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1

An 80-year old woman living in a nursing home with history of dementia is admitted to the hospital with pneumonia. In the emergency department, a peripheral intravenous line was inserted, appropriate antibiotics were initiated, she was given oxygen by nasal cannula, and a urinary catheter was placed. On physical examination, temperature is 38.3°C (101.0°F), blood pressure is 140/88 mm Hg, pulse rate is 100/min, and respiration rate is 16/min. Pulmonary auscultation reveals left lower lobe crackles. Cardiac examination is normal. Moderate cognitive impairment is noted but no inattention or focal neurologic deficits.

She is provided access to her glasses and hearing aid, and a large clock and night light are in place in her room. Which of the following additional steps should be taken to prevent delirium in this patient?


(A) Administer benzodiazepine, as needed
(B) Administer diphenhydramine for sleep
(C) Administer haloperidol twice daily
(D) Check vital signs every 4 hours through the night
(E) Remove her urinary catheter

E

  • Elderly patients with a history of dementia are at very high risk for developing delirium during hospitalization 
  • Delirium is an acute state of confusion that may manifest as a reduced level of consciousness, cognitive abnormalities, perceptual disturbances or emotional disturbances. 
  • Prevention involves addressing medical and enviornmental issues 
  • Urinary catheters are associated with an increased risk of delirium 
    • In the absence of a medical indication for a catheter (e.g. relieve urinary retention, monitor fluid status in acutely ill patients when this directly impacts medical treatment, manage patients with stage 3 or 4 pressure ulcers on buttocks), it should be removed
  • Benzodiazepines and diphenhydramine have sedating effects but can cause delirium in the elderly. 
    • Should be generally avoided unless a specific indication is presented, such as benzodiazepines for alcohol withdrawal or diphenhydramine for an allergic reaction
    • Alternative nonpharmacologic methods for relaxation include music, massage and meditation 
  • In appropriate selected patients with severe delirium, low dose haloperidol may lessen the severity and duration of delirium but it is not indicated for the prevention of delirium 
  • The use of antipsychotic medications in elderly patients with dementia is associated with an increased risk of death, primarily due to infections such as pneumonia.
  • Normal sleep wake cycle is essential

2

A 79-year-old woman was hospitalized 4 days ago after sustaining a right hip fracture in a fall. She underwent surgical repair with right hip replacement 3 days ago and did not fully awake from general anesthesia until 12 hours after extubation. As her alertness has increased, she has become increasingly agitated. The patient has a 4-year history of Alzheimer dementia. She has no other pertinent personal or family medical history.

Current medications are donepezil, memantine, and low-molecular-weight heparin.
On physical examination today, temperature is 37.2°C (99.0°F), blood pressure is 100/68 mm Hg, pulse rate is 100/min and regular, and respiration rate is 18/min. The patient can move all four limbs with guarding of the right lower limb. She is inattentive and disoriented to time and place and exhibits combativeness alternating with hypersomnolence. T he remainder of the neurologic examination is unremarkable, without evidence of focal findings or meningismus. Which of the following is the most likely diagnosis?


(A) Acute stroke
(B) Acute worsening of Alzheimer dementia
(C) Meningitis
(D) Postoperative delirium

D

The most likely diagnosis is postoperative delirium. Patients with delirium have acute, fluctuating mental status changes, with difficulty in focusing or maintaining attention and disorganized thinking. Based on psychomotor activity, there are four types of delirium: 1) hypoactive, 2) hyperactive, 3) mixed delirium with hypo- and hyperactivity, and 4) delirium without changes in psychomotor activity.

Delirium in elderly patients with chronic dementia usually results from an acute medical problem. In addition, patients with chronic dementia from almost any cause are at greater risk for delirium after surgery with general anesthesia.

This patient with a hip fracture who underwent right hip surgery with general anesthesia and did not recover from the anesthesia until 12 hours after extubation most likely has postoperative delirium. Such delirium is
highly predictable and often easily managed by identification and correction of any underlying disorders and the removal or reduction of contributing factors.


The possibility of acute stroke must be considered in a patient with a change in mental status. However, this patient has no clinical evidence of such an event, which makes this diagnosis extremely unlikely.


Surgery does not exacerbate Alzheimer dementia (or dementia of any other cause) but rather produces a superimposed delirium. Finally, dementia does not acutely worsenover several hours; the decline is steadily progressive.

This patient has had dementia for 4 years that has abruptly gotten worse after surgery. Although not impossible, meningitis is highly unlikely in this setting, especially given the absence of any supporting physical examination findings, including meningeal irritation.

KEY POINT:

Patients with chronic dementia are at a greater risk for delirium after surgery with general anesthesia 

3

A 75-year-old woman with a history of chronic obstructive pulmonary disease is evaluated in the intensive care unit for delirium. She had a median sternotomy and repair of an aortic dissection and was extubated uneventfully on postoperative day 4. Two days later she developed fluctuations in her mental status and inattention. While still in the intensive care unit, she became agitated, pulling at her lines, attempting to climb out of bed, and asking to leave the hospital. Her arterial blood gas values are normal.

The patient has no history of alcohol abuse or other substance abuse. T he use of frequent orientation cues, calm reassurance, and presence of family members has done little to reduce the patient's agitated behavior. Medical evaluation identifies no focal neurologic deficits and no evidence of infection or metabolic abnormality.

Which of the following is the most appropriate therapy?
(A) Diphenhydramine
(B) Haloperidol
(C) Lorazepam
(D) Propofol

B

The appropriate treatment for this patient is haloperidol. When supportive care is insufficient for prevention or treatment of delirium, symptom control with medication is occasionally necessary to prevent harm or to allow evaluation and treatment in the intensive care unit.

The recommended therapy for delirium is antipsychotic agents,
although no drugs are approved by the U.S. Food and Drug Administration for this indication.

Ongoing randomized, placebo-controlled trials are investigating different
management strategies for intensive care unit delirium. A recent systematic evidence review found no evidence of superiority for second-generation antipsychotics compared with haloperidol for delirium.

Haloperidol does not cause respiratory suppression, which is one reason that it is often used in patients with hypoventilatory respiratory failure
who require sedation. All antipsychotic agents, and especially "typical" agents such as haloperidol, pose a risk of torsades de pointes, extrapyramidal side effects, and the neuroleptic malignant syndrome.


Diphenhydramine and other antihistamines are a major risk factor for delirium, especially in older patients.

Lorazepam is actually deliriogenic, and its use in a delirious patient should be carefully re-evaluated, except perhaps in patients experiencing benzodiazepine withdrawal or delirium tremens. There is no evidence that propofol has any role in treating delirium.

KEY POINT

No single drug is approved for delirium but clinical practice guidelines recommend antipsychotic agents such as haloperidol. 

4

A 36-year-old woman is evaluated in the emergency department for a 3-day history of confusion and falls. The patient lives alone and is accompanied by her neighbor who says that the patient's symptoms seem to be getting worse. T he patient has a 10-year history of chronic alcoholism and has had recent weight loss due to diarrhea. She takes no medications.


On physical examination, temperature is 35.6°C (96.0°F), blood pressure is 142/76 mm Hg, pulse rate is 90/min, respiration rate is 14/min; BMI is 17.

Temporal muscle wasting, sunken supraclavicular fossae, and absent adipose stores are noted. Abdominal examination findings are normal. On neurologic examination, the patient is confused; she is unable to state the date and does not know the name of the hospital.

Marked horizontal nystagmus is noted. There is no nuchal rigidity or obvious motor weakness. Deep tendon reflexes are reduced, and plantar responses are flexor. The patient has a markedly ataxic gait.


Which of the following is the best initial management?
(A) Electroencephalography
(B) Haloperidol
(C) Thiamine
(D) Vancomycin, ampicillin, and ceftriaxone

C

This patient should receive thiamine now as the best initial management. She has Wernicke encephalopathy, a syndrome that results from deficiency of vitamin B1, an important coenzyme in several biochemical pathways of the brain.

Typical clinical manifestations of the disorder include mental status changes, nystagmus, ophthalmoplegia, and unsteady gait, all varying in intensity from minor to severe. When there is additional loss of memory with a confabulatory psychosis, the condition is described as Wernicke-Korsakoff syndrome.

The classical clinical triad of gait ataxia, encephalopathy, and ophthalmoplegia is seen in only 19% of affected patients.

Conditions associated with Wernicke encephalopathy include AIDS, alcohol abuse, cancer, hyperemesis gravidarum, prolonged total parenteral nutrition, postsurgical status (particularly bariatric surgeries), and glucose loading (in a predisposed patient).

Because Wernicke encephalopathy remains a clinical diagnosis, other neurologic disorders should be considered in this patient after thiamine has been administered.

Electroencephalography can help exclude a seizure disorder, such as nonconvulsive status epilepticus. Infections, including encephalitis and meningitis, for which intravenous administration of broad-spectrum antibiotic drugs (such as vancomycin, ampicillin, and ceftriaxone) may be appropriate also should be part of the differential diagnosis and can be excluded with cerebrospinal fluid analysis.

Haloperidol is not indicated in this patient, who is confused but has no apparent history of psychosis or agitation. Some patients with Wernicke encephalopathy do have agitation, hallucinations, and behavioral disturbances that can mimic an acute psychosis.

KEY POINT:

Wernicke Encephalopathy is caused by thiamine deficiency and may result in mental status changes, opthalmoplegia, nystagmus and unsteady gait; it is best treated with thiamine. 

 

5

A 73-year-old man is evaluated for confusion that began 2 weeks ago. He wanders aimlessly in the house, sometimes not recognizing his wife and mistaking the newspaper for his hat. He has visual hallucinations and believes he sees mice in the refrigerator. His medical history includes type 2 diabetes mellitus with painful peripheral neuropathy, coronary artery disease, depression, and heart failure.

Medications are glyburide, nortriptyline, digoxin, lorazepam, metoprolol, lisinopril, aspirin, and pravastatin. He does
not remember how long he has been taking these medications and if there have been any recent dosage changes.

The patient drinks alcohol only occasionally, usually wine
with a weekend meal.

On physical examination, the patient has asterixis. Vital signs are normal; oxygen saturation is normal with the patient breathing ambient air. He is inattentive and not oriented to time or place. His score on the Mini-Mental State Examination is 13/30 (28/30 6 months ago).

Results of laboratory studies, including electrolyte levels and liver
chemistry and renal function studies, are normal. An MRI of the brain is normal.


Which of the following is the most likely diagnosis?
(A) Alcohol hallucinosis
(B) Alzheimer dementia
(C) Depression
(D) Toxic encephalopathy (delirium)

D

The most likely diagnosis is toxic encephalopathy presenting as delirium. Delirium is an acute state of confusion that may manifest as a reduced level of consciousness,
cognitive abnormalities, perceptual disturbances, or emotional disturbances. The presence of asterixis suggests a toxic/metabolic cause of this patient's symptoms.

The patient is taking several medications that might impair cognition. A prime suspect is nortriptyline; this drug has anticholinergic properties and is likely to cause impairment in
patients with latent cholinergic deficiency (the elderly or patients with mild cognitive impairment, early dementia, or Parkinson disease).

Digoxin and the sedative-hypnotic lorazepam may also contribute to cognitive impairment.

Symptoms of alcohol withdrawal most typically occur after cessation of prolonged, sustained alcohol intake. However, most people drink in an episodic fashion, as illustrated mby this patient, and this pattern of drinking is not associated with sustained high blood alcohol levels that are requisite for withdrawal symptoms on abrupt cessation.


Alcoholic hallucinosis develops 12 to 24 hours after the last drink and resolve within 24 to 48 hours, a symptomatic period much shorter than that experienced by this
patient. Hallucinations are usually visual and are not associated with clouding of the sensorium and are not associated with asterixis.

In patients with early Alzheimer dementia, delirium is produced more readily by anticholinergic medications. Alzheimer dementia cannot be ruled out in this patient, but
establishing the diagnosis would require removal of the causative agent and re-evaluation after recovery. However, asterixis, a sign of metabolic encephalopathy, would be unusual in this setting and points strongly to a metabolic encephalopathy and not dementia.


Depression may cause chronic cognitive impairment (pseudodementia) and difficulty concentrating, but not asterixis and an altered level of consciousness.

KEY POINT

Cognitive impairment accompanied by fluctuating lethargy and inattention, hallucination and astreixis most likely result from a toxic encephalopathy. 

6

A 33-year-old woman is evaluated in the emergency department for paresthesia that began in the left face and spread over 30 minutes to the left arm and leg, clumsiness of
the left hand that began 30 minutes ago, and a subsequent right-sided throbbing headache and nausea.

This is the first time she has ever had such symptoms. She is otherwise
healthy but has a family history of migraine. Her only medication is a daily oral contraceptive pill.

On physical examination, temperature is normal, blood pressure is 140/82 mm Hg, pulse rate is 110/min, and respiration rate is 20/min. All other examination findings are
normal.


Results of laboratory studies and a CT scan of the head are also normal.


Which of the following is the most likely diagnosis?
(A) Migraine with aura
(B) Multiple sclerosis
(C) Partial complex seizure
(D) T ransient ischemic attack
(E) T rigeminal neuralgia

A

  • Patient is most likely experiencing a migraine with aura.
    • Approximately 15-20% of patients with migraine experience aura within 1 hour or during headache
    • Aura constitutes neurologic abnormalities including visual loss, hallucinations, tingling, weakness or confusion 
    • Aura is caused by spreading cortical depression - a wave of abnormal electrical discharge that travel slowly across the brain's surface and essentially a short-circuit the brain
    • Typically aura lasts a few minutes but may last up to 1 hour per symptom 
    • Additional clinical clues supporting a diagnosis of migraine are the patient's young age, the absence of vascular risk factors and the family history of migraine. 
  • In addition, the diffuseness of the patient's symptoms and their progression are more compatible with migraine than a focal vascular process such as a transient ischaemic attack. 
  • Although MS should be in the differential for neurological symptoms in a young woman - this patient is less likely to have MS than a migraine or stroke because her presentation was more acute than would be typical in MS, and MS is not typically associated with a throbbing headache
  • Partial seizures in which the patient maintains full awareness are classified as simple partial, whereas those involving an alteration of consciousness are classified as partial complex 
    • Partial seizures that originate in the temporal lobe often begin with an aura, which may consist of a feeling of deja vu, a rising epigastric sensation or autonomic disturbances
    • Automatisms such as lip smacking are also suggestive of partial complex seizures but a throbbing headache with nausea is not
  • Trigeminal neuralgia is associated with pain occuring in paraoxysms that involve one or more divisions of the trigeminal nerve 
    • Each episode may persist between a few seconds and 2 minutes, and pain may be intensely sharp or stabbing 
    • Behaviour such as face washing or touching, tooth brushing or chewing may trigger an event. 
    • The patient's symptoms are not consistent with trigeminal neuralgia 

KEY POINT 

Between 15% and 20% of patients with migraine experience aura within 1 hour of or during headache characterized by a variety of neurologic symptoms, including visual loss, hallucinations, numbness, tingling, weakness, or confusion.

 

 

 

7

A 24-year-old woman is evaluated in the office for headache that occurs once or twice a week. The pain is a constant pressure in the back of the head. She has no nausea and can continue to work during the headaches. She has had these headaches since age 13 years and notes that they now seem to be more frequent and associated with less sleep and increased stress. When treated with ibuprofen or acetaminophen, the headaches abate in 30 minutes; untreated, they last several hours. She typically uses headache medication four to six times per month.


On physical examination, vital signs are normal. All other findings from the general physical examination findings, including those from a neurologic evaluation, are normal.
Which of the following is the most likely diagnosis?


(A) Chronic daily headache
(B) Cluster headache
(C) Migraine headache without aura
(D) T ension-type headache

D

T his patient has tension-type headache, the most prevalent of all headache types. T ension-type headache is a dull, bilateral, or diffuse headache, often described as a pressure or squeezing sensation of mild to moderate intensity. There are no accompanying migraine features (nausea, emesis, photophobia, phonophobia), and the pain neither worsens with movement nor prohibits activity. The key feature that establishes a diagnosis of tension-type headache is the lack of disabling pain.


Chronic daily headache is a nonspecific term that refers to both primary (including migraine) and secondary headache disorders in which headache is present on more than 15 days per month for at least 3 months. Risk factors for chronic daily headache include obesity, a history of frequent headache (more than 1 per week), caffeine consumption, and overuse (>10 days per month) of acute headache medications, including analgesics, ergots, triptans, and opioids.

In addition, more than half of all patients with chronic daily headache have sleep disturbance and mood disorders, such as depression and anxiety. Chronic migraine and medication overuse headache overwhelmingly represent the most common and challenging of the chronic daily headache disorders in clinical practice.


Cluster headache is a painful, disabling headache that may be associated with autonomic symptoms such as tearing or rhinorrhea. Cluster headaches are typically unilateral and periorbital/temporal and are associated with at least one of the following features on the same side as the headache: conjunctival irritation/lacrimation, rhinorrhea/nasal congestion, eyelid edema, facial/forehead sweating, and miosis/ptosis. Cluster episodes usually last 6 to 8 weeks and remission periods usually last 2 to 6 months.


Migraine headache is a recurrent headache disorder that manifests in attacks lasting 4 to 72 hours. Typical characteristics of migraine are its unilateral location, pulsating
quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia. This patient does not
describe disability or any other features of migraine headache. A neurologic aura occurs in only one third of patients with migraine. The aura consists of such visual symptoms as perceptions of flashes of light, arcs of flashing light that often form a zigzag pattern, and an area of loss of vision surrounded by a normal field of vision.

 

KEY POINT

Tension-type headache is distinguished from migraine by the fact that patients with tension-type headache are not disabled and can carry out activities of daily living in a
normal, expedient manner.

 

8

A previously healthy 42-year-old woman is evaluated in the emergency department for the sudden onset of a severe occipital headache during defecation 8 hours ago,
followed by two episodes of vomiting. T he headache reached maximum intensity within seconds. She has never had a headache like this before. She reports no neck stiffness or neurologic symptoms. Her mother and two sisters have a history of migraine. On physical examination, temperature is 36.8°C (98.2°F), blood pressure is 148/88 mm Hg, pulse rate is 90/min, and respiration rate is 20/min. T he patient is in significant distress as a result of the pain. T here is no evidence of meningismus, papilledema, or focal neurologic signs. Which of the following is the most appropriate next step in management?


(A) CT angiography of the head and neck
(B) Lumbar puncture
(C) Noncontrast CT of the head
(D) Subcutaneous administration of sumatriptan

C

This patient should undergo noncontrast CT of the head. She has experienced a thunderclap headache, which is a severe and explosive headache that is maximal in intensity at or within 60 seconds of onset. Every thunderclap headache must be immediately evaluated to detect potentially catastrophic conditions, especially subarachnoid hemorrhage.

A negative CT scan of the head should be followed by a lumbar puncture to assess for blood in the cerebrospinal fluid not detected on the CT scan.

If both the CT scan of the head and lumbar puncture are negative, most of the other causes of thunderclap headache, such as an unruptured cerebral aneurysm, a carotid or vertebral artery dissection, cerebral venous sinus thrombosis, and reversible cerebral vasoconstriction syndrome, can be excluded by noninvasive angiography.

CT angiography of the head and neck can detect unruptured aneurysms as small as 3 mm in diameter and thus is adequate to exclude this diagnosis. Magnetic resonance angiography (MRA) would also be appropriate in this setting. Both CT angiography and MRA can be performed with a venous phase to exclude cerebral venous sinus thrombosis.

Given that most causes of thunderclap headache can be excluded by such noninvasive angiography, if prior cerebrospinal fluid analysis has shown no evidence of a subarachnoid hemorrhage, conventional cerebral angiography, in which a catheter is inserted into a large artery and advanced through the carotid artery, is unnecessary.

Because the patient may have intracerebral bleeding with mass effect, the performance of a lumbar puncture could result in brainstem herniation. T his is why the lumbar
puncture is performed only after a CT scan is performed. If the CT scan reveals intracerebral bleeding, a lumbar puncture is unnecessary.


Treatment with a vasoconstrictive drug, such as sumatriptan, would not be appropriate until the other causes of thunderclap headache have been excluded. Drugs with the
potential to constrict extracranial and intracranial cerebral vessels can precipitate or exacerbate the cerebral ischemia that may be associated with arterial dissection and
reversible cerebral vasoconstriction syndromes.

KEY POINT

A thunderclap headache is a potential neurologic emergency that must be immediately evaluated to detect potentially catastrophic conditions, especially subarachnoid
hemorrhage.

 

9

A 32-year-old woman is evaluated for a gradual increase in migraine frequency and severity over the past 6 months. Migraine attacks, which formerly occurred two or three
times each month, are now occurring approximately three times each week, with each attack lasting at least 12 hours. She has no other medial problems and takes only
almotriptan as needed for acute migraine.


On physical examination, vital signs and results of a general physical examination, including a neurologic examination, are normal.


An MRI of the brain shows no abnormalities.


Which of the following is the most appropriate treatment for this patient?
(A) Botulinum toxin
(B) Propranolol
(C) Nortriptyline
(D) Sertraline

B

The most appropriate treatment for this patient is propranolol. Prophylactic treatment should be considered in patients who experience 2 or more days of headache per
week. Nearly 40% of patients with migraine need preventive treatment. T here is evidence from at least two randomized, double-blind, placebo-controlled studies to support the use of eight drugs available in the United States (topiramate, valproic acid, amitriptyline, metoprolol, propranolol, timolol, and extract of the plant Butterbur root
Petasites hybridus) and two nonpharmacologic approaches (relaxation therapy and biofeedback).


Several randomized placebo-controlled trials have found no consistent, statistically significant benefits for botulinum toxin injection in the treatment of episodic migraine
headache. Similarly, there is no evidence of efficacy for nortriptyline or sertraline in the preventive treatment of migraine.

KEY POINT

Prophylactic medication should be initiated in patients with two or more migraine attacks per week.

 

10

A 75-year-old woman is evaluated in the emergency department after she was witnessed driving erratically on a city street. Initially, the patient was unable to answer any questions and had difficulty with her speech. Twenty minutes later, her speech was fluid, and, although she did not have any recollection of the past few hours' events, she was able to provide some details of her life, including her husband's name. When her husband arrived, the patient was able to recognize him, but 10 minutes later she did not
recognize him. No evidence of hallucinations or delusions exists.

The husband reports that the patient has had a gradual and progressive cognitive impairment over the previous 5 years for which she takes donepezil. She often awakens at night and roams about the house. She has chronic problems with her memory and managing activities of daily living.


Which of the following is the most likely diagnosis?
(A) Delirium
(B) Delirium superimposed on dementia
(C) Dementia
(D) Psychosis

B

This patient has delirium superimposed on dementia. Delirium is an altered level of alertness, often in connection with globally impaired cognition. It is typically
characterized by abrupt onset and may be associated with rapid fluctuations of alertness, attention, memory, and psychomotor activity (for example, lethargy or agitation).


Dementia is an acquired and persistent impairment of intellectual ability that compromises at least three areas of mental functioning: language, memory, visuospatial skills, emotion or personality, or cognition. Dementia typically has an insidious onset and is usually stable from day to day. Over the protracted course of dementia, many patients may experience an acute delirium, with confused and slurred speech, somnolence, agitation, tremulousness, unsteadiness, falls, and worsened incontinence.

Often, the delirium is from a superimposed illness (most commonly, a urinary tract infection or pneumonia), a medication error, an injury, or some other cause that must be sought and managed.

Psychosis encompasses delusions, hallucinations, disorganized speech, and disorganized or catatonic behavior. Impaired cognition, including decrements in short-term memory and attention, is also characteristic. This patient's sudden decline in the setting of dementia and absence of hallucinations and delusions is more likely to represent an acute delirium rather than an acute psychosis.

KEY POINT

Over the course of dementia, many patients may experience an acute delirium, with confused and slurred speech, somnolence, agitation, tremulousness, unsteadiness, falls, and worsened incontinence.

 

11

A 68-year-old man is evaluated for memory difficulty that, according to his wife, began insidiously 3 or 4 years earlier. He has difficulty remembering recent events. For
example, he forgets appointments and recent conversations and forgot that a close relative had recently died. He is no longer able to manage his own checkbook or operate his car without getting lost.

Medical history is otherwise unremarkable.

Physical examination findings, including vital signs, are normal. Mental status examination shows prominent memory loss and difficulty drawing a complex figure.
Laboratory studies show that a complete blood count and routine chemistries are normal. An MRI of the brain shows only mild cerebral atrophy.
Which of the following is the most likely diagnosis?


(A) Alzheimer dementia
(B) Creutzfeldt-Jakob disease
(C) Dementia with Lewy bodies
(D) Frontotemporal dementia

A

The most likely diagnosis is Alzheimer dementia. Dementia is a clinical syndrome in which multiple cognitive domains—including memory, language, spatial skills, judgment,
and problem solving—are impaired to a disabling degree. Some dementing illnesses can also affect noncognitive neurologic functions, such as gait. Diseases that cause
dementia often produce characteristic patterns of cognitive (and sometimes noncognitive) impairment that can aid diagnosis.

Alzheimer dementia is characterized by prominent memory loss, anomia, constructional apraxia, anosognosia (impaired recognition of illness), and variable degrees of personality change.

Creutzfeldt-Jakob disease (CJD) is the most common of the human prion diseases, with an annual incidence of less than 1 in 1,000,000 persons. T he main clinical features of
CJD are dementia that progresses over months (rather than years, as in this case) and startle myoclonus, although the latter may not be present early in the illness. Other
prominent features include visual or cerebellar disturbance, pyramidal/extrapyramidal dysfunction, and akinetic mutism.


Dementia with Lewy bodies is accompanied by parkinsonism, visual hallucinations, and fluctuating symptoms, none of which this patient has. T he characteristic cognitive
profile of dementia in patients with dementia with Lewy bodies includes impaired learning and attention, psychomotor slowing, constructional apraxia, and more profound visuospatial impairment but less memory impairment than in similarly staged patients with Alzheimer dementia.


Frontotemporal dementia is a progressive neuropsychiatric condition. Patients initially have behavioral and personality changes that range from apathy to social
disinhibition. They fail to change their clothes, brush their teeth, pursue their former interests, or initiate many of their previous activities that constituted a normal day.
T hey may fixate, in a seemingly idiosyncratic fashion, on a particular activity, such as going to the bathroom, sorting through a wallet, hoarding magazines, or watching
television. Some patients have greater disinhibition and emotional lability (crying or laughing inappropriately).

KEY POINT

Alzheimer dementia is characterized by prominent memory loss, anomia, constructional apraxia, anosognosia (impaired recognition of illness), and variable degrees of
personality change.

 

12

An 84-year-old man is evaluated for the gradual onset of progressive memory loss over the past 2 years. In the past 4 months, he has twice been unable to find his way home
after going to the local supermarket. His wife has assumed responsibility for the household finances after the patient overdrew their checking account for the third time. His mother had onset of Alzheimer dementia at age 79 years and died at age 86 years.

His only medication is a daily multivitamin.

On physical examination, vital signs are normal. His level of alertness, speech, and gait are normal. His score on the Folstein Mini-Mental State Examination is 24/30,
including 0/3 on the recall portion, which corresponds with a diagnosis of mild dementia.

Results of laboratory studies, including a complete blood count, serum vitamin B12 measurement, thyroid function tests, and a basic metabolic panel, are normal.
An unenhanced MRI of the brain shows no abnormalities.


Which of the following is the most appropriate treatment at this time?
(A) Donepezil
(B) Ginkgo biloba
(C) Quetiapine
(D) Sertraline

A

This patient should receive donepezil. T he Folstein Mini-Mental State Examination (MMSE) discriminates well between the major stages of dementia used for prognosis and management purposes. The MMSE score range of 21 to 25 corresponds to mild dementia, 11 to 20 to moderate dementia, and 0 to 10 to severe dementia. This patient has Alzheimer dementia and is at a mild stage of impairment.

The most appropriate medication with which to begin treatment is an acetylcholinesterase inhibitor of which there are currently three: donepezil, rivastigmine, and galantamine. In patients with mild, moderate, or severe Alzheimer dementia the use of acetylcholinesterase inhibitors are associated with a small but statistically significant improvement in performance of instrumental and functional activities of daily living and caregiver stress and may be associated with improved cognitive function compared with patients treated with placebo.

Treatment effects are small and not always apparent in practice. Cholinesterase
inhibitors are generally safe but have significantly more side effects than placebo, including diarrhea, nausea, vomiting, and symptomatic bradycardia. The gastrointestinal side effects are usually transient and mild.


Ginkgo biloba, although safe, has inconsistent and unconvincing evidence of benefit in the treatment of Alzheimer dementia. Also, there is no regulation regarding the
contents of herbal extracts, which allows for variability in dose strength and quality.
Quetiapine is an antipsychotic drug, and sertraline is an antidepressant agent. Although both can be used in patients with Alzheimer dementia, their use is limited to treatment
of behavioral symptoms of psychosis and depression, respectively, neither of which this patient has exhibited. However, if these medications are to be used in such patients,
the risks must first be carefully weighed against the benefits. Antipsychotics have limited effectiveness in treating behavioral problems and are associated with increased risk of death in patients with dementia.

KEY POINT

First-line pharmacotherapy for mild Alzheimer dementia is an acetylcholinesterase inhibitor.

13

An 81-year-old woman is evaluated in the office for increasing difficulty with activities of daily living, including dressing and feeding herself, over the past 6 months. She has
had gradually progressive cognitive decline for the past 5 years and now needs 24-hour help from a caregiver; Alzheimer dementia was previously diagnosed. Current
medications are donepezil and a daily multivitamin.


On physical examination, vital signs are normal. Her level of alertness, speech, and gait are normal. The patient scores only 12/30 on the Folstein Mini-Mental State Examination.


Results of a complete blood count, a basic metabolic panel, a serum vitamin B12 measurement, and thyroid function tests are normal.


A CT scan of the head without contrast shows no evidence of tumor, hemorrhage, or infarction.


Which of the following is the most appropriate next step in treatment?
(A) Add memantine
(B) Add quetiapine
(C) Add sertraline
(D) Stop donepezil

The most appropriate next step in treatment is the addition of memantine. This patient has Alzheimer dementia that is moderately advanced and now has difficulties with
basic activities of daily living. T he N-methyl-D-aspartate receptor antagonist memantine is the only drug approved by the U.S. Food and Drug Administration as first-line
treatment of moderate to advanced Alzheimer dementia. Memantine has been shown to improve cognition and global assessment of dementia, but while the changes have
been statistically significant, the clinical effect is not always evident. Memantine may improve quality-of-life measures, but these findings are not robust. Although evidence
is limited, there is some suggestion that the stepped approach of adding memantine to a regimen that includes a cholinesterase inhibitor (such as donepezil) results in a modest additional benefit over substituting memantine for the cholinesterase inhibitor.


Quetiapine is an antipsychotic medication and sertraline is an antidepressant agent. Although both drugs can be used in patients with Alzheimer dementia, their use is limited to the treatment of the behavioral symptoms of psychosis and depression, respectively, neither of which this patient has at this time. T he effectiveness of antipsychotic medications is on behavioral problems is limited and their use is associated with an increased risk of death in patients with dementia.


Discontinuing the donepezil taken by this patient without substituting another drug to manage her functional decline would not help slow or otherwise improve the course of
her disease.

KEY POINT

Memantine is a first line agent for treatment of moderate to advanced Alzheimer dementia

14

A 23-year-old man is evaluated in the emergency department because of the acute onset of uncontrolled head turning to one side and tongue protrusion. He was recently
diagnosed with schizophrenia and had haloperidol treatment started 3 days ago. He has no other medical problems and takes no additional medications.
On examination, he appears anxious; temperature is normal, blood pressure is 140/80 mm Hg, pulse rate is 100/min, and respiration rate is 14/min. His head is turned 40
degrees to the right, and he has sustained tongue protrusion. He is unable to turn his head back to midline or retract his tongue back into his mouth. T he remainder of his
neurologic examination is normal.


Which of the following is the most likely diagnosis?
(A) Drug-induced dystonia
(B) Huntington disease
(C) Idiopathic cervical dystonia
(D) Neuroleptic malignant syndrome

A

The most likely diagnosis is drug-induced dystonia. All medications that block D2 dopamine receptors can cause acute dystonic reactions. Dystonic movements are due to sustained contraction of agonist and antagonist muscles, which results in twisting and repetitive movements or sustained abnormal postures.

These movements most frequently affect the ocular muscles (oculogyric crisis) and the face, jaw, tongue, neck, and trunk. The limbs are rarely affected. Neuroleptic, antiemetic, and serotoninergic agents have been implicated, and symptoms usually occur within 5 days of initiation of the drug.

Treatment consists of parenteral diphenhydramine, benztropine mesylate, or
biperiden.

Cervical dystonia, formerly known as torticollis, is a focal dystonia that involves the cervical musculature and causes abnormal postures of the head, neck, and shoulders.
Quick, nonrhythmic, repetitive movements can also occur and can be mistaken for tremor. Cervical dystonia generally does not present so acutely and does not explain the sustained tongue protrusion.


Huntington disease is a hereditary, progressive, neurodegenerative disorder characterized by increasingly severe motor impairment, cognitive decline, and psychiatric symptoms. The associated movement disorder is chorea. Chorea refers to brief, irregular, nonstereotypical, nonrhythmic movements and can involve the extremities, head, trunk, and face. In addition to chorea, other motor symptoms include ataxia, dystonia, slurred speech, swallowing impairment, and myoclonus. Symptoms typically begin in the fourth and fifth decade. Huntington disease does not present acutely, as occurred in this patient.


T he neuroleptic malignant syndrome is a life-threatening disorder caused by an idiosyncratic reaction to neuroleptic tranquilizers (dopamine D2-receptor antagonists) and some antipsychotic drugs, of which haloperidol is the most common. Most patients with the syndrome develop muscle rigidity, hyperthermia, cognitive changes, autonomic
instability, diaphoresis, sialorrhea, seizures, arrhythmias, and rhabdomyolysis within 2 weeks of initiating the drug. The lack of fever and generalized muscle rigidity argue
strongly against this diagnosis.

KEY POINT

Neuroleptic, antiemetic, and serotoninergic agents have been implicated in acute dystonic reactions, which usually occur within 5 days of initiating the offending drug.

 

15

A 66-year-old man is evaluated in the office for a 6-month history of a resting right arm tremor. He says that his writing has gotten smaller during this time and that he has
had difficulty buttoning his dress shirts. T he patient reports no prior medical problems and is not aware of any neurologic problems in his family. He takes no medications.
Results of a general medical examination are normal. Neurologic examination shows a paucity of facial expression (hypomimia). Cranial nerve function is normal. Motor
examination shows normal strength but mild left upper limb rigidity and a 5-Hz resting tremor of the right upper limb. Deep tendon reflexes are normal, as are results of
sensory examination. T here is no truncal or appendicular ataxia. Diminished arm swing is noted bilaterally but is worse on the right. A tremor in the right upper limb is noted
during ambulation. Left upper limb alternating motion rates are diminished.
Which of the following is the most likely diagnosis?


(A) Cervical dystonia
(B) Essential tremor
(C) Huntington disease
(D) Parkinson disease

D

The most likely diagnosis is Parkinson disease. Parkinson disease remains a clinical diagnosis that is based on a cardinal set of clinical features, including resting tremor,
bradykinesia, rigidity, and postural instability; the tremor, bradykinesia, and rigidity are asymmetric. Sustained levodopa responsiveness is expected in Parkinson disease and
helps confirm the clinical diagnosis. Signs suggesting an alternative condition include symmetric symptoms or signs, early falls, rapid progression, poor or waning response to
levodopa, dementia, early autonomic failure, and ataxia.


T he patient's findings are not compatible with cervical dystonia, essential tremor, or Huntington disease. Cervical dystonia, formerly known as torticollis, is a focal dystonia
that involves the cervical musculature and causes abnormal postures of the head, neck, and shoulders. Quick, nonrhythmic, repetitive movements can also occur and can be
mistaken for tremor.


Essential tremor is characterized by an upper extremity high-frequency tremor, which is present with both limb movement and sustained posture of the involved extremities
and is absent at rest. The tremor is characteristically bilateral, but there can be mild to moderate asymmetry. Essential tremors typically improve with alcohol and worsen
with stress. Tremor amplitude over time generally increases and can be so severe as to interfere with writing, drinking, and other activities requiring smooth, coordinated
upper limb movements.


Huntington disease is a hereditary, progressive, neurodegenerative disorder characterized by increasingly severe motor impairment, cognitive decline, and psychiatric symptoms. In addition to chorea, other motor symptoms include ataxia, dystonia, slurred speech, swallowing impairment, and myoclonus. Various psychiatric symptoms, such as dysphoria, agitation, irritability, anxiety, apathy, disinhibition, delusions, and hallucinations, are commonly seen.

KEY POINT 

The diagnosis of Parkinson disease is based on a cardinal set of clinical features, including resting tremor, bradykinesia, rigidity, and postural instability.

 

16

A 62-year-old woman is evaluated for a 1-year history of tremor that affects both upper extremities. She says that her handwriting has become sloppier since she first noticed
the tremor and that she occasionally spills her morning coffee because of it. T he patient is otherwise healthy. Her mother, who died at age 79 years, had a similar tremor. Her only medication is a daily multivitamin.

On examination, she has a mild tremor in the upper extremities that is present with the arms extended and during finger-to-nose testing. No resting tremor is apparent.
Muscle tone and gait and limb coordination are normal.


Administration of which of the following drugs is the most appropriate treatment of this patient?


(A) Carbidopa-levodopa
(B) Pramipexole
(C) Propranolol
(D) Ropinirole

C

This patient should be treated with propranolol. She has a history and examination findings consistent with the presence of essential tremor. Essential tremor primarily
occurs when a patient maintains a posture, such as when the hands are outstretched. Essential tremor also may be present during movement, particularly postural adjustments.


Autosomal dominant transmission occurs in approximately half of patients with this condition. Essential tremor most commonly affects the upper extremities; however, the
legs, head, trunk, face, and vocal cords may be involved. Up to 15% of patients with essential tremor have major disability associated with this condition. Progression of
essential tremor is typically slow, with intermittent lengthy periods of stable symptoms. Features that may be predictive of a more severe essential tremor include a positive
family history of tremor, longer tremor duration, voice tremor, and unilateral tremor onset. Alcoholic beverage consumption suppresses symptoms in most patients with this condition.


Treatment options for essential tremor are often limited and frequently only partially effective. It has been estimated that 50% of patients with essential tremor have no
response to medical treatment. First-line medications used to treat essential tremor include propranolol, primidone, gabapentin, and topiramate. Propranolol is typically the
drug of choice in most patients with essential tremor because of its effectiveness, which has been established in multiple well-designed randomized clinical trials.
Essential tremor is distinguished from Parkinson disease by its lack of parkinsonian features, such as rigidity, bradykinesia, postural instability, and resting tremor.

Carbidopalevodopa can be an appropriate choice to treat Parkinson disease but is not useful in the treatment of essential tremor. Parkinsonian tremor is typically postural and kinetic (occurring with movement). Ropinirole and pramipexole are dopamine agonist medications used to treat Parkinson disease. Given the absence of any other signs of Parkinson disease, these medications are not indicated in this patient.

KEY POINT 

Propranolol is a first-line medication for essential tremor.

 

17

A 45-year-old woman with a history of heavy alcohol use is evaluated in the emergency department for a headache and altered mental status of 2-day's duration. One week
earlier she had a diarrheal illness that quickly resolved.


On physical examination, she is lethargic and unable to follow commands. T emperature is 38.8°C (101.9°F), blood pressure is 110/70 mm Hg, pulse rate is 105/min, and respiration rate is 22/min. Jolt accentuation of her headache is present.
T he leukocyte count is 14,500/μL (14.5 × 109/L) with 44% neutrophils, 42% bands, and 13% lymphocytes; platelet count is 146,000/μL (146 × 109/L). T he serum albumin is
2.6 mg/dL (26 g/L), the INR is 1.5, and the partial thromboplastin time is 44.1 seconds.
A noncontrast head CT scan is normal.

Cerebrospinal fluid (CSF) leukocyte count is 1500/μL (1500 × 106/L), with 60% neutrophils and 40% lymphocytes; glucose level is 5 mg/dL (0.3 mmol/L); and protein level is 328 mg/dL (3280 mg/L). T he CSF Gram stain reveals intracellular gram-positive bacilli.

Which of the following is the most likely diagnosis?


(A) Listeria monocytogenes meningitis
(B) Neisseria meningitidis meningitis
(C) Streptococcus pneumoniae meningitis
(D) Viral meningitis

A

T he most likely diagnosis is Listeria monocytogenes meningitis. Listeria monocytogenes is a gram-positive bacillus that can cause invasive disease in immunocompromised states, including alcoholism, extremes of age (neonates and those >50 years of age), malignancy, immunosuppression, diabetes mellitus, pregnancy, hepatic failure, chronic kidney disease, iron overload, collagen vascular disorders, use of antitumor necrosis factor-α agents, and HIV infection.

The gastrointestinal tract is the usual portal of entry with symptoms typically developing after consumption of contaminated cole slaw, raw vegetables, milk, cheese, processed meats, smoked seafood, and hot dogs, potentially resulting in a febrile gastroenteritis syndrome including diarrhea.

The organism can continue to multiply at refrigerator-level temperatures.
Neisseria meningitidis meningitis occurs primarily in children and young adults. T his illness is characterized by abrupt onset of flu-like illness including fever, headache, neck stiffness, altered mental status, intense myalgias, and rash. T he rash is often petechial, purpuric, or maculopapular.

The evolution of this infection can be rapid and fulminant, potentially resulting in septic shock and death. Invasive infections can be established by the growth of these gram-negative diplococci from CSF and blood cultures. Biopsy and culture of skin lesions may also reveal the organism.

Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults. T he clinical presentation of pneumococcal meningitis is not specific, but CSF and
possibly blood cultures will reveal growth of gram-positive diplococci.

Patients with viral meningitis can present with a syndrome similar to bacterial meningitis. However, CSF findings typically reveal a lymphocytic pleocytosis, a glucose level greater than 45 mg/dL (2.5 mmol/L), protein level less than 200 mg/dL (2000 mg/L), and a negative Gram stain. In the evaluation of patients with acute bacterial or viral meningitis, a CSF protein concentration greater than 220 mg/dL (2200 mg/L), CSF glucose less than 34 mg/dL (1.9 mmol/L), CSF blood-glucose ratio less than 0.2, CSF
leukocytes greater than 2000/μL (2000 × 106/L), or CSF neutrophils greater than 1180/μL (1180 × 106/L) are individual predictors of bacterial etiology with a 99% or greater
certainty.

KEY POINT

Listeria monocytogenes is a gram-positive bacillus that can cause invasive disease in immunocompromised patients, particularly those with cell-mediated immunodeficiency.

18

A 19-year-old-woman who is a sophomore in college is evaluated in December for a 24-hour history of fever and headache. She lives in a dormitory on campus. Her medical
history is unremarkable. She takes no medications and is up to date with all of her immunizations, including the meningococcal vaccine, which she received before entering college. Two cases of meningococcal serogroup B-associated meningitis have been reported on campus.

On physical examination, the patient appears ill. T emperature is 39.1°C (102.4°F), blood pressure is 95/50 mm Hg, pulse rate is 125/min, and respiration rate is 25/min. A
purpuric rash is appreciated over both lower extremities. Neck stiffness is present and jolt accentuation of the headache is elicited.


A noncontrast CT scan of the head is normal. T he leukocyte count is 19,500/μL (19.5 × 109/L) with 87% neutrophils and 13% lymphocytes; platelet count is 110,000/μL
(110 × 109/L). Cerebrospinal fluid (CSF) leukocyte count is 2000/μL (2000 × 106/L), with 95% neutrophils and 5% lymphocytes; glucose level is 20 mg/dL (1.1 mmol/L); and
protein level is 100 mg/dL (1000 mg/L). T he CSF Gram stain reveals gram-negative diplococci.


Which of the following is the most likely diagnosis?
(A) Neisseria meningitidis meningitis
(B) Rocky Mountain spotted fever
(C) Streptococcus pneumoniae meningitis
(D) Vibrio vulnificus meningitis

This patient's illness, physical examination, and CSF profile are consistent with N. meningitidis meningitis. T his infection most commonly occurs in children and young
adults. T he Centers for Disease Control and Prevention (CDC) recommends routine immunization with the meningococcal vaccine, which protects against serogroups A, C,
Y, and W-135, but not serogroup B, the causative agent in as many as one third of U.S. cases and the recent cause of other cases of meningitis on campus.
Rocky Mountain spotted fever (RMSF) can manifest as headache, fever, myalgia, abdominal pain, and rash. The purpuric rash typically develops 3 to 4 days after the onset of constitutional symptoms and begins on the wrists and ankles before spreading centripetally.

Thrombocytopenia, a relative leukopenia, and elevated transaminases may
provide clues to the diagnosis, particularly if the patient resides or has traveled to areas where RMSF-associated American dog ticks are present. T hese ticks transmit
infection in spring and early summer but not in December, which is when this patient became ill.


Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults. T he clinical presentation of pneumococcal meningitis is not specific, but CSF and,
possibly, blood cultures will reveal gram-positive (not gram-negative) diplococci.
Vibrio vulnificus is a gram-negative bacillus that can cause septicemia, wound infection, and, rarely, gastroenteritis. Wound infection typically occurs by inoculation through
the skin, and septicemia and gastroenteritis occurs after ingestion of raw or undercooked shellfish. Invasive disease typically occurs in immunocompromised hosts,
particularly those with liver disease.

These infections are more common in summer months when warmer sea water temperatures support the growth of this organism. Meningitis is not characteristic of infection with this organism.

KEY POINT

The N. meningitidis vaccine does not provide protection against N. meningitidis serogroup B meningitis.

19

A 20-year-old female college student is evaluated in December because of a 12-hour history of fever, myalgia, headache, and a rash. She takes no medications.
On physical examination, the patient appears ill. T emperature is 38.8°C (101.8°F), blood pressure is 90/45 mm Hg, pulse rate is 112/min, and respiration rate is 24/min. A
petechial rash, most prominent on the lower extremities, is present. Passive neck flexion causes discomfort.


Leukocyte count 10,500/μL (10.5 × 109/L)
Platelet count 105,000/μL (105 × 109/L)
Blood urea nitrogen 30 mg/dL (10.7 mmol/L)
Creatinine 2.5 mg/dL (221 μmol/L)
Bicarbonate 15 meq/L (15 mmol/L)
Lumbar puncture is performed. Opening pressure is 300 mm H2O. Cerebrospinal fluid leukocyte count is 1250/μL (1250 × 106/L) with 95% polymorphonuclear cells. Protein
level is 100 mg/dL (1000 mg/L) and glucose level is 40 mg/dL (2.2 mmol/L).

No organisms are seen Gram stain.


Which of the following is the most likely diagnosis?


(A) Listeria monocytogenes meningitis
(B) Neisseria meningitidis meningitis
(C) Rocky Mountain spotted fever
(D) Viral meningitis

B

T his patient's illness is most consistent with Neisseria meningitidis (meningococcal) infection, which is characterized by the sudden onset of fever, myalgia, headache, and
rash in a previously healthy patient. Early in its course, meningococcal disease may be indistinguishable from other common viral illnesses; however, the rapidity with which
the disease worsens (often over hours) and progresses to septic shock differentiates it from these other illnesses. A petechial rash is most common and may coalesce to form
purpuric lesions. T he diagnosis is established on the basis of clinical presentation and confirmed with blood and cerebrospinal fluid (CSF) cultures.


Meningitis caused by Listeria monocytogenes is associated with extremes of age (neonates and persons age >50 years), alcoholism, malignancy, immunosuppression, diabetes mellitus, hepatic failure, renal failure, iron overload, collagen vascular disorders, and HIV infection.

The clinical presentation of Listeria meningoencephalitis ranges from a
mild illness with fever and mental status changes to a fulminant course with coma. It is not associated with a rash.


T he classic presentation of Rocky Mountain spotted fever is a severe headache, fever, myalgia, and arthralgia. Thrombocytopenia and acute kidney injury can occur. A
maculopapular rash develops 3 to 5 days later, beginning on the wrists and ankles and potentially involving the palms and soles. Rocky Mountain spotted fever is transmitted
by the American dog tick in the spring and early summer, which is inconsistent with the timing of this patient's presentation.


Viral meningitis can present with fever, headache, stiff neck, and photophobia and may be associated with a maculopapular eruption. However, acute viral meningitis is rarely
associated with thrombocytopenia, metabolic acidosis, and acute kidney injury. Finally, CSF findings typically show a lymphocyte-predominant leukocytosis (leukocyte count
<1000/μL [1000 × 106/L]), a glucose level greater than 45 mg/dL (2.5 mmol/L), a protein level less than 200 mg/dL (2000 mg/L), and a Gram stain negative for organisms.

KEY POINT 

Meningococcal infection should be considered in the differential diagnosis of any previously healthy patient who presents with acute-onset fever, headache, rash, and myalgia

 

20

A 65-year-old woman is evaluated for a 1-day history of fever, headache, and altered mental status. Medical history includes type 2 diabetes mellitus and hypertension treated with glipizide and hydrochlorothiazide. She has no allergies.


On physical examination, the patient is confused. T emperature is 38.9°C (102.0°F), blood pressure is 104/66 mm Hg, pulse rate is 100/min, and respiration rate is 20/min.
Her neck is supple, and she has no rashes.


T he leukocyte count is 19,000/μL (19 × 109/L); platelet count, 90,000/μL (90 × 109/L); and plasma glucose level, 120 mg/dL (6.7 mmol/L). A non-contrast-enhanced CT
scan of the head is normal. Cerebrospinal fluid (CSF) analysis shows a leukocyte count of 1300/μL (1300 × 106/L) with 98% neutrophils, a glucose level of 20 mg/dL (1.1
mmol/L), and a protein level of 200 mg/dL (2000 mg/L). CSF Gram stain results are negative for any organisms.

Dexamethasone is begun.


Which of the following antimicrobial regimens should now be initiated?


(A) Ceftriaxone
(B) Penicillin G
(C) Vancomycin, ampicillin, and ceftriaxone
(D) Vancomycin plus ceftriaxone
(E) Vancomycin plus trimethoprim-sulfamethoxazole

C

This patient most likely has bacterial meningitis and requires therapy with vancomycin, ampicillin, and ceftriaxone. Bacterial meningitis in adults is characterized by fever,
headache, nuchal rigidity, and signs of cerebral dysfunction. In elderly patients, such as this one, insidious onset with lethargy or obtundation and variable signs of meningeal
irritation may be present, particularly in the setting of diabetes mellitus.

This patient's symptoms and cerebrospinal fluid results are consistent with acute bacterial meningitis. The most likely etiologic agents are Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis, and aerobic gram-negative bacilli. Pending culture results and results of in vitro susceptibility testing, empiric treatment with antimicrobial therapy consisting of vancomycin, ampicillin, and ceftriaxone for infection caused by penicillinresistant pneumococci and L. monocytogenes is necessary.

Administration of adjunctive dexamethasone should be strongly considered in patients with acute bacterial meningitis because clinical trials have established the benefit of adjunctive dexamethasone on adverse outcomes and death in adults with suspected or proven S. pneumoniae meningitis.

Intravenous ceftriaxone or intravenous penicillin G alone might not provide adequate cerebrospinal fluid levels for treatment of penicillin-resistant S. pneumoniae. Most
infectious disease experts would recommend vancomycin plus ceftriaxone for the treatment of penicillin-resistant S. pneumoniae; however, this combination would not
adequately treat meningitis caused by L. monocytogenes, which requires the addition of ampicillin. T rimethoprim-sulfamethoxazole does treat Listeria meningitis, but the
combination of vancomycin plus trimethoprim-sulfamethoxazole would be potentially inadequate treatment for S. pneumoniae meningitis.

KEY POINT 

Empiric therapy of acute bacterial meningitis in an older adult should include a third-generation cephalosporin, vancomycin, and ampicillin.

 

21

A 75-year-old woman with an 8-hour history of aphasia and right-sided weakness is admitted to the hospital. She has a 35-year history of hypertension treated with
chlorthalidone and a 10-year history of hyperlipidemia treated with simvastatin. Her medical history is otherwise unremarkable, and she takes no other medications.
On physical examination she is afebrile, blood pressure is 150/90 mm Hg, pulse rate is 88/min, and respiration rate is 12/min. Oxygen saturation on pulse oximetry is 96%.
She is alert but has expressive aphasia and dense right hemiplegia. No carotid bruits are heard, and the cardiopulmonary examination is normal.
Coagulation studies, serum electrolytes, and comprehensive metabolic panel are normal. T he electrocardiogram shows sinus rhythm without evidence of ischemia. T he CT
scan shows no signs of hemorrhage. Echocardiography is normal with an estimated ejection fraction of 54%.


Which of the following is the most appropriate next step in this patient's hospital management?


(A) Bed rest for the next 48 hours
(B) Bed rest for the next week
(C) Begin a mechanical soft diet
(D) Begin physical and occupational therapy

T he patient should begin physical and occupational therapy. A total of 40% of patients who have a stroke retain moderate functional impairment, and 15% to 30% have
severe disability. Current evidence points to the benefits of early mobilization and graded exercise in promoting more complete recovery from stroke and in preventing
complications such as decubitus ulcers, deconditioning, and loss of function. For this reason, early mobilization with physical and occupational therapy and a variety of
approaches is recommended. Confining the patient to bed for 48 hours or longer is associated with a greater incidence of preventable complications and less than optimal
functional recovery.


On admission to a hospital ward, a patient with stroke should be given nothing by mouth until a swallowing assessment is conducted. In a patient with significant language disturbance, there is concern for the possibility of aspiration and complications from it; the patient should not be prescribed a diet until a swallowing assessment has been conducted to determine safety in swallowing.

The American Heart Association/American Stroke Association recommends a water swallow test performed at the bedside by a trained observer as the best bedside predictor of aspiration. A prospective study of the water swallow test demonstrated a significantly decreased risk of aspiration pneumonia of 2.4% versus 5.4% in patients who were not screened.

KEY POINT 

Early mobilization of stroke patients is recommended as a strategy for reducing complications.

 

22

A 74-year-old man is brought to the emergency department by ambulance 1 hour after he had an acute witnessed onset of aphasia and right hemiparesis. He has a history of
hypertension. His current medications are hydrochlorothiazide and metoprolol.
On physical examination, blood pressure is 178/94 mm Hg and pulse rate is 80/min and regular. Neurologic examination confirms nonfluent aphasia, a right pronator drift, a
right leg drift, and an extensor plantar response on the right.
An electrocardiogram obtained on the patient's arrival at the emergency department documents sinus rhythm. A CT scan of the head obtained within 1 hour of his arrival
reveals early ischemic changes. Which of the following is the best treatment?


(A) Aspirin
(B) Continuous intravenous heparin
(C) Intravenous labetalol
(D) Intravenous recombinant tissue plasminogen activator

T his patient should receive intravenous recombinant tissue plasminogen activator (rtPA). He has clinical symptoms and signs and radiologic evidence of an acute left
hemispheric stroke. T he probable mechanism of stroke is ischemic infarction, given the results of the head CT scan. He was brought to the emergency department within 1
hour of the witnessed onset of stroke symptoms, and his evaluation is completed 1 hour later. He does not appear to have any clinical, radiologic, or laboratory
contraindication to receiving the preferred treatment of intravenous rtPA, and he can receive it within the recommended window of 3 hours from stroke onset.


Aspirin is indicated for acute ischemic stroke in patients who are not eligible for rtPA. For patients with acute stroke who are eligible for thrombolysis, aspirin should be
withheld in the emergency department and for 24 hours after rtPA administration.

Although long-term anticoagulation is an effective treatment for prevention of cardioembolic stroke in patients with atrial fibrillation, acute anticoagulation with heparin has not been shown to be beneficial in patients with acute ischemic stroke.


Elevated blood pressure is common at the time of initial stroke presentation, even among patients without chronic hypertension. Rapid lowering of blood pressure may
further impair cerebral blood flow and worsen the ischemic injury. Elevated blood pressure often will resolve spontaneously or improve gradually during the first few days after a stroke.

The threshold for acute blood pressure lowering in patients with acute stroke who are eligible for thrombolysis is 185/110 mm Hg. In such a setting, preferred agents
include intravenous infusions of labetalol or nicardipine. Because this patient's blood pressure is already below that threshold, there is no indication for intravenous use of
labetalol at this time.

KEY POINT 

The preferred treatment of ischemic stroke is intravenous recombinant tissue plasminogen activator if it can be administered within 3 hours from stroke onset.

 

 

23

A 74-year-old woman is admitted to the hospital after sustaining a severe left hemispheric ischemic stroke while alone at home. She was last known to be normal 8 hours ago.

The patient has hypertension for which she takes enalapril but no history of ischemic heart disease or heart failure.

On physical examination, blood pressure is 190/105 mm Hg, pulse rate is 80/min, and respiration rate is 16/min. The patient has right hemiparesis, right facial droop,
aphasia, and dysarthria. The remainder of the physical examination, including the cardiovascular examination, is normal.


Results of laboratory studies, including serum creatinine level, are normal.
A CT scan shows ischemic changes that occupy most of the left middle cerebral artery territory. An electrocardiogram and chest radiograph show normal findings.


Which of the following is the most appropriate treatment of her hypertension at this time?
(A) Intravenous labetalol
(B) Intravenous nicardipine
(C) Oral nifedipine
(D) No treatment at this time

D

There is no urgent need to treat hypertension in an uncomplicated ischemic stroke. For uncomplicated ischemic strokes in patients without concurrent acute coronary artery
disease or heart failure, consensus exists that antihypertensive medications, such as intravenous labetalol or nicardipine, should be withheld if the systolic blood pressure is less than 220 mm Hg or the diastolic blood pressure is less than 120 mm Hg, unless there are other manifestations of end-organ damage. T his patient's systolic and diastolic blood pressure levels are below these limits and there is no urgent need to treat hypertension, such as aortic dissection, myocardial infarction, or heart failure.

Many such patients have spontaneous declines in blood pressure during the first 24 hours after stroke onset.

Oral nifedipine is an inappropriate treatment for this patient not only because of its antihypertensive qualities, but also because of its route of administration. Given the
severity of her stroke deficits, in particular the dysarthria, she should receive nothing by mouth until a swallowing evaluation is carried out because of the high risk of
aspiration.

Notably, the patient is not eligible for recombinant tissue plasminogen activator therapy because the time interval between now and her previous symptom-free state is more
than 3 hours. Aspirin (160 to 325 mg/d) administered within 48 hours of stroke onset results in a small but significant reduction in the risk for recurrent stroke during the first
2 weeks after the stroke and improves outcome at 6 months. Therefore, aspirin is recommended as initial therapy for most patients with acute stroke. However, aspirin
should not be administered for at least 24 hours after administration of thrombolytics.

KEY POINT

For uncomplicated ischemic strokes in patients without concurrent acute coronary artery disease, aortic dissection, or heart failure, antihypertensive medications should be withheld if the systolic blood pressure is less than 220 mm Hg or the diastolic blood pressure is less than 120 mm Hg.

24

A 73-year-old retired woman is evaluated in the emergency department 6 hours after experiencing the sudden, explosive onset of a severe headache. T he patient has
hypertension controlled by diet and exercise. T here is no relevant family history. She has no allergies and takes no over-the-counter medications.

On physical examination, she is in obvious distress from the headache. T emperature is normal, blood pressure is 179/108 mm Hg, pulse rate is 119/min, and respiration rate is
14/min. T here is no meningismus. Neurologic examination shows a normal level of consciousness and no focal abnormalities.


Results of laboratory studies and a CT scan of the head without contrast are normal.
Which of the following is the most appropriate next management step?


(A) Lumbar puncture
(B) MRI of the brain
(C) Observation
(D) Sumatriptan, orally

A

This patient should have a lumbar puncture. A thunderclap headache is a severe and explosive headache that is maximal in intensity at or within 60 seconds of onset. CT
scanning is the first test to be conducted in a patient with thunderclap headache in whom a subarachnoid hemorrhage is suspected; a ruptured intracranial aneurysm is the most serious cause of such headaches.

The ability to detect subarachnoid hemorrhage is dependent on the amount of subarachnoid blood, the interval after symptom onset, the resolution of the scanner, and the skills of the radiologist. On the day of the hemorrhage, extravasated blood will be present in more than 95% of patients, but in the following days, this proportion falls sharply.

If an initial CT scan of the head reveals nothing, a lumbar puncture should be performed next in patients with this presentation. The finding of xanthochromia or gross hemorrhage is diagnostic for subarachnoid hemorrhage. Subsequent angiography (CT or MRI) can confirm the presence of a ruptured aneurysm in patients with a positive lumbar puncture.


Early in the diagnosis of subarachnoid hemorrhage, brain MRI is no more accurate than head CT . There is nothing to be gained by performing brain MRI in this patient with
negative findings on a head CT scan.

In patients with an initial subarachnoid hemorrhage, there is substantial risk of rebleeding (2% per day for the first month). Rebleeding is associated with high mortality.

The treatment of subarachnoid hemorrhage involves localizing the aneurysm with cerebral angiography and securing it to prevent subsequent bleeding. T raditionally, surgical clipping within 72 hours of onset has been recommended. Aneurysms also may be treated endovascularly by filling them with metallic coils and promoting localized
thrombosis within the aneurysm to obliterate it from the cerebral circulation. Hospital observation as the sole management option for this patient places her at increased risk
for rebleeding and death.

Treatment with sumatriptan is indicated for migraine headache. All of the triptans promote vasoconstriction and block pain pathways in the brainstem. They are
contraindicated in patients with stroke and uncontrolled hypertension. The use of sumatriptan in this patient who has a high likelihood of subarachnoid hemorrhage is
contraindicated.

KEY POINT

A lumbar puncture with subsequent cerebrospinal fluid analysis is necessary in any patient with thunderclap headache and normal findings on a CT scan to fully evaluate a
possible subarachnoid hemorrhage.

25

A 34-year-old woman is evaluated in the office for right-sided facial paralysis that she noticed on awakening 1 hour ago. She has a 10-pack-year smoking history. Personal
and family medical history is noncontributory. Her only medication is a daily oral contraceptive.


On physical examination, vital signs are normal. Limb strength, reflexes, and tone are normal bilaterally. Findings from a sensory examination, which included her face, are
also normal. When asked to raise her eyebrows, the patient does not elevate the right side. When asked to shut her eyes, she cannot close the right one but the globe rotates
upward, partially covering the iris. When asked to smile, the patient does not move the right side of her face.


Which of the following is the most likely diagnosis?
(A) Graves ophthalmopathy
(B) Left cerebral infarction
(C) Right facial nerve (Bell) palsy
(D) Right trigeminal neuralgia

This patient's physical examination findings most strongly suggest right facial nerve (Bell) palsy. T he precise cause of Bell palsy is not known, and it is still considered an
idiopathic disorder. Research strongly suggests it may be the result of herpes simplex virus infection of the facial nerve. Bell palsy is not considered contagious. The seventh
cranial nerve innervates all muscles of facial expression (the mimetic muscles).

Any cause of a complete facial neuropathy will therefore impair the entire hemiface, including the forehead corrugators typically spared by cerebral lesions. Bell phenomenon describes the reflexive rolling upwards of the globe during eye closure.

When a normal patient is asked to close the eyes, forced eyelid opening will reveal this phenomenon, as will the selective paralysis of the orbicularis oculi due to a facial neuropathy.

Facial neuropathies will otherwise spare the extraocular muscles that govern globe movement. Because Bell palsy is a diagnosis of exclusion, clinicians need to make every effort to exclude other identifiable causes of facial paralysis, such as Lyme disease, HIV disease, acute and chronic otitis media, cholesteatoma, and multiple sclerosis. Other common causes of acute peripheral facial paralysis will often have findings on history or physical examination that suggest the correct diagnosis.
Graves ophthalmopathy can cause proptosis or extraocular muscle edema with consequent eye movement abnormalities but is not associated with the facial hemiparalysis typical of facial nerve (Bell) palsy.


Cerebral infarction, brain hemorrhage, or any structural brain lesion can cause weakness of the lower face but not of the forehead because the bilateral cortical representation of the midline forehead spares the forehead corrugators. Some limb or sensory abnormality is also often, but not universally, observed in the setting of cerebral infarction; no such abnormality was observed in this patient. T herefore, despite her cerebrovascular risk factors of oral contraception and cigarette smoking, this patient is unlikely to have had a cerebral infarction.

The trigeminal nerve provides sensation, not movement, to the muscles of facial expression, so trigeminal neuralgia is not a likely diagnosis in this patient with normal
sensation.

KEY POINT 

Any cause of a complete facial neuropathy will impair the entire hemiface, including the forehead muscles.

26

A 53-year-old woman is evaluated in the office for a 1-week history of paresthesias that began symmetrically in the feet and progressed to involve the distal legs and, more
recently, the hands. She is unsteady when walking, has lower limb weakness, and has difficulty going upstairs. T he patient has no history of pain or bowel or bladder
impairment. Personal and family medical history is noncontributory, and she takes no medications.


On physical examination, vital signs are normal. Weakness of distal lower extremity muscles is noted, with stocking-glove sensory loss and areflexia. Deep tendon reflexes
are absent. Plantar responses are normal, and gait is unsteady. No sensory level is present across the thorax. Mental status, language, and cranial nerve function are normal.


Complete blood count results, erythrocyte sedimentation rate, serum creatinine and creatine kinase levels, and liver chemistry test results are normal.
A chest radiograph shows no abnormalities.


Which of the following is the most likely diagnosis?
(A) Amyotrophic lateral sclerosis
(B) Diabetic neuropathy
(C) Guillain-Barre syndrome
(D) Myelopathy

This patient has a rapidly progressive disorder affecting the peripheral nervous system, most compatible with a clinical diagnosis of Guillain-Barre syndrome. Patients with
Guillain-Barre syndrome typically develop paresthesias distally in the lower extremities that are followed by limb weakness and gait unsteadiness. In addition to sensory loss
and limb weakness, deep tendon reflexes are characteristically absent or markedly reduced. T he diagnosis is confirmed by electromyography, which usually shows a
demyelinating polyradiculoneuropathy. Cerebrospinal fluid (CSF) analysis characteristically shows albuminocytologic dissociation, whereby the spinal fluid cell count is normal but the spinal fluid protein level is elevated. CSF analysis may also yield normal results early in the course of the disease.

However, a normal CSF cell count is useful in excluding other infectious conditions, such as polyradiculoneuropathies associated with HIV and cytomegalovirus infection, infection due to West Nile virus, and carcinomatous or lymphomatous nerve root infiltration. By definition, symptoms in patients with Guillain-Barre syndrome peak within 4 weeks of onset.

Intravenous immune globulin and plasma exchange are equally efficacious in the treatment of Guillain-Barre syndrome.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of the anterior horn cells of the spinal cord and presents with both upper and lower motor neuron signs,
including hyperreflexia, spasticity, and an extensor plantar response (upper motor neuron signs) and weakness, muscle atrophy, and fasciculations (lower motor neuron signs).

The patient's findings are not compatible with ALS. Diabetes mellitus most commonly causes a slowly progressive, distal, symmetric sensorimotor polyneuropathy.

Autonomic dysfunction frequently is associated with diabetic
neuropathy and is characterized by symptoms of impotence, orthostatic hypotension, and gastroparesis.

The symptoms of a distal symmetric sensorimotor neuropathy may
be the first clinical manifestation, but the rapidly progressive course of this patient's neuropathy rules out diabetic neuropathy.

A spinal cord lesion (myelopathy) would be an unlikely cause of the symptoms noted on clinical examination. The absence of bowel or bladder impairment, the lack of a
sensory level across the thorax, and the upper and lower limb areflexia argue against a central nervous system disorder affecting the spinal cord.

KEY POINT 

Guillain-Barre syndrome is a disorder associated with rapidly progressive extremity weakness, paresthesias, and areflexia.

27

A 35-year-old woman is evaluated in the office for a 5-month history of right-hand numbness and tingling. She says that these symptoms involve the entire hand, seem to be worse when she drives or holds a book or newspaper, and have been awakening her at night. She reports no history of neck pain or hand weakness. Personal and family
medical histories are noncontributory, and she takes no medication.
General physical examination reveals no abnormalities. Neurologic examination shows normal strength but sensory loss in the first three digits and the radial half of the
fourth digit in the right hand.


Which of the following is the most likely diagnosis?
(A) Carpal tunnel syndrome
(B) de Quervain tenosynovitis
(C) Ganglion cysts
(D) Ulnar nerve compression (Guyon tunnel syndrome)

A

This patient most likely has carpal tunnel syndrome. Carpal tunnel syndrome refers to median nerve compression at the wrist in the carpal tunnel. Symptoms include aching
wrist pain with sparing of the palm, numbness and tingling in the median nerve sensory distribution of the fingers, and weakness of the thenar muscles. The paresthesias are
often worse at night or when holding a book or steering a car.


de Quervain tenosynovitis is an exercise-related injury associated with knitting and sports involving extensive wrist action. Tenderness may be elicited in the anatomic
snuffbox (the extensor pollicis brevis and abductor pollicis longus tendons). Pain elicited by flexing the thumb into the palm, closing the fingers over the thumb, and then
bending the wrist in the ulnar direction (Finkelstein test) is confirmatory.


Ganglion cysts are synovia-filled cysts arising from joints or tendon sheaths that typically appear on the dorsal hand or ventral wrist. T hey can cause pain and compress
other structures. T he absence of cystic structures on the dorsal and ventral wrist and the distribution of the patient's pain eliminate this diagnosis.


Ulnar nerve compression at the wrist is also called Guyon tunnel syndrome, because the entrapment occurs where the ulnar nerve transverses the Guyon tunnel between the
pisiform and hamate bones on the anterolateral side of the wrist, and cyclist's palsy, because the compression of the ulnar nerve often occurs as the hand rests on the
handlebars. However, the ulnar nerve can be compressed by muscles, tumors (lipomas), scar tissue, synovial cysts, or any other internal structure that passes close to the tunnel.

The presentation is similar to that of carpal tunnel syndrome, but with symptoms and signs on the ulnar distribution of the hand.

KEY POINT

Symptoms of carpal tunnel syndrome include aching wrist pain with sparing of the palm, numbness and tingling in the median nerve sensory distribution of the fingers, and
weakness of the thenar muscles.

 

28

An obese 66-year-old man has had increasing pain and tingling in his feet for more than 8 months. T he patient has not seen a physician in more than 20 years. His only
other symptoms are fatigue, blurry vision, and nocturia. He takes no medications.
On examination, vital signs are normal; BMI is 30. Results of skin, ophthalmoscopic, cardiopulmonary, and abdominal examinations are normal. On neurologic examination,
he has sensory loss in the feet and distal legs. Muscle strength and reflexes are normal.
Which of the following tests will most likely diagnose the cause of the neurologic findings?


(A) Creatine kinase level
(B) Fasting blood glucose level
(C) Lumbar puncture and cerebrospinal fluid analysis
(D) Sural nerve biopsy

The fasting blood glucose level will most likely provide a diagnosis for the patient's neurologic findings. Diabetic neuropathy involves injury to sensory, motor, and
autonomic nerves. Loss of sensation in a "stocking-glove" distribution that is associated with paresthesias or painful dysesthesias is the most common presentation of this
condition. Loss of sensation in the lower extremities is typical and plays a major part in the development of foot ulcerations, which can lead to limb loss. No direct treatment
for diabetic neuropathy exists, other than to improve glycemic control. Pharmacologic therapy, however, may help symptoms.

Partial serotonin and norepinephrine reuptake inhibitors (duloxetine), tricyclic antidepressants (amitriptyline), and various antiseizure medications (gabapentin, phenytoin, carbamazepine) are frequently used to treat the pain associated with this condition.

Obtaining a creatine kinase level would be appropriate in someone with suspected primary muscle disease, but this diagnosis is not likely in this patient, given the presence of neuropathic pain and sensory loss without muscle weakness. Lumbar puncture and cerebrospinal fluid examination should be considered in patients with acute, severe, or rapidly progressive neuropathy and in those with a demyelinating neuropathy; in these situations, lumbar puncture may help to confirm the presence of an inflammatory process in the cerebrospinal fluid but would not result in a specific diagnosis.

Multiple sclerosis, the most common example of a demyelinating disorder, is characterized by discrete subacute episodes of neurologic dysfunction that progress over days to weeks, plateau, and then improve partially or completely over subsequent days to months.

Sural nerve biopsy is most typically performed in patients with suspected vasculitis or amyloidosis. Patients with vasculitic neuropathy typically have a systemic illness with
manifestations in other organs, including the skin, lungs, and kidneys; vasculitic neuropathy as the sole presenting feature of a systemic illness would be very unusual.

Like vasculitis, amyloidosis is a systemic disease with manifestations involving many organ systems and would not likely present with symptoms confined to the peripheral
nervous system of the lower extremities.

KEY POINT 

Loss of sensation in a "stocking-glove" distribution that is associated with paresthesias or painful dysesthesias is the most common presentation of diabetic neuropathy.