International Issues: Meningoencephalitis due to Paracoccidioides brasiliensis
F. Francesconi, MD,
A. C. Francesconi do Valle, MD, PhD,
M.T.T. Silva, MD, PhD,
R. L.B. Costa, MD, MSc,
E. Carregal, MD and
S. Talhari, MD, PhD
From Fundação Centro de Controle de Oncologia do Amazonas (F.F.), Amazonas; Instituto de Pesquisa Clínica Evandro Chagas (A.C.F.d.V., M.T.T.S., R.L.B.C., E.C.), FIOCRUZ, Rio de Janeiro; and Fundação de Medicina Tropical do Amazonas (S.T.), Amazonas, Brazil.
Address correspondence and reprint requests to Dr. Fabio Francesconi, Fundação Centro de Controle de Oncologia do Amazonas, Rua Francisco Orellana, 215, Planalto Cep: 69040-010, Manaus, Amazonas, Brazil fabiofrancesconi{at}globo.com
Neurologic manifestations of paracoccidioidomycosis are uncommon.Generally, these are characterized by headache, seizures, orfocal neurologic deficits due to a focal brain lesion. We describea patient with subacute meningoencephalitis, CSF evidence ofparacoccidioidomycosis, and striking abnormalities on brainCT scan. Combined fluconazole and sulfamethoxazole/trimethoprimwas started with good response. The patient is asymptomaticafter 10 years. Cerebral paracoccidioidomycosis should be includedin the spectrum of possible causes of meningoencephalitis ina patient from an endemic region.
Paracoccidioidomycosis is endemic to Latin America. In Brazil,it is the most common deep mycosis and is prevalent mainly inrural areas, with an estimated annual incidence of 1 to 3 casesin every 100,000 inhabitants.1 In a few patients the infectionresults in overt disease that evolves into one of the two clinicalforms: juvenile or adult type paracoccidioidomycosis. The CNSis affected in very few patients, mainly in those with the adultform.2–5 Generally, cerebral paracoccidioidomycosis ischaracterized by hypodense focal brain lesions with mass effectand contrast enhancement, resulting in focal neurologic deficits,headache, and seizures. Meningoencephalitis with psychiatricsymptoms in the absence of meningeal signs or focal brain lesionshas not been reported in cerebral paracoccidioidomycosis. Wedescribe a case of meningoencephalitis and psychiatric manifestationssecondary to Paracoccidioides brasiliensis infection in a patientwith juvenile paracoccidioidomycosis without focal brain lesionson CT scan.
A 21-year-old man presented with weight loss, dysphagia, orallesions, and enlarged cervical lymph nodes evolving subacutely.P brasiliensis was diagnosed by fungal culture following a lymphnode biopsy. Diagnosis of juvenile paracoccidioidomycosis wasmade and sulfamethoxazole 800 mg/trimethoprim 160 mg (SMZ/TMP)was started in accordance with Brazilian guidelines.6 However,there was recurrence of both oral lesions and lymph node enlargementdue to failure to comply with the treatment after 16 monthsof follow-up. The same drugs were reintroduced but once againthe patient did not take the medicine correctly. He was admitted2 years later due to disseminated cutaneous lesions, daily persistentheadache, visual hallucinations, delusional beliefs, disorganizedthinking and lack of insight, psychomotor agitation, and mentalconfusion, all of which evolved within a few weeks. There weremotor incoordination and brisk tendon reflexes diffusely, butneither nuchal rigidity nor other lateralizing deficits wereobserved. Mental evaluation showed temporal and spatial disorientation,memory deficits, dyscalculia, difficulty following commands,and visuospatial disorganization (Mini-Mental State Examination7/30). Psychiatric assessment was compatible with acute delirium,with memory and attention impairment. A brain CT scan revealeddiffuse cortical contrast enhancement without focal brain lesionsor edema (figure). CSF was under normal pressure with 29 cells/mm3(80% polymorphonuclear cells), 73 mg/dL glucose, and 42 mg/dLprotein. Tests for syphilis, HSV-1/2, CMV, toxoplasmosis, HIV-1,and HTLV-1/2 were all negative. Direct examination and culturesfor fungus, bacteria, and mycobacterium were also negative.Double-immunodiffusion for P brasiliensis was positive witha titer of 1:64. Fluconazole plus SMZ/TMP was administered andmaintained for 3 years. Complex partial seizures developed duringthe treatment and phenytoin was introduced. The patient is nowasymptomatic and periodic CT scans of the brain show normalresults after 10 years of follow-up.
We describe an unusual neurologic presentation of the juvenileform of P brasiliensis infection. Although rare, meningitisdue to P brasiliensis has been reported before. However, a focalbrain lesion is normally seen in these patients. Indeed, almostall cases of cerebral paracoccidioidomycosis, including thosewith meningitis and focal brain lesions, are diagnosed in patientswith the chronic, adult form of paracoccidioidomycosis, butnot in those with the juvenile or acute form of the disease.Another important difference in our case is the clinical presentation:normally, cerebral paracoccidioidomycosis is betrayed by focalneurologic deficits, seizures, new headache, or meningeal signs,the last one when meningitis is associated. This young man presentedwith acute delirium without meningeal signs or focal neurologicdeficits.
Usually patients with this disorder are infected secondary toinhaling the conidia of the dimorphic fungus P brasiliensis,present mainly in soil. Early infection results in a primarypulmonary infection. Only in a few patients does the primaryinfection progress to overt disease, which evolves into oneof the two clinical forms: juvenile or adult type paracoccidioidomycosis.7Juvenile or acute/subacute paracoccidioidomycosis is characterizedby systemic lymphadenopathy, hepatosplenomegaly, and bone marrowdysfunction, usually affecting children, adolescents, and youngadults. Adult or chronic paracoccidioidomycosis occurs yearsafter primary infection. This chronic form affects men in thefourth decade of life and is characterized by progressive pulmonaryand extrapulmonary manifestations, which include the CNS.1
A few small case series and collected case reports show thatthe CNS can be affected in 9.9% to 27.3% of patients.2–5Generally, cerebral paracoccidioidomycosis results from hematogenousspread of a primary infectious focus and is mainly characterizedby a hypodense lesion in the cerebral hemispheres with masseffect and contrast enhancement, sometimes resembling cerebraltoxoplasmosis: this is called the pseudotumoral form of cerebralparacoccidioidomycosis. In some patients the cerebellum, brainstem,and spinal cord can also be affected. Other imaging abnormalitiesless frequently observed are calcified lesions and diffuse subarachnoidenhancement, the latter seen in less than 10% of cerebral paracoccidioidomycosiscases.8,9
The most frequent neurologic manifestations are seizures, hemiparesis,cerebellar signs, hydrocephalus, and headache.10 Meningeal symptomsand signs can be seen in a minority of patients, generally associatedwith diffuse subarachnoid enhancement and focal brain lesions.9,10Our case report illustrates an atypical presentation of cerebralparacoccidioidomycosis.
Sometimes it is difficult to distinguish cerebral paracoccidioidomycosisfrom other diseases due to a lack of specific clinical or radiologicfindings. The main differential diagnoses are bacterial abscesses,toxoplasmosis, and brain tumors. One very important aspect isthat almost 90% of patients with cerebral paracoccidioidomycosispresent evidence of paracoccidioidomycosis in other tissue,especially in the lungs.10 Clinical suspicion and epidemiologicdata are of utmost importance to achieve the correct diagnosis.Cerebral paracoccidioidomycosis should be included in the spectrumof possible causes of meningoencephalitis in a patient froman endemic region and with evidence of a P brasiliensis infection.
Wanke B, Londero A. Epidemiology and paracoccidioidomycosis infection. In: Franco M, Lacaz C, Restrepo-Moreno A, Del Negro G, eds. Paracoccidioidomycosis. Boca Raton: CRC Press; 1994:109–117.
Pla MP, Hartung C, Mendoza P, Stukanoff A, Moreno MJ. Neuroparacoccidioidomycosis: case reports and review. Mycopathologia 1994;127:139–144.[Medline]
Fagundes-Pereyra WJ, Carvalho GT, de Miranda Goes A, das Chagas Lima e Silva F, de Sousa AA. Central nervous system paracoccidioidomycosis: analysis of 13 cases. Arq Neuropsiquiatr 2006;64:269–276.[Medline]
Duarte R, Maia A, Duarte J, Furtado C. Cerebral paracoccidioidomycosis: case report and review of the literature. Res Pes Med 1997;31:37–41.
Pereira WC, Raphael A, Sallun J. Neurologic involvement in South American blastomycosis: pathologic study of 14 cases. Arq Neuropsiquiatr 1965;23:95–112.[Medline]
Shikanai-Yasuda MA, Telles Filho Fde Q, Mendes RP, Colombo AL, Moretti ML. Guidelines in paracoccidioidomycosis. Rev Soc Bras Med Trop 2006;39:297–310.[Medline]
Almeida SM. Central nervous system paracoccidioidomycosis: an overview. Braz J Infect Dis 2005;9:126–133.[Medline]
Elias J Jr Santos AC, Colli CGCBO, et al. Central nervous system paracoccidioidomycosis: diagnosis and treatment. Surg Neurol 2005;63(suppl 1):S13–21.
Gasparetto EL, Liu CB, Neto Carvalho A, Rogacheski E. Central nervous system paracoccidioidomycosis: imaging findings in 17 cases. J Comput Assisted Tomogr 2003;27:12–17.[Medline]
Almeida SM, Queiroz-Telles F, Teive HA, Ribeiro CE, Werneck LC. Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings. J Infect 2004;48:193–198.[Medline]
Top.
CASE REPORT
DISCUSSION
