Firecracker Clinical Vignettes Flashcards
A 45-year-old female with a history of atrial fibrillation develops sudden onset of left-sided hemiparesis and eye deviation to the right. She is brought to the emergency department where an evaluation with an MRI reveals a large area of restricted diffusion
The patient has suffered a middle cerebral territory artery stroke on the right (non-dominant) side. The left hemisphere is dominant (meaning that language localizes there) in almost all right-handed patients and 90% of left handed patients. Ischemic stroke in the MCA territory presents with basic exam findings, such as contralateral hemiplegia, eye deviation towards the side of the lesion (frontal eye fields), and contralateral neglect. Patients with large dominant hemisphere lesions can present with global aphasia, whereas non-dominant hemisphere infarcts result in anosogosia. Evaluation of ischemic stroke is performed with diffusion weighted MRI imaging. Anterior cerebral artery stroke commonly results in contralateral leg weakness. Posterior inferior cerebellar artery stroke can result in a Wallenberg (lateral medullary) syndrome.
A 44-year-old male presents to the hospital with a history of diffuse epigastric pain. He is found to have elevated serum amylase and lipase levels, in addition to abnormal liver function tests. An ultrasound is performed that demonstrates cholelithiasis without evidence for cholecystitis. He is admitted to the hospital for bowel rest and intravenous hydration. The following morning, all of his serum chemistries trend towards the normal range. A cholecystectomy is recommended, but the patient refuses. He feels better and is discharged to home. Two months later, he presents to the emergency department with right upper quadrant pain, fever to 104ºF, and jaundice. He is also slightly confused and is found to be hypotensive
The patient presents with symptoms of cholangitis. He has a history of gallstones as evidenced by his previous history of gallstone pancreatitis (self resolved). Cholangitis is identified by Charcot’s triad of right upper quadrant pain, fever, and jaundice. The patient also has the additional findings of mental status changes and shock (Reynold’s pentad) that is suggestive of sepsis. E. Coli and Klebsiella are the most common organisms. Cholecystitis is classically associated with prolonged right upper quadrant or epigastric pain, fever, abdominal guarding, a positive Murphy’s sign, and an elevated white blood cell count.
An 81-year-old woman is brought into the ED from her skilled nursing facility for the evaluation of fever. At baseline, she is nonverbal as the result of a left-sided CVA experienced many years ago. On arrival, her initial vitals are: T 39.05°C (102.3°F), HR 106, BP 132/74, RR 18, SpO2 98% on room air. A chest x-ray is obtained, which shows a dense consolidation in the right lower lobe. Given concern for a bacterial pneumonia, she is given 1 liter of normal saline and started on IV vancomycin, levofloxacin, and ceftriaxone. Approximately 25 minutes later, a nurse observes that the patient now has a new urticarial rash over her abdomen, trunk, and upper extremities. Repeat vitals are: T 39.1°C (102.4°F), HR 118, BP 104/76, RR 22, SpO291% on room air. On pulmonary exam she is found to have diffuse wheezing in all fields.
A. another liter of IV normal saline B. IV diphenhydraine (Benadryl) C. IV methylprenisoloe D. IM epinephrnie E. Supplemental oxygen via nasal cannula F. Nebulized ipratropium and albuterol
This patient is experiencing an anaphylactic reaction, most likely to one of the antibiotics she received. Anaphylaxis is an acute, life-threatening, multisystem type 1 hypersensitivity reaction that most commonly presents with respiratory and skin findings. In severe reactions, patients can progress to distributive shock as a consequence of systemic vasodilation. This patient is demonstrating many of the key findings of anaphylaxis, including tachycardia, hypotension, rash, and bronchoconstriction. Of primary importance in anaphylaxis is ensuring a stable airway; were this patient to have findings on physical exam suggestive of angioedema or airway compromise, a low threshold should be maintained for emergent intubation.
While all of the answer choices listed are correct therapies in the treatment of anaphylaxis, the most important is intramuscular epinephrine, which will act quickly to reverse the life threatening bronchial and upper airway constriction
Wrong choices:
A. Another liter of IV normal saline
Patients in anaphylaxis may experience a rapid drop in their blood pressure as a consequence of histamine-induced vasodilation and fluid shifts, and may need several liters of IV fluid to maintain adequate perfusion pressures. However, as indicated above, IM epinephrine should come first.
B. IV diphenhydramine (Benadryl)
In anaphylaxis, mast cells throughout the body release histamine into the circulation. As such, antihistamines such as Benadryl play a key role in the appropriate management. Longer-acting second generation antihistamines, like cetirizine and loratidine, may also be employed for prolonged histamine blockade.
C. IV methylprenisolone
Systemic glucocorticoids, such as prednisone and methylprednisolone, are important to prevent the “rebound” anaphylactoid reaction that can occur several hours after the initial reaction as epinephrine and antihistamines begin to wear off.
E. Supplemental oxygen via nasal cannula
Inhaled bronchodilators are useful adjuncts for treating the symptomatic bronchoconstriction that can occur in anaphylaxis.
F. Nebulized ipratropium and albuterol
This patient is experiencing hypoxemia, likely as a result of both anaphylaxis and her pneumonia. Supplemental oxygen is warranted, but should not supersede the administration of epinephrine.
You are evaluating a six-month-old female infant at a routine well-child check. Her parents are concerned that she appears pale. She was born full-term via ceasarian section for breech presentation. She has no significant past medical history and her immunizations are up-to-date. She has reached all the appropriate developmental milestones. She was breast fed exclusive for the first two months, but since weaning she has only been fed organic goat’s milk. On physical exam, she is small for her age
The infant in this vignette has folate deficiency. She has a megaloblastic anemia and is getting an inadequate amount of folate in her diet. The main dietary sources of folic acid are animal products, leafy green vegetables, and fortified foods; however goat’s milk does not contain adequate amounts of folic acid.
B. Vitamin B12
Vitamin B12 deficiency causes a megaloblastic anemia similar to folate deficiency, but also presents with neurologic symptoms that in a young infant include developmental delay or regression, failure-to-thrive, weakness, seizures, and irritability.
C. Niacin (Vitamin B3)
Niacin deficiency causes pellagra, which is characterized by the three D’s: dermatitis, diarrhea, and dementia.
D. Riboflavin (Vitamin B2)
Riboflavin deficiency presents with cheilosis, glossitis, keratitis, photophobia, seborrheic dermatitis, sore throat, edema, hyperemia of mucous membranes, and a normocytic anemia.
E. Thiamine (Vitamin B1)
Thiamine deficiency causes Beriberi and Wernicke-Korsakoff syndrome. Beriberi presents with cardiac failure and/or neurologic manifestations including: irritability, peripheral neuritis, decreased tendon reflexes, loss of vibratory sense, aseptic meningitis, and ataxia. Wernicke encephalopathy presents with ophthalmoplegia, nystagmus, ataxia, intracranial hemorrhage, and confusion. Korsakoff psychosis results in short-term memory loss and confabulation with normal cognition.
F. Pyridoxine (Vitamin B6)
Pyridoxine deficiency causes refractory seizures, peripheral neuritis, dermatitis, and a microcytic anemia.
A 75-year-old man presents to the emergency department after having a bowel movement with bright red blood per rectum. He otherwise denies any abdominal pain, nausea, vomiting or hematemesis. He also denies recent weight loss, fevers, or night sweats, but he does report low energy for the past 2-3 days. On arrival to the emergency department, the patient’s temperature is 36.2°C (97.2°F), his heart rate is 122/minute, and his blood pressure is 92/50 mmHg. On physical exam, the patient appears pale but in no acute distress. His abdominal exam is unremarkable, and rectal exam demonstrates no visible external hemorrhoids but some bright red blood is noted in the rectal vault.
A. Mesenteric Ischemia B. Peptic ulcer disease C. Diverticulosis D. Divertculitis E. Colon Cancer
Diverticulosis technically refers only to the presence of colonic diverticula, although in common practice the term is used to describe the syndrome of painless diverticular bleeding. Diverticulosis is the most common cause of overt (rather than occult) lower GI bleeding in adults, and typically presents with painless, often large-volume, hematochezia. The majority of cases of bleeding are self-limited, although patients can rapidly develop symptomatic hypotension and anemia requiring transfusion. Given this patient’s age and likely large volume lower GI bleed (as suggested in this vignette by the combination of bright red blood pre rectum with hypotension, tachycardia, and pallor), diverticulosis is the most likely diagnosis. After initial resuscitation and stabilization, this patient should undergo colonoscopy to rule out colorectal cancer and confirm the diagnosis of diverticulosis. In addition, if bleeding does not stop spontaneously, endoscopic intervention can be attempted. In severe cases, endovascular or surgical intervention may be required.
A. Mesenteric ischemia
Mesenteric ischemia is a common cause of GI bleeding in the elderly that is caused by mesenteric vascular insufficiency, often secondary to atherosclerosis and thromboembolic disease. Mesenteric ischemia most commonly presents with severe abdominal pain, classically described as out of proportion to the findings on physical exam. This patient’s lack of pain makes mesenteric ischemia unlikely.
B. Peptic ulcer disease
Peptic ulcer disease most commonly presents with upper abdominal pain or discomfort, often in relation to eating (dyspepsia). Bleeding from a peptic ulcer (and most other upper GI sources) most often presents as melena (black tarry stool), rather than bright red blood. As this patient has neither pain nor melena, he is unlikely to have peptic ulcer disease.
D. Diverticulitis
Diverticulitis refers to inflammation of a colonic diverticulum. It presents with abdominal pain, usually localized to the left-lower quadrant, fever, nausea, vomiting, and sometimes hemodynamic instability and shock. On exam, the abdomen is tender to palpation, and peritoneal signs may be present. This patient is afebrile without any of the signs or symptoms of diverticulitis.
E. Colon Cancer
Colorectal cancer is the third most common type of cancer in both men and women in the United States. Symptoms may be insidious at first, and include bloody stools, weight loss, anemia, a change in bowel habits, and other systemic signs of inflammation. While colorectal cancer is the most common cause of lower GI bleeding in adults, most colorectal cancers present with occult bleeding. In contrast, diverticulosis is a more common cause of overt lower GI bleeding (bright red blood per rectum).
A 54-year-old male visits his primary care physician with the complaint of back pain. While he has had some pain in his back for months, he recently became more concerned when the pain seemed to travel down the back of his right thigh and into his calf. He complains of numbness in the right foot as well, mainly on the top of the foot and great toe. On exam he has normal ankle jerk reflexes and a weak extensor hallucis longus on the right.
- L3/L4
- L4/L5
- L5/S1
- Tethered spinal cord
- Multi-level spinal stenosis
The patient suffers from a herniated lumbar disc at the L4/5 vertebral body level, corresponding to impingement of the L5 nerve root. The patient’s radicular symptoms in the L5 dermatome help to localize the pathology. The L5 dermatome typically affects the top of the foot with a unique motor distribution to the extensor hallucis longus. The L4 myotome affects dorsiflexion of the foot with the extensor hallucis longus not usually being affected. With S1 radiculopathy, patients often complain of sensory changes along the lateral aspect and bottom of their feet. The myotome distribution of the S1 nerve root focuses mainly on the gastrocnemius. Patients with an S1 radiculopathy will have weakness in their gastrocnemius (difficulty standing on their toes) and is accompanied by a diminished ankle jerk reflex. A normal MRI is unlikely given the prominent neurological signs. It would be unusual for a tethered spinal cord to present in adult life. Multi-level spinal stenosis results in neurogenic claudication.
A 15-month-old boy presents to his primary care physician after his parents observed during diaper changes that “his belly is sticking out more than usual.” They have also noticed “a black eye” despite no known trauma and “a bumpy rash.” The patient is growing and developing normally. His past medical history is only notable for constipation that has been treated with polyethylene glycol. His immunizations are up to date. His vital signs are temperature 36.8ºC (98.2ºF), pulse 102 beats/min, blood pressure 90/62 mm Hg, and respirations 22 breaths/min. Physical exam reveals left-sided proptosis and periorbital ecchymosis and diffuse, scattered, nontender subcutaneous nodules. The patient has a distended abdomen with hepatomegaly and a firm, irregular, non-tender abdominal mass that crosses the midline. There is no stool in the rectal vault. Cardiac and lung exam are unremarkable.
A. Urinary metanephrines and catecholamines B. Urinary HVA and VMA C. Serum alpha-fetoprotein (AFP) D. Serum CBC E. Serum beta-hCG
This patient has a firm, irregular abdominal mass that crosses the midline, as well as evidence of metastases to the orbital bones, liver, and skin. These findings, together with his age (50% of cases of neuroblastoma, with common sites including bone marrow, bone, liver, and skin.
Because neuroblastoma cells arise from neural crest cells, they often are able to take up and metabolize catecholamines, resulting in accumulation of VMA and HVA in the urine and serum. Evaluation for elevated urinary VMA and HVA serves as a sensitive and specific diagnostic test for neuroblastoma and is also useful for monitoring disease activity.
A. Urinary metanephrines and catecholamines
Urinary metanephrines and catecholamines (epinephrine, norepinephrine, and dopamine) are elevated with pheochromocytoma. Hypersecretion of catecholamines by this tumor, which arises from the adrenal medulla, results in episodic headaches, tachycardia, and sweating, typically accompanied by hypertension.
C. Serum alpha-fetoprotein (AFP)
Markedly elevated serum AFP levels are present with hepatoblastoma, the most common primary hepatic malignancy in children. The tumor most often occurs as a single liver mass, usually in the right lobe of the liver.
D. Serum complete blood count
Metastatic spread of neuroblastoma to bone marrow may result in blood count abnormalities, but this finding is not specific to neuroblastoma and thus does not establish the diagnosis.
E. Serum beta-human chorionic gonadotropin (beta-hCG)
Elevated serum beta-hCG levels occur with germ cell tumors. These neoplasms may be gonadal (arising from the ovary or testis) or extragonadal. Extragonadal germ cell tumors usually arise from midline sites, with sacrococcygeal and intracranial tumors being most common in children.
A 45-year-old man with a history of hypertension requiring three blood pressure lowering agents presents to his primary care physician complaining of “panic attacks.” The patient explains that the episodes have become more frequent and consist of sweating, headaches, and the sensation that his heart is racing. The symptoms make him feel anxious and he is wondering if he can get some medicine for anxiety. He has a blood pressure cuff at home and took his blood pressure during the last few episodes. His blood pressure was approximately 180/100 during the episodes and came down to his baseline of approximately 140/90 when he re-checked a couple hours after the episodes.
Von Hippel-Lindau, neurofibromatosis 1, MEN (multiple endocrine neoplasia) IIa, MEN IIb
This vignette describes the classic triad of symptoms seen in patients with a pheochromocytoma: episodic headache, sweating, and tachycardia. Other symptoms include palpitations, tremor, pallor, dyspnea, generalized weakness, and panic attack-type symptoms (particularly in pheochromocytomas that produce epinephrine).
Pheochromocytoma is associated with Von Hippel-Lindau, neurofibromatosis 1, MEN (multiple endocrine neoplasia) II and III (Note: MEN II is also referred to as MEN IIa; MEN III as IIb).
Pheochromocytoma is called a 10% tumor because 10% are malignant, 10% are found extra-adrenal, and 10% are bilateral. The other conditions mentioned do not have a known association with pheochromocytoma
You are evaluating a nine month-old female infant in a refuge camp who presents with irritability, poor appetite, and weakness. She was born via spontaneous vaginal delivery that was complicated by maternal hemorrhage and death. Her grandmother cares her for and feeds her tins of evaporated boiled milk. On physical exam, she is irritable and lying in a frog-leg position. Her weight and height are
The answer is Vitamin C deficiency also known as Scurvy. Boiling milk destroys the Vitamin C. Patient with Scurvy resents with irritability, developmental delay, decreased appetite, and fatigue. Patients then develop bleeding in the skin, mucous membranes, joints, muscle, or gastrointestinal tracts. Holding legs in the frog leg position may be caused by pain from subperiosteal hemorrhage, hemarthrosis, or muscle hemorrhage. Gingival disease begins as shiny, red, swollen gums that progress to necrosis and bleeding. Dermatologic findings include dystrophic hair, follicular keratosis, petechiae, purpura, ecchymoses, and poor wound healing. Children may also have hypertrophic cardiomyopathy, diminished adrenal and bone marrow function, and edema. Osteopenia is common in vitamin C deficiency and lateral metaphyseal spurs (corner sign) are pathognomonic. Other radiographic findings include: a white line of dense calcification at the metaphysis (Frankel lines), less dense transverse bands adjacent to Frankel lines (scurvy lines), thickened white line of calcification encircling the osteopenic epiphysis (Wimberger ring).
A. Vitamin A
Vitamin A deficiency causes night blindness, dry and scaly skin, and frequent infections.
C. Iron
Children typically have a mild microcytic anemic and iron deficiency from bleeding, however iron deficiency is not the primary problem.
D. Vitamin D
Vitamin D deficiency causes osteopenia, fracture, and rickets.
E. Vitamin E
Vitamin E deficiency causes neuropathy, retinopathy, and hemolytic anemia.
F. Vitamin K
Vitamin K deficiency causes bleeding from problems with blood clotting.
A 46-year-old male presents to his primary care physician with complaints of fatigue and skin itching. The symptoms have been gradually progressive over the course of a month. He has also lost about 10 pounds (unintentionally) and has some dull right upper quadrant pain in his abdomen. He has a history of ulcerative colitis.
- primary sclerosing cholangitis
- cholangitis
- Mirizzi syndrome
- primary biliary cirrhosis
- cholangiocarcinoma
The patient suffers from primary sclerosing cholangitis. It is an autoimmune condition that usually affects men in their 4th and 5th decades of life. There is an association of this condition with ulcerative colitis. Patients present with symptoms related to impaired bile excretion and include fatigue, jaundice, pruritus, weight loss, and right upper quadrant pain. The diagnosis is made with ERCP, which shows multiple strictures and dilations of the biliary tree (as seen in this case).Eventually, this condition progresses to cirrhosis with the resultant development of portal hypertension.
Cholangitis presents with fever, right upper quadrant pain, and jaundice. Mirizzi syndrome is the compression of the common hepatic duct by a stone in the infundibulum of the gallbladder. Primary biliary cirrhosis is seen in women where the medium-sized hepatic ducts are affected. In contrast, in primary sclerosing cholangitis both intra and extra-hepatic ducts are affected. Cholangiocaricnoma typically occurs in elderly males, where painless jaundice is the most common presentation. A focal area of bile duct stenosis is usually seen.
A 34-year-old female presents to her obstetrician. She is 18 weeks pregnant. History is notable for 2 miscarriages as well as a deep vein thrombosis (DVT) at age 22 while she was on oral contraceptives. Her oral contraceptives were stopped and no other work-up was pursued. Two weeks later, the patient experiences heavy bleeding and the diagnosis of spontaneous abortion is made. Labs were notable for an elevated PTT.
Antiphospholipid antibody syndrome (also known as lupus anticoagulant syndrome) is a commonly tested acquired thrombophilia. In the blood stream, antibodies directly activate platelets and complement, leading to a hypercoagulable state. Patients commonly present with a history of recurrent DVT and miscarriages, such as in this vignette. In vitro, the antibodies interfere with phospholipids (hence antiphospholipid) and inhibit coagulation, leading to an elevated PTT. While a homozygote for factor V Leiden may experience this degree of clotting complications, it would be unlikely in a heterozygote. Protein C deficiency is rare and is not as commonly implicated in miscarriages. The other answer choices do not cause thrombophilia.
A 60-year-old woman with a 20-year history of celiac disease is evaluated for several months of progressive abdominal discomfort, bloating, nausea, subjective fever, chills, night sweats and a 10-pound weight loss. The patient was doing well with gluten restricted diet for a long period before the onset of these symptoms. On exam, she appears malnourished. Several enlarged lymph nodes are palpated in both the cervical and inguinal chains, and her abdomen is diffusely tender to palpation. Labs reveals hemoglobin of 10 g/dl with an MCV of 78 fl. Esophagogastroduodenoscopy and colonoscopy are performed, but inconclusive. CT scan shows luminal narrowing in the small bowel.
A. Crohn's Disease B. Lymphoma of small bowel C. Ulcerative Colitis D. Small intestinal bacterial overgrowth E. Short gut syndrome
Patients with a history of celiac disease are at increased risk of developing malignancy, specifically lymphoma of the small bowel. This patient with signs/symptoms of a small bowel obstructive process, in addition to constitutional symptoms, has a presentation concerning for intestinal lymphoma. Patients with celiac disease are also predisposed to developing other gastrointestinal cancers, such as esophageal squamous cell carcinoma, intestinal adenocarcinoma, colorectal carcinoma, and hepatocellular carcinoma.
A. Crohn’s disease
Crohn’s disease may involve the entire GI tract, and can cause strictures of the small bowel. Constitutional symptoms may also be seen. While this patient does have some of these features, her history of celiac disease predisposes her to development of lymphoma, which is the most important possibility to rule out.
C. Ulcerative colitis
Ulcerative colitis is characterized by bloody diarrhea, and may also cause constitutional symptoms. This patient lacks the bloody diarrhea, and has a history of celiac disease which is more closely associated with lymphoma, which provides a better explanation of her symptoms.
D. Small intestinal bacterial overgrowth
Small intestine bacterial overgrowth can result from a variety of conditions, including short bowel syndrome, chronic pancreatitis, immunodeficiency, liver disease, among other etiologies. Patients with small bowel bacterial overgrowth may develop vitamin B12 deficiency, which is associated with a macrocytic anemia. The constitutional symptoms experienced by this patient would not be expected with bacterial overgrowth.
E. Short gut syndrome
Short gut syndrome develops when there is a resection of a portion of the small bowel. This results in a malabsorptive state that is characterized by reduced transit time and diarrhea. There is no history of bowel surgery, and this patient’s symptoms cannot be entirely explained by nutrient deficiency.
A 55 year-old longshoreman with a past medical history of hypertension, hyperlipidemia, and coronary artery disease with two prior episodes of myocardial infarction presents to the emergency department with two hours of severe nausea, vomiting, and dizziness. He says that he was preparing for work this morning when he started choking on his coffee, and suddenly became acutely dizzy and nauseous. He attempted to walk to his bathroom to vomit, but lost his balance after taking only three steps and fell to the floor. He called out to his wife, who found him lying on the floor and called 911. In the ED, he continues to complain of severe nausea and room-spinning dizziness. Neurologic exam reveals hoarse, slurred speech, a left-sided ptosis, asymmetric but reactive pupils with the right pupil larger than the left, and a symmetric smile. Sensory exam shows preserved touch and vibratory sense throughout but absent pinprick and temperature sensation on the left face, right arm, and right leg. Strength is normal throughout the upper and lower extremities.
A. MCA B. ACA C. PCA D. AICA E. PICA F. Basilar artery G. ASA
Occlusions within the vessels of the posterior circulation can be some of the most challenging to diagnose and localize. The neuroanatomy of the brainstem and cerebellum is complex, and at times even experienced clinicians can get tripped up. The most important thing to do when presented with a posterior stroke is to recognize it as a possibility so that the appropriate diagnostic studies can be obtained in a timely manner. That being said, there are a few classic posterior stroke syndromes that are worth knowing.
The collection of symptoms described here is characteristic of the lateral medullary syndrome (Wallenberg syndrome), caused by the occlusion of the posterior inferior cerebellar artery (PICA). Keys to the diagnosis include the crossed sensory findings (ipsilateral facial deficits with contralateral body deficits), ipsilateral Horner’s syndrome, dysphagia, dysarthria, and cerebellar ataxia and vertigo.
A. Middle cerebral artery
Unlike the crossed deficits of subcortical stroke illustrated above, an occlusion of the middle cerebral artery will produce sensory and motor deficits of both the contralateral face and extremities.
B. Anterior cerebral artery
Anterior cerebral artery strokes most often cause contralateral lower extremity weakness and numbness, with varying degrees of behavioral and cognitive dysfunction.
C. Posterior cerebral artery
A posterior cerebral artery stroke typically causes major contralateral visual field deficits (often with macular sparing), as well as a number of higher cognitive visual deficits.
D. Anterior inferior cerebellar artery
An occlusion of the anterior inferior cerebellar artery (AICA) may produce some similar features to a posterior inferior cerebellar artery (ICA) stroke; however, gaze palsy, facial weakness, and an acute unilateral deafness are more likely to be present, while Horner’s syndrome, dysphagia, and dysarthria are unlikely to be found. Superior cerebellar artery occlusion may also overlap with the PICA and AICA occlusion syndromes, but is more likely to feature crossed deficits of touch and vibratory sense in addition to impaired pain and temperature sensation.
F. Basilar artery
Occlusion of the basilar artery, either from thrombosis or embolus, can block blood flow to the reticular activating system, resulting in an immediate and profound reduction in the level of consciousness. Depending on the precise location of the occlusion within the basilar artery, a variety of brainstem nuclei can be affected, producing a wide range of possible cranial nerve deficits. Hemiplegia and quadriplegia are common, as are a number of complex ophthalmoplegias. Lesions of the basis pontis that spare the tegmentum can produce a “locked-in” state, in which patients have preserved consciousness and cognition but only the most rudimentary motor control remaining (typically vertical eye movements and/or blinking). This is due to involvement of the pyramidal tracts.
G. Anterior spinal artery
Occlusion of the anterior spinal artery produces a “spinal cord stroke”, characterized by complete bilateral weakness below the level of the lesion. Pain and temperature sensation, but not fine touch or vibratory sensation, will also be lost below the level of the lesion. As the lesion occurs within the spinal cord, there are no cognitive, cranial nerve, or brainstem deficits.
A 2-year-old male presents with repeated episodes of burning, red, edematous skin shortly after sun exposure. No blisters are present. Urine porphyrins are normal, but total plasma porphyrin is elevated. The patient is treated with beta-carotene, and his family is encouraged to have him avoid sun exposure.
A. Acute Intermittent Porphyria B. Porhpyria Cutanea Tarda C. Hereditary Coproporphyria D. Variegate Porphyria E. Erythropoietic Protoporphyria
The porphyrias are disorders caused by reduced activity of enzymes in the heme biosynthetic pathway. They can be categorized by their dominant clinical presentations, which include photosensitivity symptoms (cutaneous porphyrias), neurovisceral symptoms (acute porphyrias), or a combination of photosensitivity and neurovisceral symptoms. Photosensitivity in cutaneous porphyrias is due to activation of porphyrins in the skin by visible and long wave ultraviolet light.
The acute, nonblistering photosensitivity seen in erythropoietic protoporphyria (EPP) is a distinctive feature from the other cutaneous porphyrias. While the diagnosis can be suspected when urine porphyrins are normal in the presence of an elevated total plasma porphyrin, these findings are not specific; the diagnosis is confirmed by demonstrating an elevated erythrocyte protoporphyrin level. Treatment involves sun avoidance and beta carotene administration.
A. Acute intermittent porphyria
Acute intermittent porphyria is an acute neurovisceral porphyria caused by mutations in the porphobilinogen deaminase (PBG-D) gene. Inheritance is autosomal dominant but with low penetrance, so family history does not always provide clues to the diagnosis. The presentation is variable with most patients never developing symptoms. The most common symptom is abdominal pain, sometimes with other gastrointestinal symptoms such as nausea, vomiting, and constipation. Other manifestations include peripheral neuropathies, mainly manifesting as weakness of the extremities, and autonomic nervous system involvement, with tachycardia as the most common sign.
B. Porphyria cutanea tarda
Porphyria cutanea tarda, the most common human porphyria, is a cutaneous porphyria resulting from deficient activity of hepatic uroporphyrinogen decarboxylase (UROD). It tends to present in mid- to late life with increased skin fragility and blistering lesions (bullae) on sun-exposed areas that leave scars and areas of hyper- and hypopigmentation. Hirsuitism is a common feature. In addition, most affected patients have mild elevations in hepatic transaminases, and advanced liver disease is seen in some older patients. Known exacerbating factors include iron, alcohol, smoking, estrogens, hepatitis C infection, and HIV infection.
C. Hereditary coproporphyria
Hereditary coproporphyria is due to mutations in coproporphyrinogen oxidase (CPO) and is the least common of the acute neurovisceral porphyrias. Acute neurovisceral attacks are indistinguishable to those in patients with acute intermittent porphyria but are generally milder. Some patients have cutaneous manifestations similar to those in porphyria cutanea tarda, but these are uncommon.
D. Variegate porphyria
Variegate porphyria results from subnormal activity of the mitochondrial enzyme protoporphyrinogen oxidase (PPO). It has both cutaneous and neurovisceral manifestations (the basis for the name “variegate”). It causes chronic, blistering skin lesions similar to those of porphyria cutanea tarda and neurovisceral symptoms identical to those of acute intermittent porphyria.
A 14-year-old girl presents to your clinic with a 3-week history of fever and pain in her wrists and knees. She has no significant past medical history, and her immunizations are up to date. On physical exam, her vitals signs are temperature 38.3°C (100.9°F), pulse 80 beats/min, blood pressure 140/86 mmHg, and respirations 16 breaths/min. She has an erythematous malar rash, periorbital edema, and several painless ulcers on the palate and tongue. She has warmth, tenderness, and moderate effusions of her wrists and knees bilaterally. Cardiac exam reveals a regular rhythm with a pericardial friction rub and no murmur or gallop. Her lungs are clear to auscultation bilaterally. Her abdomen is soft, nontender, and nondistended with no hepatosplenomegaly. A urinalysis reveals 3+ blood.
A. Rheumatoid Factor
B. Antinuclear antibody (ANA)
C. Anti-cyclic citrullinated protein (anti-CCP) antibody
D. Anti-double-stranded DNA (anti-dsDNA)
E. C3 and C4
F. Antineutrophil cytoplasmic antibodies (ANCA)
This patient meets 5 of 11 diagnostic criteria for SLE:
Malar rash Oral ulcers Serositis (pericarditis or pleuritis) Arthritis Nephropathy (as indicated by her hypertension, periorbital edema, and hematuria)
Other criteria include:
Discoid rash Photosensitivity Neurologic manifestations, such as seizure or psychosis Hematologic manifestations, such as hemolytic anemia or lymphopenia Presence of antinuclear antibody (ANA) Immunologic manifestations, including anti-DNA, anti-Smith, or positive VDRL
Of the serologic tests performed to help diagnose SLE, anti-dsDNA is highly specific and is found in >75% of patients with SLE.
A. Rheumatoid factor (RF)
Rheumatoid factor (RF) is primarily evaluated in the diagnosis of rheumatoid arthritis; it is present in 75%-80% of patients with this disorder.
B. Antinuclear antibody (ANA)
Antinuclear antibody (ANA) is highly sensitive for systemic lupus erythematosus (SLE). It is positive in virtually all children with SLE. However, it is also found in patients with other rheumatologic diseases and up to one-third of healthy people. A higher ANA titer (≥1:1280) is more suggestive of SLE.
C. Anti-cyclic citrullinated protein (anti-CCP) antibody
Anti-CCP antibodies have a specificity of >90% and sensitivity of 50%-70% for rheumatoid arthritis.
E. C3 and C4 and CH50
Complement levels may be low in patients with SLE, but this finding is neither sensitive nor specific for the disease.
F. Antineutrophil cytoplasmic antibodies (ANCA)
Evaluation for ANCA has a central role in diagnosis of various vasculitides, including granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis).
An 18-year-old male is evaluated in the emergency department for dehydration. He recently went on a day hike, but was lost in the woods for 4 days with only one candy bar for food. His vital signs include a temperature of 37.3°C (99.14°F), heart rate of 100 beats/min, blood pressure 106/78 mmHg, respiratory rate 12 breaths/min and an oxygen saturation of 100% on room air. On exam, he is alert, awake, and oriented to person, time, and place. He appears thin and tired. His mucous membranes are dry. His heart is tachycardic with normal rhythm and his lungs are clear to auscultation bilaterally. His abdomen is soft, non-tender, and non-distended. His has generalized muscle weakness. He has badly sunburned skin over his neck, face and ears. During this period of starvation, this patient generated energy via the breakdown of protein from muscle tissue. Ammonia, a byproduct of amino acid catabolism, can be toxic at high levels. In spite of the increased levels ammonia produced during this period of starvation, this patient’s liver was able to convert it to urea for excretion in the urine.
One of the nitrogen groups found in urea is provided by ammonia and the other is provided by aspartate. What metabolic process is directly involved in providing a source of aspartate for the urea cycle?
A. glycolysis
B. citric acid cycle
C. beta oxidation
D. gluconeogenesis
Aspartate is an amino acid with multiple amino groups. It combines with citrulline to form argininosuccinate via the enzyme arginosuccinate synthetase. Argininosuccinate is subsequently cleaved to form arginine and fumarate. Arginine continues through the urea cycle, and fumarate enter the citric acid cycle. In the citric acid cycle, fumarate is converted to malate, which is then converted to oxaloacetate. Oxaloacetate re-combines with acetyl-CoA to form citrate and restarts the citric acid cycle. Oxaloacetate can also undergo transamination with glutamate, forming α-ketoglutarate and aspartate. Aspartate enters the mitochondrial matrix via the malate-aspartate shuttle and donates a second nitrogen group in the formation of urea.
A. Glycolysis
Glycolysis is the metabolic process that converts glucose to pyruvate; it does not provide a source of aspartate for the urea cycle.
C. Beta oxidation
Beta-oxidation is the metabolic process that breaks down fatty acid molecules to generate acetyle-coA, which is used by the citric acid cycle, and NADH and FADH2, which enter the electron transport chain; it does not provide a source of aspartate for the urea cycle.
D. Gluconeogenesis
Gluconeogenesis is the metabolic process that generates glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids; it does not provide a source of aspartate to the urea cycle.
A 64-year-old female is brought to her primary care physician by her husband who remarks, “There is something wrong with her head”. He says that she has problems remembering the names of various items around the house or how to conduct day-to-day tasks such as working the dishwasher. He also notices her occasionally wandering around the house in the middle of the night aimlessly, as if she were sleep walking. He says that her condition has been increasing in severity over time, and just this morning she seemed unable to recognize her niece who was visiting from out of town, precipitating the visit to the PCP. On examination, the patient is unable to correctly identify the year or current location, and she recalls zero of three unrelated objects at five minutes. She has a slightly blunted affect, but does not appear overly concerned about her condition. She incorrectly names a wristwatch a “clock”, and she cannot follow instructions to fold a piece of paper twice. Her husband comments that she has not had any major personality changes, nor has she had any urinary incontinence that he is aware of. The patient has a BMI of 32. Magnetic resonance imaging (MRI) of the head reveals a marked loss of cortical volume with a significant dilation of the lateral ventricles and subarachnoid spaces.
A. Normal Pressure Hydrocephalus B. Non-communicating (obstructive) Hydrocephalus C. Communicating hydrocephalus D. Pseudotumor cerebri E. Hydrocephalus Ex Vacuo
This patient’s history of progressive cognitive decline, aphasia, apraxia, and agnosia are highly suggestive of Alzheimer’s Disease, which is characterized microscopically by the accumulation of amyloid plaques and neurofibrillary tangles. This disease results in a progressive neurodegeneration with an accompanying atrophy of the cortex. The reduction in brain mass leaves an unoccupied space within the skull which is subsequently occupied by a relative increase in cerebrospinal fluid volume. This phenomenon is referred to as hydrocephalus ex vacuo, and does not occur exclusively in Alzheimer’s disease, but is rather part of any chronic neurodegenerative process that results in a significant loss in brain volume.
A. Normal pressure hydrocephalus (NPH)
Normal pressure hydrocephalus (NPH) is a particular form of communicating hydrocephalus, characterized by enlarged cerebral ventricles, with only intermittently elevated cerebrospinal fluid pressure. Patients with this disease tend to present with a frontal gait, urinary incontinence, and dementia (wet, wobbly, and wacky).
B. Non-communicating (obstructive) hydrocephalus
Obstructive hydrocephalus results from an obstruction within the ventricular system (hence the name), preventing the outflow of cerebrospinal fluid from its origin in the choroid plexus into the subarachnoid space. On imaging, obstructive hydrocephalus presents with large lateral ventricles with effacement of the sulci. There is usually a visibly obstructing lesion.
C. Communicating hydrocephalus
Communicating hydrocephalus is characterized by impaired cerebrospinal fluid reabsorption at the level of the arachnoid granulations in the absence of any flow obstruction within the ventricular system. On imaging, all the ventricles, including the cerebral aqueduct, are dilated.
D. Pseudotumor cerebri
Pseudotumor cerebri describes an idiopathic elevation in intracranial pressure in the absence of tumor or other disease. Imaging typically appears normal, although small or slit-like ventricles and an “empty sella sign” (flattening of the pituitary gland due to increased pressure) may be seen. It is classically seen in young women with obesity, and is diagnosed by lumbar puncture and assessment of the intracranial pressure. Papilledema is seen on fundoscopic exam.
A 55-year-old man with a history of cirrhosis undergoes a routine spinal surgery for degenerative intervertebral disc disease (lumbar discectomy). He has a history of liver cirrhosis with ascites secondary to hepatitis C, morbid obesity, as well as limited exercise capacity. Prior to surgery, he was evaluated with a cardiac stress test which was negative for ischemia. The procedure is technically uncomplicated and blood loss is estimated at
Prolonged Drug life
This patient suffers from a delayed emergence phenomenon from general anesthesia. This can cause much consternation amongst operating room personnel on both sides of the sterile drape, but it can be anticipated preoperatively in certain conditions. In patients with increased volume of distribution (defined as [ the total drug in the body / plasma concentration ]), drugs take on a longer half-life. Volume of distribution is commonly increased in cases of ascites and congestive heart failure that are associated with “third spacing” of fluid. In fact, one can track heart failure on a day-by-day basis by measuring a patient’s weight as an indicator of retained fluid. The other major variable that contributes to volume of distribution is the adipose composition of the patient. Drugs, such as propofol, distribute to adipose tissue when administered systemically. The half-life of a drug is estimated by the formula [ half-life = (0.7 * Volume of distribution)/ clearance ], therefore an increased volume of distribution will increase the half-life of a drug.
A. Propofol infusion syndrome
Propofol infusion syndrome is a condition mainly seen in pediatric patients. It can lead to cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure. For this reason, propofol is avoided in pediatric patients.
C. Higher drug clearance
Both a higher drug clearance and smaller volume of distribution would lead to a shorter half-life. When the half-life of an anesthetic agent is reduced, emergence from anesthesia is quicker, not delayed as seen in this patient.
D. Smaller volume of distribution
Both a higher drug clearance and smaller volume of distribution would lead to a shorter half-life. When the half-life of an anesthetic agent is reduced, emergence from anesthesia is quicker, not delayed as seen in this patient.
E. Centrilobular hepatic necrosis
Massive hepatic necrosis is a rare side effect of halothane, an inhaled anesthetic agent. It occurs 2 days to 3 weeks after anesthesia due to direct liver injury. Patients present with fever, anorexia, nausea, jaundice, and tender hepatomegaly. Lab values will reveal an elevated prothrombin time and elevated liver enzymes. This patient is presenting with delayed emergence from anesthesia; there is no evidence that suggests massive hepatic necrosis.
F. Cerebrovascular accident
Cerebrovascular accident is a rare complication during surgery and more commonly occurs during thoracic vascular cases secondary to embolic phenomena (e.g. aortic arch repair).
A 32-year-old female presents to the neurology clinic complaining of double vision. The patient reports that she has experienced intermittent tunnel vision and blurring of her left eye over the last three months, though she has no such symptoms now. Additionally, she has noticed a periodic tingling sensation in her neck, which he describes as “shock-like.” Physical examination reveals a horizontal gaze palsy in which the patient is unable to adduct her right eye when looking to the left. Abduction of the left eye is preserved, but accompanied by left-beating nystagmus. Fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging reveals multiple white matter lesions of varying intensity. A lumbar puncture is performed to confirm the diagnosis.
What would be found in the CSF?
A. antibodies against aquaporin 4
B. Abnormal isotypes of myelin protein zero
C. Abnormal isotypes of myelin basic protein
D. Monoclonal B lymphocytes
E. Polyclonal immunoglobulins
E. Polyclonal immunoglobulins
This patient is suffering from internuclear ophthalmoplegia (INO), a classic presenting syndrome of multiple sclerosis (MS). Plaque formation in the white matter of the medial longitudinal fasciculus (MLF) prevents communication between the contralateral abducens nucleus (origin of CN VI) and the ipsilateral oculomotor nucleus (origin of CN III). A patient with a right-sided INO, when asked to look to her left, will be unable to adduct the right eye past midline, resulting in lateral conjugate gaze palsy and double vision. The left eye will have preserved abduction, however, a resulting unilateral nystagmus in the left eye is generally (but not always) observed. Conjugate gaze to the right will be preserved. In addition to INO, the patient complains of occasional blurring of vision and shocking sensations in the neck, indicative of the common MS-related conditions of transient optic neuritis and Lhermitte’s sign, respectively. This patient’s MRI also demonstrates the characteristic white matter lesions seen in MS.
MS is an autoimmune disease in which lymphocytes initiate a response against various white matter proteins. The reaction is generally immunoglobulin driven, and typically manifests itself in the form of a limited polyclonal expansion of IgG within the CSF; these oligoclonal immunoglobulins (detected as discrete bands on agarose gel electrophoresis) are present in approximately 95% of patients with MS.
A. Antibodies against aquaporin 4
Antibodies against aquaporin 4, the major aquaporin of astrocyte foot processes, are a characteristic of neuromyelitis optica. This rare autoimmune condition, which presents similarly to MS, is also known as Devic’s disease. Unlike in MS, lesions in this disease classically affect the spinal cord and optic nerves (as the name would suggest), with relative sparing of the cerebral cortices.
B. Abnormal isotypes of myelin protein zero
Abnormal isotypes or deactivating mutations of myelin protein zero may be seen in some forms of Charcot-Marie-Tooth disease or Dejerine-Sottas disease. This protein normally interacts with peripheral myelin protein 22 (PMP22) to provide structural integrity to Schwann cell-generated peripheral myelin, and would not likely be seen in cerebrospinal fluid of a patient with MS.
C. Abnormal isotypes of myelin basic protein
Antibodies against myelin basic protein (MBP) may be seen in multiple sclerosis, but are not pathognomonic. Mutations and abnormal isotypes of MBP are not associated with any major disease.
D. Monoclonal B lymphocytes
As MS is an antibody driven autoimmune disease, B lymphocyte expansion is expected. However, the overactive B cells in MS have a polyclonal origin, each producing an antibody targeted against a different epitope of the offending antigen. Monoclonal B cell expansion indicates a common progenitor cell, and suggests an alternative diagnosis. Such a population may be seen in the context of central nervous system B cell lymphoma, often a consequence of prolonged immunosuppression of deficiency, as in patients with AIDS.
A 22-year-old female presents to her primary care physician with “episodes” that consist of severe intermittent headaches, diaphoresis, and palpitations. While in the office, she has one of these episodes. Her systolic blood pressure during the episode is measured to be 210 mmHg. A CT scan reveals a lesion in her right adrenal gland.
This patient’s symptoms are due to excess secretion of biogenic amines from malignant cells. Which enzyme catalyzes the rate-limiting step in the synthesis of these biogenic amines?
A. PMNT B. MAO C. Tyrosine Hydroxylase D. DOPA decarboxylase E. dopamine beta hydroxylase
C. Tyrosine hydroxylase
The rate-limiting step in catecholamine synthesis is catalyzed by tyrosine hydroxylase, which mediates the conversion of tyrosine to DOPA (dihydroxyphenylalanine).
A 49-year-old woman presents with right leg pain that is worse when bearing weight. She has a past medical history notable for progressive chronic kidney disease, but has not been under the care of a physician for many years. The patient shares that she went through menopause one year ago and has elected to forgo estrogen replacement therapy. Laboratory tests indicate low levels of 25-OH cholecalciferol, calcium, and phosphorus, and an elevated alkaline phosphatase and PTH.
An x-ray demonstrates bone demineralization, but no evidence of acute fracture. What is the most likely diagnosis?
A. Osteoporosis B. Osteomalacia C. Osteopetrosis D. Paget's disease E. Primary Hyperparathyroidism
B. Osteomalacia
Vitamin D deficiency results in osteomalacia in adults, and rickets in children. These are characterized by defective mineralization/calcification of osteoid leading to soft bones.
A deficiency is evidenced in this patient by the low level of 25-OH vitamin D, the storage form of the vitamin. Vitamin D3 (cholecalciferol) is predominantly derived through the consumption of milk, and is also formed in the skin with sun-exposure, with subsequent hydroxylations in the liver and kidney. The active form of vitamin D is 1,25-(OH)2 D3 or calcitriol.
In this country osteomalacia is an unusual disease, as patients with chronic kidney disease are closely monitored for their calcium and phosphorus levels. However, it may be seen in a patient with worsening renal failure who is not being followed by a physician.
Active vitamin D functions in the body to increase the intestinal absorption of calcium and phosphate. Active vitamin D induces calbindin D-28K (Ca2+ binding protein). Vitamin D also increases bone resorption, providing calcium and phosphate from ‘old’ bone to mineralize ‘new’ bone. Finally, active vitamin D increases renal reabsorption of Ca2+ and phosphate (minor effect). In children, rickets causes bone pain and deformity. In adults, osteomalacia presents as bone pain and muscle weakness. Osteoblasts are hyperactive, resulting in increased alkaline phosphatase.
Osteomalacia and rickets are both treated with vitamin D supplementation.
A. Osteoporosis
Osteoporosis is a loss of trabecular (spongy) bone despite normal bone mineralization and lab values (serum Ca2+ and PO43-). Type 1 osteoporosis occurs in postmenopausal women, when a decrease in estrogen levels increases net bone resorption by increasing osteoclast activity and decreasing osteoblast activity. Bone will lose mass and interconnections, which can lead to vertebral crush fractures. It may present as acute back pain, a loss of height, and kyphosis.
C. Osteopetrosis, also known as marble bone disease, is the failure of normal bone resorption as the result of defective osteoclasts. A mutation of carbonic anhydrase II impairs the ability of osteoclasts to generate the acidic environment necessary for bone resorption. Bone is thickened, dense, and prone to fracture. An x-ray shows a ‘bone-in-bone’ appearance. Unlike the above patient, osteopetrosis will produce normal phosphate and PTH levels (this patient has decreased serum phosphate and increased
D. Paget’s disease of bone is a localized disorder of bone remodeling. It is caused by an increase in both osteoblastic and osteoclastic activity. Like the above patient, alkaline phosphatase is elevated; however, serum calcium, phosphorus and PTH levels are normal. Bone will appear with a mosaic “woven” pattern.
E. Primary Hyperparathyroidism.
The elevated PTH in this patient is secondary to the depressed levels of serum Ca2+, and is not the primary disorder. Primary hyperparathyroidism would instead lead to elevated levels of active vitamin D, because PTH stimulates 1α-hydroxylase in the kidney. Other laboratory findings would include high serum Ca2+ and decreased serum phosphate (PTH leads to increased calcium, but decreased phosphate reabsorption in the kidney).
A 43-year-old male presents to the clinic with a maculopapular rash that started 2 days ago. The rash is non-pruritic, appearing on his forearms, wrists, and ankles. He reports that he is also experiencing fever, headache, myalgia, nausea and vomiting. He states that he went on a camping trip last week, but he was asymptomatic and did not notice any rash during the trip. Labs revealed mild leukocytosis, thrombocytopenia, mildly elevated aminotransferase levels, and elevated BUN. Lumbar puncture did not reveal the presence of a pathogen, but did show an elevated WBC count (100 cell/uL; predominantly lymphocytes) and elevated protein (150 mg/dL).
What is the next best step in the management of this patient?
A. Send a punch biopsy for indirect immunofluorescence assay (IFA)
B. Prescribe doxycycline
C. Send a blood sample for PCR
D. Prescribe ceftriaxone
This patient’s acute rash, systemic symptoms, and recent history of outdoor activity are highly indicative of Rocky Mountain Spotted Fever (RMSF), a tick-borne disease caused by the bacterium Rickettsia rickettsii. Symptoms first appear typically 2-14 days after the bite of an infected tick, but many patients do not know that they have been bitten. Therefore, obtaining a detailed history is very important. RMSF is a serious illness that can be fatal in the first 8 days of symptoms if not treated accordingly, so if the disease is suspected clinically, doxycycline should be the immediate first line of treatment. A punch biopsy should then be sent for IFA to confirm the presence of the R. rickettsii antigen, which would provide a definitive diagnosis. However, in many cases an early titer will be low or negative, which is why treatment should begin while a second titer is obtained 2-4 weeks later.
A. Send a punch biopsy for indirect immunofluorescence assay (IFA)
A punch biopsy for IFA should be performed, but that alone is not sufficient. Since RMSF is such a rapid and serious disease, treatment with doxycycline should begin even before laboratory confirmation.
C. Send a blood sample for PCR
R. rickettsii infects endothelial cells lining blood vessels, but they do not circulate in large numbers in the plasma unless the patient has progressed to a very serious stage of infection. Since the patient presented very early in the clinical course, blood specimens will often show negative results for PCR or culture. If a rash is present, a skin biopsy is always preferred to blood sample for serologic testing.
D. Prescribe ceftriaxone
Use of antibiotics other than doxycycline is associated with a higher risk of fatality. Therefore, doxycycline should always be the first-line of treatment for adults and children alike as soon as RMSF is suspected.
