MKSAP Flashcards
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
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
A
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
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.
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.
