behavioral variant FTD, semantic primary progressive aphasia, and
nonfluent/agrammatic primary progressive aphasia. These syndromes have clinical and MRI
findings that allow the clinician to determine the primary diagnosis, although patients may
evolve to have prominent features of another syndrome. This patient has behavioral variant
FTD, the most common of the FTD syndromes. Individuals with behavioral variant FTD
demonstrate social and emotional dysfunction with a variety of symptoms including apathy,
disinhibition, compulsivity, loss of empathy, and overeating. In addition, there are typically
deficits in executive control. Upper motor neuron disease is often seen as well. The MRI shows
atrophy of anterior cingulate and frontoinsular areas. In the semantic primary progressive
aphasia variant of FTD, patients slowly lose the ability to decode word, object, person-specific,
and emotion meaning, and the MRI shows prominent atrophy in the temporopolar area that is
greater on the left. The nonfluent/agrammatic primary progressive aphasia variant of FTD
demonstrates profound inability to produce words and motor speech impairment. The MRI
shows dominant frontal opercular and dorsal insula degeneration.
XI-27.
The answer is A. (Chap. 449) Parkinson disease (PD) is the second most common
neurodegenerative disorder after Alzheimer disease, affecting approximately 1 million
individuals in the United States. PD affects men and women equally, with a typical age of
symptom onset around age 60. The frequency of PD increases with age but can present as early
as the third decade of life. Most cases of PD occur sporadically, although genetic factors play a
role in some individuals. These individuals are more likely to present at a younger age. There is
no single gene found to be associated with PD. The most likely genes to be altered in PD patients
include α-synuclein, PINK1/Parkin, and LRRK2, but many others have been identified. Other
epidemiologic risk factors for PD include exposure to pesticides, rural living, and drinking well
water. Cigarette smoking and caffeine are associated with reduced risk of PD. Pathologically, the
characteristic finding in PD is degeneration of the dopaminergic neurons in the substantia nigra
pars compacta. Lewy bodies, which are intracytoplasmic inclusions containing primarily αsynuclein, may also be seen.
XI-28.
The answer is E. (Chap. 449) This patient exhibits classic features of PD, a diagnosis made
based on clinical presentation. Historically, PD could be diagnosed if the patient had two out of
three of the following: bradykinesia, tremor, and rigidity. However, given the significant overlap
of these symptoms with atypical or secondary Parkinson syndrome, the diagnosis of PD was
incorrect in about 24% of cases. More recently, it has been determined that a more predictive
trio of features is rest tremor, asymmetry, and positive response to levodopa. Imaging of the
brain may show reduced uptake of striatal dopaminergic markers in the posterior putamen with
sparing of the caudate nucleus on positron emission tomography (PET) or single-photon
emission computed tomography (SPECT) imaging. However, imaging is not required for a
diagnosis of PD and is typically only performed under research settings or if there are features
that would cause one to suspect an atypical Parkinson syndrome. This patient does not have
features that would lead one to suspect atypical parkinsonism (Table XI-28). He also has no
medications or other clinical conditions that would lead to secondary parkinsonism. The most
common causes of secondary parkinsonism include stroke, tumor, infection, exposure to toxins
such as carbon monoxide, and particularly medications. The medications most likely to cause
secondary parkinsonism are neuroleptic agents, including metoclopramide and chlorpromazine.
Treatment of PD is typically with either levodopa-carbidopa or a dopamine agonist. Levodopa
has a long history of use in PD dating to the 1960s. Levodopa is administered in combination
with carbidopa to prevent peripheral conversion to dopamine and thus prevent side effects,
especially nausea and vomiting. In Europe, levodopa is combined with benserazide to prevent
this conversion. Levodopa is the most effective symptomatic treatment of PD. It improves motor
features, quality of life, and life span as well as improving productive years of life with increased
independence and employability. However, the majority of patients treated with levodopa
develop motor complications with “on/off” periods, referring to fluctuations in motor
responsiveness to the drug. In addition, patients may develop involuntary movements as well.
Further, the duration of benefit of levodopa subsides over time to where it approaches the short
half-life of the drug. Nondopaminergic features, including falling, freezing, and autonomic
dysfunction, are also not treated with levodopa. Many providers now prefer dopamine agonists
as first-line therapy. These drugs include pramipexole, ropinirole, and rotigotine as non–ergot
derivatives. Although these agents do not show comparable efficacy compared to levodopa, they
are associated with fewer motor complications. It should be noted that even with use of the
dopamine agonists, eventual treatment with levodopa is required in most patients. Selegiline is a
monoamine oxidase inhibitor (MAOI). Although MAOIs can be used as monotherapy in early
disease, there is a risk of serotonin syndrome when used with selective serotonin reuptake
inhibitor (SSRI) agents such as fluoxetine. The risk is low overall, but because this patient is
untreated, there are other better options for his care.
TALBLE XI-28 Features Suggesting an Atypical or Secondary Cause of Parkinsonism
XI-29.
The answer is C. (Chap. 449) Deep brain stimulation (DBS) is the most common surgical
therapy performed for PD. In this surgery, an electrode is placed into a target area, typically the
subthalamic nucleus or globus pallidus pars interna. The electrode is connected to a stimulator
usually placed in the chest wall. The precise mechanism by which DBS works is not known, but
it is thought to act by disrupting the abnormal signal associated with PD and motor symptoms.
Once in place, DBS can be adjusted on many variables, including voltage, frequency, and pulse
duration. The primary indication for DBS is severe tremor or levodopa-induced motor
complications that cannot be controlled with medications. It does not improve features that fail
to respond to levodopa, including falling, freezing, and dementia.
XI-30.
The answer is F. (Chap. 452) Amyotrophic lateral sclerosis (ALS) is a common motor neuron
disease with an incidence of 1–3 per 100,000 population and prevalence of 3–5 per 100,000
population. ALS is responsible for about 1 in 1000 deaths in North America and Western Europe.
This progressive disease has no treatment and leads to disability and death due to respiratory
failure within 3–5 years after diagnosis. The pathologic hallmark of ALS is loss or death of both
upper and lower motor neurons. The upper motor neuron loss can be demonstrated by
degeneration of the corticospinal tracts typically originating in layer five of the motor cortex
and descending downward via the pyramidal tract to synapse with the lower motor neurons
both directly and indirectly via interneurons. The lower motor neuron disease is manifested by
death of anterior horn cells in the spinal cord and brainstem, which can lead to bulbar
symptoms. Clinically, this leads to the classic findings of both upper and lower motor neuron
disease in ALS. The most common presenting symptom in ALS is asymmetric weakness of
insidious onset, which is most prominent in the lower extremities. Muscle wasting and atrophy
may be prominent. A detailed history can elicit cramping with volitional movements, such as
stretching, that is most common in the early morning hours. Fasciculations may be identified.
When the muscles of the hands are involved, extensor weakness is more common than flexor
weakness. Bulbar symptoms include difficulty with chewing, swallowing, and movements of the
face and tongue. Upper motor neuron symptoms may lead to spasticity with increased deep
tendon reflexes. However, even in late stages of the disease, sensory and cognitive functions are
preserved. At present, the treatment for ALS is largely supportive. Riluzole has been approved
for treatment of ALS as it may confer a modest increase in survival, migraine or cluster
headaches, and multiple sclerosismigraine or cluster headaches, and multiple sclerosismigraine
or cluster headaches, and multiple sclerosisalthough its true benefits are not clearly known. Its
mechanism of action may be to reduce excitotoxicity by decreasing glutamate release.
Supportive therapy may include use of cough assist devices, invasive or noninvasive ventilatory
support, and gastrostomy feeding in addition to a variety of orthopedic assistive devices.
XI-31.
The answer is B. (Chap. 454) The patient is presenting with parkinsonism with symptoms of
orthostatic hypotension and constipation indicating concomitant autonomic dysfunction.
Because the patient exhibits no dementia and has no tremor, the most likely diagnosis would be
multiple system atrophy (MSA). This rare disorder has a prevalence of about 2–5 per 100,000
and is commonly grouped within a category of disorders of atypical parkinsonism that includes
progressive supranuclear palsy, corticobasal ganglionic degeneration, and frontotemporal
dementia. MSA is typically diagnosed in the sixth decade of life and is slightly more common in
men. MSA is characterized by degeneration of the substantia nigra pars compacta, striatum,
cerebellum, and inferior olivary nuclei. Glial cytoplasmic inclusions that stain positive for αsynuclein are also a defining feature. The diagnosis of MSA should be suspected in individuals
presenting with parkinsonian symptoms in combination with prominent cerebellar and/or
autonomic complaints. In most patients, either cerebellar or parkinsonian symptoms
predominate, leading to a subclassification as MSA-c or MSA-p, respectively. Autonomic
symptoms occur in all patients. The most frequent autonomic symptoms include prominent
orthostatic hypotension, severe constipation, neurogenic bladder, impotence in men, rapid eye
movement (REM) behavior disorder, and laryngeal stridor. Diagnosis is made by clinical
features. Treatment with dopaminergic agents is typically ineffective. Management is primarily
symptomatic and focused on managing the concomitant autonomic features. Orthostatic
hypotension often requires fludrocortisone. If that approach fails, other agents including
midodrine, ephedrine, pseudoephedrine, or phenylephrine may be used. Conservative treatment
of the gastrointestinal and urinary symptoms include frequent small meals, stool softeners,
bulking agents, and intermittent bladder catheterization. The median time to death after
diagnosis is 10 years. Risk factors for decreased survival include female gender, urinary
dysfunction, older age at onset, and parkinsonian variant of the disease.
XI-32.
The answer is A. (Chap. 455) Trigeminal neuralgia is a relatively common disorder with an
annual incidence of 4–8 cases per 100,000 population. It is more common in women and
typically presents in middle-aged or elderly individuals. It presents as sharp, and sometimes
excruciating, paroxysms of pain in the lips, gums, cheek, or chin. The pain typically lasts from
just a few seconds to no more than a few minutes. The painful sensations recur frequently in
clusters and can occur day or night. Episodes of pain can last for several weeks at a time. Pain
can occur spontaneously, but is often elicited by light touch or movements of the affected areas,
including chewing, speaking, or smiling. On physical examination, there are no objective signs
of sensory or motor loss. Trigeminal neuralgia is caused by ectopic generation of action
potentials by pain-sensitive afferent fibers in the fifth cranial nerve. Compression of the
trigeminal nerve root by a blood vessel is believed to be the most common cause of trigeminal
neuralgia. Demyelination near the entry of the fifth nerve root has also been implicated.
Diagnosis of trigeminal neuralgia is made based on clinical features, and laboratory or radiologic
examination is not required. There is no role for electromyography (EMG) or nerve conduction
studies in the evaluation of the disease. The initial treatment is typically with carbamazepine,
which has been demonstrated to be effective in 50%–75% of cases. The initial dose is 100 mg in
two to three divided doses daily. The medication is titrated upward to achieve pain relief. Most
patients require a dose of 200 mg qid or greater, although doses >1200 mg daily confer no
added benefit. For patients who do not tolerate carbamazepine, other antiseizure medications
have been used to control the symptoms. These include oxcarbazepine, lamotrigine, and
Dilantin. In cases that are refractory to medical therapy, microvascular surgical decompression
can be considered and has a >70% success rate in relieving pain. Gamma knife radiosurgery
may also be used. Radiofrequency thermal rhizotomy is used less frequently. Despite an initial
success rate of >95%, up to one-third of individuals will have recurrence of symptoms, and the
procedure is associated with an increased risk of complications including facial numbness and
jaw weakness. The differential diagnosis of trigeminal neuralgia includes temporal arteritis,
migraine or cluster headaches, and multiple sclerosis. Temporal arteritis may present with
superficial facial pain. One typically also has symptoms including jaw claudication, diffuse
myalgias, and potential visual symptoms. Testing of erythrocyte sedimentation rate and
performance of temporal artery biopsy are appropriate if this diagnosis is suspected. Migraine
and cluster headaches present with a deeper sensation of pain. Although the pain is often
throbbing in nature, it lacks the stabbing quality of trigeminal neuralgia. Multiple sclerosis can
present with trigeminal neuralgia, but most patients have other symptoms of the disease as well,
including weakness or visual symptoms. Multiple sclerosis may be more likely if a patient
presents with bilateral trigeminal neuralgia or at a young age, and an MRI would be appropriate
at that time.
XI-33.
The answer is F. (Chap. 456) This patient presents with spinal cord compression, which
represents an urgent need for treatment. Spinal cord compression can occur with any tumor but
is most common with tumors of the breast, lung, prostate, and kidney and lymphoma and
myeloma. The thoracic spinal column is the most commonly affected area for most tumors.
However, metastases from prostate or ovarian cancer invade locally into the spinal column.
Thus, they more commonly affect the sacral and lumbar vertebrae. Pain is typically the initial
symptom of vertebral metastases. The pain can be dull and aching or sharp and radiating. The
pain is usually worsened by movement, cough, and sneezing and at night. When cord
compression occurs, the patient will develop weakness, sensory abnormalities, and bowel or
bladder dysfunction. When spinal cord compression is suspected, imaging should be obtained
promptly. Diagnosis typically is made with MRI, which also allows one to differentiate between
metastasis, epidural abscess, epidural hemorrhage, or other lesions. On T1-weighted MRI, the
vertebral metastases will appear hypodense relative to normal bone marrow. With gadolinium
administration, the MRI may pseudo-normalize as uptake of the contrast causes the lesions to
appear at the same density as the bone marrow. Plain radiographs of the spine and radionuclide
bone scans will not identify 10%–20% of metastatic lesions. Management of cord compression
should include glucocorticoids, local radiotherapy, and treatment of the underlying malignancy.
Glucocorticoids decrease cord edema, and dexamethasone is the most commonly used
medication. Up to 40 mg daily of dexamethasone is frequently used. Prompt treatment with
radiotherapy to the area of cord compression is essential to decrease morbidity associated with
the finding. A good response to therapy is expected for individuals who are ambulatory at the
time of presentation. If motor deficits persist for longer than 12 hours, however, these will not
improve. Treatment would be expected to prevent new weakness. Finally, specific therapy for
the underlying tumor type is important. Surgical decompression of cord compression is generally
not a preferred therapy. If there is only a single metastasis to the spine, it can sometimes be
considered as a therapy. Otherwise, surgical therapy is typically limited to individuals who fail
to respond to the maximum-tolerated dose of radiotherapy.
XI-34.
The answer is C. (Chap. 456) Sarcoidosis is an important cause of acute or subacute
myelopathy. It most often presents with slowly progressive weakness or a relapsing-remitting
course. The patient affected with sarcoid myelopathy typically has concomitant sensory loss
with weakness. A distinct cord level may be demonstrated. The MRI often shows diffuse edema
of the spinal cord with gadolinium enhancement in active lesions. Nodular enhancement of the
adjacent surface of the spinal cord is frequently seen, and the disease may affect many levels of
the spinal cord. A lumbar puncture shows a lymphocyte-predominant cell count with mildly
elevated CSF protein. Because sarcoidosis is often a multisystem disease, examination for
evidence of disease outside of the spinal cord should be performed, including a chest
radiograph, slit-lamp eye examination, serum calcium levels, and electrocardiogram. If there is
evidence of abnormalities in other body systems, then definitive diagnosis can be made with a
biopsy demonstrating noncaseating granulomas on pathologic examination. Patients are treated
initially with high-dose glucocorticoids to decrease swelling and stimulate regression of the
granulomatous lesions. Many patients will also require alternative immunosuppression including
azathioprine, mycophenolate mofetil, or infliximab. Presence of caseating granulomas typically
signifies an infectious process, most commonly tuberculosis or fungal infection. Atypical
lymphocytes with clonality on flow cytometry are found in various types of lymphoma. A biopsy
with small round cells that often resemble lymphocytes and that demonstrate scant cytoplasm,
indistinct nucleoli, and mitotic figures is typical of small-cell lung carcinoma. Nonspecific
chronic inflammation is nondiagnostic, and further workup would be required.
XI-35.
The answer is D. (Chap. 456) Syringomyelia is a development disorder of the spinal cord that
results in enlargement of the central cavity of the spinal cord. More than half of all cases are
associated with a concomitant Chiari I malformation of the brainstem with protrusion of the
cerebellar tonsils through the foramen magnum and into the cervical spinal canal. Although
controversial, one theory for the pathogenesis of syringomyelia is impaired CSF flow with
secondary enlargement of the central spinal cord, and the common coexistence with Chiari
malformations may provide support of this theory. Symptoms of syringomyelia develop
gradually, often beginning in late adolescence or early adulthood. The symptoms progress
irregularly and may even arrest for a prolonged period. The presentation of syringomyelia
includes both sensory loss and muscle wasting and weakness. The sensory disturbance is
dissociative, with loss of pain and temperature sensation but preservation of vibration and
touch. Patients may present with injuries or burns that occur when the patient is unaware of a
painful sensation in the affected limb. The distribution of sensory loss is classically described as
cape-like, affecting the nape of the neck, shoulders, upper arms, and hands. Patients are
areflexic in the upper limbs. Symptoms may be asymmetric. As the cavity enlarges, it can further
lead to spasticity and weakness in the lower extremities as well. There are no definitive
treatment options for the disease. If a Chiari malformation is also present, surgical
decompression may be required. Surgeons have attempted direct decompression of the spinal
canal with varied results.
XI-36 and XI-37.
The answers are C and D, respectively. (Chap. 458) This patient presents with
visual disturbance and weakness affecting the lower extremities with a past history of prior
visual disturbance. This suggests a diagnosis of multiple sclerosis (MS), an autoimmune
demyelinating disorder of the central nervous system. This disease affects about 350,000
individuals in the United States and has a variable clinical course, with some individuals
experiencing limited symptoms and others becoming very incapacitated due to the disease. MS
is three times more common in women, with a typical age of onset between 20 and 40 years of
age. MS is more common in white individuals that those of African or Asian descent. In addition,
geographic variations in disease prevalence have also been demonstrated, with higher
prevalence in the temperate zone areas of northern North America, northern Europe, and
southern Australia and New Zealand. In contrast, the tropics have a prevalence that is 10 to 20
times less. Other well-established risk factors for development of MS include vitamin D
deficiency, exposure to Epstein-Barr virus after early childhood, and cigarette smoking. Despite
the fact that this is an autoimmune disorder, there has not been an associated between MS and
other autoimmune disorders. The clinical manifestations of MS are varied. The disease can
present with an abrupt onset of symptoms or may develop gradually. The most common initial
presenting symptoms include sensory loss, optic neuritis, weakness, paresthesias, and diplopia.
Weakness of the limbs may be asymmetric and manifest as loss of strength, speed, dexterity, or
endurance. Symptoms are upper neuron in origin and have associated spasticity, hyperreflexia,
and Babinski sign most commonly. However, if there is a spinal cord lesion, lower motor neuron
signs and loss of reflexes may also be seen. The spasticity that is present may lead to
spontaneous or movement-induced muscle spasms and affects up to 30% of patients with MS.
Optic neuritis presents with blurred vision, dimness, or decreased color perception in the central
visual fields. Visual symptoms typically only affect one eye. Periorbital pain often precedes or
accompanies visual loss. Funduscopic examination may be normal or show optic disc swelling.
Other common symptoms that occur with MS include bladder dysfunction, ataxia, constipation,
chronic pain, fatigue, and depression. A diagnosis of MS can be difficult to confirm in some
individuals. There is no definitive test for MS. The diagnostic criteria require two or more
episodes of symptoms and two or more signs of dysfunction in noncontiguous white matter
tracts. MRI characteristically shows multiple hyperintense T2-weighted lesions that can be
present in the brain, brainstem, and spinal cord. More than 90% of lesions seen on MRI,
however, are asymptomatic. Approximately one-third of lesions that appear hyperintense on T2weighted images will be hypointense on T1-weighted images. These “black holes” may be a
marker of irreversible demyelination and axonal loss. Evoked potentials are no longer commonly
used in MS and are most useful in studying pathways that are not exhibiting clinical symptoms.
Evoked potentials are not specific to MS, although a marked delay in latency of transmission
suggests demyelination. The CSF may show an increased number of mononuclear cells, although
CSF protein is typically normal. Oligoclonal bands help to assess the intrathecal production of
immunoglobulin (Ig) G. The presence of two or more discrete oligoclonal bands in the CSF that
are not present in serum is found in more than 75% of MS patients. If a patient has a pleocytosis
of >75 cells/µL, presence of polymorphonuclear cells, or protein concentration >100 mg/dL,
an alternative diagnosis should be sought.
XI-38.
The answer is D. (Chap. 458) Over the past two decades, 10 disease-modifying agents for the
treatment of MS have been approved. Due to these multiple options, it is preferred that a patient
with MS be referred to a treatment center with experience in the disease. The disease-modifying
drugs approved for MS include interferon-β-1a, interferon-β-1b, glatiramer acetate, natalizumab,
fingolimod, dimethyl fumarate, teriflunomide, mitoxantrone, and alemtuzumab. Given this
patient’s poor functional status, her disease should be treated as moderate disease. Generally, in
those with moderate disease, the preferred agents are dimethyl fumarate, fingolimod,
teriflunomide, and natalizumab, with interferon-β-1a and -1b treatment being reserved for
individuals with milder disease. However, natalizumab is not recommended in this patient due
to the presence of antibody to JC virus. About half of the population is antibody positive for JC
virus, indicating past exposure typically with an asymptomatic infection. JC virus is implicated
in the development of progressive multifocal leukoencephalopathy. This life-threatening
condition has occurred in 0.3% of all patients treated with natalizumab and in about 0.6% of
patients who are positive for JC virus antibody. The risk is lower in the first year of treatment
and increases thereafter. Thus, natalizumab should not be used in this patient unless she has
failed alternative therapies or if the disease course has been particularly aggressive. If
natalizumab is ultimately chosen for a patient who is JC virus antibody positive, it should not be
used for any longer than 1 year. In patients who are JC virus antibody negative, it is
recommended to follow the patient for development of antibody approximately every 6 months.
XI-39.
The answer is C. (Chap. 459) When evaluating a patient with peripheral neuropathy, the
clinician should consider the history and physical examination carefully to determine the
location of the lesion, which will then further identify the cause and appropriate treatment.
However, in as many as 50% of patients presenting with peripheral neuropathy, no cause is ever
found, and these patients generally have a predominate sensory polyneuropathy. Seven keys
questions in the history and physical examination can assist with the identification of the site of
the lesion and the cause (Table XI-39). The first determination the clinician should make is
which systems are involved—sensory, motor, autonomic, or some combination of these. An
isolated motor neuropathy without sensory involvement should lead to diagnostic possibilities
that include myopathy, motor neuropathy, or disorder of the neuromuscular junction.
Autonomic symptoms can accompany a diabetic neuropathy and can also be seen in amyloid
polyneuropathy. Another important determination is the distribution of the weakness (proximal
vs. distal, symmetric vs. asymmetric). A third determination is the nature of the sensory
involvement. Small-fiber neuropathy often has a burning or stabbing quality along with
temperature loss, whereas a large-fiber sensory neuropathy will show loss of vibratory sense and
proprioception. One should also consider whether upper motor neuron symptoms are also
present, which occurs with vitamin B12 deficiency most commonly, but also occurs with other
causes of combined system degeneration such as human immunodeficiency virus (HIV) and
copper deficiency. The temporal evolution of symptoms further provides the clinician with clues
as to the cause of the disease. Most neuropathies have an insidious onset over weeks to months.
Acute development of symptoms points to causes such as Guillain-Barré syndrome vasculitis or
Lyme disease. Asking about symptoms in other family members will help to establish whether a
hereditary neuropathy is present. Finally, it is important to obtain a full medical history to
assess whether any associated conditions could be contributing to the neuropathy. Once a full
history and physical examination is completed, a clinician will often order EMG and nerve
conduction studies to complete the work up. Autonomic studies may also be helpful in selected
patients.
TALBLE XI-39 Approach to Neuropathic Disorders: Seven Key Questions
XI-40. The answer is A. (Chap. 459) 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 syndrome and is an inherited
demyelinating sensorimotor neuropathy. CMT1 most often affects patients in the first to third
decades of life with distal leg weakness (ie, foot drop). There are several subtypes of CMT1,
most of which are inherited in an autosomal dominant fashion. However, the penetrance is
variable, and some affected family members may remain asymptomatic even late in life. The
most common genetic defect in CMT1 (CMT1A) is a 1.5-megabase duplication in the gene for
peripheral myelin production (PMP-22) on chromosome 17. This results in a patient having
three copies of the gene rather than two. Although patients generally do not complain of sensory
symptoms, these can be elicited often on physical examination. Muscle stretch reflexes are
unobtainable or reduced throughout, and muscles below the knee are often atrophied, which
makes legs appear to have so-called inverted champagne bottle appearance. There are no
medical therapies for CMT, but patients are generally referred for physical and occupational
therapy. Bracing and other orthotic devices are frequently used. Hereditary neuralgic
amyotrophy 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 is a 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 generally
presents acutely with rapid development of ascending paralysis. The prolonged symptom period
and distribution described here are not typical for Guillain-Barré syndrome. Fabry disease is an
X-linked disorder in which men are more commonly affected then 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 atherosclerosis from the underlying mutation in the αgalactosidase gene with accumulation of ceramide in nerves and blood vessels.
XI-41.
The answer is E. (Chap. 459) One of the most common side effects of isoniazid treatment is
peripheral neuropathy. The elderly, malnourished patients, and “slow acetylators” are at
increased risk for developing the neuropathy. Isoniazid 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 (vitamin B12) is not reduced in this condition and unaffected by isoniazid. Neurontin
and pregabalin may alleviate symptoms but will not reverse the neuropathy. There is no
indication that hypothyroidism is present.
XI-42.
The answer is C. (Chap. 459) Diabetes mellitus 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, polyradicular neuropathies, cranial neuropathies,
and other mononeuropathies. Risk factors for 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. DSPN presents with sensory loss
beginning in the toes and gradually progressives over time up the legs and into the fingers and
arms. Symptoms also may include tingling, burning, and deep aching pains. Nerve biopsy,
although rarely indicated, often shows axonal degeneration, endothelial hyperplasia, and
occasionally perivascular inflammation. Tight glucose control prevents 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.
XI-43 and XI-44.
The answers are B and B, respectively. (Chap. 460) Guillain-Barré syndrome
(GBS) is an acute demyelinating polyneuropathy that can be severe and life-threatening if not
immediately recognized and treated. Each year, there are about 5000–6000 cases in the United
States, with an incidence of about 1–4 cases per 100,000 population annually. Men are slightly
more commonly affected than women, and GBS is more commonly diagnosed in adulthood. The
typical presentation is a rapid ascending paralysis that may be first noticed as weak or “rubbery”
legs. The weakness can evolve over hours to a few days, with the legs being more affected than
the arms. Tingling dysesthesias are also frequently present, although sensory neuropathy is
always present. Facial paresis occurs in about 50% of patients, and other lower cranial nerves
may also be affected. Pain is a frequent complaint, with pain in the neck, shoulders, back, and
diffusely over the spine. In addition, vague sensation of deep aching pain in the weakened
muscles may also be present. Up to 30% of patients will require mechanical ventilation due to
weakness of the respiratory muscles. Moreover, bulbar involvement increases the risk of
aspiration and subsequent pneumonia. Deep tendon reflexes are decreased or disappear entirely
within the first few days of onset. Cutaneous sensory deficits are usually only mild if present at
all. Bladder dysfunction only rarely occurs and is transient. Persistent or severe bladder
dysfunction should stimulate a workup for other causes. Autonomic symptoms are common.
Blood pressure may be quite labile with marked postural changes. Cardiac dysrhythmias may
also occur and require continuous monitoring. Typically within 4 weeks of onset or sooner,
there is a plateau in symptoms with no further progression. Diagnosis of GBS relies upon a high
degree of clinical suspicion because there is no one test that is diagnostic for the disorder.
Typical CSF findings include a high CSF protein without pleocytosis. The presence of a high CSF
white blood cell count should prompt a search for an alternative diagnosis. Early in the disease
process, electrodiagnostic testing may be normal or only show mild findings of demyelination.
Approximately 70% of GBS cases occur within 1–3 weeks of an antecedent infectious illness.
Most commonly, the illness is respiratory or gastrointestinal in nature. About 20%–30% of all
cases in North America, Europe, and Australia are preceded by infection or reinfection with
Campylobacter jejuni. A similar proportion of individuals will have had an infection with a
human herpes virus, most often cytomegalovirus or Epstein-Barr virus. Less frequently, HIV,
hepatitis E, or Mycoplasma pneumoniae may be implicated. Recent immunizations are a rare
cause of GBS, with a risk of <1 per million. When a case of GBS is suspected, clinical vigilance
and prompt treatment are required. Admission to intensive care is often required to monitor for
development of respiratory failure or cardiac arrhythmias. If treatment is delayed longer than 2
weeks after initial symptoms or during the plateau stage, it may not be effective. Either highdose IV immunoglobulin (IVIg) or plasmapheresis should be begun as soon as possible. IVIg is
given as a daily infusion for 5 days. Plasmapheresis should be performed four to five times over
the first week. Functionally significant recovery may begin to be evident after the first week but
may take several weeks. Lack of noticeable improvement following either IVIg or plasmapheresis
is not an indication to switch to the alternative therapy as they are equally effective in
treatment. Glucocorticoids have not been shown to be effective in GBS and should not be used.
Approximately 85% of patients with GBS achieve full functional recovery after several months
to a year. However, some physical examination findings such as areflexia may persist. The
mortality rate is <5%, and death is most often due to respiratory complications. Although
macrolides have activity against Campylobacter species, most cases of diarrhea resolve
spontaneously, and treatment has no effect on the course of GBS. Pyridostigmine may increase
strength in patients with myasthenia gravis but will have no effect on strength in patients with
GBS.
XI-45.
The answer is A. (Chap. 461) Myasthenia gravis (MG) is a relatively common neuromuscular
disorder that is caused by antibody-mediated autoimmune destruction of acetylcholine receptors
at the neuromuscular junction. MG has a prevalence of about 2–7 in 10,000 individuals and
affects women more commonly than men at a ratio of 3:2. The age of presentation in women is
generally in the 20s to 30s, whereas men more commonly present in their 50s and 60s. The key
features of MG are weakness and fatigability of muscles. The weakness increases with repeated
use and is typically more prominent late in the day. The distribution of muscle weakness often
follows a typical pattern, with cranial muscles being affected early in the course of disease.
Common clinical features include diplopia, ptosis, inability to smile fully, weakness with
chewing, dysarthria, and dysphagia. Aspiration of liquids may also occur. In the majority of
patients, the weakness becomes generalized, affecting proximal muscles greater than distal
muscles. Deep tendon reflexes are preserved, and the disease may be asymmetric. The diagnosis
is suspected after the appearance of the characteristic symptoms and signs. The diagnosis should
be confirmed with further testing because treatment may involve surgery and the prolonged use
of immunosuppressive agents. The most sensitive test for the diagnosis of MG is the presence of
antibodies to the acetylcholine receptor (AChR). These antibodies are present in about 85% of
patients with MG. The presence of AChR antibodies in a patient with typical signs and symptoms
is diagnostic. If AChR antibodies are negative, additional testing for muscle-specific kinase
(MuSK) antibodies will be positive in another 40% of individuals. However, if the disease is
limited to the ocular muscles alone, both of these tests are likely to be negative. Use of repetitive
nerve stimulation characteristically shows decrements of >10%–15% in action potential
amplitude with successive electric shocks delivered at two to three per second. Patients should
be tested with repetitive stimulation in a proximal muscle group or in muscles that have been
demonstrated to be weakened in the disease. Edrophonium is an acetylcholinesterase inhibitor
that allows acetylcholine to interact repeatedly with the limited number of AChRs, producing
improvement in the strength of myasthenic muscles. An objective end point must be chosen
when performing the edrophonium test to determine if there is an improvement in muscle
strength after administration. At this time, edrophonium is only used in individuals with
suspected MG with negative antibody testing as well as negative electrodiagnostic testing. Falsepositive tests may occur in patients with other neurologic diseases, such as amyotrophic lateral
sclerosis. Antibodies to voltage-gated calcium channels are found in patients with Lambert-Eaton
syndrome, another neuromuscular disorder associated with complaints of weakness. In this
disorder, however, individuals develop improved responses with repetitive nerve stimulation.
Clinically, Lambert-Eaton syndrome can also be distinguished from MG because Lambert-Eaton
syndrome typically has prominent autonomic changes as well as depressed deep tendon reflexes.
XI-46.
The answer is E. (Chap. 461) The treatment of MG may include a variety of modalities
including anticholinesterase medications, immunosuppression, IVIg or plasmapheresis, or
surgical intervention. Initial treatment of symptoms with anticholinesterase medications such as
pyridostigmine yields partial improvement in most patients. However, few patients achieve
complete relief with this class of medications alone. In addition, dose-limiting side effects such
as diarrhea, abdominal cramping, and excessive salivation are frequent. Thymectomy should be
considered in all patients with MG. When considering thymectomy, there are two separate issues
to be considered. If the patient has evidence of thymoma, thymectomy is necessary because local
spread may occur. However, presence of a thymic shadow on CT scan is not indicative of
thymoma and is common in young adulthood. In individuals without evidence of thymoma,
thymectomy should still be considered an important therapeutic option. Even in the absence of
tumor, up to 85% of individuals will experience improvement in disease after thymectomy, with
~35% achieving drug-free remission. Current literature suggests that individuals who undergo
thymectomy are 1.7 times more likely to improve and 2 times more likely to achieve remission
than those who do not undergo thymectomy. It is now consensus that individuals between the
ages of puberty and 55 with generalized MG should be referred for thymectomy if surgically
appropriate candidates. In the absence of thymectomy, addition of immunosuppressants in the
form of glucocorticoids or other steroid-sparing agents will yield further benefits and often
control the disease. Prednisone at a dose of 15–25 mg daily is the initial choice in most patients
and should be increased for residual symptoms. Other immunomodulatory agents with proven
effectiveness in MG include mycophenolate mofetil, azathioprine, cyclosporine, and tacrolimus.
In addition, rituximab may be considered in refractory cases. In acute presentations with
myasthenic crisis, IVIg or plasmapheresis is used concomitantly with immunosuppressants.
Anticholinesterase drugs are typically withheld during a myasthenic crisis because overdosage of
these drugs can worsen weakness.
XI-47. The answer is B. (Chap. 461) Except for lumbar puncture, all of the options listed are indicated
at this time. Thymic abnormalities are present in 75% of patients with MG. 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 MG and may aggravate
weakness. Testing for rheumatoid factor and antinuclear antibodies should also be obtained
because of the association of MG with 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 patients with
MG, and they can be used as an objective measure of response to therapy.
XI-48.
The answer is E. (Chap. 462e) 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, although most cases are more mild.
Concomitant use of statins with fibrates and cyclosporine are more likely to cause adverse
muscle reactions. Elevated serum creatine kinase (CK) is often identified, and muscle weakness
is evidenced by myopathic EMG studies and myonecrosis on muscle biopsy. Severe myalgias,
muscle weakness, significant elevations in CK (>3× upper limit of normal), and myoglobinuria
are indications for stopping. After cessation, improvement generally occurs in up to several
weeks.
XI-49.
The answer is E. (Chap. 462e) A number of endocrinologic conditions are associated with
myopathy. Both hypo- and hyperthyroidism are associated with proximal muscle weakness.
Hypothyroidism is associated with an elevated CK frequently, 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, 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, correlates with the degree of myopathy. Diabetes mellitus
is a 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 disease).
XI-50. The answer is D. (Chap. 462e) There are two recognized clinical forms of myotonic dystrophy,
both of which are characterized by autosomal dominant inheritance. Myotonic dystrophy type 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.
Myotonia can also be elicited by percussion of the thenar eminence. 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 by clinical features alone in an individual
with classic symptoms and a positive family history. An EMG 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 type 2 (DM2) causes proximal muscle weakness
primarily and is also known by the name proximal myotonic myopathy. Other features of the
disease overlap with DM1. Acid maltase deficiency (glucosidase deficiency, or Pompe 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, features are
similar to one another. Nemaline myopathy is a heterogeneous disorder marked by the
threadlike appearance of muscle fibers on biopsy. Nemaline myopathy usually presents in
childhood and has a striking facial appearance similar to myotonic dystrophy with a long,
narrow face. This disease is inherited in an autosomal dominant fashion.
XI-51.
The answer is E. (Chap. 464e) 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 (Table XI-51). CFS is seen
worldwide, with adult prevalence rates varying between 0.2% and 0.4%. In the United States,
the prevalence is higher among women (~75% of cases), members of minority groups (African
and Native Americans), and individuals with lower levels of education and occupational status.
The mean age of onset is between 29 and 35 years. Many patients probably go undiagnosed
and/or do not seek help. There are numerous hypotheses about the etiology of CFS; there is no
definitively identified cause. Physical inactivity and trauma in childhood tend to increase the
risk of CFS in adults. Neuroendocrine dysfunction may be associated with childhood trauma,
reflecting a biological correlate of vulnerability. Psychiatric illness and physical hyperactivity in
adulthood raise the risk of CFS in later life. Twin studies suggest a familial predisposition to
CFS, but no causative genes have been identified. Physical or psychological stress may elicit the
onset of CFS. Most patients report an infection (usually a flulike illness or infectious
mononucleosis) as the trigger of their fatigue. Relatively high percentages of CFS cases occur
after Q fever and Lyme disease.
TALBLE XI-51 Diagnostic Criteria for Chronic Fatigue Syndrome
XI-52. The answer is B. (Chap. 464e) Cognitive behavioral therapy (CBT) and graded exercise therapy
(GET) have been found to be the only beneficial interventions in CFS. Some patient groups argue
against these approaches because of the implication that CFS is a purely mental disorder. CBT is
a psychotherapeutic approach directed at changing unhealthy disease-perpetuating patterns of
thoughts and behaviors. It includes educating the patient about the etiologic model, setting
goals, restoring fixed bedtimes and wake-up times, challenging and changing fatigue and
activity-related concerns, reducing a focus on symptoms, spreading activities evenly throughout
the day, gradually increasing physical activity, planning a return to work, and resuming other
activities. The intervention, which typically consists of 12–14 sessions spread over 6 months,
helps CFS patients gain control over their symptoms. GET targets 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 goals for maximal heart rates. CBT and
GET appear to improve fatigue primarily by changing the patient’s perception of the fatigue and
also by reducing the focus on symptoms. In general, CBT studies tend to yield better
improvement rates than GET trials. Not all patients benefit from CBT or GET. Predictors of poor
outcome are medical (including psychiatric) comorbidities, 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 for 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 median
improvement rate is 39% (range, 8%–63%). Patients with an underlying psychiatric disorder
and those who continue to attribute their symptoms to an undiagnosed medical condition have
poorer outcomes. The other listed therapies have been tried in patients with CFS with no proven
lasting benefit.
XI-53.
The answer is A. (Chap. 466) Generalized anxiety disorder (GAD) has a lifetime prevalence of
about 5%–6% and presents with persistent, excessive, and/or unrealistic worry occurring on
most days that persists for at least 6 months. The worry typically pervades most aspects of life
and is to a degree that it is uncontrollable and causes impairment in social, work, or
interpersonal functioning. Associated physical symptoms include tension, restlessness, impaired
concentration, insomnia, autonomic arousal, and feeling of being “on edge.” Typical onset of
symptoms is before the age of 20, although patients may not seek treatment for many years. A
history of childhood fears may be present. More than 80% of patients with GAD have a
concomitant mood disorder such as major depression or dysthymia or social phobia, but panic
attacks (e.g., 10–30 minute episodes including palpitations, shortness of breath, and feelings of
impending doom) generally do not occur. Comorbid substance abuse, most often with alcohol or
sedative/hypnotics, is also common, perhaps as an attempt to self-treat anxiety. Treatment of
GAD is most effective when psychotherapy is combined with medications, although complete
relief of symptoms is rare. Initial intervention with benzodiazepines is often required for a
period of 4–6 weeks. Other medications that are FDA-approved for the treatment of GAD are
escitalopram, paroxetine, and venlafaxine, although other SSRIs have been demonstrated in
clinical trials to be effective as well, typically at doses comparable to the effective dose for major
depression. Buspirone is another anxiolytic agent that is nonsedating, does not produce
tolerance or dependence, and has no abuse potential. However, it generally has mild effects and
takes several weeks to produce results. It has demonstrated best results in individuals with
dementia or head injury who develop agitation and/or anxiety. Anticonvulsants with GABAergic
properties such as gabapentin, oxcarbazepine, tiagabine, pregabalin, and divalproex also may
have efficacy against anxiety.
XI-54.
The answer is C. (Chap. 466) There are an estimated 300,000 episodes of acute schizophrenia
in the United States annually. This disorder has a high degree of morbidity, with many
individuals failing to achieve their premorbid level of functioning after an episode of acute
schizophrenia. Symptoms of schizophrenia are heterogeneous with perturbations in language,
thinking, perception, social activity, affect, and volition. The most typical age of onset is late
adolescence and young adulthood. Onset is insidious as individuals progressively experience
social withdrawal and perceptual distortion and often progress to experience frank delusions
and hallucinations. As individuals age, the positive symptoms of delusions and hallucinations
tend to recede, and the negative symptoms of anhedonia, decreased emotional expression, and
loss of function become more predominant. In a first episode, antipsychotic agents are effective
about 70% of the time. Symptoms may improve within hours or days of dosing, but full
remission often takes 6–8 weeks. If medications are discontinued, relapse will occur in 60% of
patients within 6 months. The long-term prognosis of most individuals with schizophrenia is
somewhat grim. Prognosis of schizophrenia depends not on symptom severity at initial diagnosis
but on the response to antipsychotic medication. A permanent remission rarely occurs. About
10% of schizophrenic patients commit suicide.
XI-55.
The answer is D. (Chap. 466) This patient is experiencing her first episode of a panic attack
and does not meet criteria for panic disorder. In this situation, no specific treatment is required.
The patient should be reassured that she does not have any evidence of a serious medical
disorder in a manner that is empathetic and supportive. Panic disorder is a frequently occurring
mental disorder with a lifetime prevalence of about 2%–3%. Panic attacks begin abruptly, most
commonly without an immediate precipitating cause, and peak in severity over 10 minutes. The
first episode of panic attack is most often outside the home. The symptoms usually subside
spontaneously over the course of an hour. Panic attacks are often accompanied by intense fear
and a variety of physical symptoms, including palpitations, dizziness, sweating, shortness of
breath, chest pain, and a feeling of impending doom or death. Gastrointestinal distress,
paresthesias, and syncope may occur. Panic disorder could be diagnosed if the patient developed
recurrent attacks lasting at least 1 month or exhibited excessive worry or change in behavior
related to these attacks. If the patient subsequently develops panic disorder, a variety of
treatment options can be pursued. The goals of therapy for panic attacks are to decrease the
frequency of attacks and severity of symptoms during the attack. Antidepressant medications are
the cornerstone of therapy with SSRIs 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. Because these medications take 2–6 weeks to become
effective, they are often combined with benzodiazepines early in the course of treatment to
alleviate anticipatory anxiety and provide immediate relief of panic symptoms. Alprazolam and
clonazepam are common agents used for panic disorder, although alprazolam may have more
associated dependence with 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.
XI-56.
The answer is A. (Chap. 466) There are an increasing number of antidepressant medications
available in a variety of classes. 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 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
because they are quite effective and do not have the same frequency of sexual dysfunction.
Medications in this class includes venlafaxine, desvenlafaxine, duloxetine, and mirtazapine.
Monoamine oxidase inhibitors were once a common antidepressant class of medication, but
these medications are now only rarely used because of 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, called simply
mixed-action, and includes trazodone, bupropion, and nefazodone.
XI-57. The answer is E. (Chap. 466) Posttraumatic 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 reexperience 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 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.
XI-58.
The answer is B. (Chap. 466) 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 with 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. However, up to 40% of patients treated at primary care offices
discontinue treatment if there has not been a response within 1 month. Once a patient has been
on treatment for ~2 months, the response should be evaluated, and if there has been an
insufficient response, a dose increase should be considered. In this patient, a dose 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 will likely require indefinite
maintenance treatment because it is recommended that anyone with more than two episodes of
major depression continue treatment indefinitely.
XI-59.
The answer is F. (Chap. 467) About 20% of all patients have an alcohol use disorder, even in
affluent locales. Patients should be screened for an alcohol use disorder by asking specific
questions regarding alcohol consumption, although many patients may minimize their alcohol
use. The patient in the scenario presented reports daily alcohol consumption and some
symptoms of an alcohol use disorder, including blackouts from drinking and frequent hangovers
while working. Laboratory tests may be helpful in this situation as they can be elevated in
individuals who regularly consume six or more drinks daily. The two tests with the greatest
sensitivity and specificity (≥60%) are γ-glutamyl transferase (GGT) >35 U/L and carbohydratedeficient transferrin (CDT). Using both of these tests combined is more likely to be accurate than
using either test alone. Other blood tests that may be useful include high-normal MCV >91 µm3
and serum uric acid >7 mg/dL. Elevations in AST or ALT are neither sensitive nor specific.
XI-60.
The answer is A. (Chap. 467) Alcohol is primarily absorbed through the proximal small
intestine, but small amounts can also be absorbed in the mouth, esophagus, stomach, and large
intestines as well. 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.
XI-61.
The answer is C. (Chap. 467) Alcohol has effects on many neurotransmitters in the brain. The
predominant effect of alcohol lies in its ability to cause release of γ-aminobutyric acid (GABA),
and it acts primarily at the GABAA receptors. 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 β-endorphins during acute ingestion. In addition to
these effects, alcohol also inhibits postsynaptic NMDA 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.
XI-62.
The answer is D. (Chap. 467) 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, 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 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 function
despite the presence of alcohol.
XI-63. The answer is C. (Chap. 467) In the most recent fifth edition of Diagnostic and Statistical Manual
of Mental Disorders, the term alcohol use disorder replaced the two terms used to describe
problem areas with alcohol use: alcohol abuse and alcohol dependence. Under the new
terminology, alcohol use disorder is defined as repeated alcohol-related difficulties in at least 2
of 11 life areas that cluster together in the same 12-month period, and this disorder combines
many of the criteria of dependence and abuse into a single diagnosis. The diagnosis of alcohol
use disorder is further characterized as mild, moderate, or severe based on how many criteria a
person fulfills. Examples of these criteria include failure to fulfill obligations, drinking in
hazardous situations, tolerance, withdrawal, craving, and inability to control drinking behaviors.
The lifetime risk of an alcohol use disorder 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 use. 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 an alcohol use disorder; however, this risk is
about 4 times higher, not 10 times higher. This risk is conferred even when the children are
adopted early and raised by nonalcoholics. Identical twins also exhibit a higher risk of
concurrent alcoholism 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 a subsequent alcohol
use disorder as higher doses of alcohol are required to achieve the same effects. It is estimated
that 20% of all patients have at least mild alcohol use disorder. The age at first drink is similar
between alcoholics and nonalcoholics. However, alcoholics report a slightly earlier onset of
regular drinking and drunkenness. In most individuals with alcoholism, the course of the disease
is one of remissions and relapse, but most individuals do require treatment to be able to sustain
abstinence. The chance of spontaneous remission is about 20%. If drinking continues without
remission, the lifespan will decrease by about 10 years, with leading causes of death including
heart disease, cancer, suicide, and accidents.
XI-64.
The answer is B. (Chap. 467) 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
development of delirium tremens. Other clinical features of alcohol withdrawal include anxiety,
insomnia, and autonomic nervous system overactivity 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. Although
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 to the alcohol-dependent
patient who abruptly stops all alcohol intake is a prophylactic approach, and the patient should
be screened 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 early development of symptoms and allow intervention before symptoms escalate. In
this setting, most experts recommend 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. IV medications that have a rapid onset of action and can be titrated for more
aggressive symptom management are often employed in this setting. Thus, 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. IV fluids and thiamine had been administered since hospital
admission. Administration of glucose-containing fluids without thiamine in the alcoholdependent patient can precipitate Wernicke 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 abdominal CT, 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 appropriate use
of benzodiazepines because 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 pointes arrhythmia because this patient is at risk for electrolyte
deficiencies from his alcoholism and pancreatitis.
XI-65.
The answer is D. (Chap. 467) 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 that
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. Because it inhibits an enzyme that is part of
the normal metabolism of alcohol, it allows the buildup of acetaldehyde, which creates these
unpleasant symptoms. As a result of the autonomic side effects, it is contraindicated in
individuals with hypertension, a history of stroke, heart disease, or diabetes mellitus.
XI-66.
The answer is B. (Chap. 470) Although declining in prevalence, cigarette smoking and use of
other nicotine-containing products remain a significant contributor to premature death in the
United States and account for about one out of every five deaths in the United States, for a total
of 400,000 deaths annually. Approximately 40% of cigarette smokers will die prematurely due
to the habit unless they are able to quit. The primary causes of premature death related to
cigarette smoking are cardiovascular diseases, including both myocardial infarction and stroke;
chronic obstructive pulmonary disease (COPD); and myriad cancers including lung, oral,
esophageal, urogenital, and pancreatic cancer. Cigarette smoking promotes both large- and
small-vessel vascular disease. Approximately 90% of peripheral vascular disease in the
nondiabetic population can be attributed to cigarette smoking. In addition, 50% of aortic
aneurysms, 20%–30% of coronary artery diseases, and 10% of ischemic and hemorrhagic strokes
are caused by cigarette smoking. Moreover, if additional cardiac risk factors are present, the
incremental risk added by cigarette smoking is multiplicative. As mentioned earlier, cigarette
smoking increases the risk of many different cancers, not just those of the respiratory tract. The
digestive tract appears to be particularly susceptible to the effects of cigarette smoking because
cigarette smoking has been linked to esophageal, stomach, pancreatic, liver, and colorectal
cancer. Urogenital cancers are also increased in cigarette smokers, with increases in both kidney
and bladder cancer. In women, cervical cancer is also increased among smokers. Interestingly,
however, uterine cancer may be decreased among postmenopausal woman who smoke.
Cigarette smoking is responsible for 90% of COPD. Cigarette smoking induces chronic
inflammation in the small airways, although most smokers do not develop symptomatic
respiratory disease. Chronic inflammation, narrowing of the small airways, and destruction of
the alveoli lead to symptoms of COPD and emphysema in 15%–25% of smokers. In any given
year, more than half of smokers would like to quit smoking. However, only 6% quit for 6
months, and less than 3% remain abstinent at 3 years. Most individuals have to make multiple
attempts to quit before being successful, and they are more likely to be successful if advised to
quit by a physician. Other triggers for smoking cessation include an acute illness, the cost of
cigarettes, media campaigns, and workplace smoking restrictions.
XI-67.
The answer is E. (Chap. 470) Smoking cessation is more likely to be successful when an
individual is advised to quit by a physician and has a supervised smoking cessation plan. At
every medical visit, all patients should be asked whether they smoke, how much they smoke,
and whether they are interested in quitting. Even patients who state that are not interested in
quitting should receive a clear message from their provider that smoking is an important health
hazard and be offered assistance with quitting in the future. For those interested in quitting,
negotiating a quit date is an important step in the process, and close follow-up with office
contact near the quit date is an important part of the process. In addition, sometimes a more
intensive counseling approach may be necessary. Current recommendations are to offer
pharmacologic therapy with either nicotine replacement therapy (NRT) or varenicline. A variety
of NRTs are available, including transdermal patches, nasal inhaler, gum, oral inhaler, or
lozenge, with success rates of 1.5–2.7 times greater than no intervention. Varenicline is an oral
partial agonist of the nicotinic acetylcholine receptor that has a published success rate of 2.7
times greater than no intervention. There has been some concern regarding use of varenicline in
individuals with severe psychiatric illness, including suicidal ideation, but this individual does
not meet this level of concern. With planned close follow-up, varenicline should be considered
an available option for this patient.
XI-68.
The answer is D. (Chap. 470) Varenicline is a partial agonist of the nicotinic acetylcholine
receptor and has been demonstrated to be more effective than placebo in promoting smoking
cessation. Severe psychiatric symptoms including suicidal ideation have been reported,
prompting a warning by the FDA. In addition, closer therapeutic supervision has been
recommended, but at this time, the true frequency of these responses remains unclear. A recent
publication retrospectively reviewed the use of varenicline in over 69,000 individuals in
Sweden. When compared to the general population, there was no increased risk of suicide or
psychosis in individuals prescribed varenicline even though these individuals were twice as
likely to have had a prior psychiatric diagnosis (Thomas KH et al. BMJ 347:f5704, 2013).
However, the FDA is currently continuing its surveillance of the drug until more data are
available. Alternative agents such as bupropion in combination with nicotine replacement
therapy should be considered.
XI-69.
The answer is B. (Chap. 470) Smokers regulate their blood levels of nicotine by adjusting the
frequency and intensity of their tobacco use. Smokers can compensate for the lower levels of
nicotine in low-yield cigarettes by smoking more cigarettes or by adjusting their smoking
technique with a deeper inhalation and breathhold. Therefore, smoking low-yield cigarettes is
not a reasonable alternative to smoking cessation. Moreover, there is no difference in the
harmful physical effects of smoking or in the potential for drug interactions. Finally, although
not definitively proven, there is some thought that the rise in adenocarcinoma of the lung over
the past 50 years is associated with introduction of the low-tar cigarette and the resultant
change in smoking behavior associated with this introduction.
by
Dr. Nigam Rashmi Dhar
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