Clinical Reasoning: A 35-year-old man with a right hemiplegia and a cerebral mass
G. Moretta, MD,
J. P. Pettinicchi, MD,
M. E. Talarico, MD,
P. A. Lopez, MD,
S. Cerrato, MD,
M. E. Balbuena, MD,
J. J. Poderoso, MD,
O. Mazzocchi, MD,
A. Dal Verme, MD,
C. Menghi, MD,
M. Arcavi, MD,
M. P. Grecco, MD and
J. L. Ferreiro, MD, PhD
From the Department of Neurology (G.M., J.P.P., M.P.G., M.E.T., P.A.L., M.E.B., S.C., J.L.F.), Department of Internal Medicine (J.J.P., O.M., A.D.V.), Department of Clinical Biochemistry, Clinical Immunology Division (M.A.), and Parasitology Division (C.M.), Hospital de Clínicas, Buenos Aires, Argentina.
Address correspondence and reprint requests to Dr. Gabriela Moretta, Department of Neurology, Hospital de Clínicas, Av. Cordoba 2351, 1120 AAR, Buenos Aires, Argentina gabrielamoretta{at}gmail.com
A 35-year-old man presented with progressive right face, arm,and leg weakness, and diffuse headache. He lived in rural northwestArgentina. He had a past medical history of sexually transmitteddiseases. On examination, he was alert and fully oriented, andhad a right hemiparesis with hyperreflexia and an extensor plantarreflex. Apart from low grade fever, the rest of the physicalexamination was unremarkable. The complete blood count revealedleukopenia (3,300 leukocytes/mL); renal function, liver tests,electrolytes, erythrocyte sedimentation rate, and glucose levelwere normal. He tested positive for HIV with a CD4 count of18 cells/mm3 and viral load of 133,400 copies/mm3. Brain CTshowed a nonenhancing left temporoparietal lesion with surroundingedema and midline shift.
Questions for consideration:
What are the possible etiologies of this intracerebral lesion?
What additional diagnostic testing would you consider at thispoint?
The patient was started on empirical treatment for toxoplasmosiswithout clinical improvement. A brain MRI with gadolinium performeddays later showed a left temporoparietal mass with a ring-likeenhancement pattern and marked perilesional edema (figure).Serologies for hepatitis B virus, hepatitis C virus, VDRL, andToxoplasma (immunoglobulin G, immunoglobulin M, and immunoglobulinA subtypes) were negative. Blood cultures for bacteria, fungi,and mycobacteria were also negative. Since the patient livedin an endemic area, a search for Chagas disease was performed.The serology confirmed chronic Chagas disease (both indirectimmunofluorescence and indirect hemagglutination tests werepositive). Blood parasitological tests like microconcentrationand Giemsa staining of thin and thick blood smears were alsoperformed. Neither of these revealed the presence of the trypomastigoteform of Trypanosoma cruzi.
A lumbar puncture was performed. The CSF analysis showed 5 cells/mm3,glucose 48 mg/dL (serum glucose: 97 mg/dL), Cl– 121 mEq/L,and protein 0.44 g/dL. PCR testing was negative for Toxoplasma,JC virus, and Epstein-Barr virus. A negative result for Cryptococcusneoformans was obtained with both India ink stain and antigentesting. A Giemsa-stained CSF smear revealed the presence ofthe trypomastigote form of T cruzi.
Questions for consideration:
How would you manage the treatment of an HIV-positive patientwith cerebral tumor–like Chagas disease?
As soon as the diagnosis of cerebral tumor–like Chagasdisease was made (approximately 10 days after admission), thepatient was started on benznidazole 5–7 mg/kg/d and heresumed highly active antiretroviral therapy. In the courseof treatment, seizures appeared and were partially controlledwith lamotrigine. The patient developed neutropenia later inthe course of his treatment, which was attributed to benznidazole,which was then replaced by nifurtimox 8–10 mg/kg/d. After3 months of treatment, the patient exhibited improvement inboth his neurologic condition and his immune status.
A new MRI showed a remarkable reduction in both the size ofthe lesion and its corresponding edema.
Chagas disease, also known as American trypanosomiasis, is anendemic parasitosis of Central and South America caused by theflagellated protozoan T cruzi. Although uncommon in the UnitedStates, its prevalence is expected to increase due to immigrationfrom endemic areas.1 It is transmitted to humans by hematophagousTriatominae insects, and occasionally by other routes (bloodtransfusions, IV drug use, and congenitally2).
The disease course can be divided into 3 phases: acute, indeterminate,and chronic. The chronic phase is characterized by prominentcardiac and gastrointestinal involvement (10%–30%), butoften it can remain asymptomatic.3 In AIDS and other severeimmunodeficient states, there is an increased risk of diseasereactivation, with a particular predilection for the CNS (75%of cases) both in the form of meningoencephalitis and intracranialmass lesions.4 This is especially true for patients with AIDSwith CD4 counts <200 cells/mm3. Cerebral Chagas disease presentingas a tumor-like lesion is often clinically and radiologicallyindistinguishable from other more prevalent opportunistic diseases,like toxoplasmosis and lymphoma, and should be included in thedifferential diagnosis of patients with AIDS from endemic areas.5
Diagnostic tests like CSF direct examination (Giemsa stain)and PCR techniques6,7 could provide a prompt diagnosis, avoidingthe need for a brain biopsy.
The antiparasitic drugs benznidazole and nifurtimox are consideredstandard treatment.8,9 Even though there is a lack of agreementregarding treatment duration, it would be wise to maintain antiparasitictherapy until a CD4 count >200 cells/mm3 has been reached.9
Cerebral Chagas disease has a poor prognosis, often leadingto death within weeks of diagnosis.10 A high level of suspicion,coupled with early diagnosis and treatment, is the only wayto achieve a better prognosis.
We invited residency programs, medical student preceptors, andindividuals to utilize this Mystery Case as an educational toolto develop trainees' clinical reasoning skills. Groups or individualsread the case presentation, developed their own differentialdiagnoses, and determined what would be their next step in eitherdiagnosing or treating the patient. Here are the responses toour first Mystery Case.
We had 23 responses to this first Mystery Case. All were fromindividual residents rather than groups. All responses werethoughtful and many were quite detailed, including several alternativediagnoses and extensive descriptions of the respondent's approachto the diagnosis and management of this patient.
All respondents considered the fact that the patient had HIVand was immunocompromised in their differential diagnosis. Allrespondents included toxoplasmosis and CNS lymphoma at the topof their differential. All described many of the other mostcommon considerations, and most outlined appropriate coursesof diagnosis and management. Six respondents considered thepatient's area of residence in South America as relevant tothe diagnosis, most discussing the possibility of neurocysticercosis.Only 2 respondents, however, included the diagnosis of trypanosomiasis—infectionwith T cruzi, or Chagas disease—in the differential: KateAhmad, The Canberra Hospital, Canberra, Australia, and PeterArmanas, Walter Reed Army Medical Center, Washington, DC. Additionalconsiderations, in descending order of the number of times whichthey were cited, included bacterial abscess, cryptococcus andother fungal infections, viral infections, neurocysticercosis,glioma, metastases, tuberculoma, syphilis, progressive multifocalleukoencephalopathy, infarction, and tumefactive multiple sclerosis.
Half of the respondents recommended starting empiric therapyfor toxoplasmosis, followed by brain biopsy if there were noresponse after several weeks. All suggested measuring serologiesagainst many infectious organisms, though several expressedconcerns about performing lumbar puncture due to the presenceof the mass lesion. Seven suggested magnetic resonance spectroscopyas a way to distinguish tumor, infection, and vascular lesions.
This first Resident & Fellow Section Mystery Case pointsto the importance of considering diagnoses of infections uncommonlyseen in the United States when evaluating immunocompromisedpatients from other countries. It is likely that with the increasein international travel we will all see more patients like thisone.
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