55 30. A 48-year-old woman with a history of hypertension, alcoholic cirrhosis, esophageal varices, and several remote episodes of head trauma was brought to the emergency department because of confusion. She had been normal earlier in the day, but during supper she had started to make bizarre and irrelevant comments, and her family said she "just seemed out of it." She was afebrile. Her blood pressure was 150/90 mm Hg, and her heart rate was 92/min. Her speech was fluent, but tangential. At times, she was able to answer complex questions and do two- digit subtraction in her head, but at other times she acted as if she hadn't even heard the question. Her cranial nerves, motor examination, deep tendon reflexes, and sensation were normal. A head CT scan showed a region of encephalomalacia in the right temporal lobe; a lumbar puncture was normal except for a mildly elevated protein level, and an EEG showed repetitive sharp-and-slow wave complexes at a frequency of 5/s in the right temporal lobe. Which of the following is the most likely diagnosis? A. Hepatic encephalopathy B. Herpes simplex virus encephalitis C. Hypertensive encephalopathy D. Nonconvulsive status epilepticus E. Subdural hematoma Correct Answer: The correct answer is D. The EEG features meet criteria for nonconvulsive status epilepticus. Her blood pressure is not high enough to cause hypertensive encephalopathy; her examination and EEG show no features suggestive of hepatic encephalopathy; her spinal fluid, head CT, and EEG show no features suggestive of herpes simplex virus encephalitis; and her head CT shows no evidence of subdural hematoma. 31. Plateau waves (A waves) on an intracranial pressure tracing represent which of the following? A. Decreased intracranial pressure B. Increased cerebral blood flow C. Increased cerebral blood volume D. Increased cerebral perfusion pressure E. Increased intracranial compliance Correct Answer: The correct answer is C. Plateau waves (A waves) represent vasodilation in response to a decrease in cerebral perfusion pressure, causing a simultaneous reduction in cerebral blood flow and increase in cerebral blood volume. The vasodilation results in an increase in intracranial pressure and reduced intracranial compliance. 32. A 74-year-old hypertensive man with past history of atrial fibrillation, hypertension, hyperlipidemia, and a small embolic right parietal infarct 1 year ago presents with a right hemiparesis and aphasia. His medications include warfarin, atorvastatin, and lisinopril; his wife reports that he has been taking significant amounts of over- the-counter cimetidine recently due to heartburn. His cranial CT shows a large lobar hemorrhage in the left frontal lobe. His international normalized ratio (INR) is 4.8. Of the following sets of interventions, which is most appropriate for this man? A. Subcutaneous vitamin K and fresh frozen plasma B. Intramuscular vitamin K and prothrombin complex concentrate C. Intravenous vitamin K and fresh frozen plasma D. Recombinant activated factor VII alone E. Do not reverse his INR, as atrial fibrillation puts him at risk for an embolic stroke Correct Answer: The correct answer is C. Expert opinion endorses rapid reversal of anticoagulant effect following intracerebral hemorrhage, despite theoretical concerns of increased risk of thromboembolism. Intravenous vitamin K is preferable because of variable absorption via the subcutaneous and intramuscular routes. Most experts recommend fresh frozen plasma or prothrombin complex concentration (PCC). In this case, there is no known history of congestive heart failure so the volume load of fresh frozen plasma will likely be tolerated. PCC may be associated with thromboembolic complications. Recombinant activated factor VII has not yet been tested in controlled trials in patients with warfarin-associated intracerebral hemorrhage, but its use has been reported in case series. 33.Hypertensive encephalopathy preferentially affects which of the following arterial distributions? A. Anterior cerebral B. Anterior choroidal C. Middle cerebral D. Ophthalmic E. Vertebrobasilar Correct Answer: The correct answer is E. Hypertensive encephalopathy has a predilection for involvement of the vertebrobasilar circulation with the occipital lobes and posterior parietal lobes being preferentially involved. 34. A 47-year-old woman experiences a cardiac arrest after a run of ventricular tachycardia. Emergency resuscitation requires 25 minutes of acute efforts before stabilization. One of the physicians involved in the 56 resuscitation performs a neurological examination after the code and records absence of pupillary response in either eye. On morning rounds, the intern reports that he has read at least one study in which the absence of pupillary responses was almost uniformly predictive of severe deficit or worse neurological outcome. What do more recent studies report as the percentage of patients who never awaken if pupillary light responses are not present immediately after resuscitation? A. 95% B. 90% C. 85% D. 80% E. 75% Correct Answer: The correct answer is E. In one study (Edgren et al, 1994) of 89 patients with absence of pupillary light reflexes after cardiac arrest, 21 of 89 (24%) awoke (11 with slight, 5 with moderate, and 5 with severe neurological deficits). Levy and colleagues (1985) may have observed a higher positive predictive value for severe neurological deficits from the finding of absence of the pupillary light reflex in their 1985 paper because the timing of the initial examination varied from immediately to up to 24 hours postarrest. Correct Answer: Edgren E, Hedstrand U, Kelsey S, et al. Assessment of neurological prognosis in comatose survivors of cardiac arrest. BRCT I Study Group. Lancet 1994;343:1055-1059. Correct Answer: Levy DE, Caronna JJ, Singer BH, et al. Predicting outcome from hypoxic-ischemic coma. JAMA 1985;253:1420-1426. 35. Treatment for status epilepticus should be initiated whenever a generalized convulsive seizure persists for more than: A. 1 to 2 minutes B. 5 to 10 minutes C. 20 to 30 minutes D. 45 to 60 minutes E. 90 to 120 minutes Correct Answer: The correct answer is B. The definition of status epilepticus continues to evolve. Because typical seizures last 1 to 2 minutes, and because the likelihood of irreversible neuronal injury increases as a function of seizure duration, the American Academy of Neurology and the American Epilepsy Society consider any seizure event lasting longer than 5 to 10 minutes to be status epilepticus. 36. Which of the following, by itself, is sufficient justification for intracranial pressure monitoring in a patient with an abnormal head CT scan after head trauma? A. Age 30 years or less B. Decorticate posturing C. Glasgow Coma Scale score of 8 or less D. Hemiparesis E. Systolic blood pressure 160 mm Hg or greater Correct Answer: The correct answer is C. The clearest indication for placing an intracranial pressure monitor is severe head injury (Glasgow Coma Scale score of 8 or less) with an abnormal head CT scan. Even if the head CT scan is normal, there is a strong indication for placing an intracranial pressure monitor in patients with severe head injury if two of the following are present: age 40 years or more, motor posturing, or systolic blood pressure 90 mm Hg or less. 37. Which of the following clinical presentations represents the strongest immediate indication for surgical intervention for intracranial hemorrhage? A. Cerebellar hemorrhage of 4.5 cm diameter B. Parietal lobe hemorrhage of 2 cm C. Thalamic hemorrhage with extension of blood into third ventricle D. Large frontal lobe hemorrhage with slight effacement of lateral ventricle E. Pontine hemorrhage Correct Answer: The correct answer is A. Patients with cerebellar hemorrhages of 3-cm diameter or greater are generally offered surgical intervention. Other patients with intracerebral hemorrhage who may benefit from surgical intervention include those with elevated intracranial pressure, deteriorating neurological function, significant mass effect, or hydrocephalus. 38. The predilection of hypertensive encephalopathy for certain regions of the brain is thought to be due to regional variation in which of the following? A. Concentration of glutamate receptors B. Extent of collateral supply 57 C. Extent of myelination D. Pattern of sympathetic innervation E. Pattern of venous drainage Correct Answer: The correct answer is D. The sympathetic innervation of the arteries in the vertebrobasilar system is less robust than the sympathetic innervation of arteries in the anterior circulation. This is thought to underlie the vulnerability of territory supplied by the vertebrobasilar system to injury from severe hypertension. 39. A 29-year-old man suffers a cardiopulmonary arrest in the setting of an opiate overdose. After 48 hours, he has not regained pupillary light reflexes or motor response to pain. Cerebrospinal fluid is collected from a lumbar puncture and sent for a cerebrospinal fluid creatine kinase-BB level. Which is the lowest of the following levels that would yield a 95% probability of never awakening according to the logistic regression analysis derived from data from the study of Tirschwell and colleagues (1997)? A. 50 U/L B. 100 U/L C. 150 U/L D. 200 U/L E. 250 U/L Correct Answer: The correct answer is C. In Tirschwell and colleagues' study, a cerebrospinal fluid creatine kinase- BB level of 150 U/L gave an estimated 95% probability that the patient would not awaken from cardiac arrest. None of the patients with levels greater than 50 U/L regained independence in activities of daily living. Correct Answer: Tirschwell DL, Longstreth WT Jr, Rauch-Matthews ME, et al. Cerebrospinal fluid creatine kinase BB isoenzyme activity and neurologic prognosis after cardiac arrest. Neurology 1997;48:352-357. 40. Which of the following is the primary end point in determining pentobarbital dosing for treatment of status epilepticus by induction of pharmacological coma? A. Absence of pupillary light reflex B. Burst-suppression pattern on EEG C. Disappearance of brain stem auditory evoked response D. Infusion rate of 0.5 mg/kg per hour E. Serum pentobarbital level of 10 µg/mL to 20 µg/mL Correct Answer: The correct answer is B. Target pentobarbital levels and infusion rates serve as guidelines, but the goal of therapy when treating status epilepticus by inducing pharmacological coma is a burst-suppression record, with the suppression periods lasting 5 to 30 seconds. In this condition, the neurological examination resembles that of brain death, but a sluggish pupillary light reflex is occasionally preserved. Evoked potentials may continue to demonstrate peripheral and central signals. INFECTIOUS DISEASES April 2006 TYPE A QUESTIONS (ONE BEST ANSWER) 1. A 55-year-old man presents in the emergency department because of headache, fever, and somnolence developing over the past 8 hours. Examination reveals a temperature of 39.4°C, pain on flexion of the neck, and stupor. Which of the following is the most appropriate approach? A. Computed tomography (CT) scan of the head prior to lumbar puncture, followed by empiric antibiotic and adjunctive therapy B. Lumbar puncture and blood culture prior to CT scan of the head, followed by empiric antibiotic and adjunctive therapy C. Blood culture and empiric antibiotic and adjunctive therapy prior to CT scan of the head and lumbar puncture D. CT scan of the head and blood culture, followed by empiric antibiotic and adjunctive therapy and lumbar puncture E. Empiric antibiotic and adjunctive therapy, followed by lumbar puncture and blood culture Correct Answer: The correct answer is C. The clinical features are strongly suggestive of bacterial meningitis. The initial step in management is to obtain blood cultures and initiate empiric antimicrobial therapy after receiving an initial dose of dexamethasone. After this initial step, the patient should have a CT scan of the head prior to the lumbar puncture, as he has a depressed level of consciousness. 2. A 55-year-old previously healthy businessman is evaluated for headache, neck stiffness, and progressive somnolence over the past 2 weeks. Two days ago, he developed gait difficulties and double vision. He returned from a summer vacation in Arizona 3 weeks ago. Examination reveals a temperature of 38.5°C. He is somnolent, has mild nuchal rigidity, and has a left sixth nerve palsy. He has a nodular lesion in the right thigh. A head MRI with gadolinium reveals diffuse meningeal enhancement, particularly of the basal meninges, and mild hydrocephalus. Cerebrospinal fluid (CSF) examination reveals 500/mm 3 white blood cells (20% neutrophils, 30% eosinophils, 50% mononuclear), glucose concentration of 40 mg/dL (CSF-plasma glucose ratio 0.3), and protein of 58 100 mg/dL. Gram's stain is negative. Which of the following CSF studies is most likely to provide the diagnosis in this patient? A. Polymerase chain reaction (PCR) assay for Borrelia burgdorferi DNA B. Complement-fixing antibody against Coccidioides immitis C. Latex agglutination for Cryptococcus neoformans antigen D. Acid-fast stain for Mycobacterium tuberculosis E. Enzyme immune assay for Histoplasma capsulatum antigen Correct Answer: The correct answer is B. In a patient with severe chronic meningitis, the history of recent travel to an endemic area (southwest United States), the presence of a cutaneous nodule, and the CSF eosinophilia are highly suggestive of coccidioidal meningitis. This can be confirmed by detection of CSF antibodies and identification of typical spherules on the biopsy of the skin nodule. CSF cultures are positive in only 50%. 3. Three days after visiting his grandson at a summer camp, a 72-year-old man developed fever, headache, confusion, and leg weakness. Neurological examination 1 day later revealed decreased level of arousal, mild nuchal rigidity, facial weakness, and weakness and areflexia in the left arm and right leg. Bilateral arm tremor with occasional myoclonus was observed. A CT scan of the head without contrast was essentially normal. CSF examination revealed an opening pressure of 200-mm H 2 O, 200/mm 3 white cells (70% polymorphonuclear), a glucose concentration of 60 mg/dL (CSF-plasma ratio of 0.8), and a protein concentration of 100 mg/dL. Which of the following is the most likely cause of his symptoms? A. Varicella-zoster virus B. Coxsackie B virus C. Herpes simplex virus 2 (HSV-2) D. West Nile virus E. Epstein-Barr virus (EBV) Correct Answer: The correct answer is D. The clinical picture is that of a viral meningoencephalitis. The presentation in summer suggests a mosquito-or tick-borne disease. In this clinical setting, the presence of weakness with lack of muscle stretch reflexes, tremor, myoclonus, and polymorphonuclear predominant pleocytosis with normal glucose concentration in the CSF is highly suggestive of West Nile virus encephalitis. Although varicella- zoster virus may cause meningoencephalitis and radiculopathy, these tend to occur primarily in immunosuppressed patients. HSV-2 causes recurrent meningitis and radiculopathy but rarely encephalitis. EBV may trigger Guillain- Barré syndrome, which may resemble the acute anterior horn involvement by West Nile virus. However, encephalitis would be an unusual association in that setting. 4. A 55-year-old man undergoes bone marrow transplantation for treatment of chronic myelogenous leukemia. In the posttransplant period, he receives cyclosporine and prednisone. His posttransplant course has been complicated by graft versus host disease and candidal esophagitis. Six months following transplant, he develops a subacute progressive right hemiparesis. He has recently traveled to Mexico and then the midwestern United States, where he went camping and had multiple mosquito bites. He has three cats at home, and his house recently underwent repairs for damage related to black mold. Magnetic resonance imaging (MRI) demonstrates multiple areas of abnormal T2 signal in the white matter, the largest of which is in the left frontal lobe. There is minimal mass effect and no contrast enhancement. CSF examination is remarkable for positive PCR for JC virus. Which of the following features in this patient's history is the most significant risk factor for progressive multifocal leukoencephalopathy? A. Cat exposure B. Mosquito bites C. Graft versus host disease D. Travel to Mexico E. Candidal esophagitis Correct Answer: The correct answer is C. Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder due to infection with the JC virus. The increased immunosuppression required for treatment of graft versus host disease placed the patient at increased risk for PML due to impairment of cell-mediated immunity. The JC virus is ubiquitous in the environment; therefore, travel history and mosquito and cat exposure do not increase his risk of PML. No direct association exists between candidal infection and PML. 5. A 35-year-old man with a history of human immunodeficiency virus (HIV) infection presents with a 4-day history of headache, malaise, and low-grade fever. He recently had been on a camping trip, and he has two cats in his home. He has a previous history of Pneumocystis pneumonia. His medications include trimethoprim- sulfamethoxazole; he is not receiving highly active antiretroviral therapy (HAART). His temperature is 38°C. No meningismus is noted, and the neurological examination is normal. His CD4 count is 20 cells/µL. Serum anti- Toxoplasma serum immunoglobulin G (IgG) is negative. Which of the following is the most significant risk factor for opportunistic central nervous system (CNS) infection in this patient? 59 A. HAART B. Cat exposure C. Negative serum Toxoplasma IgG D. CD4 count E. History of Pneumocystis pneumonia Correct Answer: The correct answer is D. The strongest risk factor for opportunistic CNS infection in this patient is the CD4 count below 200 cells/µL. Patients with previous Pneumocystis pneumonia who have low CD4 counts receive trimethoprim-sulfamethoxazole (TMP-SMX) for pneumocystis prophylaxis. This treatment also lowers the risk of Toxoplasma encephalitis. The absence of serum Toxoplasma IgG makes the possibility of Toxoplasma encephalitis less likely. Most patients develop Toxoplasma encephalitis as reactivation of latent disease, not by new exposure to infected cats. 6. A 40-year-old woman presents with a 3-day history of fever, headache, and confusion. She returned from a vacation in southern India 10 days ago. She spent 3 weeks in India, largely in rural areas. Her husband reports that she had no illness while on vacation other than a mild diarrheal illness. On examination her temperature is 39°C. She is drowsy but able to follow one-step commands with all extremities. She has a bilateral internuclear ophthalmoplegia and bilateral facial weakness. There is no papilledema. Limb strength appears normal, but there is generalized rigidity. The deep tendon reflexes are brisk symmetrically, and bilateral Babinski signs are present. Mild meningismus is present. CSF examination reveals a protein of 150 mg/dL, glucose 80 mg/dL, WBCs 200/mm 3 (100%) lymphocytes. An MRI of the brain reveals increased T2 signal bilaterally in the globus pallidus, thalami, and in the pons and midbrain. Serum enzyme-linked immunoabsorbent assay (ELISA) for Japanese encephalitis virus immunoglobulin M (IgM) is positive. Which of the following activities or exposures during her trip has placed the patient at highest risk for developing her current illness? A. Mosquito exposure B. Consumption of undercooked pork C. Exposure to live poultry D. Snorkeling in the Bay of Bengal E. Eating unwashed vegetables Correct Answer: The correct answer is A. This patient most likely has encephalitis caused by Japanese encephalitis virus. Japanese encephalitis virus typically affects the basal ganglia, thalami, cerebellum, and brain stem as well as the cerebral cortex. It is the leading cause of viral encephalitis in Asia with 30,000 to 50,000 reported cases each year. The virus is transmitted by the Culex mosquito, which typically breeds in rice paddies. Most cases occur between June and September, and the incubation period is 5 to 14 days. No treatment for the encephalitis is known, other than supportive care. A vaccine is available, although it is not usually recommended for travelers due to the rarity of infection in this population and the risk of hypersensitivity reactions. The best protection against Japanese encephalitis virus is avoidance of mosquito bites. The other activities listed in the option set would not put the patient at risk for the development of encephalitis. 7. A 65-year-old woman with a history of rheumatoid arthritis on chronic corticosteroid therapy presents in the emergency department because of headache, fever, and confusion developing over the past 12 hours. Examination reveals temperature of 38.9°C, pain on flexion of the neck, and decreased level of arousal. She has a right focal motor seizure with secondary generalization during the examination. Which of the following is the most appropriate initial empiric antibiotic combination in this case? A. Cefepime, vancomycin, and acyclovir B. Cefepime, vancomycin, and ampicillin C. Penicillin, vancomycin, gentamicin, and doxycycline D. Cefepime, ampicillin, gentamicin, and acyclovir E. Cefepime, vancomycin, ampicillin, and acyclovir Correct Answer: The correct answer is E. The clinical picture is consistent with either bacterial meningitis or herpes simplex encephalitis. Prior to obtaining cerebrospinal fluid, the empiric antibiotic combination should include a third- or fourth-generation cephalosporin plus vancomycin, based on the assumption that the cause may be a penicillin- and cephalosporin-resistant strain of Streptococcus pneumoniae, as well as ampicillin due to the possibility of Listeria monocytogenes in the setting of immunosuppression (corticosteroid therapy) and acyclovir (until the results of the CSF exclude the possibility of herpes simplex encephalitis). 8. A 67-year-old farmer from Ohio with a history of rheumatoid arthritis treated with corticosteroids for several years developed fever, chest pain, and cough approximately 3 weeks ago. Two weeks ago, he started experiencing headache, neck pain, and increased somnolence. Two days ago he developed eye pain, floaters, and decreased vision. He had the acute onset of right arm weakness and diplopia 12 hours ago. Examination reveals a temperature of 39.5°C. He is somnolent but arousable to loud voice and has mild nuchal rigidity. He also has conjunctival 60 injection, decreased visual acuity, a right sixth nerve palsy, and right hemiparesis. Funduscopy reveals multiple white foci consistent with retinochoroiditis. A head MRI with gadolinium reveals diffuse meningeal enhancement, particularly of the basal meninges, and an area of acute infarction in the left frontal lobe. A magnetic resonance angiogram reveals multisegmental narrowing of the middle cerebral artery. CSF examination reveals an opening pressure of 300 cm H 2 O, white blood cells 200/mm 3 (50% neutrophils), glucose concentration of 40 mg/dL (CSF- plasma glucose ratio 0.3), and protein of 100 mg/dL. Gram's stain is negative. A chest x-ray shows parenchymal granulomas and hilar adenopathy. Which of the following is the most likely cause of this patient's condition? A. Listeria monocytogenes B. Histoplasma capsulatum C. Cytomegalovirus D. Treponema pallidum E. HSV-2 Correct Answer: The correct answer is B. The patient has anterior and posterior uveitis and severe chronic meningitis resulting in cranial nerve palsy and vasculitis. The endemic area of origin, history of immunosuppression, chorioretinitis, and neutrophil predominant CSF pleocytosis, together with pulmonary lesions, strongly suggest H. capsulatum as a probable cause. Cytomegalovirus may produce retinitis and CSF polymorphonuclear pleocytosis, but this typically occurs in the setting of polyradiculopathy in patients with HIV infection. Neurosyphilis can produce chorioretinitis, vasculitis, and chronic meningitis, but in general CSF mononuclear pleocytosis and hypoglycorrhachia are less common or milder, and pulmonary lesions are not a feature. HSV-2 is typically associated with recurrent aseptic meningitis. 9. Approximately 2 weeks after Christmas, a 28-year-old neuroscience graduate student comes to the emergency department complaining of fever, headache, photophobia, and myalgias over the past 12 hours. He has been studying the neuroprotective effects of hypothermia in a hamster model of stroke. Prior to the onset of the current symptoms, he had a mild fever that subsided spontaneously and was attributed to a "flu." Neurological examination reveals nuchal rigidity but is otherwise normal. He has a mild erythematous rash and mild generalized lymphadenopathy. CSF examination shows an opening pressure of 280-mm H 2 0, white blood cells 1000/mm 3 (98% mononuclear), a glucose concentration of 30 mg/dL (CSF-plasma glucose ratio of 0.3), and a protein concentration of 60 mg/dL. Laboratory tests show mild leukopenia and thrombocytopenia. Human immunodeficiency virus type 1 (HIV-1) serology is negative. Which of the following is the most likely etiological agent? A. Varicella-zoster virus B. Herpes simplex virus 1 (HSV-1) C. West Nile virus D. Lymphocytic choriomeningitis virus E. Cytomegalovirus Correct Answer: The correct answer is D. Lymphocytic choriomeningitis virus should be considered in patients with aseptic meningitis and history of exposure to rodents, including hamsters, particularly in the fall and winter. The presence of a mild erythematous rash, lymphadenopathy, and marked CSF mononuclear pleocytosis and hypoglycorrhachia are consistent with this diagnosis. Varicella-zoster virus may cause encephalitis, meningitis, myelitis, or radiculitis, particularly in an immunocompromised patient. HSV-1 produces focal encephalitis more commonly than aseptic meningitis. West Nile virus is a mosquito-borne agent that commonly causes aseptic meningitis in summer and early fall. Cytomegalovirus would be an unusual cause of aseptic meningitis in an immunocompetent host. 10. A 55-year-old woman develops progressive headache 6 months following bone marrow transplantation for acute myelogenous leukemia. She has a temperature of 38°C and scores 25/30 on the Mental Status Examination. She has mild papilledema, and the remainder of her neurological examination is unremarkable. An MRI of the brain demonstrates multiple ring-enhancing lesions. Noncontrast head CT demonstrates mild hemorrhage associated with 1 lesion. Chest x-ray shows a 3-cm nodular lesion in the right lower lobe. Bronchoalveolar lavage is performed, and galactomannan index is noted to be greater than 0.5 in both the serum and bronchoalveolar lavage fluid. Which of the following medications is most appropriate to treat this patient's condition? A. Pyrimethamine B. Trimethoprim-sulfamethoxazole C. Isoniazid D. Amphotericin B E. Ganciclovir Correct Answer: The correct answer is D. This patient most likely has infection with Aspergillus, the most common cause of CNS focal infection in patients with organ or bone marrow transplantation. Concurrent pulmonary infection is common in Aspergillus, Mycobacterium tuberculosis, Toxoplasma gondii, and nocardiosis. The 61 presence of an elevated galactomannan in the serum and bronchoalveolar lavage fluid is highly suggestive of Aspergillus, since galactomannan is a polysaccharide marker on the surface of the Aspergillus cell wall. Amphotericin is an appropriate treatment for Aspergillus. 11. A 44-year-old Laotian man with a history of HIV infection presents to the emergency department with a 1- week history of headache and neck pain, fever, diplopia, and right-sided facial weakness. He has a history of candidal esophagitis for which he has taken fluconazole for the last 6 months. His neurological examination reveals mild meningismus, bilateral sixth nerve palsies, and a right seventh nerve palsy. His CD4 count is 40 cells/µL. A noncontrast CT of the head is negative. CSF examination reveals an opening pressure of 230-mm H 2 O, protein 140, glucose 40 mg/dL, and white blood cell count 150/mm 3 (100% lymphocytes). CSF acid-fast bacillus stain, india ink stain, and cryptococcal antigen are negative. Which of the following is the most likely responsible organism for this patient's infection? A. Toxoplasma gondii B. Cryptococcus neoformans C. Borrelia burgdorferi D. West Nile virus E. Mycobacterium tuberculosis Correct Answer: The correct answer is E. The cranial nerve abnormalities suggest that the patient has basal meningitis. In patients infected with HIV, the most likely etiologies for meningitis are C. neoformans, M. tuberculosis, and Treponema pallidum. Toxoplasma usually produces parenchymal lesions and not meningitis. This patient would not be at higher risk for Lyme meningitis because he is immunocompromised. West Nile virus may produce a meningoencephalitis in immunocompromised patients but should not produce a low CSF glucose. The fact that the patient is on fluconazole prophylaxis for Candida esophagitis would lower the risk for Cryptococcus infection. Moreover, the patient comes from Laos, a developing country with a high likelihood of exposure to M. tuberculosis. 12. A 35-year-old man is brought to the emergency department for evaluation of fever, somnolence, and a single seizure. He is originally from a rural community in the Sudan but immigrated to the United States 5 days ago. Three days ago he developed high fever and chills with nausea and vomiting. This morning he was unarousable and had a 2-minute generalized tonic-clonic seizure. He was previously healthy and takes no medication. Vital signs are temperature 40°C, heart rate 110 regular, blood pressure 105/70 mm Hg, respiratory rate 18/min. An airway is placed, and he is given supplemental oxygen. A finger-stick glucose is 80 mg/dL. His examination is significant for retinal hemorrhages without evidence of papilledema. His examination is nonfocal. A noncontrast CT of the head is normal. CSF examination reveals an opening pressure of 190-mm H 2 O, protein 60 mg/dL, glucose 70 mg/dL, WBCs 5/mm 3 (100% lymphocytes), red blood cell count 0. Gram's stain, acid-fast bacilli, and india ink stain are negative. What additional testing would be most likely to yield a diagnosis in this patient? A. Giemsa stain of the peripheral blood B. Cerebral angiogram C. Brain biopsy D. Single-photon emission computed tomography scan E. Japanese encephalitis virus IgM antibody in the CSF Correct Answer: The correct answer is A. In a patient from sub-Saharan Africa who presents with fever, encephalopathy, and seizures, a diagnosis of cerebral malaria should always be considered. Cerebral malaria is usually caused by infection with Plasmodium falciparum or less likely Plasmodium vivax. The parasite-infected red blood cells become adherent to brain capillaries and venules, causing microvascular obstruction. This in turn produces diffuse encephalopathy, focal neurological deficits, and seizures. The best way to detect the parasite is with a thick-and-thin peripheral blood smear with Giemsa staining. Serological tests are available but less reliable. This patient is not from an area endemic for Japanese encephalitis virus. 13. A 65-year-old previously healthy man presents in the emergency department because of headache, fever, and neck stiffness over the past 12 hours. Examination reveals temperature of 40°C, pain on flexion of the neck, and an apical systolic murmur. A chest x-ray reveals a left lower lobe pneumonia. Which of the following is the most appropriate statement regarding dexamethasone treatment in this patient? A. Dexamethasone is contraindicated, given the presence of presumed bacterial meningitis, endocarditis, and pneumonia. B. Dexamethasone should be administered if the patient's mental status deteriorates despite appropriate empiric antimicrobial therapy. C. A 10-mg dose of dexamethasone should be given prophylactically against brain edema after 24 hours of antimicrobial therapy if blood cultures are negative. 62 D. A 10-mg intravenous (IV) dose of dexamethasone should be given prior to initiation of antimicrobial therapy and continued every 6 hours for 4 days. E. Dexamethasone, 10 mg intravenously every 8 hours for 2 days, should be initiated after the first dose of antimicrobial therapy. Correct Answer: The correct answer is D. This patient probably has bacterial meningitis, which, in the setting of pneumonia and endocarditis, is likely due to Streptococcus pneumoniae. There is evidence that corticosteroids may reduce the potential detrimental effects of cytokines released during the acute inflammatory reaction and presumably prevent further cytokine release triggered by antimicrobial-induced bacterial lysis. Dexamethasone is administered at a dose of 10 mg intravenously prior to initiation of antimicrobial therapy and continued at the same dose every 6 hours for 4 days. 14. A 28-year-old man is evaluated for fever, headache, neck stiffness, irritability, and impaired memory over the past 6 days. Two days ago, he developed weakness in the right arm, diplopia, and imbalance. He has experienced 2 episodes of eye pain and blurred vision, diagnosed as anterior uveitis, over the past 3 years. He has also experienced recurrent episodes of arthralgia associated with painful subcutaneous nodules in the pretibial areas. Examination reveals impaired attention, neck stiffness, papilledema, right oculomotor palsy, gait ataxia, and upper motor weakness in the right upper limb. He has several painless ulcers in the mouth and the penis. Head MRI reveals several T1-hypointense and T2-hyperintense lesions in the pons and midbrain, cerebellum, and internal capsule. Some lesions enhance with gadolinium. A magnetic resonance venogram reveals a partial occlusion of the superior sagittal sinus. CSF examination reveals an opening pressure of 400 cm H 2 O, white blood cells 400/mm 3 (80% mononuclear), glucose of 60 mg/dL, and a protein of 200 mg/dL. HIV-1 serology is negative. Two days after admission, he suffers one episode of hemoptysis, and a CT angiogram of the chest reveals an aneurysm in the left pulmonary artery. What is the most likely diagnosis? A. Granulomatous angiitis B. Neurosarcoidosis C. Behçet's disease D. Meningovascular neurosyphilis E. Varicella-zoster meningoencephalitis Correct Answer: The correct answer is C. The history of recurrent anterior uveitis and the presence of oral and genital ulcers are characteristic of Behçet's disease. This disorder may manifest with an uveomeningeal syndrome and multifocal cerebral lesions, particularly in the brain stem, and is typically associated with predisposition to venous thrombosis. The presence of aneurysms in visceral vessels is typical of the disease. Sarcoidosis can also produce uveitis and meningoencephalitis but is not typically associated with oral or genital ulcers or pulmonary artery aneurysm. Granulomatous angiitis of the central nervous system and systemic lupus erythematosus may also manifest with meningeal and brain lesions but are not typically associated with uveitis or oral and genital ulcers. Meningovascular syphilis and varicella-zoster meningoencephalitis may be associated with uveitis. However, the oral and genital ulcers are distinct from the maculopapular rash or vesicles associated with syphilis and herpes zoster, respectively. 15. In the fall, a 5-year-old girl presents to the emergency department with headache, neck pain, and vomiting starting approximately 8 hours prior to evaluation. Examination reveals fever (38.9°C), nuchal rigidity, tender papules and vesicles in the palms and soles, and ulcers in the gingiva and soft palate. She is somnolent but has no focal neurological deficits. CSF examination reveals an opening pressure of 260-mm H 2 O, white blood cells 200/mm 3 (50% polymorphonuclear and 50% mononuclear), glucose concentration of 65 mg/dL (CSF-glucose ratio 0.7), and protein concentration of 70 mg/dL. Which of the following CSF studies is most likely to provide a definite diagnosis? A. IgM for EBV viral capsid antigen B. Reverse transcriptase polymerase chain reaction (RT-PCR) for enterovirus C. PCR for HSV-2 D. Latex agglutination study for Neisseria meningitidis E. Venereal Disease Research Laboratory (VDRL) testing Correct Answer: The correct answer is B. Enteroviruses are responsible for approximately 80% of aseptic meningitis cases, particularly in the fall. The presence of exanthem and enanthem (hand-foot-and-mouth syndrome) is supportive of enteroviral aseptic meningitis. As in this case, the CSF may show pleocytosis with polymorphonuclear predominance in the first 48 hours, with subsequent shift to mononuclear cells. EBV is a relatively infrequent cause of aseptic meningitis, and the rash present in this patient would be atypical for EBV. HSV-2 is a common cause of aseptic meningitis but produces focal encephalitis more commonly than aseptic meningitis, and the rash, characterized by grouped vesicles in the genitalia, occurs in sexually active adults. Despite the polymorphonuclear pleocytosis in the CSF, the clinical picture and the normal CSF glucose suggest a viral 63 rather than bacterial meningitis caused by meningococcus, and the rash produced by N. meningitidis is purpuric. Secondary neurosyphilis may cause a maculopapular rash affecting the palms but would be a much less likely cause of aseptic meningitis in this age group. 16. Prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX) in transplant recipients is effective in preventing which of the following CNS infections posttransplant? A. Scedosporium apiospermum B. Listeria monocytogenes C. Mycobacterium avium-intracellulare D. Pseudomonas aeruginosa E. Cryptococcus neoformans Correct Answer: The correct answer is B. TMP-SMX is an effective drug in primary prophylaxis for L. monocytogenes, Toxoplasma gondii, and Nocardia asteroides. This drug would have no efficacy in preventing the other infections listed. 17. A 42-year-old woman with HIV infection presents to the physician with a 2-week history of right visual field loss and progressive right-sided weakness. She has a previous history of Pneumocystis pneumonia. Her current medication is trimethoprim-sulfamethoxazole. Findings from neurological examination reveal a right homonymous hemianopia and mild pyramidal distribution weakness in the right face, arm, and leg with right hyperreflexia and right Babinski sign. Her CD4 count is 30/µL. An MRI of the head with contrast reveals multiple areas of abnormal T2 signal in the white matter, sparing the U fibers. The largest lesion is in the left frontoparietal region. No mass effect or enhancement is associated with the lesions. CSF examination shows a protein of 70 mg/dL, glucose 80 mg/dL, white blood cell count 6/mm 3 , and positive PCR for JC virus. Which of the following is the most effective treatment for this patient's neurological condition? A. HAART B. Interferon alpha C. AraC D. Amphotericin B E. Pyrimethamine Correct Answer: The correct answer is A. HAART is the only proven treatment for HIV-associated PML. Even with treatment, the neurological deficits may not completely resolve. Without HAART, HIV-associated PML is almost always fatal. Amphotericin B is an antifungal agent used to treat cryptococcal infection. Pyrimethamine is used to treat toxoplasmosis. Neither interferon alpha nor AraC has any proven effectiveness in the treatment of HIV-associated PML. 18. A 29-year-old woman presents with fever, headache, and facial weakness 4 days after returning from a 3-week vacation in Thailand. She had felt well during her trip. She used no malaria prophylaxis. Two days ago she developed retro-orbital headache, myalgias, fever, and generalized rash. Today she noted bilaterally facial weakness with difficulty closing her eyes. On examination, her temperature is 40°C. She has bilateral facial weakness but an otherwise normal neurological examination, including normal mental status. A generalized macular rash spares the palms and soles. An MRI of the head is normal. Lumbar puncture reveals a protein of 90 mg/dL, glucose of 80 mg/dL, WBCs 30/mm 3 (100% lymphocytes). CSF cultures are negative. PCR for Lyme and herpes simplex in the CSF is negative. Which of the following tests would be most helpful in making a diagnosis? A. Giemsa-stained peripheral blood smear B. Dengue-specific IgM in the serum C. Skin biopsy for rabies virus antigen D. CSF ELISA for Taenia solium E. IgM ELISA for Japanese encephalitis virus Correct Answer: The correct answer is B. The constellation of symptoms and signs in this patient suggests dengue fever, a mosquito-borne flavivirus particularly common in Asia, although it can be found in most tropical areas. The illness has a 3- to 7-day incubation period, followed by high fever, myalgias, arthralgias, retro-orbital headache, and generalized rash. Neurological manifestations are uncommon but include encephalitis, mononeuropathy or polyneuropathy, and transverse myelitis. Confirmatory diagnosis is by detection of dengue- specific IgM in the serum or identification of the virus in the CSF by PCR. Cerebral malaria, rabies encephalitis, cysticercosis, and Japanese encephalitis would be unlikely to present in this manner. 19. A 35-year-old previously healthy man presents to the emergency department complaining of headache and neck pain over the past 6 hours. He has just returned from coaching his son's soccer team at a summer camp. Examination reveals temperature of 39.4°C, mild tachycardia, and normal blood pressure. He is mildly somnolent, has pain on flexion of the neck but no focal neurological deficits, and has an erythematous maculopapular rash on 64 his chest and forearms. Which of the following antimicrobial agents should be added to the empirical regimen with cefepime and vancomycin until the CSF results are available? A. Ampicillin B. Gentamicin C. Rifampin D. Doxycycline E. Meropenem Correct Answer: The correct answer is D. The history and findings are suggestive of meningitis. Since the patient has a maculopapular rash and his disease occurred in summer, the possibility of a tick-borne infection such as Rocky Mountain spotted fever or ehrlichiosis should be considered. In these circumstances, doxycycline is added to the empirical regimen until the results of the CSF examination are available and support an alternative diagnosis. Rifampin is used to treat patients with meningitis due to Neisseria meningitidis after they finish a course of IV antibiotic therapy to eradicate nasopharyngeal colonization. Ampicillin is added if there is suspicion of Listeria monocytogenes meningitis, which would be unusual in a previously healthy and immunocompetent host. Gentamicin is added to ampicillin in critically ill patients with Listeria meningitis. Meropenem is the preferred antibiotic for Pseudomonas aeruginosa meningitis. 20. A 38-year-old woman is evaluated for a 3-week history of progressive headache, blurred vision, and gait difficulties. She developed double vision 12 hours ago. She has a history of left Bell's palsy diagnosed 8 months ago with almost complete recovery. Prior to this episode, she developed painful subcutaneous nodules in the pretibial areas, which also resolved. Examination reveals nuchal rigidity, mild papilledema, a mild residual left facial palsy, and a new right sixth nerve palsy. A head MRI with gadolinium reveals diffuse meningeal enhancement, particularly of the basal meninges, with mild hydrocephalus. CSF examination reveals white blood cells 50/mm 3 (80% mononuclear), glucose concentration of 40 mg/dL, and protein of 100 mg/dL. Gram's stain is negative. A chest x-ray reveals mediastinal adenopathies, and the patient has hypercalcemia. Which of the following is the most likely diagnosis? A. Cryptococcal meningitis B. Tuberculous meningitis C. Carcinomatous meningitis D. Neurosarcoidosis E. Behçet's disease Correct Answer: The correct answer is D. The patient most likely has neurosarcoidosis, particularly given the history of a previous episode of facial palsy and erythema nodosum and the presence of hypercalcemia. Hypercalcemia is not a typical feature of Behçet's disease. Although it can occur in many granulomatous disorders or as paraneoplastic manifestation, the spontaneous improvement of facial palsy would make the diagnosis of tuberculous, cryptococcal, or carcinomatous meningitis unlikely. 21. A 22-year-old previously healthy student in Minnesota is evaluated for fever, headache, and neck pain over the past 18 hours. He has become progressively more somnolent over the past 6 hours and had a right focal motor seizure with secondary generalization 30 minutes ago. One week ago, on New Year's Eve, he complained of a sore throat. He received ampicillin, but this had to be discontinued because he developed a diffuse maculopapular rash. Examination reveals somnolence, neck stiffness, and mild right hemiparesis with a Babinski sign. He has mild hepatomegaly. A CT scan of the head is negative. CSF examination shows an opening pressure of 290-mm H 2 O, total white blood cell count of 200/mm 3 (90% mononuclear), glucose concentration of 60 mg/dL (CSF-plasma glucose ratio 0.6), and protein of 100 mg/dL. Gram's stain is negative. Which of the following CSF studies is most likely to determine the etiology of the patient's condition? A. RT-PCR for enterovirus RNA B. IgM antibody against EBV viral capsid antigen C. PCR for Cytomegalovirus DNA D. IgG antibody against varicella-zoster virus E. IgM antibody against West Nile virus Correct Answer: The correct answer is B. The history of maculopapular rash triggered by ampicillin is highly suggestive of EBV infection. The patient's clinical picture is consistent with EBV meningoencephalitis. Focal encephalitis, sometimes resembling HSV-1 encephalitis, complicates less than 1% of cases of infectious mononucleosis. Acute EBV virus infection is confirmed by detection of antiviral capsid antigen-positive IgM antibodies in serum or CSF. The history, time of the year of occurrence, and findings on physical examination are not consistent with enteroviral infection. In the absence of immunosuppression, meningoencephalitis due to Cytomegalovirus or varicella-zoster virus is unlikely. West Nile virus is a mosquito-borne pathogen and therefore an unlikely cause of encephalitis during winter. [...]... following mechanisms may account for the drop in lipids? A Suppression of hepatocellular enzymes B Increase in number of LDL receptors C Suppression of sterol regulatory element binding protein (SREBP) cleavage activating protein (SCAP) D Increase in circulating LDL E De-activation of sterol regulatory element binding proteins (SREBPs) Correct Answer: The correct answer is B Statin mechanisms include up-regulating... homogeneous staining or patchy staining of the sarcolemma In patients with other neuromuscular diseases, staining is homogeneous and of normal or slightly reduced intensity 4 A 65-year-old woman is seen by a physician for a 2-month history of difficulty getting out of a chair She has no complaints of back pain or leg pain She has a history of type II diabetes and well-controlled hypertension When examined,... with a 2-week history of increasing confusion He takes no prescription medications and uses injected heroin on a regular basis CD4 count is 100 Findings from his neurological examination reveal a Mental Status Examination score of 23/30 He has mild papilledema but an otherwise nonfocal neurological examination An MRI of the brain with gadolinium shows multiple 1-cm to 2-cm brain lesions with ring enhancement... protein concentration of 120 mg/dL Gram's stain demonstrates gram-negative diplococci Latex particle agglutination test detected Neisseria meningitidis antigen Culture confirms that the strain is sensitive to penicillin Which of the following is the recommended specific antibiotic treatment in this patient? A Ampicillin intravenously for 5 to 7 days followed by oral rifampin for 2 days B Nafcillin intravenously... Babinski signs A head MRI with gadolinium reveals diffuse meningeal enhancement, particularly of the basal meninges, with mild hydrocephalus CSF examination reveals an opening pressure of 200-cm H2O, white blood cells 60/mm3 (70% lymphocytes and 30% neutrophils), glucose concentration of 40 mg/dL (CSF-plasma glucose ratio 0.3), and protein of 100 mg/dL Gram's stain is negative CSF acid-fast staining... cover for varicella-zoster virus E Continue acyclovir, as HSV-1 PCR obtained within 72 hours may be false-negative Correct Answer: The correct answer is E The clinical features and neuroimaging findings are highly suggestive of HSV-1 encephalitis, a potentially fatal and treatable disease Although detection of HSV-1 DNA by PCR has sensitivity of 95% and specificity of 100%, initially false-negative results... lymphocytes) The cryptococcal antigen titer in the CSF is 1: 64 Which of the following etiologies is most likely responsible for her clinical worsening and current CSF findings? A Refractory cryptococcal infection B Co-infection with Mycobacterium tuberculosis C Chemical meningitis from amphotericin B D Immune restoration inflammatory syndrome 70 E Communicating hydrocephalus Correct Answer: The correct... following other neurosurgical procedures S pneumonia is not a common cause of meningitis in neurosurgical patients, and L monocytogenes would be unlikely in the absence of a predisposing condition affecting cellular immunity 40 A 42 -year-old Vietnamese man who has recently migrated to the United States developed a flulike illness associated with headache, neck pain, tinnitus, and hearing loss Examination... bacterial meningitis in patients with skull fracture and CSF rhinorrhea HSV-2 is the most common cause of recurrent viral meningitis, which is not supported by the CSF findings S aureus causes meningitis in neurosurgical patients Varicella-zoster virus may produce meningitis in patients with impaired cell-mediated immunity Although Cytomegalovirus may produce a CSF neutrophilic pleocytosis, this occurs in the... infection, and frontotemporal dementia is not associated with HIVinfection 25 A 40 -year-old woman from Guatemala presents to the emergency department 30 minutes after a 2-minute generalized tonic-clonic seizure She was previously healthy and takes no medications There is no history of recreational drug use On examination she is afebrile She is alert and oriented Findings from her neurological examination . reduction in cerebral blood flow and increase in cerebral blood volume. The vasodilation results in an increase in intracranial pressure and reduced intracranial compliance. 32. A 7 4- year-old hypertensive. after cardiac arrest. Neurology 1997 ;48 :35 2-3 57. 40 . Which of the following is the primary end point in determining pentobarbital dosing for treatment of status epilepticus by induction of pharmacological. meningitis or herpes simplex encephalitis. Prior to obtaining cerebrospinal fluid, the empiric antibiotic combination should include a third- or fourth-generation cephalosporin plus vancomycin,