Question: A 47-year-old man is brought in after a motor vehicle accident. He was driving under the influence of alcohol when he sustained a crash against a pole. His medical history is significant for hypertension but he does not take any medications. 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 a ventilator. His Glasgow coma score (GCS) on presentation is 6. Initial urine toxicology is negative. The patient is admitted to the intensive care unit and appropriate care is initiated. One week later, the patient’s GCS score is now 3. Laboratory studies do not show significant electrolyte, acid-base, or endocrine disturbances. Sedative and paralytic agents are withdrawn. Which of the following findings on physical exam would be compatible with brain death?

Grimacing after noxious stimulus to the arm

Flexion of the thigh, leg, and foot upon noxious stimulation of the foot

Answer: Flexion of the thigh, leg, and foot upon noxious stimulation of the foot

Explanation:
This patient with a Glasgow coma score (GCS) of 3 and a known mechanism of injury due to motor vehicle accident trauma is normothermic, normotensive, not on sedatives, and without laboratory abnormalities so they are appropriate for examination of brain death. Cortical and brain stem function must be absent in brain death; however, spinal cord reflexes such as triple flexion (flexion of the thigh, leg, and foot upon noxious stimulation of the foot) may remain intact in patients with brain death.

The clinical brain death exam may be performed in patients with evidence of irreversible central nervous system catastrophe after a known mechanism of trauma or medical injury. The patient must not have other causes for obtundation, and should be euthermic, not on sedative or paralytic agents, not be intoxicated due to drugs or poisoning, and not have other severe electrolyte, acid-base, or endocrine disturbances. In brain death, there must be no cerebral motor response such as moaning or grimacing to pain in all extremities and the face. Brain stem reflexes such as the pupillary light reflex, corneal reflex, oculocephalic reflex, vestibulo-ocular reflex, gag reflex, and apnea test should also be absent in brain death. Spinal cord and deep tendon reflexes may still be present in brain death. Complex movements mediated by the spinal cord such as triple flexion and the Lazarus sign (raising the arms and dropping them crossed on the chest after noxious stimulus) do not preclude a diagnosis of brain death.

Greer et al. review neurologic criteria for the determination of brain death. They discuss how to clinically differentiate spinal motor responses from brain-mediated motor responses. They recommend understanding these distinctions in order to properly examine patients with brain death.

Incorrect Answers:
Answer A: Blinking after saline is applied to the cornea indicates a positive corneal reflex. In the corneal reflex, the ophthalmic branch of the trigeminal (V1) nerve senses stimulus to the cornea, and bilateral temporal branches of the facial nerve (VII) activate the orbicularis oculi muscles to blink. Brainstem reflexes must be absent in brain death, so the presence of a corneal reflex is not compatible with a diagnosis of brain death.

Answer B: Conjugate eye movement to the left with rotation of the head to the right describes the oculocephalic reflex. In this reflex, movement of the head stimulates endolymph in the horizontal semicircular canal to rotate, causing the firing of the ipsilateral vestibulocochlear (VIII) nerve. This leads to activation or inhibition of the contralateral abducens (VI) and oculomotor (III) nerves. Brainstem reflexes must be absent in brain death, so the presence of an oculocephalic reflex is not compatible with a diagnosis of brain death.

Answer D: Grimacing after the noxious stimulus of the arm indicates some residual cortical function. Grimacing is not a spinal cord reflex and requires some cortical processing of sensory information. All cortical function must be absent in brain death, so grimacing to pain would not be compatible with brain death.

Answer E: Spontaneous respiration 1 minute after disconnection from a ventilator in a patient without diabetes insipidus and with normal blood gas values and systolic blood pressure above 90 mmHg indicates a negative apnea test. The apnea test assesses respiratory control system reflexes in the brainstem. Apnea testing is an important component of the brain death exam, and a negative apnea test is incompatible with brain death.

Bullet Summary:
Although brain death criteria universally include the absence of cortical and brainstem function, spinal cord and deep tendon reflexes may be preserved in patients with brain death.


Question: A 14-year-old boy presents to his pediatrician with a 2-month history of intermittent arm and leg spasms. He says that the spasms usually occur after he wakes up as he is getting ready for school, and consist of disorganized jerking motions that stop after a few minutes. He has also noticed that they occur when he stays up late to cram last minute for exams. He has not noticed any other symptoms. He has no medical history and takes no medications. He recently started experimenting with alcohol and marijuana that one of his friends has been stealing from their parents. His temperature is 98.6°F (37.0°C), blood pressure is 115/70 mmHg, pulse is 70/min, and respirations are 12/min. Physical exam reveals a healthy child. Which of the following is the most likely cause of this patient's symptoms?

Answer: Juvenile myoclonic epilepsy

Explanation:
This patient who presents with intermittent jerking of his extremities that occur primarily after waking up or when sleep-deprived most likely has juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a poorly understood condition that presents with intermittent myoclonic jerks of the extremities. These myoclonic jerks usually have an onset occurring in early adolescence in otherwise healthy children. Myoclonic jerks are most frequently seen right after waking from sleep, but they may also be triggered by lack of sleep, stress, or alcohol consumption. Patients with this disease rarely have associated symptoms but may occasionally also experience absence seizures or generalized tonic-clonic seizures. The diagnosis can be secured with a history of seizures alongside an interictal electroencephalogram (EEG) that shows 4 to 6 Hz bilateral polyspikes. Valproate is the first-line treatment.

Johannessen et al. discuss the treatment of juvenile myoclonic epilepsy. They find that standard antiepileptic treatment with agents such as valproate leads to only 33% of patients remaining seizure-free. They recommend trials of alternative antiepileptic medications such as levetiracetam, lamotrigine, and topiramate in patients that do not respond to valproate.

Incorrect Answers:
Answer A: Absence seizures commonly present during childhood in otherwise healthy children; however, these seizures are typically characterized by short episodes of loss of awareness known as "staring spells" without physical manifestations.

Answer B: Alcohol intoxication is a risk factor for precipitating juvenile myoclonic epilepsy, but alcohol use does not cause this condition. Seizure activity may also occur during alcohol withdrawal, but the timing of this patient's symptoms is more suggestive of seizure symptoms. Alcohol withdrawal requires chronic drinking of large amounts leading to an increase in central nervous system N-methyl-D-aspartate receptors and a decrease in CNS gamma-aminobutyric acid type A receptors. When alcohol cessation occurs, seizures ensue.

Answer C: Cannabinoid use is not associated with seizure activity either during intoxication or withdrawal. Patients may have altered mental status, but this does not manifest as myoclonic jerks.

Answer E: West syndrome is an infantile seizure disorder that usually presents between 3 months and 12 months of age. These patients will present with recurrent flexion spasms of the extremities.

Bullet Summary:
Juvenile myoclonic epilepsy presents in adolescents with recurrent spasms after waking from sleep or when sleep-deprived.


Question: A 65-year-old man presents to the emergency department with low back pain. The pain started 6 hours ago when he was gardening and carrying a heavy bag. The pain is rated as 10/10 in severity and radiates down the posterior aspect of the right thigh. He reports no fevers or chills. His only medical problem is hypertension for which he takes amlodipine. The patient is a non-smoker, uses alcohol infrequently, and has never used illicit drugs. His temperature is 99.6°F (37.6°C), blood pressure is 140/70 mmHg, pulse is 90/min, and respirations are 20/min. Physical examination reveals 3/5 strength to hip extension, knee flexion and extension, and plantar flexion bilaterally. Sensation to pinprick is diminished over the posterolateral legs and lateral aspects of both feet. Ankle and knee reflexes are absent bilaterally. The patient’s underwear is wet and a bladder scan reveals 800 mL of urine. Which of the following is the most likely underlying diagnosis?

Answer: Cauda equina syndrome

Explanation:
This patient presenting with acute, severe, radiating low back pain with sensorimotor deficits (3/5 strength in hip extension, knee flexion/extension, plantar flexion, reduced sensation to pinprick) in multiple nerve root distributions (L3-S5), lower motor neuron signs, urinary incontinence (wet underwear), and acute urinary retention (bladder scan showing 800 mL of urine) most likely has cauda equina syndrome.

Cauda equina syndrome is characterized by deficits in 2 or more nerve roots that comprise the cauda equina of the spinal cord. It has multiple etiologies, including disc herniation, epidural abscess, tumor, or lumbar spine spondylosis. Cauda equina syndrome presents with severe low back pain radiating into the legs, flaccid paralysis or lower extremity weakness which can be symmetric or asymmetric (often asymmetric), bladder and/or rectal sphincter paralysis, impotence/erectile dysfunction, sensory loss in affected dermatomes, and saddle anesthesia (sensory loss in the perineum). Urinary retention occurs due to bladder paralysis. Diagnosis is aided by emergency magnetic resonance imaging. Cauda equina syndrome is a surgical emergency; the goal of surgical treatment is to decompress the cauda equina to prevent permanent neurological injury, such as with a lumbar laminectomy. This can be differentiated from conus medullaris syndrome, which has perianal numbness without numbness through other dermatomes (down the leg in the S1 or S2 patterns), less severe pain (cauda equina presents with more severe pain), and hyperreflexia in the knees (cauda equina presents with lower motor neuron signs in the legs which lead to decreased reflexes - though conus medullaris may present with absent ankle reflexes, the knees are typically hyperreflexic).

Gardner et al. review the symptoms, diagnosis, and medico-legal landscape of cauda equina syndrome. They discuss how the most frequent etiology is a large central lumbar disc herniation. They recommend being vigilant for urinary retention in patients who may have compression as many patients have urinary retention on presentation.

Incorrect Answers:
Answer A: Acute inflammatory demyelinating polyneuropathy, also known as Guillain-Barre syndrome, occurs after respiratory or gastrointestinal infections and presents with ascending paralysis and diminished reflexes. While bladder dysfunction can occur, back pain is not typical. Guillain-Barre syndrome can be treated with intravenous immunoglobulin.

Answer C: L5/S1 disc herniation affects the traversing S1 nerve root. S1 radiculopathy presents with posterolateral leg and dorsolateral foot sensory loss and absence of the ankle reflex. Typically, bowel/bladder symptoms are not present. Treatment includes decompression of the affected nerve root.

Answer D: Overflow incontinence is caused by either bladder outlet obstruction or poor bladder tone. While this could explain this patient’s urinary retention, it does not account for his back pain or sensorimotor deficits. Isolated overflow incontinence can be treated with catheterization.

Answer E: Spinal stenosis presents with lower extremity claudication, characterized by pain with standing or ambulation. The pain of neurogenic claudication is characteristically relieved by spinal flexion (“shopping cart sign”). Sensory loss and motor weakness can be present; however, bladder dysfunction is atypical. Treatment includes surgical decompression of the area of stenosis.

Bullet Summary:
Cauda equina syndrome is characterized by impingement of 2 or more nerve roots of the cauda equina, resulting in radicular pain, bilateral lower extremity weakness, lower motor neuron signs, sensory loss in affected dermatomes, bowel/bladder dysfunction, and saddle anesthesia.


Question: A 65-year-old woman presents to her family doctor to reestablish care since losing her insurance. She has not had time for regular check-ups. She exercises 3-4 times a week and consumes red meat sparingly. She drank and smoked cigarettes socially with coworkers but never at home or on vacation. She wakes up with achy wrists and elbows that she suspects is from years of using a computer keyboard. She completed menopause at age 52. Her family history is notable for coronary artery disease on her father's side and colon cancer on her mother's side. She last had a colonoscopy 5 years ago that revealed no abnormal findings. Her temperature is 99°F (37.2°C), blood pressure is 125/83 mmHg, pulse is 82/min, respirations are 12/min, and oxygen saturation is 99% on room air. Her physical exam is grossly unremarkable. What diagnostic test should this patient receive?

Answer: Mammography

Explanation:
This vignette describes an otherwise healthy elderly woman seeking to establish primary care. Among the answer choices, mammography is the most appropriate diagnostic test to recommend.

Mammography is a screening tool for breast cancer that becomes most effective in postmenopausal patients because of less glandular breast tissue compared to younger patients. According to the United States Preventive Services Task Force, all women aged 50-74 should have mammograms every 1-2 years. It is controversial whether screening mammography should begin as early as age 40. Women with 1st-degree relatives with breast cancer should begin screening 10 years before the age of the family member's diagnosis.

Seely and Alhassan review the evidence regarding the screening methods used for breast cancer. They discuss how screening every 1-2 years decreases breast cancer mortality. They recommend using judicious mixed modal methods of screening.

Incorrect Answers:
Answer A: Routine chest radiography for lung cancer screening in low-risk patients is not recommended by the USPSTF. Chest imaging can be used to screen for lung cancer in patients with a significant smoking history.

Answer B: Colonoscopy for colon cancer screening is recommended every 10 years starting at age 50. This patient already had a colonoscopy 5 years ago so she does not need another exam at this time.

Answer D: Pelvic ultrasound for ovarian cancer screening is not currently recommended by the USPSTF. Ovarian cancer detection should also be performed in patients who are symptomatic.

Answer E: Vitamin D level for osteoporosis screening is not recommended. DEXA scans would be more appropriate for testing bone density.

Bullet Summary
According to the United States Preventive Services Task Force, all women aged 50-74 should have mammograms every 1-2 years.


Question: A 25-year-old man presents to his gastroenterologist for trouble swallowing. Whenever he eats solids, he regurgitates them back up. Given this patient's suspected diagnosis, the gastroenterologist performs a diagnostic test. Several hours later, the patient presents to the emergency department with chest pain and shortness of breath. His temperature is 99.5°F (37.5°C), blood pressure is 130/85 mmHg, pulse is 60/min, respirations are 12/min, and oxygen saturation is 99% on room air. On physical exam, the patient demonstrates a normal cardiopulmonary exam. His physical exam demonstrates no tenderness of the neck, a normal oropharynx, palpable crepitus above the clavicles, and minor lymphadenopathy. Which of the following is the most appropriate next step in management?

Answer: Gastrografin swallow

Explanation:
This patient is presenting with chest pain and palpable crepitus after endoscopy suggesting a diagnosis of esophageal perforation. The most appropriate next step in management is a gastrografin swallow.

Esophageal perforation presents with severe chest pain and palpable crepitus typically occurring after endoscopy or repeated forceful vomiting. The most appropriate initial step in management is a water-soluble contrast image (gastrografin) in order to confirm the diagnosis. Alternatively, a CT scan or radiograph may also be appropriate initially. Once the diagnosis is confirmed, surgical correction is necessary in order to prevent gastric contents from continuing to enter the mediastinum. Broad-spectrum antibiotics and proton pump inhibitors should also be administered.

Kim reviews the factors associated with esophageal perforation and rupture. They discuss how causes include foreign body, iatrogenic, trauma, and forceful vomiting. They recommend urgent surgical treatment.

Incorrect Answers:
Answer A: Barium swallow would be inappropriate as it is an irritating substance and could travel out of the perforated esophagus. This substance is only used in rare cases when gastrografin is not revealing, per the discretion of the surgeon.

Answer C: MRI would appropriately diagnose the condition but acquiring such imaging would take too long for such an urgent presentation. A gastrografin swallow is a more appropriate initial test.

Answer D: Ultrasound is inappropriate as it does not demonstrate the location of the perforation and the information obtained is dependent on the habitus of the patient and the operator.

Answer E: Urgent surgery would be necessary once the diagnosis is confirmed. Performing a rapid diagnostic step is necessary in order to establish the diagnosis first.

Bullet Summary:
The most appropriate initial step in the management of esophageal perforation is a gastrografin swallow followed by surgery.


Question: A 60-year-old woman presents to the emergency department with back pain after gardening. Her pain is 7/10 in severity, non-radiating, and not relieved by rest. She has never experienced this pain in the past and denies fever, night sweats, unintentional weight loss, and bowel or bladder incontinence. She has hypertension for which she takes hydrochlorothiazide and had a recent asthma flare requiring a prednisone taper. She does not drink alcohol or smoke. Her temperature is 98.6°F (37.0°C), blood pressure is 120/80 mmHg, pulse is 90/min, and respirations are 18/min. Physical exam reveals an uncomfortable middle-aged woman in no acute distress. There is no tenderness to palpation of the spinous processes. Flexion of the hip with the knee extended while the patient is supine does not elicit any pain, nor does forced dorsiflexion of the foot at terminal hip extension. She has 5/5 strength to hip flexion, extension, abduction, and adduction; knee flexion and extension; and ankle dorsiflexion and plantarflexion bilaterally. Bilateral patellar and Achilles reflexes are 2+. Serum laboratory results are as follows: Hemoglobin: 12.0 g/dL Creatinine: 1.1 mg/dL Ca2+: 10.6 mg/dL Which of the following is the most likely diagnosis?

Answer: Lumbosacral strain

Explanation:
This patient presents with acute low back pain after physical exertion without radicular signs (e.g., motor or sensory changes in a nerve root distribution) and a negative straight leg raise, which are most consistent with lumbosacral strain.

The evaluation of acute low back pain is focused on eliciting clinical history and signs that would indicate further work-up. In patients without significant trauma, the presence of signs of spinal cord compression (e.g., urinary retention, bowel incontinence, saddle anesthesia, focal neurologic deficits), history of or strong risk factors for cancer, signs of infection, or risk of vertebral compression fracture should prompt additional work-up with imaging such as radiographs or magnetic resonance imaging. If none of these findings are present (most patients with acute low back pain in the primary care setting), then conservative therapy for 4-6 weeks consisting of non-steroidal anti-inflammatory drugs with or without physical therapy is indicated.

Patel and Ogle review the management of acute low back pain in the primary care setting. They outline the Waddell signs, which indicate the presence of a functional (signs of excessive pain behavior) aspect of pain. The authors recommend surgical evaluation only in patients with worsening neurologic deficits or intractable pain resistant to conservative treatment.

Incorrect Answers:
Answer A: Herniated discs occurs when the nucleus pulposus herniates through a weakened part of the annulus fibrosus of an intervertebral disc, resulting in spinal nerve root compression. This causes radicular findings at the level of compression, including weakness in hip abduction and ankle dorsiflexion with L5 involvement and weakness in ankle plantarflexion and reduced Achilles reflex with S1 involvement, and radiation of pain into the ipsilateral lower extremity. The straight leg raise test would be positive, as it exacerbates the nerve root compression.

Answer C: Multiple myeloma presents with hypercalcemia, anemia, renal failure, and lytic bone lesions causing bone pain. This patient has no constitutional symptoms to suggest a malignant process and has a mild elevation in serum calcium, which is likely due to her thiazide diuretic. The clear association of her back pain with exertion makes lumbosacral strain more likely.

Answer D: Spondylolisthesis occurs when a vertebral body is forwardly subluxated relative to the adjacent vertebral body. This presents as back pain alleviated by rest. Since this can narrow the spinal canal, it may also present with neurogenic claudication, manifesting as buttock or leg pain with walking that can be alleviated by bending forward. This patient’s back pain is not alleviated by rest and is associated with exertion.

Answer E: Vertebral compression fractures can present as back pain in a patient with minor or no trauma. These patients have osteoporosis and other risk factors like advanced age or chronic corticosteroid use and would have point tenderness at the site of fracture. This patient does not have point tenderness or risk factors.

Bullet Summary:
Lumbosacral strain is a common cause of acute low back pain that presents after physical exertion with no radicular signs and a negative straight leg raise test.


Question: A 30-year-old man is evaluated in the post-anesthesia care unit for neck pain. He underwent a laparoscopic appendectomy and was treated for post-operative nausea and vomiting with metoclopramide. Approximately 20 minutes after receiving the medication, he developed pain and stiffness in his neck and eventually was unable to move his neck. His temperature is 98.6°F (37.0°C), pulse is 90/min, blood pressure is 130/80 mmHg, respirations are 16/min, and oxygen saturation is 98% on room air. Examination reveals an uncomfortable appearing man. His neck is rotated to the right and is unable to return to midline. Examination of the patient is shown in Figure A. Which of the following is the most appropriate next step in management?

Answer: Diphenhydramine

Explanation:
This patient is suffering from a metoclopramide-induced acute dystonic reaction. Treatment of this complication includes IV diphenhydramine or benztropine.

Dystonic reactions are reversible extrapyramidal symptoms that may include involuntary spasms or sustained contractions of the face, neck, torso, pelvis, extremities, and larynx. Medications that block dopamine D2 receptors carry the greatest risk for development of a dystonic reaction, most notably including neuroleptics, antidepressants, and antiemetics. A family history of dystonia increases the risk of developing a reaction (there is likely an underlying genetic predisposition). Diagnosis is typically based on history and clinical presentation. Intravenous anticholinergic agents are the first-line treatment, and symptoms typically resolve rapidly (within 1 hour) after initiation of these agents.

Dressler et al. discuss the diagnosis and management of medication-induced acute movement disorders, notably dystonic reactions. These reactions are most commonly caused by dopamine-receptor blocking agents, including antipsychotics and antiemetics. Cranial, pharyngeal, and cervical muscles are typically affected within the first 4 days of initiating treatment.

Figure A shows a patient with dystonia and torticollis; note the posturing of the extremities as well as how the head is tilted to the patient's right side while the chin is directed up and towards the left.

Incorrect Answers:
Answer A: Intramuscular botulinum toxin injection may be appropriate for chronic torticollis or other forms of chronic dystonia. This patient has acute dystonia that is generally able to be easily reversed with intravenous diphenhydramine.

Answer C: Intravenous haloperidol, a D2 receptor antagonist would not be appropriate. This patient's condition is due to the dopamine antagonist action of metoclopramide and would therefore be worsened with haloperidol.

Answer D: Observation would not be appropriate. This patient is experiencing an acute dystonic reaction that is uncomfortable and potentially dangerous. Acute dystonia is not likely to self resolve in a reasonable amount of time.

Answer E: Intravenous ondansetron may be a more appropriate option to treat this patient's nausea given his reaction to metoclopramide. However, it will not reverse the acute dystonic reaction and is not the most appropriate first step.

Bullet Summary:
Acute dystonic reaction may occur with administration of medications that block dopamine receptors (such as metoclopramide), and can be treated with intravenous diphenhydramine.


Question: A 27-year-old woman presents to the emergency department with altered mental status. Her boyfriend found her at home next to a suicide note and brought her into the emergency department. According to her boyfriend, the patient has a medical history of bipolar disorder for which she takes lithium, as well as chronic lower back pain for which she sees a pain specialist. Her temperature is 100.5°F (38.1°C), blood pressure is 102/78 mmHg, pulse is 127/min, respirations are 19/min, and oxygen saturation is 99% on room air. An ECG is performed as seen in Figure A. Which of the following findings is also likely to be present at some point in this patient’s course?

Answer: Urinary retention

Explanation:
This patient is presenting after a suicide attempt with an unknown overdose and is confused, febrile, tachycardic, and has QRS widening on ECG. This combination of symptoms is highly concerning for a tricyclic antidepressant (TCA) overdose which can cause an anticholinergic toxidrome and urinary retention.

Tricyclic antidepressants (TCAs) were once a mainstay in the treatment of depression before the advent of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs). They are sometimes still used for depression and neuropathic pain. In overdose, TCAs block sodium channels in the heart and cause a pathognomonic QRS widening. Sodium bicarbonate should be administered until the QRS duration normalizes. TCAs also have anticholinergic properties and can cause an anticholinergic toxidrome including delirium, confusion, constipation, decreased bowel sounds, urinary retention, dry, warm, and flushed skin, and fever. Although physostigmine is typically the antidote of choice for an anticholinergic toxidrome, it is avoided in TCA toxicity due to the theoretical concern for inducing a cardiac arrest.

Urquhart et al. studied the utility of tricyclic antidepressants in the treatment of chronic lower back pain. They found no significant difference in pain reduction compared to placebo. They recommend further study of the potential benefits of TCAs, independent of sleep improvement, for the treatment of lower back pain.

Figure/Illustration A is an ECG demonstrating QRS widening (note how long the red lines are which demarcate the QRS duration) which is highly concerning for TCA overdose.

Incorrect Answers:
Answer A: Diaphoresis, tachycardia, increased bowel sounds, and agitation would be seen in a sympathomimetic toxidrome from drugs like cocaine or amphetamines. Rather, dry, flushed skin would be seen in an anticholinergic toxidrome.

Answer B: Jaundice, nausea, vomiting, and abdominal pain would be seen in acetaminophen overdose which can cause fulminant liver failure. It is also possible that patients may initially be asymptomatic in acetaminophen overdose, and a high level of suspicion must be maintained for this diagnosis. A serum acetaminophen level should be drawn in any patient suspected of overdose.

Answer C: Miosis, bradypnea, decreased bowel sounds, and somnolence would be seen in an opioid toxidrome. Rather, dilated and minimally responsive pupils would be seen in an anticholinergic toxidrome.

Answer D: Wheezing, bronchorrhea, urinary incontinence, fecal incontinence, confusion, and drooling would be seen in a cholinergic toxidrome from agents such as organophosphates or nerve gases like sarin. None of these symptoms are seen in this patient.

Bullet Summary:
A tricyclic antidepressant overdose can cause QRS widening on ECG as well as an anticholinergic toxidrome (dry, flushed skin, constipation, decreased bowel sounds, urinary retention, and altered mental status).


Question: A 35-year-old man presents to the emergency department with altered mental status. He was found by his roommate to be disoriented this morning. He had complained of a right-sided headache for the past 5 days. He has a history of human immunodeficiency virus (HIV) infection being treated with bictegravir, emtricitabine, and tenofovir. His last CD4 cell count was 500/mm^3. He does not smoke tobacco and drinks alcohol socially. His temperature is 104.2°F (40.1°C), blood pressure is 110/70 mmHg, pulse is 110/min, and respirations are 22/min. Examination reveals 3/5 strength to right shoulder abduction and elbow flexion/extension and 4/5 strength to right hip flexion/extension. The remainder of the strength exam on the right and left sides is normal. Neck flexion does not elicit pain, and there are no tongue lacerations. During the exam, the patient’s eyes are seen to roll backward with repeated flexion/extension of his extremities and loss of urine. This stops after 1 minute. Which of the following is the most likely diagnosis?

Answer: Brain abscess

Explanation:
This HIV-positive patient presents with fever, unilateral headache, altered mental status, focal neurological deficits (3/5 strength to right shoulder abduction, elbow flexion/extension, hip flexion/extension), and a generalized tonic-clonic seizure, suggestive of a brain abscess.

A brain abscess typically presents in patients with underlying risk factors for infection, such as positive HIV status or bacterial endocarditis with hematogenous bacterial seeding. Patients present with fever, unilateral headache, altered mental status, focal neurological deficits, and fevers. Work-up consists of blood cultures, CT scan, and confirmatory magnetic resonance imaging with gadolinium contrast, showing a focal, hyperintense lesion with restricted diffusion. Treatment is with empiric broad-spectrum antibiotic therapy (e.g., vancomycin, metronidazole, and cefepime for gram-positive, gram-negative, and Pseudomonas coverage in immunocompromised patients) and surgical drainage.

Brouwer et al. review the causes, diagnosis, and treatment of brain abscesses. They discuss the importance of rapid initiation of antimicrobial therapy in these patients.

Incorrect Answers:
Answers 1 & 5: Bacterial or fungal meningitis can present with fever, headache, focal neurological deficits, and seizures but patients typically have meningeal signs such as pain with neck flexion. Cryptococcal meningitis is commonly seen in HIV-positive patients with CD4 counts < 100/mm^3.

Answer C: Cytomegalovirus encephalitis can present with fever, altered mental status, headache, and focal neurological deficits in patients with HIV infection. It typically presents in patients with severe immunodeficiency, often with CD4 cell count < 50/mm^3. This patient’s CD4 cell count is 500/mm^3, making this less likely than an abscess.

Answer D: Epilepsy is a primary neurological disorder that can cause generalized tonic-clonic seizures but would not explain this patient’s fever or unilateral headache. While Todd paralysis (focal weakness after a seizure) can occur after seizures, this patient’s focal weakness predates his seizure. A primary seizure disorder is not diagnosed when seizures occur secondary to another process.

Bullet Summary:
Brain abscess presents with fever, altered mental status, unilateral headache, seizures, and focal neurological deficits in patients with risk factors for infection (for example HIV, bacterial endocarditis).


Question: A 33-year-old woman presents to the emergency department with muscle spasms. She has noticed "twitching" in both her upper and lower extremities over the past 3 days that have interfered with her training for a marathon. She has felt more fatigued over the past month. She has no significant medical history. She takes no medication other than whey protein supplements, a multivitamin, and fish oil. Her temperature is 98.5°F (36.9°C), blood pressure is 103/71 mmHg, pulse is 105/min, respirations are 11/min, and oxygen saturation is 100% on room air. Physical exam reveals a thin woman with thinning hair. She appears pale and her mucous membranes are dry. Her neurological and cardiac exams are unremarkable. Laboratory studies are ordered as seen below. Hemoglobin: 10 g/dL Hematocrit: 30% Leukocyte count: 6,100/mm^3 with normal differential Platelet count: 187,500/mm^3 Serum: Na+: 130 mEq/L Cl-: 100 mEq/L K+: 2.3 mEq/L HCO3-: 28 mEq/L BUN: 40 mg/dL Glucose: 79 mg/dL Creatinine: 0.9 mg/dL Ca2+: 8.2 mg/dL Mg2+: 1.8 mg/dL Thyroid stimulating hormone (TSH): 4.0 mIU/L Free T4: 0.4 ng/dL (normal: 0.7-1.53 ng/dL) The patient is given 4 liters of lactated ringer solution and 40 mEq of potassium. Her repeat whole blood potassium 3 hours later is 2.4 mEq/L, and her repeat BUN is 20 mEq/L. Another 40 mEq of potassium is administered. Another repeat whole blood potassium is 2.5 mEq/L. The patient’s muscle spasms persist. Which of the following is the most likely underlying etiology for this patient’s chief concern?

Answer: Hypomagnesemia

Explanation:
This patient is presenting with what appears to be anorexia nervosa (thin habitus, possible excessive exercise in the setting of marathon running, thinning hair, dry mucous membranes, decreased free T4 level, and multiple electrolyte derangements). The lack of improvement in either her muscle spasms with fluid repletion or her hypokalemia with adequate repletion, even in the setting of normal serum magnesium, suggests depleted magnesium stores are the underlying etiology of her symptoms.

Hypomagnesemia typically occurs in alcoholics, malnourished patients, and patients with eating disorders such as anorexia or bulimia nervosa. Patients may present with a wide array of symptoms including weakness, confusion, dysrhythmias, hypotension, and overall malaise. Hypomagnesemia can cause hypocalcemia as magnesium is needed for proper parathyroid hormone secretion. Another pathognomonic finding associated with hypomagnesemia is hypokalemia which is refractory to repletion. The pathophysiology is thought to be due to increased potassium wasting in the kidney due to increased activity of renal outer medullary potassium (ROMK) channels. The serum magnesium level should be checked and repletion should occur accordingly. Serum magnesium levels represent 1% or less of total body magnesium stores and do not reflect if a patient truly has hypomagnesemia, particularly if there is intracellular depletion (such as in chronically malnourished patients). Thus, any patient with findings consistent with hypomagnesemia with normal serum magnesium should have their other electrolytes repleted and be given magnesium. Magnesium repletion is a safe intervention with a wide therapeutic index, and the serum level often does not correlate with total body stores.

Razzaque discusses the relationship between serum magnesium levels and total body magnesium status. The author finds that inadequate magnesium balance is associated with myriad disorders including skeletal deformities, cardiovascular diseases, and metabolic syndrome. The author recommends the use of the magnesium loading test to provide more accurate reflections of total body magnesium status.

Incorrect Answers:
Answer A: Hypocalcemia may present with perioral numbness, paresthesias, and muscle spasms. It can occur secondary to poor nutrition, vitamin D deficiency, and hypoparathyroidism. Low serum calcium may also be seen in patients with low albumin and in states of hyperventilation (which lowers the free calcium but not the total calcium due to a respiratory alkalosis that causes albumin to bind free calcium and release protons). Hypomagnesemia can also cause hypocalcemia as magnesium is needed for proper parathyroid hormone release.

Answer C: Hyponatremia may present with malaise, nausea, vomiting, headache, and confusion. Patients may also be asymptomatic in mild cases. Asymptomatic patients with hyponatremia and functioning kidneys require only fluid restriction. On the other hand, severe hyponatremia presents with very low sodium (often < 120 mEq/L) and neurological symptoms such as profound confusion or seizures. Treatment with hypertonic saline would be indicated in this situation.

Answer D: Hypothyroidism presents with fatigue, malaise, weight gain, bradycardia, scarce lanugo, and depression. This patient’s TSH is on the high end of normal and her T4 is lower than the cutoff value. However, this is likely a compensatory response to her low BMI and excessive exercise in order to slow down her metabolism to conserve energy.

Answer E: Hypovolemia was certainly present in this patient given her dry mucous membranes and prerenal pattern of labs (BUN:Cr ratio > 20:1). After receiving 4L of fluids, it is clear that dehydration is not the cause of her symptoms as her BUN corrects and her symptoms persist. In general, hypovolemia should be treated with oral rehydration, if possible.

Bullet Summary:
Hypomagnesemia can cause hypocalcemia and hypokalemia refractory to repletion (a normal serum level does not indicate normal intracellular levels of magnesium).


Question: A 6-year-old boy is brought to the emergency department by his father for elbow pain. He was riding his bicycle when he fell onto his outstretched right hand. He immediately clutched his right elbow in pain and began crying. He refuses to move his elbow. He has no medical problems and takes no medications. His temperature is 98.4°F (36.9°C), blood pressure is 108/64 mmHg, pulse is 100/min, and respirations are 20/min. On exam, the boy is holding his right wrist with his left hand and cries upon palpation of a region that is 2 cm proximal to his elbow. The radial head is palpated just distal to the lateral epicondyle. He is unable to make a pincer with his right thumb and index finger. When asked to hold a pen between his right thumb and index fingers, he drops it. The radial pulse is diminished on the right. Which of the following is the most likely diagnosis?

Answer: Supracondylar humerus fracture

Explanation:
This young patient presenting with elbow pain and associated signs of anterior interosseous nerve neurapraxia (inability to make pincer, weak pincer grasp) and vascular injury (diminished radial pulse) after a fall on an outstretched hand most likely has a supracondylar humerus fracture.

Supracondylar humerus fractures are one of the most common fractures seen in the pediatric population. This site is particularly prone to fracture due to the thin bone separating the coronoid and olecranon fossae in the supracondylar region. Due to the proximity of the brachial artery and median nerve, which course anteriorly, these structures are at risk for injury. Neurapraxia of the anterior interosseous nerve, which is a pure motor branch of the median nerve, presents as motor deficits in interphalangeal (IP) joint flexion of the thumb and distal IP joint flexion of the index finger. The radial and ulnar arteries are terminal branches of the brachial artery, which if injured results in diminished distal pulses. The diagnosis is made with anteroposterior and lateral view elbow radiographs. Radiographs will demonstrate the "fat pad sign" seen as a posterior fat pad that is indicative of fracture. Management depends on fracture type but can consist of cast immobilization (if minimally displaced with no neurovascular injury) or closed reduction and percutaneous pinning (for more displaced fractures).

Micheloni et al. reviews supracondylar fractures in children. They note it is the most common elbow fracture in the pediatric population. They recommend early and correct diagnosis and management to avoid early and late complications including neurovascular impairment and malunion.

Incorrect Answers:
Answer A: Both bone forearm fracture is another common pediatric fracture sustained from a fall, involving both the radius and ulna. It can be associated with neurovascular injury depending on the plane of deformity, but the location of the pain would be in the forearm, not proximal to the elbow.

Answer B: Distal radius fracture is a common fracture after a fall on an outstretched hand mechanism of injury. Neurovascular injury is possible, though uncommon. This patient’s pain is localized around his elbow, rather than near the distal radius. Often, a deformity can be visualized on exam.

Answer C: Monteggia fracture-dislocation is characterized by a proximal ulna fracture with radial head dislocation. It is commonly caused by direct trauma to the ulna. In contrast, this patient’s radial head is located inferior to the lateral epicondyle.

Answer D: Olecranon fracture is an uncommon pediatric fracture caused primarily by a fall onto the elbow in flexion. Median nerve and brachial artery injury are unlikely, given that these structures pass anteriorly in the cubital fossa.

Bullet Summary:
Supracondylar humerus fractures are common in the pediatric population and may present with elbow pain and concomitant median nerve and/or brachial artery injury.


Question: A 23-year-old woman presents with a 7-day history of abdominal pain, and now bloody diarrhea that brings her to her primary care physician. Review of systems is notable for a 12-pound unintentional weight loss and intermittent loose stools. She has a family history notable for a father with coronary artery disease and a mother with primary sclerosing cholangitis. Her temperature is 37.2°C (98.9°F), blood pressure is 100/72 mmHg, pulse is 72/min, respirations are 12/min, and oxygen saturation is 100% on room air. Her abdomen is soft, mildly diffusely tender to deep palpation, and non-distended. She is found to have the finding on colonoscopy in Figure A. Serum perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are positive. Which of the following is most likely to be present in this patient?

Continuous lesion beginning in the rectum

Answer: Continuous lesion beginning in the rectum

Explanation:
This patient presents with features suggestive of inflammatory bowel disease (IBD), and her colonoscopic and serologic studies suggest ulcerative colitis (UC). UC typically begins in the rectum and progresses proximally towards the ileocecal valve in a continuous fashion.

The diagnosis of IBD should always prompt further investigation to better delineate between UC, Crohn disease, or indeterminate colitis. Further delineation guides treatment and informs prognosis. UC has a peak incidence in the second and third decades of life. It is characterized by disease extending from the rectum proximally towards the ileocecal valve in a continuous fashion. UC presents as mucosal and submucosal inflammation, with characteristic crypt distortion and presence of crypt abscesses. P-ANCA is positive in most individuals with UC. Repeated mucosal injury can induce pseudopolyp formation, and pancolitis or disease in the descending colon warrants screening colonoscopy due to increased risk of colon cancer. On imaging, the colon can be dilated by edema, losing its haustral markings and giving it a "lead pipe" appearance.

Gajendran et al. review the pathophysiology, diagnosis, and treatment of UC. They found that colonoscopy with biopsy is the best way to make a definitive diagnosis of UC. They recommend the Mayo scoring system as a commonly used method of assessing disease severity, guiding treatment options, and monitoring patients during therapy.

Figure A is a colonoscopy image showing continuous colonic mucosal inflammation typical of ulcerative colitis.

Incorrect Answer:
Answer A: Cobblestoning and skip lesions refer to the patchy areas of inflammation noted in Crohn disease. In contrast, the inflammation seen in UC involves continuous stretches of colon mucosa.

Answer C: Fistulae and stricture formation are features of Crohn disease, not UC. Fistulizing and stricture formation can affect the entire gastrointestinal tract in Crohn disease.

Answer D: Perianal disease is a feature of Crohn disease. Although UC commonly affects the rectum, it tends to spare the anus.

Answer E: Worse disease severity near the ileocecal valve is a feature of Crohn disease and not UC. UC tends to be characterized by more uniform disease severity spanning in continuous fashion from rectum towards the cecum.

Bullet Summary:
Ulcerative colitis is characterized by disease extending from the rectum proximally towards the ileocecal valve in a continuous fashion.


Question: A 3-week-old boy presents to the emergency department with vomiting. His parents report that he suddenly started vomiting this morning and has shown no interest in feeding since then. They describe the vomitus as green and without any traces of blood. Prior to today, the patient was feeding, voiding, and stooling well. He was noted to have surpassed his birth weight at his last office visit 1 week ago. His temperature is 97.6°F (36.4°C), blood pressure is 78/56 mmHg, pulse is 148/min, and respirations are 44/min. On physical exam, the patient is in mild distress. He has no dysmorphic features, and his mucous membranes are dry. His abdomen is soft and distended. Bowel sounds are hypoactive. An abdominal radiograph is performed as in Figure A. Which of the following is the most appropriate next step in the diagnosis of this condition?

Answer: Upper gastrointestinal contrast series

Explanation:
This neonatal patient presents with sudden-onset bilious vomiting and an abdominal radiograph revealing a gasless abdomen, which is consistent with intestinal malrotation complicated by a midgut volvulus. The most appropriate next step in the diagnosis of intestinal malrotation is an upper gastrointestinal series.

Malrotation classically presents with bilious vomiting due to the formation of midgut volvulus. These patients will have normal development until the development of the obstruction followed by inability to feed and abdominal distention. Findings of malrotation on an upper gastrointestinal series include an abnormally placed ligament of Treitz on the right side of the abdomen and a "corkscrew" appearance of the distal duodenum. If an upper gastrointestinal contrast series confirms the diagnosis, patients should undergo surgery to reduce the volvulus in order to avoid intestinal perforation or other complications.

Adams and Stanton review the evidence regarding the diagnosis and treatment of neonatal bowel obstruction. They discuss how malrotation, jejunoileal atresia, duodenal atresia, and colonic atresia are common causes of this finding. They recommend surgical management of these conditions.

Figure/Illustration A is an abdominal radiograph demonstrating the nonspecific finding of a paucity of air in the abdomen (red circle). This is consistent with intestinal malrotation complicated by midgut volvulus.

Incorrect Answers:
Answer A: Although abdominal CT would detect intestinal malrotation, CT should be avoided in the pediatric population in light of the radiation exposure. A CT scan with oral contrast can be useful in the adult setting in order to determine if there is extravasation of fluid from the gastrointestinal tract.

Answer B: Abdominal ultrasound is the test of choice for diagnosing pyloric stenosis, which presents with non-bilious vomiting and a palpable olive mass in the abdomen. Treatment of this condition is with surgical release of the stenotic pyloric muscle.

Answer C: A contrast enema is used to differentiate between Hirschsprung disease and meconium ileus but would not be helpful in diagnosing malrotation as the midgut volvulus occurs in the small intestine. Both Hirschsprung disease and meconium ileus present in neonatal patients with bilious vomiting and failure to pass meconium in the first 48 hours of life. Treatment is with excision of the defective segment or removal of the meconium respectively.

Answer D: Rectal suction biopsy is the most accurate test to diagnose Hirschsprung disease. Although Hirschsprung disease commonly presents in neonatal patients with bilious vomiting, an abdominal radiograph in Hirschsprung disease would likely show dilation of the proximal colon.

Bullet Summary:
The most appropriate diagnostic test for malrotation in an infant is an upper gastrointestinal series, which will show the abnormal placement of the duodenum and ligament of Treitz on the right side of the abdomen.


Question: A 66-year-old woman presents to the emergency room after experiencing a tonic-clonic seizure. She has been having worsening headaches and intermittent nausea over the past 5 months. The headaches are constant and dull, and they typically worsen when she sneezes or laughs. Recently, she has become increasingly nauseous and has vomited twice in the past 10 days. Her medical history is significant for type 2 diabetes mellitus and hypertension for which she takes metformin and losartan. Her temperature is 98.6°F (37.0°C), blood pressure is 115/70 mmHg, pulse is 70/min, and respirations are 12/min. She is noted to have papilledema on fundoscopy, but physical exam is otherwise normal. Her CT scan findings are presented in Figure A. Which of the following is the most likely diagnosis?

Answer: Glioblastoma multiforme

Explanation:
This patient is presenting with symptoms of increased intracranial pressure (i.e., positional headaches, nausea, vomiting, and papilledema). Combined with her CT finding of a space-occupying butterfly-shaped lesion, the most likely diagnosis is glioblastoma multiforme.

Glioblastoma multiforme is the most common malignant primary nervous system cancer, most commonly occurring in adults above the age of 65. The tumor arises from the cerebral hemispheres and classically crosses the corpus callosum, producing a butterfly appearance on CT/MRI. Pseudopalasading necrosis is seen on biopsy, and tissue biopsy is usually glial fibrillary acidic protein (GFAP) positive. It has an unfavorable prognosis with a life expectancy of 6 months to 1 year. Management of glioblastoma includes surgical resection and palliative radiotherapy/chemotherapy.

Stupp et al. studied the role of electrical field therapy (TTFields) in conjunction with temozolomide in the treatment of glioblastoma multiforme. The authors found that combination therapy improved median progression-free survival (6.7 vs. 4.0 months, p < 0.001). The authors recommend that clinicians consider the use of TTFields to treat selected patients with glioblastoma multiforme.

Figure/Illustration A demonstrates a non-contrast axial head CT showing the classic butterfly lesion characteristic of glioblastoma multiforme (red arrow).

Incorrect Answers:
Answer A: Cerebral toxoplasmosis presents on imaging with multiple ring-enhancing lesions and is most common in patients with acquired immunodeficiency syndrome (AIDS), especially with CD4 T-cell counts of less than 100 cells/mm^3. This patient has no signs of infection or ring-enhancing lesions.

Answer C: Hemorrhagic stroke presents acutely with hemiparesis, altered mental status, slurred speech, or sensorimotor symptoms. CT imaging would reveal a hemorrhage.

Answer D: Metastatic brain tumor often presents with imaging findings of multiple well-circumscribed lesions with surrounding edema. These lesions are generally found at the highly vascularized gray-white junction. In a patient with no smoking history, a single brain lesion, and no other extra-cranial symptoms, this is a less likely diagnosis.

Answer E: Neurosarcoidosis can be caused by infiltrative sarcoidosis and often presents with bitemporal hemianopsia due to infiltration of the pituitary gland. Patients with sarcoidosis typically also present with pulmonary symptoms (e.g., wheezing and coughing) which are absent in this patient.

Bullet Summary:
Glioblastoma multiforme should be suspected in patients presenting with symptoms of increasing intracranial pressure and classic CT/MRI findings of a butterfly shaped lesion with central necrosis.


Question: A 62-year-old woman is brought to a physician by her husband for fluctuating changes in behavior and hallucinations over the past 2 years. On occasion, she becomes difficult to understand and her speech becomes disorganized. She also frequently sees "small people" and animals on the dining room table, which is disturbing to her. Her medical problems include hypertension and chronic obstructive pulmonary disease for which she takes amlodipine, albuterol, ipratropium, and a fluticasone inhaler. She was formerly an executive at a software company but had to retire due to frequent memory lapses. Her temperature is 98.6°F (37°C), blood pressure is 120/80 mmHg, pulse is 80/min, and respirations are 12/min. Physical exam is notable for slowed movements and difficulty with balance at rest, which were not present at her wellness visit 1 year ago. Which of the following pathological findings (Figures A-E) would most likely be seen if a brain biopsy were performed?

Answer: Figure C

Explanation:
This patient with fluctuating changes in behavior and cognition, visual hallucinations, memory loss, and extrapyramidal symptoms (bradykinesia, postural instability) most likely has Lewy body dementia. Lewy body dementia is characterized histologically by Lewy bodies, which are intracytoplasmic eosinophilic inclusions of alpha-synuclein (shown in Figure C).

Alpha-synuclein is normally abundantly present in its unfolded form in neurons. Abnormal folding of alpha-synuclein leads to aggregation into insoluble fibrils. These intracytoplasmic aggregates (Lewy bodies) are seen in Parkinson disease, Lewy body dementia, and multiple system atrophy, which are collectively referred to as alpha-synucleinopathies. Lewy body dementia is the second most common degenerative dementia and presents with fluctuating cognition, visual hallucinations, parkinsonism (bradykinesia, postural instability, rigidity, and a resting tremor), rapid eye movement (REM) sleep disorder, autonomic dysfunction, and sensitivity to antipsychotics. Lewy body dementia can be distinguished from Parkinson disease with dementia by the timing of symptoms. In Lewy body dementia, cognitive symptoms begin at the same time as or 1 year prior to the onset of movement symptoms whereas in Parkinson disease the cognitive symptoms classically occur over 1 year after motor symptoms. There is no cure for Lewy body dementia, and treatment is aimed at alleviating symptoms.

Arnaoutoglou et al. reviewed the epidemiology, pathology, treatment, and future directions for research of Lewy body dementia. The authors found potential genetic bases for Lewy body dementia, including mutations in the GBA gene. They recommended that further research be conducted on the therapeutic implications of these genetic findings.

Figure/Illustration A shows a hematoxylin and eosin (H&E) stained brain biopsy of a patient with Creutzfeldt-Jakob disease. Characteristic spongiform changes in neurons (yellow boxes) and agglomerated prions (orange arrows) are seen in this slide.

Figure/Illustration B shows an H&E stained brain biopsy of a patient with a small lacunar infarct on low magnification. A central area of tissue loss (yellow outline) and surrounding residual gliosis (orange arrows) are seen in this slide.

Figure/Illustration C shows a brain biopsy of a patient with Lewy body dementia stained with mouse anti-alpha-synuclein antibody and counterstained with hematoxylin. Lewy bodies (intracytoplasmic eosinophilic inclusions of alpha-synuclein) are indicated by orange arrows. Note that Lewy bodies are always found intracellularly (neurons highlighted by blue boxes).

Figure/Illustration D shows an H&E stained brain biopsy of a patient with Alzheimer disease. Extracellular neurofibrillary tangles found in Alzheimer disease are indicated by black arrows.

Figure/Illustration E shows an H&E stained brain biopsy of a patient with frontotemporal dementia. A characteristic Pick cell (red box), or ballooned neuron, with dissolved chromatin (yellow arrow), is seen in this slide.

Incorrect Answers:
Answer A: Figure A shows an H&E stained brain biopsy of a patient with Creutzfeldt-Jakob disease. Creutzfeldt-Jakob disease is a rapidly progressive dementia that manifests with poor concentration, declining executive function, startle myoclonus, 14-3-3 protein on lumbar puncture, and synchronous sharp wave complexes on electroencephalogram (EEG). Clinical decline occurs over the course of weeks and months, culminating in death within a year. Creutzfeldt-Jakob disease shows spongiform vacuolation due to the accumulation of abnormal prion protein (PrPsc).

Answer B: Figure B shows an H&E stained brain biopsy of a patient with a small lacunar infarct. Lacunar infarcts may be asymptomatic or cause focal neurologic deficits such as motor hemiparesis, pure sensory stroke, ataxic hemiparesis, or dysarthria-clumsy hand syndrome depending on the territory involved. Lacunar strokes will show diffuse eosinophilia of the affected area, followed by liquefactive necrosis with neutrophilic infiltration, followed by macrophages with surrounding reactive gliosis, finally leading to an area of tissue loss with residual gliosis.

Answer D: Figure D shows an H&E stained brain biopsy of a patient with Alzheimer disease. Alzheimer disease presents with a gradual cognitive decline with difficulty completing activities of daily living. Memory is the most prominently affected domain. Visual hallucinations, fluctuating levels of cognition, and extrapyramidal symptoms are not common in Alzheimer disease. Amyloid plaques and neurofibrillary tangles may be seen on brain biopsy.

Answer E: Figure E shows an H&E stained brain biopsy of a patient with frontotemporal dementia (Pick disease). The behavioral variant of frontotemporal dementia is associated with early-onset personality and behavioral changes, and it may be associated with extrapyramidal symptoms. Unlike Lewy body dementia, memory is usually not affected in frontotemporal dementia until late in the disease course. frontotemporal dementia is characterized by Pick cells (ballooned neurons with dissolved chromatin) and Pick bodies, round intracellular aggregates of hyperphosphorylated tau protein.

Bullet Summary:
Lewy body dementia presents with alterations in consciousness, disorganized speech, visual hallucinations, extrapyramidal symptoms, early compromise of executive functions, and eosinophilic intracytoplasmic inclusions of alpha-synuclein (Lewy bodies) on biopsy.


Question: A 69-year-old woman presents with pain in her hip and groin. The pain is present in the morning but is nearly unbearable by the end of the day. Her medical history is notable for a treated episode of acute renal failure, diabetes mellitus, obesity, and hypertension. Her current medications include losartan, metformin, insulin, and ibuprofen. The patient recently started taking high doses of vitamin D as she believes that it could help her symptoms. She also recently fell off the treadmill while exercising at the gym. Her temperature is 98.6°F (37°C), blood pressure is 135/91 mmHg, pulse is 72/min, and respirations are 12/min. On exam, an obese woman in no distress is noted. There is pain, decreased range of motion, and crepitus on exam of her right hip. The patient points to the areas that cause her pain stating that it is mostly over the groin. Which of the following is most likely to be found on plain radiographic imaging of this patient?

Answer: Loss of joint space and osteophytes

Explanation:
This patient is presenting with pain worse on exertion, decreased range of motion, and crepitus in her hip, suggesting a diagnosis of osteoarthritis. A loss of joint space and osteophytes (reactive bone formation) would be seen on radiography.

Osteoarthritis occurs due to wear and tear of the joint typically from repeat trauma in the setting of risk factors such as obesity. Pain can be located in the hip, and can be referred to the groin or knee. The classic presentation is pain that worsens with activity. Crepitus and decreased range of motion can be found on physical exam. Common radiological findings include a loss of joint space and osteophytes. Treatment should start with conservative measures such as activity modification, weight loss, and an unloading brace. A corticosteroid injection may be appropriate as a second-line measure. Refractory cases can be treated with a total joint replacement.

Glyn-Jones et al. review the evidence regarding the diagnosis and treatment of osteoarthritis. They discuss how total joint arthroplasty operations can be limited by the lifestyle of the prosthesis and other complications. They recommend considering joint preserving options such as lifestyle modification.

Incorrect Answers:
Answer A: Femoral neck fracture would present acutely with pain in the hip and a shortened and externally rotated leg. This diagnosis is possible given the patient's recent fall; however, her other symptoms and less acute presentation suggest a diagnosis of osteoarthritis. Treatment is with a hemiarthroplasty.

Answer B: Hyperdense foci in the ureters suggest a diagnosis of renal calculi. Though this patient's referred pain to the groin, history of renal failure, and possible hypercalcemia (due to increased vitamin D intake) could suggest this diagnosis, her other symptoms are more suggestive of osteoarthritis. Treatment is lithotripsy or stone removal for larger kidney stones.

Answer D: Normal radiography would be found with a minor sprain/muscular injury which presents with a self-limited course of pain and tenderness over the affected muscle. Treatment is with rest, ice, compression, and elevation.

Answer E: Posterior displacement of the femoral head suggests a diagnosis of posterior hip dislocation. Posterior hip dislocation would present with a shortened and internally rotated leg and a more acute presentation. Treatment is with closed reduction of the hip under sedation.

Bullet Summary:
Osteoarthritis presents with joint pain that is worse with exertion and radiographical findings of decreased joint space and osteophytes.


Question: A 30-year-old man presents to the emergency room with a laceration over the 4th metacarpophalangeal (MCP) joint of his right hand. He reports that he is a mailman, and his closed fist was bitten by a dog while he was delivering mail yesterday. He reports pain but denies fevers, chills, drainage, or any other symptoms. The dog is up to date on vaccinations. His last tetanus vaccine was 3 years ago. He has no medical history and takes no medications. His temperature is 98.6°F (37.0°C), pulse is 80/min, blood pressure is 125/75 mmHg, and respirations are 16/min. Examination of the patient's right hand is shown in Figure A. Which of the following is the most appropriate next step in management?

Answer: Amoxicillin-clavulanate

Explanation:
This patient has suffered a clenched fist injury which are generally managed with irrigation and amoxicillin-clavulanate.

Amoxicillin-clavulanate is the usual first-line antibiotic for patients with a human or dog bite. Lacerations sustained from animal or human bites should not be sutured due to the risk of infection. Amoxicillin-clavulanate is first-line therapy for prophylaxis and treatment of human bites and dog bites, in general. Closed fist injuries put the patient at a high risk for osteomyelitis, septic arthritis, and tenosynovitis; therefore, prophylactic antibiotics are appropriate. Amoxicillin-clavulanate provides essential coverage against Pasturella multocida, commonly found in the mouths of dogs, cats, and other mammals. In patients with a penicillin allergy, agents such as TMP-SMX, doxycycline, or cefdinir paired with anaerobic coverage (clindamycin or metronidazole) is appropriate.

Presutti discusses the prevention and treatment of dog bites. Appropriate treatment consists of immediate, copious irrigation, assessment for risk of tetanus and rabies, and administration of prophylactic antibiotics as discussed above.

Figure A shows a dog bite wound over the 4th MCP of the right hand.

Incorrect Answers:
Answer B: Cephalexin does not cover species that are typically present in the mouths of dogs and other mammals and is therefore not an appropriate antibiotic choice for this patient as monotherapy.

Answer C: Clindamycin provides coverage of anaerobic species, but is not sufficient alone for treatment of this patient's injury.

Answer D: Clindamycin plus doxycycline may be appropriate coverage for a dog bite in a patient with an allergy to amoxicillin-clavulanate. However, this patient has no stated allergies and should receive amoxicillin-clavulanate.

Answer E: Wound closure and amoxicillin-clavulanate would not be appropriate. Lacerations sustained from dog or cat bites are not sutured closed due to the risk of infection.

Bullet Summary:
Amoxicillin-clavulanate is the first line antibiotic choice for patients with dog or cat bites.


Question: A 2-year-old girl presents to the pediatrician with her mother for a routine well-child visit. Her mother is concerned that the patient is a picky eater and refuses to eat vegetables. She drinks milk with meals and has juice sparingly. She goes to sleep easily at night and usually sleeps for 11-12 hours. The patient has trouble falling asleep for naps but does nap for 1-2 hours a few times per week. She is doing well in daycare and enjoys parallel play with the other children. Her mother reports that she can walk downstairs with both feet on each step. She has a vocabulary of 10-25 words that she uses in the form of 1 word commands. She is in the 42nd percentile for height and 48th percentile for weight, which is consistent with her growth curves. Her temperature is 98.6°F (37°C), blood pressure is 92/56 mmHg, pulse is 106/min, and respirations are 23/min. On physical exam, she appears well nourished. She can copy a line and throw a ball. She can follow the command to “give me the ball and then close the door.” Which of the following is abnormal in this patient?

Answer: Expressive language skills

Explanation:
This child is meeting her milestones in every category but expressive language. By 2 years of age, a child should have a vocabulary of over 50 words and be using 2-word phrases.

Assessing whether a child is meeting developmental milestones is important for identifying delays and enabling early intervention. In the gross motor category, a 2-year-old child should be able to jump and walk both up and down stairs with both feet on each step. In the fine motor category, a child should be able to copy a line and build a tower of 6 cubes. In the expressive language category, a child should have a vocabulary of over 50 words and be using 2-word phrases. In the social category, a child should participate in parallel play and be able to follow 2-step commands. Detecting a persistent developmental delay can be important as the first step in identifying a correctable condition such as hearing loss.

Scharf et al. review the evidence regarding the use of developmental milestones in assessing children. They discuss how early identification of delays can allow for referral to required services. They recommend paying special attention to sensory function to avoid missing a correctable hearing deficit.

Incorrect Answers:
Answer B: This child's fine motor skills are appropriate, as she can copy a line. She may also be able to copy a circle and make a tower of 6 cubes at this age.

Answer C: This child's gross motor skills are appropriate because she can walk downstairs with both feet on each step and throw a ball. She should also be able to jump and run at this age.

Answer D: This child's social and receptive language skills are developing appropriately since she can follow 2-step commands and engages in parallel play. She should also be able to point to pictures, body parts, and pieces of clothing when named.

Answer E: This child is not developmentally normal due to her deficits in expressive language. She should be using 2-word sentences and have a vocabulary of over 50 words. Her language should also be intelligible to strangers 50% of the time.

Bullet Summary:
By 2 years of age, a child should be able to walk up and down stairs, copy a line, follow a 2-step command, have a vocabulary of at least 50 words, and use 2-word phrases.


Question: A 36-year-old man presents to the office for follow up after initiating antidepressant therapy. Two months ago, he was started on citalopram after several weeks of depressed mood, loss of interest in activities, depressed appetite, and inability to sleep. Today, he reports minimal improvement in his symptoms. He had some nausea after starting the medication, but this has resolved. He denies thoughts of suicide or self-harm. His temperature is 98.6°F (37.0°C), pulse is 80/min, blood pressure is 120/80 mmHg, respirations are 22/min, and oxygen saturation is 97% on room air. Exam reveals a depressed, tired appearing man. Which of the following is the most appropriate next step in management?

Answer: Add mirtazapine

Explanation:
This patient is being treated for depression without improvement in his symptoms after 6 weeks of medication use. In the setting of his reduced appetite and trouble sleeping, mirtazapine is an appropriate medication to add.

SSRIs (including paroxetine, citalopram, fluvoxamine, sertraline, and fluoxetine) are the first line treatment for major depression. For patients in whom an adequate trial of SSRI therapy has been ineffective, the first step in management is a trial of augmentation with a separate agent prior to switching to a different primary antidepressant medication. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, acts by inhibiting pre-synaptic alpha-2 receptors as well as 5HT2 and 5HT3 serotonin receptors. Notably, its side effect profile includes increased appetite and mild sleepiness, making it a good option for depressed patients with insomnia or decreased appetite. Mirtazapine is commonly used to augment primary antidepressant therapy. Augmentation with an additional agent should generally be attempted prior to switching to a different SSRI or other first line medication.

Davies et. al review the pharmacologic management of depression. They note that while evidence is limited, there is some data to suggest benefit in augmentation with a secondary agent prior to switching to another first line therapy.

Incorrect Answers:
Answer B: Electroconvulsive therapy, while often extremely effective, is typically reserved for patients that are actively suicidal, unable to eat, or displaying psychotic symptoms. It is more commonly used after medications have failed.

Answer C: Switching to amitriptyline, a tricyclic antidepressant, would not be appropriate. Tricyclic antidepressants have a negative side effect profile and potential for severe toxicity.

Answer D: Switching to paroxetine, another SSRI medication, may be appropriate. However, this patient's particular constellation of symptoms (decreased appetite and insomnia) suggest that he would likely respond well to mirtazapine.

Answer E: Switching to phenelzine, a monoamine oxidase inhibitor, would not be appropriate. Monoamine oxidase inhibitors have a negative side effect profile and potential for severe drug-drug interaction.

Bullet Summary:
Mirtazapine (a noradrenergic and serotonergic antidepressant) is an appropriate next step for depressed patients with significant insomnia and decreased appetite who fail to respond to a trial of SSRI monotherapy.


Question: A 28-year-old man is brought to the emergency department by helicopter after a high speed motorcycle crash. He was intubated and 2 large bore IVs were placed in the field with administration of 2 liters of lactated ringer's solution while en route. On arrival to the emergency department, his temperature is 98.6°F (37.0°C), pulse is 130/min, blood pressure is 80/50 mmHg, respirations are 22/min, and oxygen saturation is 97%. Examination reveals an ill-appearing intubated patient. Endotracheal tube placement is confirmed with end tidal CO2, and bilateral breath sounds are present. No external bleeding or wounds are noted on exam. Pulses are present in all extremities but are weak and rapid. Significant bruising is noted over the abdomen. The pelvis is stable. Infusion of packed red blood cells is initiated. Which of the following is the most appropriate next step in management?

Answer: FAST exam

Explanation:
This patient with hemodynamic instability and abdominal bruising after a high speed motorcycle crash likely has shock secondary to blood loss. The first step in management of patients with blunt trauma and hemodynamic instability is a focused assessment with sonography for trauma (FAST exam)

For any patient with blunt or penetrating trauma, the first step in management is an evaluation of airway, breathing, and circulation. This is referred to as the primary survey and includes the verification of endotracheal tube placement, auscultation of bilateral breath sounds, and assessment of external wounds or bleeding. This is followed by the secondary survey which involves a detailed head to toe inspection for injuries. Blunt abdominal trauma with bruising as well as hemodynamic instability warrants a FAST exam. The FAST exam visualizes the heart chambers and pericardium, left upper quadrant (spleen, splenorenal recess), right upper quadrant (Morrison pouch) and the rectovesical (males) or rectouterine (females) pouch. The extended FAST exam (eFAST) includes an examination of the lungs as well to assess for pneumothorax or hemothorax. Hemodynamically unstable patients with free fluid identified in the abdomen on initial FAST exam should proceed directly to the operating room for emergent surgical intervention with ongoing volume resuscitation. Patients with hemodynamic instability and a negative FAST exam should be evaluated for sources of bleeding elsewhere such as the pelvis.

Barloon et al. review diagnostic imaging in the evaluation of blunt abdominal trauma. Blunt abdominal trauma is a common cause of death and injury, leading to hemodynamic instability. Intra-abdominal imaging is especially important in comatose or sedated (intubated) patients who are unable to provide a history or provide a reliable physical examination. In stable patients, CT of the abdomen often has a role in deciding whether to pursue observation versus surgical intervention.

Stengel et al. evaluate emergency ultrasound-based algorithms for diagnosing blunt abdominal trauma. The systematic review showed that ultrasound-based pathways reduced the number of CT scans obtained. Use of ultrasound can enhance the speed of the primary assessment and cut costs. However, the authors conclude that there is insufficient evidence to promote justification of ultrasound-based pathways for the evaluation of blunt abdominal trauma in terms of patient outcomes.

Incorrect Answers:
Answer A: AP and lateral radiographs of the abdomen and pelvis may be useful for identifying pelvic fracture or intraperitoneal free air. However, this patient's presentation is suggestive of abdominal trauma warranting FAST exam.

Answer B: CT scan of the abdomen and pelvis with contrast would be appropriate for evaluation of blunt abdominal trauma in a patient that is hemodynamically stable. However, this patient's vital signs indicate hemodynamic instability.

Answer C: Diagnostic peritoneal lavage is no longer commonly used in the evaluation of blunt abdominal trauma.

Answer E: Norepinephrine infusion would not be appropriate for this patient with shock secondary to blood loss. Resuscitation for this patient should be achieved with transfusion of blood products.

Bullet Summary:
The most appropriate initial step in management for hemodynamically unstable patience with blunt abdominal trauma is a FAST exam.


Question: A 4-day-old girl presents with her parents to the pediatrician for a routine visit. She was feeding well until this morning when she had several episodes of vomiting. The parents describe the vomitus as “bright green” and the patient has shown little interest in feeding since then. She was born at 36 weeks gestation to a 37-year-old G2P2 mother. The pregnancy was complicated by gestational diabetes, and all prenatal testing was unremarkable. The patient has not yet regained her birth weight and is in the 46th percentile for height and the 36th percentile for weight. The patient’s temperature is 99.2°F (37.3°C), blood pressure is 68/46 mmHg, pulse is 132/min, and respirations are 32/min. On physical exam, the patient is in mild distress. She has no dysmorphic features. Her abdomen is distended and firm without guarding. Bowel sounds are hypoactive. The patient’s abdominal radiograph can be seen in Figure A and the patient’s upper gastrointestinal series can be seen in Figure B. Which of the following is the most likely etiology of this patient’s condition?

Answer: Intestinal malrotation

Explanation:
This patient presents with bilious vomiting and an upper gastrointestinal series demonstrating the “corkscrew” appearance of the distal duodenum and proximal jejunum, which is consistent with a diagnosis of intestinal malrotation.

Intestinal malrotation most commonly presents in newborns with bilious emesis. This condition increases the risk of midgut volvulus where the intestines create a closed loop. Abdominal radiographs are rarely diagnostic but are useful in excluding bowel perforation. An upper gastrointestinal series is the diagnostic test of choice and demonstrates an abnormally placed duodenum with a ligament of Treitz on the right side of the abdomen and a “corkscrew” appearance of the distal duodenum and proximal jejunum. Treatment is with surgical derotation of the bowel or exploratory laparotomy if perforation has occurred.

Adams and Stanton review the evidence regarding the diagnosis and treatment of neonatal bowel obstruction. They discuss how malrotation, jejunoileal atresia, duodenal atresia, and colonic atresia are common causes of this finding. They recommend surgical management of these conditions.

Figure/Illustration A is an abdominal radiograph showing a paucity of air in the abdomen (red circle). These findings are consistent with nonspecific findings of intestinal malrotation.

Figure/Illustration B is an upper gastrointestinal series showing a right-sided ligament of Treitz and a “corkscrew” appearance of the distal duodenum (red circle). These are classic findings of intestinal malrotation.

Incorrect Answers:
Answer A: Although duodenal atresia presents with bilious vomiting, the “double bubble” sign would be seen on an abdominal radiograph, which reflects air trapping in both the stomach and the 1st portion of the duodenum. Treatment is with surgical repair of the obstructed segment.

Answer B: Hirschsprung disease may also cause bilious vomiting, but an abdominal radiograph would demonstrate proximal colonic distension with little air in the rectosigmoid colon. Hirschsprung disease is also well visualized on contrast enema, on which a transition point can be seen between the proximal dilated colon and the narrow sigmoid. Treatment is with excision of the defective segment.

Answer D: Jejunal atresia can also lead to bilious vomiting, although a “triple bubble” sign would be seen on an abdominal radiograph with air additionally filling the proximal jejunum. Treatment is with excision of the atretic segment and anastomosis of the bowel lumen.

Answer E: Meconium ileus may present with bilious emesis, but multiple dilated loops of bowel would be seen on an abdominal radiograph. Meconium ileus is better characterized by contrast enema, on which a microcolon can be visualized. Treatment is with the removal of the meconium and treatment of the underlying cystic fibrosis, if present.

Bullet Summary:
Intestinal malrotation presents in newborns with bilious emesis, an upper gastrointestinal series demonstrating a misplaced duodenum, and a “corkscrew” appearance of the distal duodenum and proximal jejunum.


Question: A 25-year-old man presents to his primary care provider for a routine appointment. He feels well and has no complaints. His medical and surgical history is significant for the reconstruction of a torn anterior cruciate ligament in his right knee. His family history is significant for a mother with “thyroid problems” and a father with coronary artery disease. The patient is an information technology specialist at a local company. He is sexually active with men. His temperature is 98.6°F (37.0°C), blood pressure is 124/82 mmHg, pulse is 71/min, and respirations are 12/min. On physical exam, the patient is tall and slender with a BMI of 21 kg/m2. A single nodule can be palpated on the patient’s thyroid. He has palpable cervical lymphadenopathy. On cardiac exam, he has a normal S1/S2 with no murmurs, rubs, or gallops, and his lungs are clear bilaterally. His abdomen is soft and non-tender without hepatosplenomegaly. A physical exam of the perioral region can be seen in Figure A. Which of the following additional findings is most likely to be found in this patient?

Answer: Elevated plasma metanephrines

Explanation:
This patient presents with tall stature, mucosal neuromas of the lips and tongue, an isolated thyroid nodule, and a family history of thyroid disease, which suggests a diagnosis of multiple endocrine neoplasia type 2 (MEN2B). MEN2B is also associated with pheochromocytomas, which cause elevated plasma metanephrines.

MEN2B is caused by a gain-of-function mutation in the RET proto-oncogene and presents with medullary carcinoma of the thyroid, pheochromocytoma, Marfanoid habitus, and mucosal neuromas. Medullary thyroid carcinoma (MTC) occurs in almost all patients with MEN2B and is often metastatic at the time of diagnosis. Patients should be screened for pheochromocytoma using plasma fractionated metanephrines at the time of diagnosis of MTC. Intestinal neuromas may also lead to intestinal manifestations such as chronic constipation and megacolon. Treatment is with surgical excision of malignant lesions and active screening for future development of tumors.

Castinetti et al. review the evidence regarding the diagnosis and treatment of MEN2B. They discuss how often the first presentation of this disease involves the diagnosis of medullary thyroid carcinoma. They recommend developing techniques for earlier diagnosis of this disease in order to allow for better survival.

Figure/Illustration A is a clinical photograph demonstrating mucosal neuromas, which are painless nodules on the lips or tongue (red circles). These findings are characteristically seen in multiple endocrine neoplasia type 2B.

Incorrect Answers:
Answer B: An elevated serum calcium level would suggest parathyroid hyperplasia, which is a feature of both type 1 and type 2A multiple endocrine neoplasia. Rather than hypercalcemia, this patient is likely to have an elevated serum calcitonin level due to his medullary thyroid carcinoma.

Answer C: An elevated serum prolactin level would suggest the presence of a prolactinoma, which is a pituitary tumor that may be seen in type 1 multiple endocrine neoplasia (MEN1). Other findings in this disorder include parathyroid and pancreatic tumors. Treatment is with surgical excision of malignant lesions.

Answer D: Fasting hypoglycemia would suggest the presence of an insulinoma, which is a less common pancreatic tumor that may be seen in MEN1. Other findings in this disorder include parathyroid and pancreatic tumors. Patients with an insulinoma require surgical excision in order to allow for proper glucose homeostasis.

Answer E: A positive fecal occult blood test would raise suspicion for colorectal cancer, which is a feature of Peutz-Jeghers syndrome (PJS). The extraintestinal manifestations of PJS include mucocutaneous pigmented macules on the lips and perioral region. Treatment is with screening for colorectal cancer and surgical excision of malignant lesions.

Bullet Summary:
Multiple endocrine neoplasia type 2B presents with medullary thyroid carcinoma, pheochromocytoma, Marfanoid habitus, and mucosal neuromas.


Question:
A 27-year-old woman presents to her primary care physician with new hair growth on her face and lower abdomen over the last month. She has started to develop pimples on her face and back over the last several months. Her last menstrual period was over 3 months ago and her periods have been irregular over the last year. She has been gaining weight recently. The patient has a medical history of obesity and prediabetes with a hemoglobin A1c of 6.0% last year. Her temperature is 98.5°F (36.9°C), pulse is 80/min, blood pressure is 139/88 mmHg, and respirations are 13/min. Cardiopulmonary exam is unremarkable, and the patient’s abdomen appears slightly distended but exhibits no tenderness to palpation. The patient’s face has coarse stubble along the jawline and on the upper lip, and there is similar hair along the midline of her lower abdomen. A pelvic exam reveals mild clitoromegaly, a normal anteverted uterus, and a large left adnexal mass that is mildly tender. Her laboratory test results are shown below:

Hemoglobin: 13.9 g/dL
Leukocyte count: 8,000 cells/mm^3
Platelet count: 142,000/mm^3

DHEAS: 73 ug/dL (Normal: 145-395 ug/dL)
Testosterone: 256 ng/dL
17-hydroxyprogesterone: 214 ng/dL (Normal: < 200 ng/dL)

Ultrasound findings are shown in Figure A. Which of the following is the most likely diagnosis in this patient?

Answer: Ovarian tumor

Explanation:
This young woman presents with rapid virilization, elevated testosterone, and a large left adnexal mass that is primarily solid on ultrasound. These findings are most consistent with an ovarian androgen-secreting tumor.

Sertoli-Leydig cell tumors are the most common androgen-secreting tumor of the ovaries and classically result in rapid virilization of affected women. Testosterone levels are often over 200 ng/dL, and 17-hydroxyprogesterone may also be slightly elevated as it is an androgen precursor. The androgen excess may result in symptoms such as facial and abdominal hirsutism, oligomenorrhea, deepening voice, and acne. Treatment involves staging the tumor and surgical resection of the tumor if possible.

Durmus et al. review the evidence regarding the diagnosis and treatment of Sertoli-Leydig cell tumors. They discuss how this tumor generally has a favorable prognosis compared to malignant epithelial tumors. They recommend using fertility-preserving surgeries in younger patients.

Figure/Illustration A shows an ultrasound of the left ovary, which has a predominantly solid mass with vascularity and some cystic spaces (red circle). These findings are consistent with an ovarian tumor.

Incorrect Answers:
Answer A: Adrenal tumors may secrete androgens and cause similar symptoms of virilization, but the presence of a malignant-appearing ovarian mass in this patient is more consistent with ovarian pathology. Furthermore, adrenal tumors typically secrete DHEAS, which can be a helpful test for localizing the source of androgen excess. Treatment is with surgical excision.

Answer B: Congenital adrenal hyperplasia (CAH) results from one of several possible enzyme deficiencies in the steroid pathway and may appear later in life as virilization of a woman. While 17-hydroxyprogesterone elevation is a strong indicator of the most common subtype of CAH, this patient’s ultrasound findings suggest ovarian pathology instead, which could also elevate this androgen precursor. Treatment is with hormone replacement therapy.

Answer C: Ovarian hyperthecosis is hyperplasia of the theca interna of the ovary, which produces androgens. Testosterone levels would be elevated and virilization may occur, but ultrasound findings would show a bilateral increase in stromal tissue as opposed to a unilateral solid mass. Treatment is with hormonal therapy.

Answer E: Polycystic ovary syndrome (PCOS) can also cause elevated testosterone, though levels are typically lower than 100 ng/dL. Frank virilization with clitoromegaly and voice deepening would not be expected with PCOS, nor would an ovarian mass. Treatment is with metformin and lifestyle modifications.

Bullet Summary:
Sertoli-Leydig cell tumors of the ovary can produce androgens and result in rapid onset of virilization with elevated testosterone levels and an adnexal mass on ultrasound.


Question: A 59-year-old man presents accompanied by his wife with nausea and dizziness. He is unsure when his symptoms started, but they have been affecting him for “a while.” It began as episodes of “unsteadiness” that progressed to a feeling of “spinning.” He cannot tell if his symptoms change with position but reports that if he does not lie down he will become nauseous. He also has worsening hearing loss worse on his right side. The patient’s medical history is significant for hypertension, alcohol use disorder, and chronic obstructive pulmonary disease. His medications include aspirin, amlodipine, and fluticasone-salmeterol. He drinks a glass of red wine every night with dinner and smokes a cigar on the weekends. His temperature is 98.6°F (37°C), blood pressure is 135/91 mmHg, pulse is 72/min, and respirations are 12/min. Examination shows delayed horizontal nystagmus. Which of the following is the most appropriate treatment for this patient's condition?

Answer: Low-salt diet

Explanation:
This patient is presenting with chronic vertigo, hearing loss, and horizontal nystagmus, which is suggestive of Meniere disease. The most appropriate initial step in the management of this disease is a low-salt diet.

Meniere disease is caused by an abnormal accumulation of endolymph within the inner ear. Symptoms will include chronic relapsing and remitting episodes of vertigo, sensorineural hearing loss, tinnitus, and nausea. Physical exam, audiometry, and vestibular testing can be performed to confirm the diagnosis. First-line treatment is a thiazide diuretic as well as lifestyle modifications including a low-salt diet as well as avoidance of alcohol, nicotine, and caffeine. If symptoms persist, additional therapy may involve vestibular nerve ablation or a labyrinthectomy.

Tassinari et al. review the evidence regarding the treatment of Meniere disease. They discuss how vertigo, low-pitched tinnitus, and hearing loss are characteristic of this disease. They recommend creating a database to allow for better research into this disease.

Incorrect Answers:
Answer A: CN VIII ablation can be used to treat Meniere disease that is uncontrolled by diet modifications or thiazide diuretics. Patients usually respond to conservative care so a complete course of these treatments should be trialed first.

Answer B: The Epley maneuver can be used to treat benign paroxysmal positional vertigo (BPPV). Patients will present with vertigo that changes with the patient's position without hearing loss or tinnitus. This maneuver functions by dislodging otoliths from the semicircular canals.

Answer D: Meclizine can be used to treat other types of vertigo such as BPPV or viral labyrinthitis. Labyrinthitis can present with similar symptoms to the symptoms of Meniere disease, but they will be acute and self-limited. There will also be inflammation of the cochlear portion of the inner ear.

Answer E: Thiamine can be used for Wernicke-Korsakoff syndrome. A history of chronic heavy alcohol use, confusion with confabulation, ataxia, memory loss, and nystagmus are all concerning signs that may indicate thiamine deficiency.

Bullet Summary:
Meniere disease should be treated initially with a low-salt diet, avoidance of triggers, and thiazide diuretics.


Question: A 35-year-old G0P0000 woman presents to her gynecologist with complaints of irregular menstruation. She has had only 2 periods in the last year. She feels flushed without provocation and is experiencing occasional dyspareunia with post-coital spotting. She has also had more frequent headaches than usual. The patient has a medical history of Hashimoto thyroiditis and takes levothyroxine daily. Her mother has type 1 diabetes mellitus. Her temperature is 98.5°F (36.9°C), pulse is 70/min, blood pressure is 118/76 mmHg, and respirations are 13/min. Cardiopulmonary and abdominal exams are unremarkable. The patient has Tanner 5 breasts and pubic hair. A pelvic exam reveals a normal cervix, an anteverted uterus without tenderness, and no adnexal masses. The following laboratory studies are performed: Serum: Thyroid stimulating hormone (TSH): 28 µIU/mL (9-30 µIU/mL) Cycle day 3 follicle stimulating hormone (FSH): 49 mIU/mL (4.7-21.5 mIU/mL) Cycle day 3 estradiol: 8 pg/mL (27-123 pg/mL) Prolactin: 14 ng/mL (4-23 ng/mL) Testosterone: 42 ng/dL (15-70 ng/dL) Which of the following is the most appropriate next step in management?

Estradiol patch with oral medroxyprogesterone

Answer: Estradiol patch with oral medroxyprogesterone

Explanation:
This patient presents with oligomenorrhea, hot flashes, and dyspareunia, and her labs are notable for a high FSH and low estradiol, most consistent with premature ovarian insufficiency/failure (POI). The most appropriate next step in management is an estradiol patch with oral medroxyprogesterone.

POI is defined by the depletion or dysfunction of ovarian follicles, resulting in oligomenorrhea or amenorrhea with symptoms of menopause (hot flashes, vaginal atrophy and dryness, mood swings, etc.) in women under age 40. The cause is unclear and thought to be autoimmune. The main diagnostic markers are a high FSH and low estradiol at the start of the follicular phase. Patients require estrogen supplementation until around age 50, as low estrogen increases the risk of coronary artery disease, osteoporosis, and sexual dysfunction. Vaginal gel or a transdermal patch is the first-line option, but both must be used in conjunction with medroxyprogesterone to avoid unopposed estrogen and the risk of endometrial hyperplasia.

Tsiligiannis et al. review the evidence regarding the outcomes of patients with POI. They discuss how this diagnosis is made in patients younger than the age of 40. They recommend closely managing the cardiovascular risk factors associated with this disease.

Incorrect Answers:
Answer A: Brain MRI would be useful for evaluating for the presence of a prolactinoma, which could cause the headaches and oligomenorrhea seen in this patient. However, her prolactin level is normal, and she has no visual disturbances (e.g., bitemporal hemianopsia), making this study less relevant.

Answer B: The combined oral contraceptive has both estrogen and progesterone, but the doses are higher than those needed for hormone replacement. For this reason, it is generally not considered first-line for the treatment of POI.

Answer D: Increasing this patient’s levothyroxine dose is unnecessary, as her TSH level is within the normal range. Furthermore, while hypothyroidism may cause menstrual irregularities and temperature dysregulation, it is unlikely to cause vaginal dryness and subsequent dyspareunia.

Answer E: Vaginal estradiol gel is an effective method of estrogen replacement in women with POI. However, used alone it may increase the risk of endometrial hyperplasia and cancer, so it should only be used in combination with a systemic progesterone.

Bullet Summary:
Premature ovarian insufficiency should be treated with estrogen and progesterone replacement.