Question: An 8-year-old boy is brought to the emergency department by his parents for evaluation. He has had headache and fever for the last 2 days, and this morning he was confused and had difficulty answering questions. He also developed a rash this morning. He recently returned from summer camp. He has no significant medical history and takes no medications. His temperature is 104°F (40°C), pulse is 120/min, blood pressure is 105/60 mmHg, and respirations are 22/min. On exam, flexion of the neck causes flexion of the hips and knees. Fundoscopic exam reveals no papilledema. Examination of the patient's rash is shown in Figure A. Which of the following is the most appropriate next step in management?

Lumbar puncture, ceftriaxone, vancomycin, and methylprednisolone

Vancomycin, ceftriaxone, and dexamethasone

Answer: Lumbar puncture, ceftriaxone, vancomycin, and methylprednisolone

Explanation:
This patient with fever, headache, signs of meningeal irritation, and a purpuric rash likely has bacterial meningitis. The most appropriate initial step in management is a lumbar puncture as well as ceftriaxone, vancomycin, and methylprednisolone.

Meningitis classically presents with fever, neck stiffness or headache, and altered mental status. Specific physical exam findings that can suggest the diagnosis include meningeal signs such as a positive Kernig sign (inability to extend the knee while the hip is flexed) and Brudzinski sign (flexion of the neck results in flexion of lower extremities). Common causative agents include Streptococcus pneumoniae and Neisseria meningitidis. The latter of which is associated with the purpuric rash seen in this patient. The best initial step in management is a lumbar puncture followed promptly by IV broad spectrum antibiotics. Once the diagnosis/infectious agent is confirmed, the antibiotic agents can be refined. Other early steps in management include early blood cultures and fluid resuscitation. Steroids should be given in the setting of suspected Waterhouse-Friderichsen syndrome and concern for adrenal failure.

Linder et. al review meningococcal meningitis. They discuss the pathophysiology, clinical manifestations, and diagnosis. They describe the association of purpuric rash with meningococcal infection, and note that this is indicative of disseminated intravascular coagulation.

Figure A. demonstrates a purpuric rash over the lower extremities, which is classically associated with meningococcal meningitis. However, this can occur with meningitis or bacteremia from other infectious agents, as it is indicative of disseminated intravascular coagulation.

Incorrect Answers:
Answer A: Blood and urine cultures would be appropriate initial management for a fever of unknown origin and in this patient. Early antibiotics must be given as well to reduce mortality and improve outcomes.

Answer C: MRI brain would not be appropriate in this setting. While CNS imaging is sometimes indicated prior to lumbar puncture if signs of increased intracranial pressure such as papilledema are present, CT imaging is typically preferred. Time required to obtain MR imaging is prohibitive and would delay definitive care for this patient.

Answer D: Vancomycin and ceftriaxone are an appropriate initial antibiotic regimen for meningitis in children and adults. However, steroids are often added empirically. Lumbar puncture should be performed prior to administration of antibiotics (if possible) to avoid sterilization of the CSF.

Answer E: Vancomycin, ceftriaxone, and prednisone are an appropriate initial regimen for meningitis in adults. Steroids have been shown to reduce inflammation and prevent neurologic sequelae. However, lumbar puncture should be performed prior to administration of antibiotics if possible to avoid sterilization of the CSF. Also, IV steroids are preferred rather than oral in ill patients.

Bullet Summary:
The best initial step in management for meningitis is a lumbar puncture followed by broad-spectrum antibiotics and steroids.


Question: A 72-year-old man presents to his primary care physician with weakness. He has felt very weak every morning with his symptoms persisting throughout the day. He notes minor improvement when he rides his bike but otherwise has not noticed any change in his symptoms with rest or ibuprofen use. The patient has lost 12 pounds recently and has had a chronic cough. The patient lives alone and drinks 7 alcoholic beverages per day and smokes 1-2 packs of cigarettes per day for the past 40 years. His temperature is 99.5°F (37.5°C), blood pressure is 177/108 mmHg, pulse is 93/min, respirations are 17/min, and oxygen saturation is 92% on room air. A chest radiograph is ordered as seen in Figure A. Which of the following diagnostic tests would most likely elucidate the cause of this patient's weakness?

Answer: Electromyography

Explanation:
This patient who presents with weakness that improves with activity in the setting of a lung mass most likely has Lambert-Eaton syndrome. The most appropriate diagnostic test to confirm this syndrome is electromyography.

Small cell lung cancer presents with fatigue, weight loss, cough, and a coin lesion on chest radiograph typically in a smoker. A common paraneoplastic syndrome in small cell lung cancer is Lambert-Eaton syndrome which presents with muscle weakness that improves with activity and worsens with rest. Activity improves symptoms due to accumulation of calcium with exercise which allows for acetylcholine release. This occurs secondary to antibodies against presynaptic calcium channels which decrease acetylcholine release. The diagnosis of Lambert Eaton syndrome can be confirmed with electromyography. Treatment includes addressing the underlying lung tumor.

Kesner et al. review the diagnosis and etiology of Lambert-Eaton syndrome. They discuss how this disease is associated with lung cancer. They recommend making the diagnosis using electrophysiologic studies.

Figure/Illustration A is a chest radiograph with a coin lesion in the left lung field (red circle). This finding is suggestive of small cell lung cancer.

Incorrect Answers:
Answer A: Blood laboratory tests could assess for multidrug resistance 1 protein (MDR-1 aka P-glycoprotein or ABCB1) which predicts resistance to chemotherapy for small cell lung cancer; however, it would not further elucidate this patient's muscle weakness.

Answers 2 & 4: CT scan of the chest and lung biopsy would further elucidate this patient's small cell lung cancer; however, it would not explain his weakness that improves with activity. In the setting of an elderly smoker with fatigue and weight loss and a coin lesion, the diagnosis of lung cancer is essentially established.

Answer E: Muscle biopsy would be the most accurate diagnostic test for dermatomyositis, polymyositis, and inclusion body myositis; however, it would not assess for conditions such as myasthenia gravis and Lambert-Eaton syndrome.

Bullet Summary:
Electromyography is the diagnostic test of choice for Lambert-Eaton syndrome.


Question: A 10-year-old girl is admitted to the medical floor for a respiratory infection. The patient lives in a foster home and has been admitted many times. Since birth, the patient has had repeated episodes of pain/pressure over her frontal sinuses and a chronic cough that produces mucus. She was recently treated with amoxicillin for an infection. The patient is in the 25th percentile for height and weight which has been constant since birth. Her guardians state that the patient has normal bowel movements and has been gaining weight appropriately. The patient has a history of tricuspid stenosis. She also recently had magnetic resonance imaging (MRI) of her chest which demonstrated dilation of her airways. Her temperature is 99.5°F (37.5°C), blood pressure is 90/58 mmHg, pulse is 120/min, respirations are 18/min, and oxygen saturation is 94% on room air. Physical exam is notable for bruises along the patient's shins which the guardians state are from playing soccer. The rest of the exam is deferred because the patient starts crying. Which of the following findings is associated with this patient's most likely underlying diagnosis?

Diastolic murmur best heard along the right lower sternal border

Answer: Diastolic murmur best heard along the right lower sternal border

Explanation:
This patient is presenting with recurrent sinus infections suggestive of Kartagener syndrome. Dextrocardia is a common feature in this pathology, which results in right-sided heart sounds or a diastolic murmur best heard along the right lower sternal border for this patient's tricuspid stenosis.

Kartagener syndrome (primary ciliary dyskinesia) occurs secondary to a genetic defect in a patient's cilia. This results in a clinical picture of recurrent sinusitis, recurrent upper respiratory infections, bronchiectasis, and situs inversus (all major organs are a mirror image of where they should be). A physical exam will reveal right-sided heart sounds and a chest radiograph will demonstrate dextrocardia. Treatment is with respiratory support, assistance with mucociliary clearance, and treatment of infections.

Leigh et al. review the evidence regarding the manifestations of Kartagener syndrome. They discuss how about 50% of patients have situs inversus. They recommend respiratory support for these patients given the overlap with other mucociliary clearance disorders such as cystic fibrosis.

Incorrect Answers:
Answer B: Hypocalcemia would be seen in DiGeorge syndrome which presents with CATCH-22 (Cleft palate/lip, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia, and chromosome 22 deletion). Treatment is with calcium repletion, surgical treatment of cardiac defects, and treatment of infections.

Answer C: Increased chloride in the patient's sweat describes cystic fibrosis which would present with weight loss, failure to thrive, and fatty/foul-smelling stools. Treatment is with respiratory support, assistance with mucociliary clearance, and treatment of infections.

Answer D: Repeat sinus infections secondary to seasonal allergies describe sinusitis, which may be present in this patient but does not explain the entire clinical picture. Treatment is with antihistamines.

Answer E: Social withdrawal and avoidance of eye contact describe child abuse which seems unlikely in this case given the constellation of symptoms that suggest Kartagener syndrome.

Bullet Summary:
Kartagener syndrome presents with recurrent sinusitis, bronchiectasis, and situs inversus.


Question: A 55-year-old man presents to the emergency department with chest pain and shortness of breath. He has a medical history of hypertension, diabetes, and obesity. His temperature is 98.6°F (37.0°C), blood pressure is 177/118 mmHg, pulse is 127/min, respirations are 11/min, and oxygen saturation is 98% on room air. An ECG is performed and notable for ST elevation in leads II, III, and aVF. The patient is treated appropriately and transferred to the medical floor. On the 2nd day of his hospitalization, the patient has abdominal pain. His serum lipase is 272 U/L and his creatinine is 1.6 mg/dL. A physical exam is notable for the finding in Figure A. He is requesting pain medication for his abdominal pain. Which of the following is the most likely underlying diagnosis?

Answer: Cholesterol embolism

Explanation:
This patient is presenting with abdominal pain and livedo reticularis after a catheterization procedure. These symptoms are suggestive of a cholesterol embolism.

A cholesterol embolism typically presents after any vascular procedure due to a dislodged cholesterol emboli. Symptoms include livedo reticularis, gastrointestinal problems such as mesenteric ischemia or pancreatitis, and acute kidney injury. Patients who have undergone cardiac catheterization should be monitored for the development of this complication. Treatment is centered around treating the current complications, often using supportive therapy as they self-resolve. In addition, patients should be treated carefully to prevent recurrent embolism.

Maningding and Kermani review the evidence regarding the presentation of vasculitis mimics. They discuss how cholesterol embolism can cause diverse systemic symptoms and livedo reticularis. They recommend carefully considering the history of each patient.

Figure/Illustration A is a clinical photograph demonstrating a netlike reticular bluish discoloration of the skin (red circle). These findings are consistent with livedo reticularis.

Incorrect Answers:
Answer B: Heart failure and reinfarction could present with renal failure but would likely present with other symptoms of heart failure as well (pulmonary crackles, edema, and jugular venous distension). Treatment of a repeat infarct involves catheterization and fluid overload involves volume optimization.

Answer C: Medication side effects could explain this patient's livedo reticularis, but the drugs that may cause this (certain antivirals and amantadine) would not have been given to this patient. These medications also typically do not cause abdominal pain.

Answer D: Pancreatitis presents with abdominal pain and an elevated lipase; however, it is not the underlying pathology for this patient's presentation but rather is a complication of the cholesterol embolism. Treatment of pancreatitis is with gastrointestinal rest and fluid support.

Answer E: Renal failure is another complication in this patient secondary to the cholesterol embolism as revealed by the elevated creatinine, but is not the underlying pathology. Treatment is with renal replacement therapy if renal function does not return promptly.

Bullet Summary:
Cholesterol embolism presents after a vascular procedure with livedo reticularis, gastrointestinal complications, and acute kidney injury.


Question: A 31-year-old man presents to the emergency department for fever, malaise, and cough. For the last week, his cough has been progressively worsening, and he has been noticing blood in his sputum. He denies any recent travel or sick contacts and infrequently smokes cigarettes. Approximately 5 weeks ago, he presented with similar symptoms and was found to have a right upper lobe lung infiltrate, a CD4 count of 40/mm^3, and an HIV viral load of 115,000 copies/mL. He was appropriately treated and discharged home. Four weeks after initiation of treatment, his CD4 count was over 400/mm^3 and HIV viral load was negligible. His temperature today is 102°F (38.9°C), blood pressure is 130/90 mmHg, pulse is 100/min, and respirations are 20/min. A radiograph of the chest demonstrates new nodules in the left upper lobe and hilar adenopathy. Which of the following is the most appropriate next step in management?

Continue current anti-retroviral treatment, antimicrobial, and anti-tuberculoid therapies

Determine drug sensitivities against the patient’s pulmonary infection

Answer: Continue current anti-retroviral treatment, antimicrobial, and anti-tuberculoid therapies

Explanation:
This patient with recently diagnosed HIV and tuberculosis infection (upper lung lobe infiltrate) is presenting with worsening symptoms after being appropriately treated. Worsening of symptoms after initiation of these therapies is concerning for immune reconstitution inflammatory syndrome (IRIS), which is managed by continuing current combined antiretroviral medications, antibiotics for opportunistic infections and symptom management.

IRIS describes a paradoxical worsening of a patient's underlying infection after initiating antiretroviral therapy for patients with HIV. IRIS can also occur in HIV-uninfected patients with tuberculosis or leprosy who are started on antimycobacterial treatment. The pathogenesis of IRIS is unclear, but in patients with HIV, antiretroviral therapy increases the amount of CD4+ T-helper cells, which can lead to an exaggerated inflammatory response (e.g., increased cytokine release) towards the infection. Thus, there is a paradoxical worsening of the infection symptoms. When patients have a paradoxical worsening of their symptoms in the setting of starting their antiretroviral therapy, the therapy should be continued with symptomatic management (acetaminophen for fever).

Nelson et al review IRIS. They note it is seen in patients with HIV. They recommend antiretroviral therapy and antibiotics for bacterial infections.

Incorrect Answers:
Answer B: Determining drug sensitivities against the patient’s pulmonary infection would be of low diagnostic utility since IRIS best explains his current clinical presentation.

Answer C: Discontinuing antimicrobial treatment would not be appropriate since the patient has findings concerning for tuberculosis (upper lobe lung infiltrate), and lack of treatment can lead to progression of his infection.

Answer D: Obtaining a D-dimer level is only indicated in low-risk patients for pulmonary embolism by Wells criteria.

Answer E: Starting high-dose glucocorticoid treatment and discontinuing antiretroviral therapy would not be appropriate since discontinuing his antiretroviral therapy would not control his HIV infection, which would place him at greater risk of acquiring opportunistic infections. Corticosteroid use is part of symptom management as it decreases the inflammatory response.

Bullet Summary:
Immune reconstitution inflammatory syndrome (IRIS) can result in worsening of infectious symptoms and is managed by continuing antiviral therapy with symptomatic treatment.


Question: A 55-year-old man presents to the emergency department with chest pain and shortness of breath. He has a medical history of hypertension, diabetes, and obesity. His temperature is 98.6°F (37.0°C), blood pressure is 177/118 mmHg, pulse is 127/min, respirations are 11/min, and oxygen saturation is 98% on room air. An ECG is performed and notable for ST elevation in leads II, III, and aVF. The patient is treated appropriately and transferred to the medical floor. On the 2nd day of his hospitalization, the patient has abdominal pain. His serum lipase is 272 U/L and his creatinine is 1.6 mg/dL. A physical exam is notable for the finding in Figure A. He is requesting pain medication for his abdominal pain. Which of the following is the most likely underlying diagnosis?

Answer: Cholesterol embolism


Question: A 23-year-old woman is admitted to the inpatient psychiatry unit after her boyfriend reported she was “acting funny and refusing to talk.” The patient’s boyfriend states that he came home from work and found the patient sitting up in bed staring at the wall. When he said her name or waved his hand in front of her, she did not respond. When he tried to move her, she would remain in whatever position she was placed. Her temperature is 99°F (37.2°C), blood pressure is 122/79 mmHg, pulse is 68/min, and respirations are 12/min with an oxygen saturation of 98% on room air. The patient is lying on the bed with her left arm raised and pointing at the ceiling. She resists any attempt to change her position. The patient remains mute and ignores any external stimuli. The patient’s medical history is significant for depression. She was recently switched from phenelzine to fluoxetine. Which of the following is the most appropriate initial therapy?

Answer: Lorazepam

Explanation:
The patient has a history of depression and is presenting with decreased motor activity, waxy flexibility, lack of response to external stimuli, and mutism, suggesting the diagnosis of catatonia. Catatonia should initially be treated with benzodiazepines like lorazepam.

Catatonia is a state of psychomotor immobility and apathy that is associated with a mood disorder or psychosis. The diagnosis is made clinically by having at least 3 of the following symptoms: stupor (no psychomotor activity), negativism (no response to external stimuli), catalepsy (muscle rigidity in a position against gravity), waxy flexibility (maintaining positioning placed by the examiner), mutism, echolalia (mimicking speech), echopraxia (mimicking movements), stereotypy, grimacing, and non-purposeful agitation or mannerisms. Initial treatment involves benzodiazepines for symptomatic relief. If the patient is unresponsive to benzodiazepines, electroconvulsive therapy (ECT) can be used.

Francis reviews the evidence regarding the treatment of patients with catatonia. He discusses how benzodiazepines can be used with rapid improvement in symptoms. He recommends electroconvulsive therapy in refractory cases.

Incorrect Answers:
Answer A: Benztropine and IV diphenhydramine can be used to treat an acute dystonic reaction. Dystonic reactions present as involuntary spasms or sustained contractions of the face, neck, torso, pelvis, extremities, and larynx. Medications that block dopamine D2 receptors, such as neuroleptics and antiemetics, carry the greatest risk.

Answer B: Cyproheptadine is a serotonin antagonist that may be part of the treatment for serotonin syndrome. Serotonin syndrome may occur as a result of the simultaneous use of monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), or serotonin-norepinephrine reuptake inhibitors (SNRIs). It presents with myoclonus, hyperthermia, flushing, tachycardia, and delirium.

Answer C: Electroconvulsive therapy is an effective treatment for catatonia but would be considered 2nd line to benzodiazepines for refractory cases.

Answer D: Haloperidol is an antipsychotic, which may worsen catatonia. It can cause neuroleptic malignant syndrome, which can mimic catatonia.

Bullet Summary:
Catatonia can present in patients with a history of mood disorders and psychosis with symptoms of decreased motor activity, rigid posture, and mutism, and should be treated initially with a benzodiazepine.


Question: A 59-year-old woman presents to her primary care physician for trouble sleeping. When she goes to bed at night, she has an urge to get up out of bed and walk around. The patient often wakes her husband when she does this which irritates him. There is a perpetual uneasiness and feeling of a need to move at night which is relieved by getting up and walking around. The patient denies symptoms during the day. She works as a mail carrier and is nearing retirement. She has a medical history of anxiety, depression, irritable bowel syndrome, and dysmenorrhea. She is not currently taking any medications. Her temperature is 99.5°F (37.5°C), blood pressure is 157/98 mmHg, pulse is 80/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam reveals 5/5 strength in the upper and lower extremities, 2+ reflexes in the upper and lower extremities, a stable gait pattern, and normal sensation. Cardiopulmonary and abdominal exams are within normal limits. Which of the following is the most appropriate initial step in management?

Answer: Iron studies

Explanation:
This patient is presenting with the need to get up and walk around at night, which is suggestive of restless leg syndrome. The most appropriate initial step in management is collecting iron studies to assess for iron deficiency.

Restless leg syndrome presents with a sustained sense of restlessness and a feeling of a need to move one's legs. Symptoms typically occur at night and are relieved by activities such as walking. Iron deficiency can be a precipitating factor in restless leg syndrome as iron is a cofactor in the production of dopamine. Prior to administering iron, it is important to first confirm or rule out the diagnosis of iron deficiency with laboratory values which should include a CBC and iron studies. If iron deficiency exists, iron should be administered. If iron deficiency is not present, then dopamine agonists such as pramipexole or ropinirole can be administered.

Gossard et al. review the evidence regarding the diagnosis and treatment of restless leg syndrome. They discuss how iron deficiency is associated with the development of this disorder. They recommend iron repletion in deficient patients.

Incorrect Answers:
Answer A: Alprazolam could be an appropriate step in management if the patient suffers from episodic panic attacks/anxiety. It is not an optimal long-term therapy for anxiety or depression. Benzodiazepines are not first-line in treating restless leg syndrome.

Answer B: Ferrous sulfate would not be indicated until iron deficiency is confirmed. Iron deficiency is associated with restless leg syndrome as iron is a cofactor in the production of dopamine.

Answer D: Pramipexole is a dopamine agonist that is an effective therapy for restless leg syndrome. However, it is more important to treat any underlying causes for restless leg syndrome such as iron deficiency prior to starting a dopamine agonist.

Answer E: Supportive therapy and an exercise routine ignore the potential underlying pathology and do not offer any specific treatment for this patient's restless leg syndrome. Exercise can improve symptoms of restless leg syndrome but iron deficiency must still be ruled out.

Bullet Summary:
Patients with restless leg syndrome should be assessed for iron deficiency and treated if they are iron deficient.


Question: A 24-year-old man with epilepsy refractory to valproic acid, phenytoin, and levetiracetam undergoes magnetic resonance imaging of his brain while monitored by anesthetic care. He wakes up screaming in pain due to an electrocardiogram lead having caused a significant thermal burn circumferentially around his left leg. He is admitted to the medical intensive care unit for continuous electroencephalogram monitoring while on a midazolam infusion for seizure suppression and supportive care for his burn. Overnight, the nurse continued to increase the patient's midazolam infusion rate, but she also noticed that his left toes were cold to the touch with significant edema. His temperature is now 100°F (37.8°C), blood pressure is 110/75 mmHg, pulse is 80/min, respirations are 10/min and oxygen saturation is 95% on 2 liters nasal cannula. No dorsalis pedis or posterior tibial pulses are detected on the left lower extremity. A delta pressure of 25 mmHg is obtained in the left leg. What is the most appropriate next step in management?

Intravenous fluid infusion based on Parkland formula

Answer: Escharotomy

Explanation:
This patient with a circumferential burn due to an ECG cable wrapped around his leg in an MRI machine now has clear evidence of compartment syndrome due to the eschar. The most appropriate next step in management is emergent escharotomy to restore blood flow.

Burns can be caused by chemical, thermal, electrical, and radiation sources. The initial inflammation causes vasodilatation and hyperemia, which can progress to edema and local microvascular thrombosis. If not promptly addressed, tissue necrosis and irreversible damage can occur. Circumferential burns can evolve into eschars that constrict blood flow and cause distal compartment syndrome. A delta pressure (diastolic pressure minus local compartment pressure) lower than 30 mmHg is diagnostic. In the case of eschar-induced compartment syndrome, the most appropriate next step is escharotomy to alleviate pressure.

Ormiston and Marappa-Ganeshan review the evidence regarding the diagnosis and treatment of patients with compartment syndrome. They discuss how this condition can be caused by many different pathologies including burns. They recommend the emergent release of constrictive structures.

Incorrect Answers:
Answer A: Amputation may be necessary if the distal limb is completely necrotic and not salvageable. Timely release of the eschar can allow for reperfusion of the limb and prevent this outcome.

Answer C: Fasciotomy is the treatment of choice for compartment syndrome not due to a circumferential eschar, but in this case the least invasive surgical intervention should be performed first without releasing all the compartments of the lower leg. If escharotomy does not relieve the compartment syndrome then fasciotomy may be required.

Answer D: Intravenous fluid infusion based on the Parkland formula is part of comprehensive burn management, but would not address the underlying compartment syndrome, which is more urgent at this time.

Answer E: Transfer to a specialized burn center can be considered since circumferential burns are one of the admission criteria, but early escharotomy should be performed first.

Bullet Summary:
Circumferential burns that cause eschars and compartment syndrome require an escharotomy.


Question: A 35-year-old man presents to the emergency department for evaluation of chest pain. The pain starts in his chest and moves into his back, arms, and abdomen. He describes the pain as tearing. He has no known medical history and takes no medications. His temperature is 37.0°C (98.6°F), pulse is 130/min, blood pressure is 210/145 mmHg, respirations are 22/min, and pulse oximetry is 98% on room air. Exam reveals a diaphoretic, anxious-appearing man. Pulses are diminished over the left wrist when compared to the right. A chest radiograph is obtained as shown in Figure A. Which of the following is the most appropriate next step in management?

Answer: CT angiography of the chest, abdomen, and pelvis

Explanation:
This patient with "tearing" chest pain, hypertension, and a chest radiograph demonstrating mediastinal widening likely has an aortic dissection. The most appropriate next step in management would be to obtain CT angiography of the chest, abdomen, and pelvis to confirm the diagnosis.

Aortic dissections develop due to a tear in the intimal layer of the aorta, causing a second blood-filled lumen to form. Risk factors include hypertension, trauma, Marfan syndrome, Turner syndrome, and pregnancy. Prognosis depends on the location and severity of the intimal tear. Aortic dissections are often described by using the Stanford classification, where Type A involves the ascending aorta and Type B involves tears distal to the left subclavian artery. Patients classically present with chest pain described as "tearing" or "ripping" with radiation into the back, arms, or abdomen. Hypertension is common. Chest radiography characteristically demonstrates widening of the mediastinum due to accumulation of blood between layers of the wall of the aorta. Type A dissections are managed with heart rate control, blood pressure control, and surgery. Type B dissections are managed with blood pressure and heart rate control only.

Cooper et al. report on aortic dissections in adolescence. Although rare, aortic dissections have been seen in children with congenital heart disease, connective tissue disorders, or severe traumatic accidents. Severe, migrating abdominal pain should heighten suspicion for this diagnosis. The patient will often look worse clinically than can be explained by physical findings.

Figure A depicts a chest radiograph demonstrating a widened superior mediastinum.

Incorrect Answers:
Answer A: Aspirin is administered for chest pain that is thought to be due to acute coronary syndrome. This patient's presentation, exam, and imaging findings suggest aortic dissection. Aspirin is contraindicated in aortic dissection due to the increased risk for bleeding.

Answer C: Echocardiography offers information on cardiac contractility, valve function, and the presence of effusions. It would not be an appropriate initial diagnostic test in aortic dissection. Transesophageal echocardiography may be used to make the diagnosis in patients who cannot undergo a CTA.

Answer D: Lorazepam would be appropriate for patients presenting with chest pain that is secondary to use of cocaine or other sympathomimetic drugs. Tachycardia, tachypnea, diaphoresis, hyperactive bowel sounds, and dilated pupils suggest a sympathomimetic toxidrome.

Answer E: Serum troponin testing is indicated for risk stratification of patients with suspected acute coronary syndrome.

Bullet Summary:
The most appropriate next step in management for patients with suspected aortic dissection and mediastinal widening on chest radiograph is CT angiography of the chest, abdomen, and pelvis.


Question: A 55-year-old woman presents to the emergency department for evaluation of headache. She had a headache that was present for a few hours before subsiding 2 days ago, and then today she developed a headache that was sudden in onset and at maximal intensity within minutes. She has never had a headache like this in the past. Her temperature is 99.0°F (37.2°C), blood pressure is 157/99 mmHg, pulse is 90/min, respirations are 16/min, and oxygen saturation is 99% on room air. On exam, she has pain with passive and active movement of the neck. No focal neurologic deficits are appreciated. A non-contrast head CT is obtained as shown in Figure A. Which of the following is the most likely underlying etiology of this patient's headache?

Answer: Rupture of a berry aneurysm

Explanation:
This patient with sudden-onset headache, neck pain, and a CT scan showing blood in the basal cisterns likely has a subarachnoid hemorrhage. The most common cause of non-traumatic subarachnoid hemorrhage (SAH) is rupture of a saccular (berry) aneurysm.

SAH typically presents with a sudden onset "thunderclap" headache that is often described as the "worst headache of my life." Hypertension is a common risk factor. The diagnosis can be confirmed with a non-contrast head CT. Non-contrast CT scan of the head is sufficient to rule out subarachnoid hemorrhage if performed within 6 hours of symptom onset. If the head CT is negative but SAH is still suspected, a lumbar puncture can help confirm the diagnosis (demonstrating xanthochromia) or CT angiography can be performed. Patients should be admitted for neurosurgery and neuro-IR consultation and may require calcium channel blockers and possible intervention.

Macdonald et. al review spontaneous subarachnoid hemorrhage. They discuss the pathophysiology, clinical manifestations, and diagnosis. They note the typical finding of accumulation of blood in the basal cisterns and sylvian fissures on CT imaging.

Figure A shows a non-contrast head CT demonstrating blood in the subarachnoid space supporting the diagnosis of SAH. Note the hyperdensity in the sylvian fissures and basal cisterns.

Incorrect Answers:
Answer A: CNS vascular endothelial dysfunction results in posterior reversible encephalopathy syndrome, which typically presents with hypertension and encephalopathy.

Answer B: Dehydration and stress could explain a migraine headache or a tension headache. Migraine headaches are often pulsating and may be associated with aura.

Answer C: Hypersensitivity of the trigeminal nerve is thought to be involved in the pathophysiology of migraine headache, and also could describe trigeminal neuralgia which presents with sudden and severe electrical pain in the distribution of the trigeminal nerve with minor stimulation.

Answer D: Muscular pain and strain describes a tension headache which presents with diffuse head pain that is mild and not localized. CT imaging is normal in tension headache.

Bullet Summary:
Spontaneous subarachnoid hemorrhages are most commonly caused by rupture of a berry aneurysm.


Question: A 1-year-old girl is brought to a neurologist due to increasing seizure frequency over the past 2 months. She recently underwent a neurology evaluation which revealed hypsarrhythmia on electroencephalography (EEG) with a mix of slow waves, multifocal spikes, and asynchrony. Her parents have noticed the patient occasionally stiffens and spreads her arms at home. She was born at 38-weeks gestational age without complications. She has no other medical problems. Her medications consist of lamotrigine and valproic acid. Her temperature is 98.3°F (36.8°C), blood pressure is 90/75 mmHg, pulse is 94/min, and respirations are 22/min. Physical exam reveals innumerable hypopigmented macules on the skin and an irregularly shaped, thickened, and elevated plaque on the lower back. Which of the following is most strongly associated with this patient's condition?

Answer: Cardiac rhabdomyoma

Explanation:
This patient with a seizure disorder, ash-leaf spots (innumerable hypopigmented macules), Shagreen patch (elevated irregular plaque on the lower back), and West syndrome (hypsarrhythmia on EEG and movements consistent with infantile spasms) likely has tuberous sclerosis. Tuberous sclerosis is associated with cardiac rhabdomyomas.

Tuberous sclerosis is a neurocutaneous disorder that is inherited in an autosomal dominant fashion. Mutations in TSC1 and TSC2 lead to unregulated cell growth, leading to the formation of hamartomas in various locations. Manifestations of tuberous sclerosis include seizures (secondary to subependymal nodules and cortical dysplasia), mental retardation, renal angiomyolipomas, facial angiofibromas, mitral regurgitation, and hypomelanotic macules (ash-leaf spots). Cardiac rhabdomyoma is strongly associated with tuberous sclerosis and can lead to arrhythmias. West syndrome, which is characterized by infantile spasms, intellectual disability, and hypsarrhythmia (a chaotic mixture of high-amplitude slow waves, multifocal spikes, and intrahemispheric-interhemispheric asynchrony) on EEG, is also associated with tuberous sclerosis. Diagnosis of tuberous sclerosis is made with genetic testing. Advanced imaging (CT or MRI) may reveal cortical tubers and lesions in the third and fourth ventricles. Abdominal imaging may reveal renal angiomyolipomas. The management of seizures in tuberous sclerosis includes anti-seizure medications, though surgery may also be pursued in select cases.

Hinton et al. studied the cardiac manifestations of tuberous sclerosis. They found that cardiac rhabdomyomas can lead to arrhythmia later in life. They recommended that infantile spasms in tuberous sclerosis be treated with vigabatrin but other seizure types should be treated similar to other epileptic disorders.

Incorrect Answers:
Answer B: Glaucoma may occur in patients with Sturge-Weber syndrome, which is characterized by "tram-track" calcifications in the brain, port-wine stains of the face, mental retardation, and epilepsy. Diagnosis is with MRI of the brain with contrast to demonstrate leptomeningeal vascular malformations that are characteristic of the disease.

Answer C: Optic glioma is associated with neurofibromatosis type 1 (NF1), which presents with hyperpigmented macules (cafe-au-lait spots), axillary freckling, and cutaneous neurofibromas. Neurofibromas in NF1 may also grow on peripheral nerves, leading to malignant peripheral nerve sheath tumors. Lisch nodules, or benign growths of the iris, may also be seen in NF1. Diagnosis of NF1 is clinical, but can be aided by genetic testing.

Answer D: Polyostotic fibrous dysplasia is associated with McCune-Albright syndrome. Polyostotic fibrous dysplasia causes fibrous tissue in bones, leading to growth abnormalities and pathologic fractures. McCune-Albright syndrome is also associated with cafe-au-lait macules, which have irregular borders, and endocrine abnormalities such as precocious puberty and hyperthyroidism. Diagnosis is supported with endocrine tests as well as genetic testing.

Answer E: Renal cell carcinoma is associated with Von-Hippel-Lindau syndrome (VHL), which presents with tumors arising in multiple organs. Patients with VHL present with hemangioblastomas in the brain, spinal cord, cerebellum, and retina, and pheochromocytoma. Pheochromocytomas release catecholamines, leading to episodic hypertension, diaphoresis, and palpitations. Diagnosis of VHL is with genetic testing.

Bullet Summary:
Tuberous sclerosis has numerous manifestations including seizures, angiofibromas, mitral regurgitation, renal angiomyolipoma, ash-leaf spots, mental retardation, and cardiac rhabdomyoma.


Question: A 55-year-old man presents to urgent care for weakness and weight loss. For the past several months, he has felt progressively weaker and has lost 25 pounds with intermittent abdominal pain. The patient has not seen a physician in 30 years and recalls being current on most of his vaccinations. A few years ago, he went to the emergency department due to abdominal pain and was found to have increased liver enzymes due to excessive alcohol use and incidental gallstones. The patient has a 50 pack-year smoking history. His temperature is 99.5°F (37.5°C), blood pressure is 161/108 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 95% on room air. Physical exam reveals an emaciated man. The patient has a negative Murphy sign and his abdomen is non-tender. Cardiopulmonary exam is within normal limits. Which of the following is the most appropriate next step in management?

Smoking cessation advice and primary care follow up

Answer: CT scan of the abdomen and pelvis

Explanation:
This patient with weight loss and painless liver dysfunction has symptoms that are suggestive of pancreatic cancer. The most appropriate next diagnostic test is a CT scan of the abdomen and pelvis.

Pancreatic cancer presents with weight loss, jaundice, epigastric pain, and fatigue/malaise typically in an older male smoker who uses alcohol. Laboratory tests will demonstrate an elevated alkaline phosphatase and bilirubin. If a patient is presenting with the classic "painless jaundice" then the most appropriate next step in management could be an ultrasound to evaluate for obstruction. Otherwise, the best diagnostic test for this condition is a CT scan of the abdomen to characterize the pancreas and any metastasis to local organs. Treatment is with excision of the tumor through a Whipple procedure in appropriate candidates.

Lee and Lee review the evidence regarding the diagnosis of pancreatic cancer. They discuss how abdominal CT or MRI are important in making this diagnosis. They recommend having a high clinical index of suspicion given this diagnosis carries a high mortality rate.

Incorrect Answers:
Answer B: CT scan of the chest would be appropriate to screen a smoker for lung cancer. If this patient had concern for malignancy with a smoking history, then a CT scan of the chest would be appropriate. It would be appropriate at a later time to assess for pulmonary nodules and lung cancer.

Answer C: HIDA (hepatobiliary iminodiacetic acid) scan is an appropriate diagnostic test to characterize a gallstone blockage of the common bile duct if a right upper quadrant ultrasound is not revealing in the diagnosis of acute cholecystitis.

Answer D: A right upper quadrant ultrasound can assess the gallbladder for stones and the liver for an abscess, but it will not assess the pancreas for pancreatic cancer (at least in a reliable manner that assesses the entire pancreas).

Answer E: Smoking cessation and primary care follow up would be appropriate management for this patient if he only presented requesting general advice to improve his health or stop smoking. His current symptoms are too alarming for malignancy. He should stop smoking regardless.

Bullet Summary:
The most appropriate initial test for pancreatic cancer is an abdominal CT.


Question: A 32-year-old man presents to the emergency department for evaluation of headache. His symptoms started last night and have persisted. He occasionally has migraine headaches, but he has not had a headache like this in the past. He reports associated nausea, vomiting, fevers, and neck pain. He has a medical history of asthma. His temperature is 100.4°F (38.0°C), blood pressure is 110/60 mmHg, pulse is 95/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, he appears uncomfortable. Neurologic exam reveals no focal deficits. There is pain with passive neck flexion. No edema or rashes are noted. Lungs are clear to auscultation bilaterally. Lumbar puncture is performed and CSF results are obtained as shown below. Cerebrospinal fluid (CSF): Cell count: 175/mm^3 RBCs: 0/mm^3 Cl-: 119 mEq/L Glucose: 49 mg/dL Pressure: 150 mmH2O Total protein: 55 mg/dL Based on these results, which of the following is the most appropriate treatment regimen for this patient?

Answer: Supportive care and monitoring

Explanation:
This patient with headache, fever, and neck stiffness has a presentation and CSF studies consistent with a diagnosis of viral or aseptic meningitis. Supportive care is the most appropriate management strategy for patients with viral meningitis.

Aseptic (viral) meningitis presents similarly to bacterial meningitis with neck stiffness, photophobia, fever, malaise, and flu-like symptoms. Patients should be worked up and treated as if they have bacterial meningitis until proven otherwise. CSF findings in aseptic meningitis show an elevated cell count (though typically < 300/mm^3 in contrast to bacterial meningitis), a normal or elevated protein, and a normal glucose. CSF should be sent for Gram stain and culture to confirm the diagnosis and rule out bacterial meningitis. Once the diagnosis has been confirmed, management of viral meningitis consists of supportive care and monitoring for complications such as seizures, cerebral edema, or SIADH.

Kohil et. al review viral meningitis. They discuss the pathophysiology, clinical manifestation and diagnosis. They recommend that most patients with viral meningitis be treated with supportive care.

Incorrect Answers:
Answer A: Acyclovir would be appropriate for suspected HSV or varicella encephalitis or meningitis. This patient with no RBCs in the CSF and no changes in mental status is not likely to have infection with HSV or varicella.

Answer B: Amphotericin and 5-flucytosine followed by long-term fluconazole is the appropriate management of cryptococcal meningitis. Cryptococcal meningitis presents similarly to bacterial and viral meningitis, almost exclusively in immunocompromised patients.

Answer C: Ceftriaxone and vancomycin would be appropriate if bacterial meningitis was suspected. Steroids are generally added if a bacterial source is likely. However, this patient has a presentation that is less concerning for bacterial meningitis, and CSF studies that are more consistent with aseptic meningitis.

Answer D: Ceftriaxone, vancomycin and steroids are an appropriate initial regimen for bacterial meningitis. Dexamethasone reduces inflammatory injury while patients are being treated with antibiotics.

Bullet Summary:
Viral or aseptic meningitis is managed with supportive care and monitoring.


Question: A 31-year-old man presents to the emergency department for fever, malaise, and cough. For the last week, his cough has been progressively worsening, and he has been noticing blood in his sputum. He denies any recent travel or sick contacts and infrequently smokes cigarettes. Approximately 5 weeks ago, he presented with similar symptoms and was found to have a right upper lobe lung infiltrate, a CD4 count of 40/mm^3, and an HIV viral load of 115,000 copies/mL. He was appropriately treated and discharged home. Four weeks after initiation of treatment, his CD4 count was over 400/mm^3 and HIV viral load was negligible. His temperature today is 102°F (38.9°C), blood pressure is 130/90 mmHg, pulse is 100/min, and respirations are 20/min. A radiograph of the chest demonstrates new nodules in the left upper lobe and hilar adenopathy. Which of the following is the most appropriate next step in management?

Continue current anti-retroviral treatment, antimicrobial, and anti-tuberculoid therapies

Determine drug sensitivities against the patient’s pulmonary infection

Start high-dose glucocorticoid treatment and discontinue antiretroviral therapy

Answer: Continue current anti-retroviral treatment, antimicrobial, and anti-tuberculoid therapies


Question: A 57-year-old woman presents to her primary care physician with weakness for the past 6 months with symptoms that have worsened recently. She feels fatigued, depressed, and has gained 10 pounds which she attributes to feeling too weak to go to the gym. She was recently treated for an ear infection with an antibiotic which she completed 3 weeks ago, and experienced a rash which she believes was an allergic reaction to her treatment. The patient has a medical history of diabetes mellitus that is well-controlled with insulin and metformin. She has been admitted multiple times for hypoglycemia secondary to missing meals. Her temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 80/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for 2/5 strength in the patient's upper and lower extremities, sparse fine hair on her body, and a rash on her face and arms. Laboratory values are ordered as seen below. Serum: Na+: 139 mEq/L K+: 3.3 mEq/L Cl-: 100 mEq/L HCO3-: 25 mEq/L BUN: 20 mg/dL Glucose: 70 mg/dL Creatinine: 1.1 mg/dL Ca2+: 10.2 mg/dL AST: 12 U/L ALT: 10 U/L A muscle biopsy is obtained as seen in Figure A. Which of the following is the most likely explanation for this patient's presentation?

Answer: Inclusion body myositis

Explanation:
This patient who presents with weakness and a rash has a biopsy suggestive of inclusion body myositis.

Inclusion body myositis presents with an insidious onset of weakness, a mildly elevated CRP and CK, and a rash. A muscle biopsy in this disease will demonstrate endomysial inflammation with basophilic-rimmed vacuoles within the muscle fiber sarcoplasm. Electromyography is typically abnormal, and the most accurate/confirmatory test is a muscle biopsy. There is no cure for this disease and no standard course of treatment. Corticosteroids are not usually effective but intravenous immunoglobulins can be effective.

Naddaf et al. review the evidence regarding the diagnosis and treatment of patients with inclusion body myositis. They discuss how this disease is still refractory to treatment. They recommend a muscle biopsy to establish a definitive diagnosis.

Figure/Illustration A is a muscle biopsy demonstrating endomysial inflammation with basophilic-rimmed vacuoles (red circle) within the muscle fiber sarcoplasm. These findings are classically seen in patients with inclusion body myositis.

Incorrect Answers:
Answers 1 & 5: Dermatomyositis and polymyositis present similarly with muscle weakness and an elevated CK, CRP, and aldolase. However, dermatomyositis presents with dermatologic findings. A biopsy would demonstrate inflammation surrounding the muscle fascicle (dermatomyositis) or within the muscle fascicle (polymyositis). Treatment may include azathioprine and methotrexate.

Answer B: Hypokalemia could present with weakness and cardiac abnormalities. Though this patient is hypokalemic, her biopsy demonstrates inclusion body myositis. Treatment of hypokalemia is with potassium repletion.

Answer C: Hypothyroidism presents with depression, fatigue, scarce lanugo, myopathy, and weight gain (as this patient has). Though myopathy from hypothyroidism is plausible, her symptoms of weakness have a confirmatory biopsy. Treatment of hypothyroidism is with thyroid hormone replacement.

Bullet Summary:
Inclusion body myositis presents with weakness and an elevated CRP/CK with a muscle biopsy demonstrating endomysial inflammation with basophilic-rimmed vacuoles within the muscle fiber sarcoplasm.


Question: A 6-month-old girl is brought to the pediatrician by her father for a scheduled check-up. She was in her usual state of health until 6 weeks ago when she was hospitalized for bacterial pneumonia. She received amoxicillin and had a resolution of her symptoms. Her father reports that she seems “back to normal.” She can roll over by herself and can sit up without support. She often babbles but sometimes does make identifiable sounds like “dada” and “baba.” They recently started feeding her mushy cereal, which she seems to like but occasionally spits up. She has started teething and sometimes becomes “fussy.” Vital signs are within normal limits. A physical examination is unremarkable. The patient’s father brought a 4-week follow-up chest radiograph taken at the hospital, as shown in Figure A. Which of the structures labeled in Figure A would be most likely to change in response to another infectious illness?

Answer: A

Explanation:
The thymus gland (labeled in A) is visible on a chest radiograph in infants and will change in response to illness due to its immunologic role.

The thymus gland is the site of T-cell maturation. The thymus is visible on a chest radiograph in infants and continues to grow throughout childhood. It is located in the anterior part of the superior mediastinum. On a chest radiograph, the thymus may appear as a “widened mediastinum,” continuous with the superior border of the heart (Figure A) or as a triangular-shaped opacity known as the thymic “sail sign," located towards the right of the mediastinum. At puberty, the gland will decrease in size and eventually be replaced by fatty tissue.

Askin and Young review the evidence regarding the history and function of the thymus. They discuss how this structure is involved in immune function. They recommend monitoring for the absence of this structure in immunodeficient patients.

Figure A shows a normal chest radiograph of an infant with a normal cardiothymic contour.

Incorrect Answers:
Answer B: B points to the trachea. Deviation of this structure can be seen in patients with tension pneumothorax. Treatment is with needle thoracostomy followed by chest tube placement.

Answer C: C points to the apex of the heart. This structure can be enlarged in congenital heart conditions. Treatment is with surgical correction of these conditions.

Answer D: D points to the stomach. This structure can be abnormal in patients with pyloric stenosis. Treatment is with pyloromyotomy.

Answer E: E points to the diaphragm. This structure can be abnormal in patients with diaphragmatic hernias. Treatment is with surgical closure of the defect.

Bullet Summary:
The thymus is normally visible on a pediatric chest radiograph, but it is replaced by fatty tissue after puberty.


Question: A 24-year-old man presents to the emergency department with abdominal pain, nausea, and vomiting. The symptoms began towards the end of running a marathon and persisted after finishing the race. The patient is otherwise healthy and has no other medical problems. His temperature is 98.0°F (36.7°C), blood pressure is 105/71 mmHg, pulse is 113/min, respirations are 19/min, and oxygen saturation is 98% on room air. Physical exam reveals a distended and tender abdomen. A radiograph is performed as seen in Figure A. Which of the following is the most likely diagnosis?

Answer: Cecal volvulus

Explanation:
This young, healthy patient presents with abdominal pain, nausea, vomiting, and a distended, tender abdomen with a radiograph demonstrating the "coffee bean sign," likely has a cecal volvulus.

Cecal volvulus is the second most common cause of volvulus after sigmoid volvulus and presents with abdominal pain, constipation, vomiting, abdominal distention, and a tympanitic abdomen. It is more common in young patients who are active (e.g. marathon runners). The classic conventional radiographic finding in cecal volvulus is the coffee bean sign, in which closed loops of intestine distend with gas, making visible the medial and lateral walls of dilated bowel. Diagnosis of cecal volvulus can be confirmed with a CT scan. Management involves analgesia, intravenous fluids, and surgical detorsion.

Hasbahceci et al. review the presentation, diagnosis, and management of cecal volvulus. The authors find that abdominal radiography has a low sensitivity for cecal volvulus. The authors recommend surgical management of cecal volvulus with resection with right hemicolectomy and primary ileocolic anastomosis.

Figure/Illustration A is a radiograph demonstrating the "coffee bean" sign which is suggestive of a cecal volvulus.

Incorrect Answers:
Answer B: Ileus presents after surgery or manipulation of the intestines with decreased peristalsis of the intestine leading to a failure to pass gas or have bowel movements. Treatment involves treating any electrolyte abnormalities, encouraging ambulation, and avoiding medications that decrease peristalsis (such as opioids).

Answer C: Ogilvie syndrome occurs when the colon wall is not appropriately undergoing peristalsis leading to a dilated colon with abdominal distension. It is more common in the elderly and critically ill patients. Treatment involves the placement of a rectal tube to decompress the intestines and treatment of any underlying medical conditions.

Answer D: Sigmoid volvulus is more common in elderly and critically ill patients and presents with constipation, an absence of bowel movements, and a distended, tympanitic abdomen. Although the coffee bean sign may also be seen in patients with sigmoid volvulus, patients tend to be older. In addition, plain radiography typically demonstrates multiple air-fluid levels in a sigmoid volvulus versus usually only a single air-fluid level in a cecal volvulus. Treatment involves flexible sigmoidoscopy and surgery.

Answer E: Small bowel obstruction presents with a distended and tympanitic abdomen with nausea, vomiting, and an absence of flatus or bowel movements. Radiography may demonstrate distended bowel and air-fluid levels, and the most accurate test is a CT scan of the abdomen. It occurs secondary to adhesions entrapping the bowel. Management involves the placement of a nasogastric tube, intravenous fluids, and surgery.

Bullet Summary:
Cecal volvulus presents in younger patients with abdominal pain, distention, constipation, nausea, vomiting, and the "coffee bean" sign on radiography.


Question: A 57-year-old man is brought to a neurologist by his wife for abnormal behavior. He was normal until around 3 months ago when he started forgetting important meetings and misplacing items around the house. One month ago, the patient was fired from his job as a software engineer after attempting to grope a coworker. The patient expresses frustration that he is no longer able to concentrate enough to enjoy his hobby of solving puzzles. His medical history is significant for gastroesophageal reflux disease for which he takes omeprazole. He has no family history of neurologic disease. His temperature is 98.6°F (37.0°C), blood pressure is 120/75 mmHg, pulse is 70/min, and respirations are 16/min. During the examination, the patient’s cell phone rings unexpectedly causing the patient to suddenly jerk his arms and legs. Further diagnostic investigation is performed which reveals an elevated 14-3-3 protein on cerebrospinal fluid analysis. Which of the following is the most likely diagnosis?

Answer: Creutzfeldt-Jacob disease

Explanation:
This patient with rapidly progressive dementia over 3 months, declining executive function, impaired concentration, decreased memory, startle myoclonus (sudden jerking of extremities in response to unexpected stimulus), and elevated 14-3-3 protein levels on cerebrospinal fluid (CSF) analysis most likely has Creutzfeldt-Jakob disease (CJD).

CJD is a human prion disease in which the normal prion protein (PrPc) converts to a beta-pleated sheet disease-associated form (PrPsc) which is resistant to proteases. CJD is usually spontaneous. Rarely, CJD may be familial or acquired (from iatrogenic transmission or dietary exposure). Aggregates of PrPsc lead to spongiform vacuolation. Clinically, this manifests with rapidly progressive mental deterioration with prominent executive dysfunction (declining concentration, judgment, and memory) and startle myoclonus. Further diagnostic investigation may reveal 14-3-3 protein on CSF analysis and synchronous sharp wave complexes on electroencephalogram (EEG). CJD usually leads to death within 1 year. There is no known effective treatment for this disease.

Uttley et al. review the diagnosis, clinical presentation, and epidemiology of Creutzfeldt-Jakob disease (CJD). They discuss how CJD in a global context is increasing in prevalence and how incubation periods as long as 40 years have been observed for iatrogenic cases. They recommend heightened awareness of this disease in order to mitigate iatrogenic transmission.

Incorrect Answers:
Answer A: Alzheimer disease is characterized by gradual cognitive decline with difficulty completing activities of daily living. Impaired executive function early in the disease course, rapidly progressive disease, elevated 14-3-3 protein on CSF analysis, and startle myoclonus are not found in Alzheimer disease.

Answer C: Lewy body dementia (LBD) presents with alterations in consciousness, disorganized speech, visual hallucinations, extrapyramidal symptoms, and early compromise of executive function. Although this patient’s dementia is characterized by early compromise of executive function, the absence of fluctuating levels of consciousness, absence of extrapyramidal symptoms, and presence of startle myoclonus make CJD more likely than LBD.

Answer D: The behavioral variant of frontotemporal dementia (FTD) is associated with early-onset personality and behavioral changes, and it may be associated with extrapyramidal symptoms. Memory is not usually affected until late in the disease course.

Answer E: Subcortical leukoencephalopathy (Binswanger disease) is a type of small vessel vascular disease that presents with prominent subcortical dementia. This manifests clinically as slowed mental processing, impaired cognition, apathy, and depression. This disease almost always presents in the context of chronic hypertension and is usually seen in older patients.

Bullet Summary:
Creutzfeldt-Jacob disease is a fatal prion disease that presents with sudden-onset and rapidly progressive dementia and startle myoclonus or seizures.


Question: A 55-year-old man presents to the emergency department with nausea and vomiting for the past week. He decided to come in when his symptoms worsened. He feels that his symptoms are exacerbated with large fatty meals and when he drinks alcohol. His wife recently returned from a cruise with symptoms of vomiting and diarrhea. The patient has a medical history of poorly managed diabetes, constipation, anxiety, dyslipidemia, and hypertension. His temperature is 99.5°F (37.5°C), blood pressure is 197/128 mmHg, pulse is 100/min, respirations are 17/min, and oxygen saturation is 95% on room air. Physical exam reveals a systolic murmur heard loudest along the left upper sternal border. Abdominal exam reveals an obese, tympanitic and distended abdomen with a 3 cm scar in the right lower quadrant. Vascular exam reveals weak pulses in the lower extremities. Which of the following is the most likely underlying etiology of this patient's symptoms?

Answer: Adhesions

Explanation:
This patient is presenting with abdominal pain and a tympanitic abdomen, which are symptoms suggestive of a small bowel obstruction. In developed countries, these typically occur secondary to adhesions.

Small bowel obstructions (SBO) typically present with an absence of bowel sounds, bowel movements, and flatus, as well as abdominal distension, nausea, and vomiting. They typically occur secondary to adhesions which entrap the bowel and disrupt its normal peristalsis. Adhesions can occur after abdominal surgery or trauma as part of the normal healing process. The diagnosis of SBO can be confirmed using abdominal imaging such as a CT scan. Treatment often involves observation; however, surgical decompression of the SBO may be needed if there is a closed-loop obstruction or an obstruction that does not resolve on its own.

Rami Reddy and Cappell review the evidence regarding the diagnosis and treatment of SBO. They discuss how this disease has a 30% mortality rate if the diagnosis is missed and bowel perforation occurs. They recommend early evaluation and treatment of these patients.

Incorrect Answers:
Answer B: Enteric nervous system damage describes diabetic gastroparesis which can present similarly to SBO; however, this patient's age and history of surgery points toward SBO as the most likely diagnosis. Treatment is with pro-motility agents.

Answer C: Impacted stool describes constipation which could present similarly to SBO; however, this diagnosis is less likely to cause nausea and vomiting unless it is severe. The vomit typically smells like stool. Treatment is with dis-impaction of the colon.

Answer D: Norovirus typically causes nausea, vomiting, and diarrhea but does not cause distension and a tympanitic abdomen. Treatment is supportive as the virus self-resolves.

Answer E: Twisting of bowel describes a volvulus which presents similarly to SBO; however, it is a more common diagnosis in the elderly and is a less common diagnosis than is SBO in a patient with a history of abdominal surgery. Treatment is with surgical untwisting of the bowel.

Bullet Summary:
Small bowel obstruction (commonly caused by adhesions) presents with nausea, vomiting, absence of flatus/bowel movements, and a distended/tympanic abdomen.


Question: A 37-year-old machinist presents to his primary care physician with eye problems. He has felt a mass in his eye that has persisted for the past month. The patient has a medical history of blepharitis treated with eye cleansing and squamous cell carcinoma of the skin treated with Mohs surgery. His temperature is 99.5°F (37.5°C), blood pressure is 157/102 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for a firm and rubbery nodule palpable inside the patient's left eyelid. Physical exam does not elicit any pain. Which of the following is the most likely diagnosis?

Answer: Chalazion

Explanation:
This patient presenting with a painless firm and rubbery nodule has symptoms that are suggestive of a chalazion.

Chalazion presents with a hard and painless eyelid nodule. This pathology occurs secondary to granulomatous inflammation of the Meibomian gland. The lesion can be treated with simple excision; however, recurrent lesions are concerning for Meibomian cell carcinoma. The most important differential diagnosis to consider in these patients is a hordeolum which presents with a firm and painful lid nodule (in contrast to painless). Treatment is with warm compresses followed by incision and curettage in refractory cases.

Li et al. review the evidence regarding the diagnosis and treatment of chalazion. They discuss how gland loss is a possible sequelae from this disorder. They recommend using warm compresses for symptomatic relief.

Incorrect Answers:
Answer B: Foreign body is a possible diagnosis given this patient's occupation as a machinist; however, this would typically present with pain over the patient's cornea with a sudden onset of symptoms. Treatment is with removal of the foreign body.

Answer C: Hordeolum presents with a hard and painful lid nodule in contrast to a hard and painless lid nodule. Treatment is with warm compresses and possible debridement in refractory cases.

Answer D: Ingrown eyelash follicle could present with a firm lid nodule; however, it would be located near the margin of the eyelid and would likely be inflamed and tender. Treatment is with warm compresses and possible debridement in refractory cases.

Answer E: Meibomian cell carcinoma is a possible diagnosis but is epidemiologically less common than a chalazion. This diagnosis would be more likely if the lesion was recurrent despite excision. Treatment is with wide excision of the lesion.

Bullet Summary:
Chalazion presents with a firm and painless eyelid nodule.


Question: A 67-year-old man presents to the emergency department 1 hour after sudden-onset weakness and double vision. His medical history is significant for hyperlipidemia and poorly controlled hypertension. His current medications include atorvastatin and amlodipine. His temperature is 98.6°F (37.0°C), blood pressure is 175/95 mmHg, pulse is 90/min, respirations are 16/min. On cranial nerve exam, his left pupil is 6 mm in diameter compared to 3 mm on the right. His left eye is displaced laterally and downward and he also has left-sided ptosis. Strength is 2/5 in the right upper and right lower extremities and 5/5 in the left upper and left lower extremities. He has marked right-sided dysdiadochokinesia. Sensation is intact throughout. Which of the following regions of his brain is most likely affected?

Answer: Midbrain

Explanation:
This patient with a history of poorly controlled hypertension, acute onset of left-sided oculomotor nerve palsy (mydriasis, ptosis, and “down and out” pupil), right-sided paresis, and right-sided dysdiadochokinesia most likely has a lacunar stroke of the left midbrain.

Important structures in the midbrain often affected by stroke include the oculomotor nucleus, substantia nigra, corticospinal tract, red nucleus, and superior cerebellar peduncle. Occlusions to branches of the basilar artery lead to infarctions of various parts of the midbrain. Midbrain lesions almost always manifest with an ipsilateral oculomotor palsy (ptosis from the levator palpebrae muscle; mydriasis from loss of parasympathetic inflow; abduction and excyclotorsion of the globe from the superior rectus, medial rectus, inferior rectus, and inferior obliques). There may also be contralateral ataxia (cerebellar peduncle after decussation and red nucleus), contralateral hemiparesis (corticospinal tract before decussation at the medulla), and parkinsonian tremor (substantia nigra).

Sciacca et al. review the anatomy and clinical signs of strokes of the midbrain, pons, and medulla. They discuss how a stroke of the midbrain will present with oculomotor palsy and paresis. They recommend being vigilant for symptoms of strokes to allow for early diagnosis.

Incorrect Answers:
Answer A: Lateral medullary syndrome (Wallenberg syndrome) is usually due to a stroke of the posterior inferior cerebellar artery. This presents with ipsilateral ataxia, loss of pain and temperature sensation in the face, dysarthria, and Horner syndrome, as well as contralateral loss of pain and temperature sensation in the body. In this patient with intact sensorium and without dysarthria, lateral medullary syndrome is less likely.

Answer B: Lateral pontine syndrome can be caused by interruption of blood supply by the anterior inferior cerebellar artery. It presents with ipsilateral limb and gait ataxia, ipsilateral Horner syndrome, ipsilateral facial hemianesthesia, ipsilateral facial paralysis, nystagmus and vertigo, and contralateral loss of pain and temperature in the body. In this patient with intact sensorium and without facial paralysis, vertigo, and oculomotor palsy, midbrain stroke is more likely than a pontine stroke.

Answer C: Medial pontine syndrome can be due to occlusion of the paramedian branches of the basilar artery and disrupts the abducens nerve, the dorsal column-medial lemniscus, and the corticospinal tract. This results in contralateral spastic hemiparesis, ipsilateral lateral rectus paralysis (eye turned down and in), and contralateral loss of vibration and stereognosis. In this patient with ptosis, and an eye turned down and out, oculomotor palsy and a midbrain stroke are more likely than a pontine stroke.

Answer E: Strokes of the posterior limb of the internal capsule lead to contralateral hemiparesis. Strokes of the internal capsule would not be expected to lead to oculomotor nerve palsy or dysdiadochokinesia. The constellation of ataxia, hemiparesis, and cranial nerve palsy is more suggestive of a brainstem pathology than of a lacunar stroke in the internal capsule.

Bullet Summary:
Midbrain strokes commonly present with ipsilateral oculomotor nerve palsy and contralateral hemiparesis/hemiplegia, contralateral hemiataxia, and/or contralateral tremor.


Question: A 27-year-old woman presents to her primary care physician for an abnormal vaginal discharge. The patient has engaged in unprotected intercourse with 12 different partners. She has a medical history of asthma, IV drug abuse, and depression. She has 1 to 2 alcoholic drinks per day. She feels ashamed of her behavior and is requesting treatment for her condition and advice for safe sex. The patient is given antibiotics and is advised on safe sex practices. The patient presents to the emergency department 3 days later with a complaint of a rash. She states that every time she has sex a rash has emerged on her skin. Her temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 91/min, respirations are 14/min, and oxygen saturation is 98% on room air. A physical exam is notable for the finding in Figure A. Which of the following is the most likely cause of this patient's symptoms?

Answer: Antigen exposure

Explanation:
This patient is presenting with urticaria whenever she engages in sexual intercourse suggesting a latex allergy (found in condoms). These allergies are due to antigen exposure.

Anaphylaxis and urticaria are immunologically mediated responses to environmental antigens that are typically IgE-mediated. This results in crosslinking of antigen receptors and the subsequent release of histamine and other inflammatory signals. Patients can present with a spectrum of symptoms from urticaria (hives alone) all the way to full-blown anaphylaxis (hypotension, tachycardia, and bronchoconstriction). Minor cases can be treated with avoidance of antigen exposure. Anaphylaxis is treated with intramuscular epinephrine (1:1,000).

Gawchik reviewed the evidence regarding the diagnosis of latex allergy. She discusses how the diagnosis is primarily made by observing the relationship between exposure and symptoms. She recommends avoidance of latex in these patients.

Figure/Illustration A is a clinical photograph that demonstrates dermal edema and urticaria (red circles). This can occur secondary to allergen exposure such as from a new drug or latex.

Incorrect Answers:
Answer B: Drug reaction could be possible if this patient has an antibiotic allergy (ceftriaxone is a treatment for gonorrhea); however, a rash that only occurs during intercourse is more likely related to latex exposure.

Answer C: Infection is possible given this patient’s IV drug abuse and risky behavior; however, the hives present in this patient are likely not related to an infection. Infectious rashes tend to be painful, ulcerative, or vesicular.

Answer D: IV drug use could expose this patient to any number of foreign substances that could induce an allergic reaction; however, the symptoms that are associated with sexual intercourse point toward latex exposure.

Answer E: Photosensitivity would not present as hives but could occur in this patient given that doxycycline is an appropriate drug to treat her initial sexually transmitted infection and offers coverage for Chlamydia trachomatis. Patients would present with a photosensitive rash.

Bullet Summary:
Anaphylaxis and urticaria can occur secondary to latex exposure (such as from condoms or gloves).


Question: A 22-year-old woman presents to the emergency department with shortness of breath. She was hiking when she suddenly felt unable to breathe and had to take slow deep breaths to improve her symptoms. The patient is a Swedish foreign exchange student and does not speak any English. Her medical history and current medications are unknown. Her temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 120/min, respirations are 22/min, and oxygen saturation is 90% on room air. Physical exam is notable for poor air movement bilaterally and tachycardia. The patient is started on treatment. Which of the following parameters including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of carbon monoxide (DLCO) most appropriately describes this patient's underlying pathology?

Answer: Normal DLCO

Explanation:
This patient who presents with dyspnea and poor air movement bilaterally most likely has an acute asthma exacerbation. DLCO is the one parameter that is normal in these episodes.

Asthma is an obstructive lung disease that results in intermittent episodes of respiratory compromise. Asthma presents with shortness of breath typically secondary to an allergen/antigen or with exposure to exercise or cold air that causes bronchospasm. Pulmonary function testing will typically reveal a decreased FEV1, a decreased FVC, and a decreased FEV1/FVC in both asthma and emphysema. The DLCO will be normal in asthma in contrast to emphysema where the DLCO is decreased. Patients should be treated with inhaled beta-adrenergic agonists and corticosteroids for acute exacerbations.

Peng et al. review the evidence regarding patients who have COPD versus asthma. They discuss how patients with COPD have reduced DLCO. They recommend measuring parameters to distinguish between these entities.

Incorrect Answers:
Answer A: Decreased airway tone does not describe asthma. Rather, hyperreactive airways with increased tone describes an asthma attack. Decreased airway tone may be seen in patients with connective tissue diseases such as Ehlers-Danlos syndrome.

Answers 2-4: Increased FEV1, FEV1/FVC, and FVC do not describe asthma. All of these laboratory values are decreased in asthma and emphysema. Increased respiratory performance can be seen in patients who are athletes or training for marathons.

Bullet Summary:
Both asthma and emphysema present with a decreased FEV1, FVC, and FEV1/FVC; however, asthma has a normal DLCO while COPD has a reduced DLCO.


Question: A 27-year-old man presents for an appointment to establish care. He recently was released from prison. He has felt very fatigued and has had a cough. He has lost roughly 15 pounds over the past 3 weeks. He attributes this to intravenous drug use in prison. His temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 100/min, respirations are 18/min, and oxygen saturation is 98% on room air. QuantiFERON gold testing is positive. The patient is started on appropriate treatment. Which of the following is the most likely indication to discontinue this patient's treatment?

Answer: Elevated liver enzymes

Explanation:
This patient is presenting with weight loss and cough with a positive quantiFERON gold test suggestive of tuberculosis and has been started on treatment. The most likely indication to discontinue tuberculosis therapy is elevation of liver enzymes.

Tuberculosis typically presents with weight loss, cough, and night sweats usually in high-risk patients (prisoners or the immunosuppressed). It can be diagnosed using sputum samples as these organisms will be positive on an acid-fast test. These bacteria are slow to grow so cultures need to be held for an extended period of time. QuantiFERON gold testing can be used to make the diagnosis as well. Treatment for tuberculosis is RIPE therapy: Rifampin, Isoniazid, Pyrazinamide, and Ethambutol. The most common indication to alter or discontinue therapy is an elevation of liver enzymes 5 times greater than baseline.

Tweed et al. review the evidence regarding liver injury in patients with RIPE therapy. They discuss how patients on HIV therapy are at higher risk. They recommend measuring liver enzymes to detect this potential side effect.

Incorrect Answers:
Answer B: Hyperuricemia is a side-effect of pyrazinamide; however, this is not the most common indication for discontinuing RIPE therapy. Patients can be treated with supportive therapy or with uric acid lowering agents in those with arthralgias.

Answer C: Optic neuritis is a side-effect of ethambutol; however, it is not the most common indication for discontinuing RIPE therapy. Treatment is with discontinuation of ethambutol.

Answer D: Peripheral neuropathy is a side-effect of isoniazid; however, it is typically not an indication to discontinue RIPE therapy. Treatment is with supplementation of vitamin B6.

Answer E: Red body excretions are a side-effect of rifampin; however, this is a cosmetic concern rather than an indication to discontinue RIPE therapy. Patients should be counseled regarding this side effect prior to initiation of treatment.

Bullet Summary:
Elevation of liver enzymes 5 times above normal is the most common indication to alter or discontinue RIPE therapy when treating tuberculosis.


Question: A 27-year-old woman presents to her primary care physician with pain in her hands, shoulders, and knees. The pain has lasted for several months but seems to have worsened recently. Any activity such as opening jars, walking, or brushing her teeth is painful. The patient has a medical history of a suicide attempt in college, constipation, anxiety, depression, and a sunburn associated with surfing which was treated with aloe vera gel. Her temperature is 99.5°F (37.5°C), blood pressure is 137/78 mmHg, pulse is 92/min, respirations are 14/min, and oxygen saturation is 98% on room air. Laboratory values are obtained and shown below. Hemoglobin: 9 g/dL Hematocrit: 33% Leukocyte count: 2,500/mm^3 with normal differential Platelet count: 107,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 102 mEq/L K+: 4.4 mEq/L HCO3-: 24 mEq/L BUN: 21 mg/dL Glucose: 90 mg/dL Creatinine: 1.0 mg/dL Ca2+: 10.2 mg/dL AST: 12 U/L ALT: 10 U/L Which of the following findings is the most likely to be positive in this patient?

Anti-cyclic citrullinated peptide antibodies

Answer: Anti-dsDNA antibodies

Explanation:
This patient is presenting with arthralgias, pancytopenia, possible malar rash, and a history of depression/abnormal behavior. Epidemiologically, the most likely diagnosis is systemic lupus erythematosus (SLE) which is associated with anti-dsDNA antibodies.

SLE is an autoimmune disorder that most commonly occurs in young adult women. It presents with at least 4 criteria from SOAP BRAIN MD - Serositis, Oropharyngeal ulcers, Anti-nuclear antibodies, Photosensitivity, Blood disorders (pancytopenia and hemolytic anemia), Renal abnormalities (proteinuria), Arthralgias, Immune disease (hemolytic anemia and anti-dsDNA), Neurologic (psychosis, stroke, and seizure), Malar rash, and Discoid rash. The most common presenting symptoms for SLE can often be just arthralgias/arthritis with vague other symptoms suggestive of a rheumatologic disorder. Anti-nuclear antibodies are very sensitive for this pathology and anti-dsDNA antibodies are very specific. Treatment may include hydroxychloroquine as well as other immunomodulators and management of end-organ dysfunction.

Wang and Xia review the evidence regarding double stranded DNA in patients with SLE. They discuss how these antibodies are a very specific finding in this disease. They recommend measuring these levels.

Incorrect Answers:
Answer A: Anti-cyclic citrullinated peptide is associated with rheumatoid arthritis which is a possible diagnosis in this patient, but it is less likely epidemiologically given her age and other symptoms of pancytopenia and a history of sunburn (which is likely a malar rash or photosensitivity). Treatment is with methotrexate.

Answer C: Anti-histone antibodies would be found in drug-induced lupus. This patient's medication history is not known; however, this is a less likely diagnosis compared to SLE. Treatment is with discontinuation of the offending medication.

Answer D: Degenerated cartilage in weight bearing joints describes osteoarthritis which tends to affect the knees and hips in older patients. Treatment is with conservative management or with total joint replacement.

Answer E: IgM against parvovirus B19 describes a parvovirus B19 infection which commonly presents with arthralgias; however, her other symptoms point towards a diagnosis of SLE. Treatment is supportive.

Bullet Summary:
Arthritis/arthralgias are often the most common presenting symptom for SLE.


Question: A 6-month-old boy is brought to the physician by his mother for abnormal movements. Several times a day, he experiences paroxysmal episodes of crying, bending at the waist, and jerking of the arms and legs. These episodes last 1-2 seconds, but occur in clusters every 20-30 seconds for several minutes. His mother's pregnancy, labor, delivery, and his neonatal course have been unremarkable. He is rolling over less frequently than before, has worse head control, and no longer smiles socially. His temperature is 98.6°F (37°C), blood pressure is 92/46 mmHg, pulse is 115/min, and respirations are 34/min. On examination, no dysmorphic features are noted. A 24-hour electroencephalography (EEG) is performed, during which the patient has one of these spells. A chaotic pattern of slowing and multifocal epileptiform charges is seen. Which of the following is the pathophysiology of this patient's condition?

Decreased gamma aminobutyric acid (GABA) levels

Excess of corticotropin releasing hormone

Answer: Excess of corticotropin releasing hormone

Explanation:
This patient with infantile spasms (bending at the waist and jerking out the arms and legs), developmental regression (rolling over less frequently, worsening head control, loss of social smile), and hypsarrhythmia on video-EEG (slowing and multifocal epileptiform discharges) are characteristic of West syndrome. West syndrome is caused in part by an excess of corticotropin-releasing hormone which leads to increased neuronal excitability.

The pathogenesis of West syndrome is incompletely understood. Infantile spasms are often idiopathic, but may also be secondary to tuberous sclerosis, hypoxic-ischemic encephalopathy, congenital brain malformations, aminoacidopathies, and organic acidopathies. Brain insults may activate a neuroendocrine stress response, which in turn leads to abnormalities of the hypothalamic-pituitary-adrenal axis. Disturbed immune activation may also play a role. Patients will present with infantile spasms, developmental regression, and slowing and multifocal epileptiform discharges known as hypsarrhythmia. Many affected infants are responsive to ACTH therapy, with cessation of spasms and resolution of hypsarrhythmia in many cases.

D’Alonzo et al. review the epidemiology, clinical presentation, pathophysiology, and treatment of West syndrome. They discuss how patients will present with the classic symptoms of spasms and regression. They recommend early diagnosis of this syndrome so that patients can be treated appropriately.

Incorrect Answers:
Answer B: Abnormalities in T-type calcium channels may contribute to absence seizures. Absence seizures are generalized seizures that involve brief, sudden lapses of consciousness and are more common in children. This child’s developmental regression, infantile spasms, and EEG findings are more consistent with West syndrome.

Answer C: Anti-N-methyl-D-aspartate (NMDA) receptor antibodies may cause anti-NMDA encephalitis. Anti-NMDA encephalitis presents with seizures, psychiatric manifestations, and decreased level of consciousness. Hypsarrhythmia is characteristic of West syndrome and is not consistent with anti-NMDA encephalitis.

Answer D: Decreased gamma-aminobutyric acid (GABA) levels were once theorized to be the basis of epilepsy syndromes. This theory is less accepted today. Moreover, West syndrome is likely not mediated by disturbances in GABA. Nonetheless, vigabatrin, which in part works by inhibiting GABA metabolism, is an effective medication for patients with West syndrome.

Answer E: Vitamin B6 deficiency has not been documented in West syndrome. Some studies have suggested vitamin B6 may be of some benefit in the treatment of infantile spasms; however, there is no evidence that response rates to B6 are different from the spontaneous remission rates predicted from natural history data. Therefore, the pathophysiology of West syndrome is more likely CRH-excess mediated rather than due to a deficiency of vitamin B6.

Bullet Summary:
West syndrome, which may be caused by CRH excess, presents with hypsarrhythmia, developmental regression, and infantile spasms.


Question: A 55-year-old man presents with a 2-day history of mono-articular joint pain. He is otherwise healthy and denies fever, chills, or recent trauma. His medical history is notable for a kidney stone 6 months ago. He underwent a dental procedure to extract an infected wisdom tooth 3 weeks ago. The patient does not take any medications. He is a non-smoker and does not drink alcohol or use recreational drugs. His family history is significant for osteoarthritis in his father who is 78. His temperature is 98.6°F (37°C), blood pressure is 133/84 mmHg, pulse is 84/min, and respirations are 15/min. His body mass index is 27 kg/m^2. Physical examination shows a swollen and tender joint with overlying erythema. Diagnostic arthrocentesis is performed and shows a leukocyte count of 30,000/mm^3 with 85% neutrophils. Polarized microscopy of the synovial fluid is shown in Figure A. Which of the following would most likely be found on this patient’s radiograph?

Answer: Chondrocalcinosis

Explanation:
This patient is presenting with a joint aspiration positive for calcium pyrophosphate dehydrate crystals, suggesting a diagnosis of pseudogout, which may show chondrocalcinosis on radiography.

Pseudogout presents classically with mono- or oligo-articular arthritis that most often affects the knee and proximal joints of elderly patients (> 60 years of age). The disease can be associated with hyperparathyroidism, Gitelman syndrome, familial hypocalciuric hypercalcemia, and hemochromatosis. The patient will have a leukocyte count < 50,000/mm^3 on joint aspiration and positively birefringent, rhomboid-shaped cells on microscopy, which represent calcium pyrophosphate dehydrate (CPPD) crystals. On radiography, chondrocalcinosis can be found, which is the calcification of adjacent cartilaginous structures. Treatment is with indomethacin.

Sidari and Hill review the evidence regarding the diagnosis and treatment of gout and pseudogout. They discuss how diagnosis can be made with fluid microscopy. They recommend treatment with non-steroidal anti-inflammatory drugs.

Figure/Illustration A is polarized microscopy of joint fluid showing rhomboid-shaped crystals that are positively birefringent (red circles). These represent calcium pyrophosphate dehydrate crystals seen in pseudogout.

Incorrect Answers:
Answer A: Boutonniere deformity is characterized by proximal interphalangeal (PIP) joint flexion and distal interphalangeal (DIP) joint extension and is a common hand deformity of rheumatoid arthritis. Rheumatoid arthritis is characterized by insidious onset of morning stiffness and pain that usually affects symmetric PIP and metacarpophalangeal (MCP) joints first. On joint aspiration, leukocyte count ranges from 5,000-50,000/mm^3, but rheumatoid arthritis would not explain the CPPD crystals. Treatment may include methotrexate.

Answer C: Heberden nodes are bony protuberances in the DIP joints, which are characteristic of osteoarthritis. Osteoarthritis presents with insidious onset of joint pain that worsens with activity and weight-bearing. On joint aspiration, the leukocyte count is < 2,000/mm^3.

Answer D: Juxta-articular osteoporosis is decreased bone density of the bone surrounding the joint space. It is a nonspecific sign that can be seen with many inflammatory joint diseases such as rheumatoid arthritis or septic arthritis. Septic arthritis presents with mono-articular joint pain, erythema, and swelling. Joint aspiration will show a leukocyte count > 50,000/mm^3 and Gram stain may be positive.

Answer E: Tophi are deposits of urate crystals in the soft tissue, which are nearly pathognomonic for gout. Gout presents as acute, mono-articular joint pain with physical examination showing a red, inflamed joint (usually the first metatarsophalangeal, knee, or ankle joint). Needle-shaped, negatively birefringent urate crystals are seen in the joint fluid aspirate. Prevention may include allopurinol.

Bullet Summary:
Pseudogout is associated with positively birefringent, rhomboid-shaped crystals and chondrocalcinosis.


Question: A 45-year-old man presents to a physician due to difficulty swallowing and slurred speech. For the past 3 months, the patient has been coughing when he drinks liquids. His speech also sounds different according to his wife. The patient has no significant medical history. His temperature is 98.6°F (37.0°C), blood pressure is 110/80 mmHg, pulse is 60/min, and respirations are 12/min. On physical exam, he is unable to fully extend his tongue, and there are fasciculations on his tongue. When tapping the mandible at the chin while the mouth is held open, there is pronounced upward movement of the lower jaw. Sensory exam reveals no deficits. Which of the following therapies is most likely to improve survival for this patient's disease process?

Answer: Riluzole

Explanation:
This patient with dysphagia (difficulty swallowing water), dysarthria (altered and slurred speech), lower motor neuron deficits (tongue fasciculations and weakness), upper motor neuron deficits (exaggerated jaw jerk reflex), and preserved sensory function most likely has amyotrophic lateral sclerosis (ALS). Riluzole, a glutamate inhibitor, is currently the only Food and Drug Administration (FDA) approved medication that improves survival in patients with ALS.

ALS is a neurodegenerative disease that affects both upper and lower motor neurons. Upper motor neuron signs include spasticity and hyperreflexia, while lower motor neuron signs include muscle atrophy and fasciculations (spontaneous, involuntary muscle contraction and relaxation). In patients with bulbar-onset ALS, the initial clinical presentation is dysarthria, dysphagia, tongue atrophy, and abnormal jaw jerk reflex. Riluzole decreases the rate of glutamate release from presynaptic neurons, which is thought to decrease excitatory neurotoxicity. Riluzole improves survival by 2-6 months in patients with ALS and may have a greater survival benefit in patients with bulbar-onset ALS.

Masori and Van Damme review the genetics, pathophysiology, classic clinical presentation, extra-motor manifestations, diagnostic workup, and treatment for ALS. They discuss how riluzole provides a survival benefit in patients with this disease. They recommend treating patients with ALS using riluzole as tolerated.

Incorrect Answers:
Answer A: Baclofen is a gamma-aminobutyric acid (GABA) agonist that reduces the release of excitatory neurotransmitters to decrease spasticity in ALS. Along with tizanidine, baclofen is a first-line symptomatic treatment for spasticity in ALS. Baclofen does not improve survival in ALS.

Answer B: Dextromethorphan and quinidine is a combination of a sigma opioid receptor agonist and a sodium channel blocker used to control pseudobulbar affect in patients with ALS. Pseudobulbar affect is a sudden uncontrollable outburst of laughter or tearfulness that affects almost half of patients with ALS. Dextromethorphan and quinidine has not been shown to improve survival in ALS.

Answer C: Edaravone is an intravenous antioxidant that may decrease the progression of early ALS. Although it is now FDA approved, studies have not yet shown that edaravone improves survival in patients with ALS. Further studies will be needed in order to determine the risks and benefits of using this drug.

Answer E: Tizanidine is a central alpha-2-adrenergic receptor agonist that decreases spasticity in ALS by increasing presynaptic inhibition of motor neurons. Excess spasticity in ALS can negatively impact coordination, ambulation, and other activities of daily living. Tizanidine and other antispastic medications do not improve survival in patients with ALS.

Bullet Summary:
Riluzole is a glutamate inhibitor that improves survival in patients with amyotrophic lateral sclerosis.