The Case Files

Welcome to the Case Files!
The Case Files is an anecdotal collection of emergency medicine cases to enable physicians and researchers to find clinically important information on unusual conditions.

Case reports should focus on:

  • Unusual side effects or adverse interactions.
  • Unusual presentations of a disease.
  • Presentations of new and emerging diseases, including new street drugs.
  • Findings that shed new light on a disease or an adverse effect.

Comment on a case or submit your own case following the instructions in the Submissions box to the right.

Tuesday, January 17, 2017

​​BY THOMAS BARROWS, MD

Barrows-Tramadol.jpeg

A 43-year-old woman presented to our emergency department with complaints of anxiety, intermittent “cramping” in her left hand, and jerking movements of her body that had been going on for five days. She had depression following the death of her son 14 months earlier, for which she was started on Effexor 37.5 mg once daily two weeks earlier.

One week before this visit, the patient had back pain and headache, for which she was evaluated at a local emergency department. She had lumbar x-rays showing mild degenerative changes in her spine and a normal head CT scan. The emergency physician who saw her prescribed tramadol 50 mg for every eight hours as needed for pain and cyclobenzaprine 10 mg for every eight hours as needed for spasm.

The patient subsequently developed uncontrollable anxiety and clenching of her left hand. The patient called her psychiatrist to inquire if it might be related to her taking Effexor, but her psychiatrist said the patient's symptoms were unlikely to be side effects of the drug.

The patient then followed up with her primary care physician, who observed an episode of uncontrollable clenching of the patient's left hand and was concerned about hypocalcemia or a central neurologic issue such as focal motor seizure. Her primary care provider then ordered laboratory tests, including calcium levels, ionized calcium levels, PTH, vitamin D levels, TSH, C-reactive protein, complete blood counts, electrolytes including magnesium and phosphorus levels, and liver function tests, all of which returned normal results. The primary provider scheduled an outpatient MRI of the brain and wrote prescription refills for tramadol and cyclobenzaprine.

The patient subsequently developed jerking movements involving her entire body, which seemed worse on the left side. The patient had not yet had her MRI brain scan, which was scheduled for later that afternoon, but presented to our emergency department with uncontrollable flinging and jerking movements of her body along with worsening anxiety.

Her physical exam was remarkable for frequent myoclonic jerking, tremor, hyperreflexia, and some incoordination with finger-to-nose and heel-to-shin testing. The patient was able to ambulate, but she intermittently had truncal ataxia while sitting. Otherwise, neurologic examination found her motor, sensory, and cranial nerve functions to be normal. Routine labs were normal, and the myoclonus was considerably improved with lorazepam 1 mg via IV.

We suspected that the patient had serotonin syndrome and recommended discontinuation of her meds, except for Ativan, to control the myoclonus. MRI of the brain was normal. Symptoms rapidly improved after discontinuing the medications, and the patient completely recovered within a few days.

Serotonin Syndrome

Signs and symptoms of serotonin syndrome include agitation or restlessness, diarrhea, rapid heart rate, elevated blood pressure, increased body temperature, loss of coordination, hyperreflexia, ataxia, myoclonus, agitation, nausea and vomiting, and hallucinations. (Ochsner J 2013;13[4]:533; Pain Med 2014;15[8]:1429.) Diagnosis of serotonin syndrome is typically made by identifying the clinical signs and symptoms when the patient is exposed to drugs known to elevate serotonin. The simple-to-follow Hunter Serotonin Toxicity Criteria offer simple if-then-else rules to diagnose the condition. (Am Fam Physician 2010;81[9]:1139; QJM 2003;96[9]:635.)

Offending drugs increase serotonin levels by inhibiting serotonin reuptake, inhibiting degradation of serotonin, or increasing serotonin release. (Am J Case Rep 2014;15:562.) A few drugs are also direct or indirect serotonin receptor agonists. (See table.)

The Rise of Tramadol

Tramadol is a blockbuster drug, and it became the 20th most prescribed drug in the United States by 2015. (IMS Health, Dec 2015; http://bit.ly/2h3QPMO.) A total of 424 tons of tramadol was consumed worldwide in 2012 alone. (WHO, 2014; http://bit.ly/2h3PTrw.)

The Drug Enforcement Agency re-categorized hydrocodone from a schedule III to a schedule II drug on Oct. 6, 2014, requiring it to be prescribed using triplicate prescription pads. This move was a response to the growing problem of prescription opioid abuse and diversion. Consequently, the burden of having to write triplicates may prompt physicians to seek alternatives such as tramadol. Tramadol had previously been placed into the schedule IV category on July 7, 2014.

Beware Cyclobenzaprine

Antidepressant medications are the most prescribed class of drugs in the United States, and one in 10 Americans is on antidepressants, according to the CDC. SSRIs are widely used as antidepressants, but frequent prescribing of tramadol and a lack of knowledge about the major drug interaction between tramadol and SSRIs can result in a growing number of patients experiencing the negative effects of these interactions.

Emergency physicians often prescribe a muscle relaxant in cases of muscle strain, spasm, or blunt trauma. Cyclobenzaprine should also be given with caution (if at all) to patients on other drugs that increase serotonin levels. The FDA instituted a safety labeling change to cyclobenzaprine in April 2013: “The development of a potentially life-threatening serotonin syndrome has been reported with Flexeril when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors.” (http://bit.ly/2h3D9kX.)

Physicians should be aware that cyclobenzaprine potentially poses some risk in combination therapies.

Toxic Combinations

Our patient on Effexor was prescribed a potentially toxic cocktail of tramadol and cyclobenzaprine by an emergency physician. This combination can result in a major reaction, potentially increasing serotonin levels and lowering the seizure threshold. (Psychiatry [Edgmont] 2009;6[4]:17.) Pairing any two of the three drugs prescribed to our patient — Effexor, tramadol, and cyclobenzaprine — will have major interactions.

Studies show only 15 to 20 percent of physicians are aware of the potentially serious interaction between tramadol and SSRIs. (Clinical Therapeutics 2015;37[8]:e43.) Symptoms of serotonin syndrome can range from mild to severe. It is likely that many patients with mild symptoms are simply overlooked by their physicians. Many patients who receive concomitant tramadol and SSRIs will likely have no symptoms, but it is difficult to anticipate which patients will have problems. A physician who prescribes tramadol monotherapy cannot predict whether a second physician may add other medications that can cause severe drug interactions. The use of electronic medical record systems that include drug interaction checking is encouraged.

The patient in this case either did not disclose these new medications or the psychiatrist failed to recognize the combination as dangerous. The patient then saw her own primary care provider who issued a new prescription for the same medications, apparently also not recognizing the risk of the combination. It is unfortunately common for physicians to fail to recognize the risk of serotonin syndrome from commonly prescribed drugs. (Eur J Hosp Pharm 23 March 2016 [ePub Ahead of Print].) Physicians who prescribe tramadol as part of their practice should take note of the myriad problems associated with tramadol in polypharmacy, and hospital pharmacies may play an important role in signaling the interactions and advising prescribers.

Partial List of Drugs Known to Increase Serotonin Levels

* Amphetamines and derivatives

* Ecstasy

* Dextroamphetamine

* Methamphetamine

* Sibutramine

* Analgesics

* Cyclobenzaprine

* Fentanyl

* Meperidine

* Tramadol

* Antidepressants/mood stabilizers

* Buspirone

* Lithium

* Monoamine oxidase inhibitors (selegiline, phenelzine, tranylcypromine)

* Selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, dapoxetine, seproxetine, zimelidine, mesembrine)

* Serotonin-norepinephrine reuptake inhibitors (venlafaxine, duloxetine, desvenlafaxine, milnacipran)

* Serotonin 2A receptor blockers (trazodone)

* Tricyclic antidepressants (amitriptyline, imipramine, nortriptyline)

* Antiemetics (metoclopramide, ondansetron)

* Antimigraine drugs

* Carbamazepine

* Ergot Alkaloids

* Triptans

* Valproic acid

* Miscellaneous

* Cocaine

* Dextromethorphan

* Linezolid

* L-tryptophan

Dr. Barrows is a physician with Code 3 Emergency Physicians in Dallas. He trained at Baylor College of Medicine and the University of Texas, Southwestern, in Houston and Dallas, respectively.


Tuesday, December 27, 2016

BY KIRSTEN FILL; JAMES MACGREGOR; ANDREW VICTOR; & AHMED RAZIUDDEN, MD​

A 32-year-old man was found unresponsive at home by his mother who immediately called the paramedics. The patient was in asystole upon their arrival, and CPR/ACLS protocol was started along with intubation. The patient was transported to the hospital, where ACLS protocol was continued and eventually resulted in the return of a stable pulse. The patient had a significant history of alcohol abuse resulting in liver disease, but had no prior episodes of such events. He also was a smoker of tobacco and marijuana. The patient's mother reported that he had had dark, tarry, melanotic stools and palpitations beginning a few days prior to his unresponsive episode.

The EMT on site administered 6 amps of epinephrine, 2 mg of naloxone, 1 amp of bicarbonate, and D50 via intraosseous line. Resuscitation continued in the ED with another 4 amps of epinephrine administered, resulting in a pulse being re-established. Two peripheral intravenous lines and a subclavian line were then placed to maintain the patient hemodynamically.

The patient was transfused a unit of O negative blood along with a bicarbonate bolus. This allowed for blood to be drawn for tests, and a CBC, CMP, troponin, lactic acid, arterial blood gas, urine analysis, and toxicology screens were ordered. A unique clinical finding in this patient was that the fluid aspirated into the catheter lumen appeared serosanguinous (like pink water) when the central access line was placed, raising the question of whether the catheter was appropriately placed in the subclavian vein.

The blood results correlated with the observed findings in reporting a hemoglobin level of 1.2 g/dL with a hematocrit value of 6.3% and a normal MCV. The patient was found to be acidotic with a pH value of < 6.8, lactic acid of 20.5 mmol/L, troponin elevated at 0.166 ng/mL, and ammonia at 473.3 ug/dL. The patient's WBC count was elevated at 16,260, but the rest of his laboratory workup was relatively normal except for mildly elevated LFTs. The patient's stool sample was melanotic and tested heme-positive.

Despite continued maintenance efforts, the patient eventually expired later in the ICU before further workup could be done to explain the cause of his sepsis and dramatically low hemoglobin value. This raises the question of how low a hemoglobin value can be while sustaining life in a normal individual.

Anemia in Alcoholics

Hemoglobin levels of less than 13.5 g/dL in men and less than 12.0 g/dL in women defines anemia. Anemia in chronic alcoholics is often multifactorial and involves poor nutrition, chronic inflammation, blood loss, liver dysfunction, and ineffective erythropoiesis. (Medicine [Baltimore] 1986;65[5]:322.) Alcohol also has direct toxic effects on the bone marrow red blood cell production as well as red blood cell functionality and lifespan. The table summarizes contributory factors to anemia in alcoholics.

Compensatory Mechanisms

anemia.jpeg 

Factors causing anemia in chronic alcoholics.

Physiologic mechanisms will compensate for the decrease in red blood cell mass primarily by alterations in hemoglobin oxygen affinity, blood flow redistribution, and cardiac output adjustments. These mechanisms work in unison to attempt adequate oxygenation, butthe body cannot decrease its tissues' oxygen requirement.

Increases in oxidative metabolism occur as a consequence of the energy required for the compensatory activities. The severity of the clinical presentation relates less to the hemoglobin level and more to the length of time in which the condition develops. Anemias that develop over years will allow the compensatory mechanisms to maintain the patient in an asymptomatic state despite a greater RBC mass loss than an acute hemorrhage. (http://bit.ly/2eOTUCL.)

anemia2.jpeg

Normochromic normocytic RBC on peripheral smear.

* Hemoglobin oxygen affinity: Anemic blood undergoes an increased extraction of oxygen from tissues, increasing the deoxyhemoglobin in the RBC. The hemoglobin-oxygen curve is shifted to the right due to an increased production of 2,3-diphosphoglycerate. The overall decrease in hemoglobin oxygen affinity improves oxygen delivery to target tissues.

* Blood flow redistribution: Chronic anemic states cause selective vasoconstriction of vessels supplying the kidneys and non-vital areas of the body such as cutaneous sites leading to the clinical finding of pallor. Chronic anemic patients will also paradoxically increase total blood volume due to a plasma volume expansion despite the decrease in RBC mass.

* Increased cardiac output: Severe anemics (Hgb < 7 g/dL) will compensate for tissue hypoxia by increasing cardiac output. The change in output is counteracted by a lower blood viscosity and decreased peripheral vascular resistance so it does not cause a rise in blood pressure. (Semin Hematol 1980;17[3]:164.)

These mechanisms allow the body to adapt, but at what point are these adaptations no longer adequate to maintain vital organ oxygenation? How low can the hemoglobin fall before life can no longer be sustained? Several case reports have attempted to answer this question. De Araujo Azi, et al., presented a case of a 27-year-old Jehovah's Witness patient who survived a hemoglobin level as low as 1.4mg/dL following surgery for scoliosis without receiving blood transfusions. (Transfusion 2014;54[4]:1153.) Further case reports have suggested that patients have survived with hemoglobin levels below 2.0mg/dL even in the setting of aging comorbidities.

Imaizumi, et al., reported a case of a 61-year-old man with bladder cancer and previous gastrectomy for cancer who survived a preoperative hemoglobin level of 1.8mg/dL. (J Anesth 1999;13[2]:125.) The most dramatic of all cases recorded low hemoglobin values with patient survival occurring intraoperatively during a liver transplant for a patient with hepatocellular carcinoma and decompensated liver failure. This patient was recorded as having a hemoglobin level of 0.6 g/dL with associated ventricular tachycardia, sustained ST depressions, and elevated serum lactate levels. (A A Case Rep 2015;4[10]:132.)

It is clear that the human body has a formidable capacity to heal itself and maintain life in the direst of circumstances. Prolonged episodes of chronic anemia lead to significant changes in body homeostasis, allowing it to operate at critically low values of hemoglobin. Notwithstanding patient comorbidities, the human body may appear relatively asymptomatic while demonstrating dangerously low hemoglobin values. We have seen the body's compensatory mechanisms given these circumstances and confirmed sustainability of life even in unique situations such as severe chronic anemia.


Tuesday, September 13, 2016

​BY MARK ​GRANT, DO

A 31-year-old man presented to the emergency department with dyspnea, fever, cough, and weakness for two weeks. He had recently seen his internist, and was diagnosed with a viral infection. He was seen again at an urgent care center a few days before his ED presentation, and was diagnosed with bronchitis and an ear infection and placed on an antibiotic.

The patient said in the ED that he was not improving, and was now experiencing back pain, shortness of breath, and occasional fevers and sweats. The patient stated he had sharp chest pain at times and was coughing up clear sputum more often over the previous few days, but had no hemoptysis, orthopnea, abdominal pain, vomiting, diarrhea, dysuria, hematuria, headache, neurologic complaints, or rashes. Physical examination revealed no otitis media or pain to palpation of the joints or spine. His lungs were clear to auscultation.

The patient in the past two weeks had driven from Texas to Michigan. The patient had no history of pulmonary embolism or DVT, and had no significant past medical history. He was born in India, moved here as a child, and was up​ to date with immunizations. The patient and his family have no history of tuberculosis. His initial vital signs were blood pressure of 112/72 mm Hg, temperature of 98.7°F, pulse ox of 99% on room air, and respiratory rate of 18 bpm.

An IV was established, and the patient was hydrated and labs obtained. The patient's CBC, basic metabolic panel, and urinalysis were unremarkable. An influenza swab was performed and returned negative. The sedimentation rate was 50 mm/hr and the C-reactive protein was 73 mg/LD. The D-dimer was positive at 525 ng/ml.

A chest x-ray interpreted by radiology is negative for an acute process. A chest CT is obtained because of the patient's recent travel history, dyspnea, and positive D-dimer. The CT thorax images show no pulmonary embolism, but a lytic and sclerotic lesion involving the T7 vertebrae and thickening of the soft tissue surrounding the perivertebral tissue of T7. The CT of the thorax also shows mild right hilar lymphadenopathy.


CT and MRI images showing Pott disease.

This patient has Pott disease, the name given to tuberculous spondylitis by British surgeon Percivall Pott (1714-1788). Pott disease results from hematogenous spread of tuberculosis from other sites, most often the lungs, to the upper and lower vertebrae. Most commonly, however, spread of this acid-fast bacilli Mycobacterium is to the thoracic vertebrae, as seen in this patient. (Neurosurg Rev 2001;24[1]:8.) The infection then spreads from adjacent vertebrae through the intervertebral discs, and destroys the disc and vertebrae, which can lead to disc collapse and spinal cord damage. (Spine 2007;32[4]:E130.) Bone and soft-tissue tuberculosis accounts for approximately 10-15 percent of extrapulmonary tuberculosis cases and between one and two percent of total cases. Tuberculous spondylitis is the most common manifestation of musculoskeletal tuberculosis, accounting for approximately 40-50 percent of cases. (N Am J Med Sci 2013;5[7]:404.)

Patients with Pott disease typically present with back pain. The average duration of nonspecific back pain before diagnosis is around four months, and can be accompanied by fever, night sweats, cough, and weight loss, which can clue a clinician into the diagnosis. (Postgrad Med J 2006;82[963]:46.)

The sedimentation rate and the C-reactive protein are uniformly elevated while the CBC, basic metabolic panel, and other tests are usually normal. The tuberculin skin test (PPD) is positive in 85-95 percent of patients with Pott disease who are not HIV-positive. Bone tissue or abscess samples through CT-guided biopsy for acid-fast bacilli stain and culture is anywhere from 50 percent to 83 percent sensitive. (S Afr Med J 2013;104[1]:29.) This patient underwent interventional CT-guided biopsy and grew out the organism Mycobacterium chelonae.

Radiologic findings occur late in the diagnosis of Pott disease, and they suggest the diagnosis on plain x-ray as osteoporotic-appearing vertebral end plates, intervertebral discs that are shrunken or destroyed, bony lytic lesions, and hilar lymphadenopathy on PA and lateral chest x-ray. (Orthopedics 1998;21[11]:1213.) CT scanning reveals much more detail of the bony lytic lesions, disc collapse, and classic calcification abscess lesions of tuberculosis. (Radiol Clin North Am 1995;33[4]:787.)

Magnetic resonance imaging is the standard for evaluating disk-space infection and osteomyelitis of the spine, and it is most effective for demonstrating the extension of disease into soft tissues and the spread of tuberculous debris under the anterior and posterior longitudinal ligaments. MRI is also effective in demonstrating abscess formation as well as neuronal involvement. (Eur J Radiol 2005;55[2]:193.) The MRI images in this patient confirm spread of the infection from T6 through T8 with discitis, osteolytic lesions, and epidural abscess but no cord edema.

Once the diagnosis of Pott disease is established, treatment options vary, and is typically individualized for each patient (J Int Med Res 2013;41[5]:1395), including a combination of chemotherapy and surgical management with consideration of the patient's medical stability and neurologic symptomatology.

A four-drug regimen should be used empirically to treat Pott disease, according to 2003 recommendations from the Centers for Disease Control and Prevention, the Infectious Diseases Society of America, and the American Thoracic Society. Isoniazid and rifampin should be administered during the whole course of therapy. (Am J Respir Crit Care Med 2003;167[4]:603.) Additional drugs are administered during the first two months of therapy, generally chosen from among the first-line drugs, which include pyrazinamide, ethambutol, and streptomycin. The use of second-line drugs is indicated in cases of drug resistance. (Int Orthop 2012;36[2]:277.) Studies performed by the British Medical Research Council indicate that tuberculous spondylitis of the thoracolumbar spine should be treated with combination chemotherapy for six to 12 months. (J Bone Joint Surg Br 1993;75[2]:240.)

Indications for surgical treatment of Pott disease generally include neurologic deficits, unstable spinal deformity, a large paraspinal abscess, intractable pain, and continued bony spread and destruction. (J Bone Joint Surg Am 1996;78[2]:288.) Vertebral damage is considered severe if greater than 50 percent of the vertebral body is collapsed or destroyed.

Pott disease is the most severe form of musculoskeletal tuberculosis because of the bony destruction, deformity, and subsequent neurologic disability (paraplegia) that can occur. This case highlights the importance of keeping a wide differential diagnosis for patients with multiple visits with no clear-cut diagnosis and the importance of addressing any potential lab abnormalities. The busy times in the emergency department should never detour the clinician from performing a good history and physical examination.

Dr. Grant is an assistant clinical professor of emergency medicine at Michigan State University/College of Osteopathic Medicine/College of Human Medicine.​​


Tuesday, September 13, 2016

​​BY SEFAKO PHALA; ​ROBERT STATZ; ANDREW VICTOR; MOHAMMED HASSAN-ALI, MD, MSC; & AHMED RAZIUDDIN, MD

A 65-year-old Caucasian man was brought to the ED via ambulance complaining of worsening upper back pain for one week. His primary care physician had recently prescribed him NSAIDs and muscle relaxants, which failed to provide relief. The newest symptoms were numbness and weakness over his left arm and leg. The patient reported no history of trauma to his back nor did he have any chronic illnesses. Physical exam showed paresthesia in the left upper extremity in a dermatomal distribution pattern that suggested further evaluation in determining the underlying cause of this atypical back pain.

A laboratory workup was ordered including CBC, CMP, TSH, PSA, blood glucose, and urine analysis in addition to a CT scan of the thoracic and lumbar spine. The laboratory results were within normal limits. The CT report of the thoracic spine scan revealed a soft tissue mass associated with a pathologic fracture containing lytic lesions of the T2 and T3 vertebral bodies. An MRI confirmed CT findings alongside additional spinal cord displacement at the level of T2. A differential diagnosis of a single thoracic spinal tumor was made.


CT and MRI images showing vertebral disc lesion at T2 & T3.

The patient was admitted for futher investigation. A full-body bone scan was performed to rule out other lytic lesions. A fine needle aspiration biopsy of the tumor was performed revealing numerous plasma cells consistent with solitary bone plasmacytoma.

Plasma cells within the bone marrow normally produce large volumes of antibodies. (Blood 2003;101[5]:1715.) Born from precursor B cells, the antibodies are released into the blood and lymph with a function to attach to and aid in antigen eradication. Plasma cells play a very important role in the development of several diseases. A plasmacytoma is a localized collection of malignant plasma cells without any proof of a systemic plasma cell disorder. (Blood 2000;96[6]:2037.)

Diagnostic criteria for solitary plasmacytoma of the bone (SPB) include a single area of bone destruction due to clonal plasma cells; normal marrow without clonal disease; normal results on a skeletal survey and MRI of the spine, pelvis, proximal femora, and humeri; no anemia, hypercalcemia, or renal impairment attributable to myeloma; and absent or low serum or urinary level of monoclonal protein and preserved levels of uninvolved immunoglobulins. (Blood 2000;96[6]:2037.)

A study by Hirano (2002) has implicated the overexpression of interleukin-6 in severe autoimmune reactions as well as plasmacytosis with progression to plasmacytoma and multiple myeloma. (Proc Jpn Acad Ser B Phys Biol Sci 2010;86[7]:717.) Moreover, it should be noted that studies have shown progression to multiple myeloma from the initial SPB lesion within two to four years. (Hematology Am Soc Hematol Educ Program 2005:373.)

Bones of active hematopoiesis are the most commonly involved structures of solitary plasmacytoma of the bone. (“Diagnosis and Management of Solitary Plasmacytoma of Bone.” In: UpToDate, Waltham, MA. Accessed March 1, 2016.) Rarely, SPB can extend into surrounding soft tissue. More specifically, bone sites most commonly affected (in descending order) are the vertebrae, pelvis, ribs, upper extremities, face, skull, femur, and sternum. Thoracic vertebrae have higher incidence than lumbar, sacral, or cervical spine vertebrae. Multiple myeloma cannot be ruled out in patients with SPB because of possible undetected immunoglobulin or active focal sites. In fact, M protein is present in 30-75 percent of all cases of SPB. If present, patients have a 50 percent higher risk of developing multiple myeloma and have an overall survival of 10 years. This M protein will not disappear after treatment.

Approximately 450 new cases of SPB are diagnosed each year (0.15 cases/100,000 persons per year; Hematology Am Soc Hematol Educ Program 2005:373), with the highest demographic being blacks, making this case an anomaly. Men are diagnosed almost twice as much as women with median ages ranging from 55 to 65. This patient's family history was unknown, but the condition does have a genetic aspect. An increased risk of plasma cell dyscrasia is observed in patients who have a first-degree relative with monoclonal gammopathy of undetermined significance or multiple myeloma. (“Diagnosis and Management of Solitary Plasmacytoma of Bone.” In: UpToDate, Waltham, MA. Accessed March 1, 2016.)

A full week of diagnostic testing ultimately discovered something far more exceptional than a benign case of back pain. Very little is known about this cancer diagnosis. Advancements in medicine will better characterize and identify medical anomalies such as SPB sooner. The patient is being currently treated with radiation therapy, and is expected to recover successfully.

Special thanks to Manjeet Chawla, MD, of Thorek Memorial Hospital for his contributions to this article.

Mr. Phala and Mr. Victor, clockwise from top left, are fourth-year medical students at the University of Medicine and Health Sciences in St. Kitts. Mr. Statz is a fourth-year medical student at Xavier University School of Medicine in Aruba. Dr. Hassan-Ali is a research assistant at McMaster University in Ontario. Dr. Raziuddin is an emergency physician at Thorek Memorial and Weiss Memorial hospitals in Chicago and at Westlake Hospital in Melrose Park, IL.​


Tuesday, August 23, 2016

​​BY ​MEGHAN JONES, MD; ANN HAYNES, MD; & ANDREW KING, MD

When patients present to the emergency department complaining of headache, the emergency physician must consider a large list of differential diagnoses. Emergency physicians often hope patients will fall into pre-existing, well-known patterns, helping them to establish the appropriate workup quickly. Despite common illness scripts and presentations, many patients will present unusually and lead physicians to findings they were not expecting.

A 54-year-old woman with a history of hepatitis C presented to the emergency department for a headache that had been present for several months. Her symptoms had acutely worsened on the day of presentation, and she also reported itching and discomfort of her posterior right scalp with associated swelling that had progressed since onset. She thought this swelling may have resulted from hitting her head on her oven range hood a year or two earlier. Our patient was the primary caregiver for an ill family member and had no insurance; she said that was why she had not presented earlier for the increasing scalp swelling.

During the course of her illness, she never experienced numbness, weakness, paresthesias, or other associated neurologic complaints. She did report feeling off-balance, however, in addition to the worsened headache. Our patient also reported poor vision at baseline with loss of her lateral visual fields recently, but had no other focal neurologic complaints upon presentation.

The patient was found to have a baseball-sized mass to her posterior right scalp. The patient was otherwise neurologically intact including all cranial nerves. A head CT was obtained in the emergency department, revealing a large extra-axial mass extending both intracranially and extracranially with destruction of the portions of the right parietal and occipital skull. Mass effect caused a 4 mm midline shift to the left. A subsequent MRI defined the dimensions of the mass, 7.7 cm x 8.6 cm x 7.9 cm, as well as small ischemic foci within the right occipital lobe, adjacent to the splenium of corpus callosum. MR angiography illustrated a hypervascular tumor with several hemorrhagic foci. The arterial supply to the tumor was predominantly from external carotid arteries, specifically the right occipital artery.


Patient's posterior right scalp mass.


Computed tomography of the head showing large extra-axial mass extending both intracranially and extracranially with destruction of the right parietal calvarium.


Magnetic resonance imaging of brain showing extra-axial mass extending intracranially and extracranially with destruction of right parietal calvarium.

Neurosurgery was consulted, and the patient was admitted for further workup. Intraoperative cerebral arteriogram showed hypervascular parieto-occipital tumor with a robust blood supply from the right and left occipital arteries. She underwent embolization of branches of the right and left occipital arteries with subsequent right occipital craniotomy with extradural tumor removal. Staging imaging showed a heterogenous lesion in the left lobe of her liver. Surgical pathology from the intracranial mass was identified as hepatocellular carcinoma (HCC). This was thought to be metastatic HCC secondary to the patient's known history of untreated hepatitis C.

Hepatocellular carcinoma, although prevalent in the developing world, is relatively rare in the United States, with an incidence of 10 per 10,000 individuals. (Rosen's Emergency Medicine, Eighth edition. Chapter 90. Elsevier/Saunders, Philadelphia; 2014. 1186-1204.) This oncologic disorder often presents with vague symptoms, and is difficult to diagnose without historical evidence of specific risk factors, such as hepatitis viruses and chronic alcohol use. Metastasis of this primary liver tumor is very advanced and carries a poor prognosis. Hepatocellular carcinoma can certainly metastasize to many areas of the body, but brain metastases from HCC are the most rare. Timely diagnosis and workup is essential in treating these patients.

The consideration of primary tumors as potential diagnoses is imperative, but emergency physicians must also remember to include the possibility of metastatic disease as a cause of vague patient presentations. Our patient carried risk factors for the potential diagnosis of a rare primary liver cancer, but it was not expected that her complaints would be tied to an even rarer brain metastasis of this tumor. It is especially difficult to diagnose this presentation when symptoms associated with brain metastasis have a wide range of symptoms from altered consciousness and vision changes to imbalance, incoordination, and hemiparesis, and everything in between. (Oncologist 2011;16[1]:82.) Brain metastasis of HCC carries a poor prognosis, but the picture becomes even more concerning when the mass becomes symptomatic, resulting in a trip to the emergency department.

Hepatocellular carcinoma is a prevalent primary liver malignancy worldwide. Primary liver cancers are listed as the fifth most common for men and eighth most common for women worldwide. (Gastroenterology 2004;127[5 Suppl 1]:S5.) In higher risk or developing countries, liver malignancies can arise before age 20, and several new cases — in the magnitude of hundreds of thousands — are diagnosed yearly. In developed or low-risk countries, liver cancer is rare before age 50. (Gastroenterology 2004;127[5 Suppl 1]:S5.) These hepatic primary cancers are also on the rise in developed countries, including the United States. This trend is thought to be most likely due to increased exposure of hepatitis B and C via contaminated blood transfusion and increased intravenous drug use in the 1960-1970s. (Gastroenterology 2004;127[5 Suppl 1]:S5.)

Seventy-five to 80 percent of primary liver malignancies in the United States are attributed to persistent viral infections including the hepatitis B virus (HBV) and the hepatitis C virus (HCV). (Rosen's Emergency Medicine, Eighth edition. Chapter 90. Elsevier/Saunders, Philadelphia; 2014: 1186.) Other risk factors contributing to increasing incidence of this disease include chronic alcohol use, tobacco, and increasing nonalcoholic steatosis of the liver. There are an estimated four million HCV carriers in the United States. Of these, 60 percent will go on to develop cirrhosis, and another five percent will develop HCC. This will account for about 20,000 annual cases. It is estimated that by adding in HBV and chronic alcoholism, this will total about 60,000 new cases annually in the United States. (Harrison's Principles of Internal Medicine, 18th edition. Chapter 92, McGraw-Hill, New York; 2012.)

Clinical presentations of HCC are usually vague and varied. These patients can present with nausea, weight loss, weakness, and abdominal pain. Some patients may have more leading complaints of right upper quadrant abdominal pain and jaundice. Laboratory testing is not always helpful because results may remain normal. Ultrasound or computed tomography imaging are the best initial testing modalities in a diagnosis of primary liver metastasis. (Rosen's Emergency Medicine, Eighth edition. Chapter 90. Elsevier/Saunders, Philadelphia; 2014: 1186.) Clearly, diagnosing HCC as a primary malignancy is difficult, and it may be even more difficult when someone presents with symptoms that could be attributed to many different disease patterns. Our patient presented solely with symptoms related to her intracranial metastasis including headache, visual changes, and imbalance.

Extrahepatic metastasis is found in only five percent to 15 percent of presentations at time of initial HCC diagnosis. (J Neurooncol 2009;91[3]:307; World J Gastroenterol 2007;13[3]:414.) One study found patients with HCC presented with symptoms associated with brain metastasis in only five percent of presentations. (J Neurooncol 2009;91[3]:307.) Tumors larger than 5 cm and large vascular invasion make extrahepatic metastasis more likely. The most common sites of extrahepatic metastasis are the lungs, intra-abdominal lymph nodes, bones, and adrenal glands, in order of frequency of occurrence. (Radiology 2000;216[3]:698.) Brain metastases are much rarer; in fact, they are only present in 0.2 percent to two percent of cases of advanced metastatic HCC, making this patient's presentation even more unusual. (Oncologist 2011;16[1]:82.) Brain metastasis has also been related to poor prognosis and thought to be a late finding. Now, with new chemotherapeutic agents and targeted, anti-tumor therapy, increased survivability is seen in patients even with advanced stage HCC. Some theories suggest that these improvements may be causing an increased frequency of brain metastasis and other late complications that used to be rarer. (Oncologist 2011;16[1]:82.)

The prognosis of HCC with brain metastasis is thought to be so advanced that it carries a median survival of six weeks to four months from time of brain lesion diagnosis, even with treatment. (Oncologist 2011;16[1]:82; J Neurooncol 2009;91[3]:307.) Emergency physicians must continue to keep an open mind about the possibility of metastatic disease in vague presentations. Obviously, the emergency physician will be unable to make tissue diagnoses of HCC lesions in the emergency department, but it is imperative that these patients have immediate follow-up and diagnostic workup, whether that is through admission or outpatient referral depending on their initial presentations.

Dr. Jones was a third-year emergency medicine resident at the Ohio State University Wexner Medical Center when this article was written, but is now an attending emergency physician in Lexington, KY. Dr. Haynes is a clinical assistant professor at the Ohio State University East Hospital. Dr. King is a clinical assistant professor at the Ohio State University Wexner Medical Center, both in Columbus.