The following cases and commentary, which involve diagnostic testing, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Elderly man with syncope and back pain
A 78-year-old man is evaluated in the emergency department following a syncopal episode. He was at home when he suddenly developed severe back pain and he then collapsed. On the way to the hospital, he regained consciousness. He has no history of syncope prior to this episode.
On physical examination, temperature is normal, blood pressure is 148/80 mm Hg in the right arm and 125/70 mm Hg in the left arm, pulse is 65/min and regular, and respiration rate is 12/min. The patient is awake and in significant pain. Cardiac examination shows a normal S1 and S2 with no murmur. The lungs are clear. Neurologic examination shows left facial droop and right hemiparesis. Right upper extremity pulse is 2+; left upper extremity pulse is 1+.
Complete blood count, electrolytes, and cardiac enzymes are normal. Electrocardiogram shows sinus rhythm with no acute ST-T wave changes. A chest radiograph shows no infiltrates, effusions, or mediastinal widening.
Which of the following is the most appropriate diagnostic test?
A. Carotid duplex ultrasound
B. CT angiography of the chest and aorta
C. MRI of the brain
D. Transthoracic echocardiogram
Case 2: Transverse myelitis and severe paraparesis
A 33-year-old woman is admitted to the hospital for evaluation and treatment of new-onset transverse myelitis that has resulted in severe paraparesis. The patient also has had two recent episodes of optic neuritis. She reports no systemic symptoms, such as fever, rash, arthralgias, or pulmonary problems. She has a history of hypothyroidism but no family history of any neurologic disorders. Her only medication is levothyroxine.
Vital signs are normal on physical examination. Visual acuity is 20/200 in the right eye and 20/30 in the left. Bilateral optic disc pallor and severe spastic paraparesis with loss of all sensory modalities below T10 are noted. The patient requires bilateral assistance to ambulate 5 meters.
Results of laboratory studies are normal, including a complete blood count, liver chemistry and renal function tests, and measurement of erythrocyte sedimentation rate and C-reactive protein level. The antinuclear antibody is positive, but anti–double-stranded DNA and anti–SSA/SSB antibodies are negative. Analysis of the cerebrospinal fluid shows a normal IgG index and no abnormalities in oligoclonal banding.
An MRI of the spinal cord reveals an increased signal extending over five vertebral segments with patchy gadolinium enhancement. An MRI of the brain shows no abnormalities.
Which of the following is the most appropriate next diagnostic test?
B. Serum antineutrophil cytoplasmic antibody test
C. Serum neuromyelitis optica (NMO)-IgG autoantibody test
D. Testing of visual evoked potentials
Case 3: Pneumonia and acute abdominal pain
A 67-year-old woman is evaluated in the hospital for acute abdominal pain. She was admitted for community-acquired pneumonia, and her condition was improving on therapy with antibiotics and fluids. However, on day 3 she developed acute abdominal pain associated with nausea. Her medical history includes a 7-year history of peripheral arterial disease, type 2 diabetes mellitus, hyperlipidemia, and an episode of diverticulitis 2 years ago. Her medications are pravastatin, aspirin, dipyridamole, and metformin.
On physical examination, she appears anxious and in distress; temperature is 38.3°C (101.0°F), the blood pressure is 170/100 mm Hg, the pulse rate is 120/min, and the respiration rate is 25/min. She rates her pain as 10 out of 10. She has diffuse abdominal tenderness, more pronounced in the left lower quadrant with rebound tenderness.
Which of the following is the most appropriate next diagnostic test in this patient?
B. CT scan of the abdomen
C. Left pelvic ultrasonography
D. Leukocyte count and differential
E. Supine and upright abdominal radiographs
Case 4: Confusion and headaches followed by seizure
A 71-year-old woman is admitted to the hospital after having a witnessed morning seizure. She has a 3-week history of increasing gait unsteadiness and daytime somnolence and a 3-month history of progressive confusion and headaches; she typically naps 3 hours daily. Six month ago, the patient had fungal pneumonia caused by Coccidioides immitis infection. She has a 20-year history of type 2 diabetes mellitus and no relevant family history. Current medications are insulin glargine, metformin, and intravenous fosphenytoin (started on hospital admission).
On physical examination, temperature is 38.2°C (100.8°F), blood pressure is 116/70 mm Hg, pulse rate is 96/min, respiration rate is 18/min, and BMI is 32. The patient is somnolent but arouses to voice. She is disoriented to time and place and scores only 12/30 on the Folstein Mini–Mental State Examination. There is mild diffuse symmetric hyperreflexia, and plantar responses are extensor bilaterally; the patient moves all four limbs equally. There is no papilledema.
Leukocyte count is 14,000/µL (14 × 109/L), and erythrocyte sedimentation rate is 64 mm/h. All other results of laboratory studies, including measurement of serum vitamin B12 level, a basic metabolic panel, thyroid function tests, and urinalysis, are normal.
A noncontrast CT scan of the head shows mildly dilated ventricles. An electroencephalogram shows moderately severe diffuse slowing but no epileptiform activity.
Which of the following is the most appropriate next diagnostic test for this patient?
A. Apolipoprotein E genotyping
B. Cerebral CT angiography
D. Lumbar puncture and cerebrospinal fluid analysis
E. Repeat electroencephalography
Case 5: Progressive dull chest pressure
A 45-year-old woman is admitted to the hospital for evaluation of a 6-week history of progressive, dull chest pressure associated with mild dyspnea and nausea. At onset, the chest pain occurred during physical exertion (housework) and was relieved by rest within 5 minutes. For the past several days, the patient has had similar episodes that occurred with minimal activity, such as walking, and also at rest, including an episode this morning, which she described as 8/10 in severity of the pain and lasted for 10 to 15 minutes. The chest discomfort is not pleuritic or positional and is not related to eating. She has hypertension, treated for the past 6 years, and systemic lupus erythematosus for 24 years, with a history of pericarditis, arthritis, and a photosensitive facial rash. Her medications include prednisone, hydroxychloroquine, aspirin, and enalapril.
On physical examination, she is afebrile, blood pressure is 132/78 mm Hg, pulse is 86/min, and respiration rate is 18/min. Oxygen saturation on ambient air is 98%. BMI is 25. Her lungs are clear to auscultation. Estimated central venous pressure is normal; there is no Kussmaul sign or hepatojugular reflux. Cardiac auscultation reveals regular rhythm with normal S1 and S2 and no murmur, rub, or gallop.
Laboratory studies show: erythrocyte sedimentation rate, 39 mm/h; creatine kinase, 65 U/L; creatine kinase MB fraction, 3%; and troponin T, 0.04 ng/mL (0.04 µg/L). Electrocardiogram demonstrates sinus rhythm, with a rate of 92/min. There are symmetric T-wave inversions in leads V1 through V4; there is no ST-segment depression or elevation. Chest radiograph shows a normal cardiac silhouette with no infiltrate or edema.
Which of the following diagnostic tests is most appropriate at this time?
A. Coronary angiography
B. Exercise stress echocardiogram
C. High-sensitivity C-reactive protein level
D. Transthoracic echocardiography
Answers and commentary
Correct answer: B. CT angiography of the chest and aorta.
This patient presents with syncope, back pain, neurologic deficits, and blood pressure and pulse differentials between the upper extremities. The most likely diagnosis is acute aortic dissection; therefore, diagnostic evaluation of the aorta is indicated. Patients who present with syncope associated with severe chest or back pain should be presumed to have an aortic dissection or pulmonary embolism until proven otherwise.
Patients with dissection of the thoracic aorta typically present with abrupt onset of severe, sharp, or tearing pain of the back or chest. Decreased cardiac output associated with aortic dissection may cause syncope, and an associated carotid or coronary artery occlusion or dissection may cause stroke or myocardial infarction, respectively. A pulse differential is one of the most useful findings (positive likelihood ratio = 5.7). Focal neurologic deficits can be present in a minority of patients but are highly suggestive of aortic dissection. Although a widened mediastinum on chest radiograph is a common initial finding, it is absent in at least 40% of patients and thus lacks sufficient sensitivity to rule out aortic dissection.
When aortic dissection is suspected, imaging is indicated. The most common imaging studies to diagnose aortic dissection include MRI or CT angiography of the chest and transesophageal echocardiography, all of which have excellent test characteristics (sensitivity and specificity 98%-100%).
A patient presenting with neurologic deficits in the distribution of the left internal carotid artery may well have had a thrombotic or embolic cerebrovascular accident. However, a stroke would not explain the severe back pain or the blood pressure and pulse differentials noted in this patient. Therefore, an MRI of the brain and carotid duplex ultrasound are not the best initial diagnostic studies.
Transthoracic echocardiography may be helpful in diagnosing ascending dissections, but its overall test characteristics (sensitivity of 59%-85% and specificity of 93%-96%) make it a poor diagnostic test for aortic dissection compared with MRI, CT, or transesophageal echocardiography.
- Patients who present with syncope associated with chest pain should be presumed to have an aortic dissection or pulmonary embolism as the cause of their chest pain until proven otherwise.
Correct answer: C. Serum neuromyelitis optica (NMO)-IgG autoantibody test.
This patient very likely has neuromyelitis optica (NMO), a severe demyelinating disease of the central nervous system that is distinct from multiple sclerosis (MS). She should be tested for the autoantibody marker NMO-IgG (anti–aquaporin-4). NMO occurs more commonly in nonwhite persons, is often associated with serum autoantibodies or other autoimmune diseases, and has a predilection for the optic nerves and spinal cord with relative sparing of the brain. This patient's spinal cord lesion is also characteristic of NMO because it extends over more than three vertebral segments; cord lesions in typical MS are usually less than two segments in length. The finding of the NMO-IgG autoantibody marker is approximately 75% sensitive and more than 90% specific for NMO. Differentiating between NMO and MS as early in the disease course as possible is important because the prognosis and treatment of the two diseases are different. NMO is a more severe disease treated with immunosuppressive drugs, whereas MS is initially treated with immunomodulatory therapies, such as β-interferon and glatiramer acetate.
There are no symptoms or signs of peripheral nerve or muscle involvement in this patient. Therefore, electromyography is not indicated.
Cytoplasmic and perinuclear-staining antinuclear cytoplasmic antibodies (ANCAs) may be detected in patients with systemic vasculitis. Although vasculitis is a rare cause of transverse myelitis, it is very unlikely to explain multiple episodes of optic neuritis and transverse myelitis in the absence of systemic symptoms.
Visual evoked potential testing will confirm the known involvement of the optic nerves in this patient but will not otherwise aid diagnosis and so is unnecessary.
- Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system that is distinct from multiple sclerosis and associated with the autoantibody marker NMO-IgG (anti–aquaporin-4).
Correct answer: E. Supine and upright abdominal radiographs.
The term acute abdomen refers to sudden and severe abdominal pain less than 24 hours in duration. Rebound tenderness and severe diffuse abdominal pain are suggestive of an acute abdomen with peritonitis. Pain that is acute in onset generally points to acute inflammatory, infectious, or ischemic causes. Upper abdominal pain is usually of gastric, hepatobiliary, or pancreatic origin, whereas pain in the lower abdomen originates from the hindgut and genitourinary organs. All patients with abdominal pain should have measurements of serum amylase and lipase to evaluate for acute pancreatitis.
Although an abdominal CT scan is usually necessary for a definitive diagnosis of acute abdominal pain, initial screening with supine and upright abdominal radiographs to look for air-fluid levels, suggestive of a bowel obstruction, and free peritoneal air, suggestive of a perforated viscus, should be done.
Chest radiograph and supine and upright abdominal radiographs should be obtained in every patient with significant acute abdominal pain to exclude bowel obstruction or perforation or intrathoracic processes (for example, pneumonia, pneumothorax, or aortic dissection) that can present as abdominal pain. This patient's history of diverticulitis suggests possible diverticular rupture. An elevated leukocyte count may suggest an intra-abdominal infection or abscess, but the onset is usually not abrupt. Based on its relatively low cost, convenience, and noninvasive nature, ultrasonography has been utilized as a diagnostic tool for acute diverticulitis. However, the examination remains operator-dependent and in the absence of well-designed prospective comparative studies, it remains a second-line diagnostic tool. Colonoscopy is not indicated in a patient with acute peritoneal signs and has the potential to worsen the situation by causing a perforation of inflamed bowel wall.
- Although an abdominal CT scan is usually necessary for a definitive diagnosis of acute abdominal pain, initial screening with supine and upright abdominal radiographs to look for air-fluid levels, suggestive of a bowel obstruction, and free peritoneal air, suggestive of a perforated viscus, should be done.
Correct answer: D. Lumbar puncture and cerebrospinal fluid analysis.
This patient has fungal meningitis due to Coccidioides immitis infection and thus should undergo lumbar puncture and subsequent cerebrospinal fluid analysis to detect the potentially reversible cause of her cognitive and other impairments. A 71-year-old woman with declining cognition may seem an obvious candidate for Alzheimer dementia, but any pathologic process affecting the brain can impair cognition. The symptoms described—subacute onset, headache, fluctuating level of alertness, fever, peripheral blood markers of inflammation, and mildly dilated ventricles on the CT scan—should all provoke suspicion of an infectious, inflammatory, or otherwise reversible cause rather than a degenerative one. The scenario described is of a patient with encephalopathy whose clinical, laboratory, and radiologic findings suggest some type of meningitic process. Because of the time course, an atypical infectious agent, such as fungal meningitis, should be considered, especially in light of her history of fungal pneumonia in the past. Other causes of chronic or subacute meningoencephalitis, such as autoimmune encephalopathy and carcinomatous meningitis, need also be considered.
Apolipoprotein E (APOE) genotyping will not provide useful information in this patient. Specifically, discovering if this patient carries the APOE e4 allele and thus has an elevated risk for Alzheimer dementia would not help explain or treat her current symptoms and signs but could delay finding the probable infectious, inflammatory, or related cause of her symptoms.
Although cerebral vasculitis can produce a clinical picture similar to this one, cerebral CT angiography is not sufficiently sensitive to diagnose vasculitis of the central nervous system. Making that diagnosis usually requires either invasive intra-arterial angiography or brain and leptomeningeal biopsy. The more usual application of cerebral CT angiography is in the assessment of acute stroke, of which there is no evidence in this patient.
The finding of mildly dilated ventricles on this patient's CT scan is not relevant to her signs and symptoms, so further confirmatory testing by cisternography is unlikely to reveal the underlying cause of her findings.
It is highly unlikely that a repeat electroencephalogram (EEG) will give much further insight into this patient's condition, given that the EEG obtained during the patient's symptomatic period showed no epileptiform activity. Seizures are a potential complicating feature of any meningitic or encephalitic process, but the occurrence of a seizure or EEG finding of occasional interictal epileptiform activity will not provide any additional information about the underlying cause of this patient's symptoms.
- Cerebrospinal fluid analysis should be considered in any patient with potentially reversible causes of impaired cognition, particularly if meningoencephalitis is suspected.
Correct answer: A. Coronary angiography.
The patient is a young woman with hypertension but no other traditional risk factors for coronary heart disease. However, she has a long history of systemic lupus erythematosus, which is an autoimmune inflammatory disease. Inflammation is a possible mechanism of vascular endothelial injury and may promote the development of atherosclerotic disease. Coronary artery disease is a major cause of premature death in patients with systemic lupus erythematosus, and atherosclerosis has been found to develop prematurely in this disease. In addition, persons with systemic lupus erythematosus may have other cardiac involvement including pericardial disease (acute or recurrent pericarditis, pericardial effusion and tamponade, constrictive pericarditis), myocarditis, cardiomyopathy, and valvular regurgitation due to noninfective endocarditis.
The patient's presenting symptoms are typical of unstable angina: the pain is new in onset, progressive, and occurs with minimal activity or at rest. In light of the severity of her symptoms, electrocardiographic abnormalities consistent with ischemia (probably in the distribution of the proximal left anterior descending coronary artery), and the indeterminate troponin T level, coronary angiography and possible revascularization are indicated. Exercise stress echocardiography should not be performed because of her unstable symptoms and her high pretest probability of coronary artery disease.
High-sensitivity C-reactive protein level, a nonspecific biomarker of inflammation, would likely be abnormally elevated in this patient with systemic lupus erythematosus and is not diagnostically useful in this setting. In fact, this test, which is often used to assess ongoing inflammation as a predictor of future risk of cardiovascular events, is not valid in the setting of recent infection or chronic inflammatory conditions.
Transthoracic echocardiography is not indicated for this patient. Although she has a history of pericarditis, her symptoms, examination findings, and electrocardiographic findings are not consistent with either recurrent pericarditis or constrictive pericarditis. Acute pericarditis is associated with sharp, pleuritic, positional chest pain and diffuse ST-segment and T-wave abnormalities not in a distribution consistent with a coronary artery territory.
- Chronic inflammatory conditions, such as systemic lupus erythematosus, may be associated with cardiac complications, including premature atherosclerotic coronary artery disease.