Journal of Computer Assisted Tomography 27(1):1217 2003 Lippincott Williams & Wilkins, Inc.

, Philadelphia

Central Nervous System Paracoccidioidomycosis: Imaging Findings in 17 Cases

Emerson L. Gasparetto, Christian B. Liu, Arnolfo de Carvalho Neto, and Enio Rogacheski

Purpose: To quantify the imaging findings of 17 patients with central nervous system (CNS) paracoccidioidomycosis. Method: Retrospective analysis of the clinical data, films, and laboratory findings of 17 patients with CNS paracoccidioidomycosis. The clinical data were obtained by medical records review. Plain chest films, cranial computed tomography scans (CT), and serum and liquor analysis were evaluated. Results: All the patients were male, with a mean age of 46.5 years. Headache and hemiparesis were the most frequent symptoms. The head CT scans revealed two or more granulomas in 53% of the cases, frequently confined to the parietal lobes (35%) and cerebellar hemispheres (35%). The lesions were hypodense (53%) and irregular (76%) and showed ring-like contrast enhancement (94%). Perilesional edema was seen in 82% of the patients, and hydrocephalus was seen in 41%. Conclusion: Although CNS paracoccidioidomycosis might represent a suspicious lesion pattern on CT scan examination, correlation of the CT scan findings, clinical data, plain chest films, and laboratory results is necessary to define the diagnosis of this uncommon entity. Index Terms: ParacoccidioidomycosisCentral nervous systemComputed tomography.

Paracoccidioidomycosis, also known as South American blastomycosis, is the most frequent endemic systemic mycosis in Latin America, with the largest series reported in Brazil, Argentina, Colombia, and Venezuela (13). The disease is caused by Paracoccidioides braziliensis, a dimorphic fungus that grows as a budding yeast in tissue and as yeast or mold in culture medium. Infection is generally acquired after inhalation of spores that are in suspension in the air, with the lungs being the usual site of primary infection (4,5). Paracoccidioidomycosis usually affects rural male workers aged 30 to 50 years who live in endemic areas and inhale the infecting form of P. braziliensis (1,6). The disease may present in two forms: the acute or subacute (juvenile) form, which is more aggressive, and the chronic (adult) form, which is more common (1). Central nervous system (CNS) involvement has been reported in 0%27% of patients with paracoccidioidomycosis (7
From the Discipline of Diagnostic Radiology, Department of Internal Medicine, University of Parana School of Medicine (A. de Carvalho Neto), and Section of Diagnostic Radiology, Hospital de Clnicas, Uni versity of Parana (E. L. Gasparetto, C. B. Liu, and E. Rogacheski), Curitiba, PR, Brazil. Address correspondence and reprint requests to Dr. Emerson Leandro Gasparetto, Av Silva Jardim 296, Apto 502, CEP 80230-000, Curitiba, PR, Brazil. E-mail: gasparetto@hotmail.com

10). The disease may present as a meningeal form, which frequently involves skull base leptomeninges, or as a granulomatous or pseudotumoral form, which is characterized by intraparenchymal, single or multiple, habitually supratentorial granulomas (2,7,11). Several authors have reported the head computed tomography (CT) scan as a sensitive method in the diagnosis and evaluation of CNS paracoccidioidomycosis (2,8,12). The authors describe the clinical and radiologic data of 17 patients diagnosed with CNS paracoccidioidomycosis in our hospital between 1982 and 2002. At the present time, this is the largest casuistic study of CNS paracoccidioidomycosis described in the medical literature.

MATERIALS AND METHODS We analyzed retrospectively the clinical data, films, and laboratory findings of 17 patients with CNS paracoccidioidomycosis diagnosed at our institution between 1982 and 2002. The clinical data and laboratory findings were obtained by retrospective review of medical records. We evaluated gender, age, occupation, clinical presentation, symptomatic period before diagnosis, liquor, and imaging studies (plain chest films and head CT 12

CENTRAL NERVOUS SYSTEM PARACOCCIDIOIDOMYCOSIS scan). The CT scans were performed with thirdgeneration equipment: Tomoscan 350 (Philips, Eindhoven, Netherlands), Somaton ART (Siemens, Munich, Germany), and Exel 1.800 (Elscint, Haifa, Israel). All patients were studied with 5- and 10-mm axial slices before and after administration of intravenous meglumine ioxithalamate by means of injection of 300 mg iodine per milliliter (70100 ml). We evaluated the following findings on head CT scans: number and size of lesions, presence of perilesional edema or hydrocephalus, topography, density and contrast enhancement pattern, and presence of intralesional septations and/or calcifications. The Fisher exact test was applied to conduct the statistical analysis, and a probability value < 0.05 was defined as statistically significant. RESULTS All the patients were male, with ages ranging from 10 to 70 years (mean age of 46.5 years). The analysis of the symptomatic period before diagnosis yielded a mean time of 5 months, ranging from 1 day to 18 months. The most frequent clinical presentations were headache (70%), hemiparesis (30%), and partial complex seizures (30%). Most of the patients were from rural areas. The plain chest films showed findings of pulmonary paracoccidioidomycosis in 88% of the cases (Fig. 1). The cerebrospinal fluid analysis to P. braziliensis antibodies was positive in 57% of the cases (four of seven cases). Liquor analysis and cultures were performed in all patients, but the findings were nonspecific. All patients were submitted to head CT scans (Figs. 26). In all cases, we observed the granulomatous or pseudotumoral form. There were no cases of meningeal enhancement, neither isolated as the meningeal form nor associated with the granulomatous form. Forty-seven percent of patients (n 8) had one lesion, 23% (n 4)

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FIG. 2. Computed tomography scan showing a large, irregular, hypodense left frontal lesion, which presents a ring-like pattern of enhancement. Severe edema is also present.

FIG. 1. Plain chest film showing a bilateral lung lesion with a reticular pattern that is more prominent in the central areas. Opacities with an alveolar aspect are also seen on both lungs.

had two lesions, and in five cases (30%), we observed three or more lesions. The diameter size of granulomas ranged from 10 to 45 mm (mean of 23 mm). Perilesional edema was present in 82% of the cases (n 14), being severe in 57% (n 8). Forty-one percent (n 7) of patients had hydrocephalus, which was severe in three cases (42%). The lesions were frequently hypodense (53%, n 9) and irregular (76%, n 13) and showed ring-like contrast enhancement (94%, n 16). Intralesional calcification and septation were observed in four cases (23%). When we correlated the symptomatic period before diagnosis with the lesion attenuation, we observed hyperdense signal in patients with more than 5 months of symptoms and hypodense signal in the cases with less than 5 months of symptoms (P 0.0020). Granulomas were distributed proportionally in the supraand infratentorial compartments. Forty-seven percent (n 8) of the patients had supratentorial lesions, 30% (n 5) had infratentorial lesions, and 23% (n 4) had supra- and infratentorial granulomas. Granulomas were located in cerebella and parietal hemispheres (35%, n 6); occipital hemispheres (11%, n 3); and cerebral peduncles, thalamus, and frontal hemispheres (11%, n 2) (Table 1). Both clinical forms were observed in our patients. There were 16 cases of chronic presentation (adult type) and 1 case of acute/subacute presentation (juvenile type). Fifty-three percent of the patients had CNS and lung lesions; 18% had CNS, lung, and mucocutaneous lesions; 12% had CNS, lung, and adrenal involvement; and 7% had CNS and mucocutaneous lesions. Only one patient had exclusively CNS lesions. Definitive diagnosis was established by CNS biopsy (35%), sputum culture (30%), and biopsy at another involved site (24%). The remaining two patients had plain chest films compatible with paracoccidioidomycosis and positive blood serologic tests and showed clinical and
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FIG. 3. Computed tomography scan revealing multiple, irregular, isodense lesions (A), which, after contrast injection, show a ring-like pattern of enhancement (B). Severe surrounding edema and discrete hydrocephalus are also present.

radiologic improvement after specific treatment of paracoccidioidomycosis. DISCUSSION Paracoccidioidomycosis, or South American blastomycosis, is the most common systemic mycosis in Latin America. The estimated number of affected individuals in this endemic area is 10 million people. Almost all South and Central American countries have large regions where paracoccidioidomycosis is endemic, particularly in Brazil, Colombia, Venezuela, and Argentina (1,2,3,5). P. braziliensis, the etiologic agent, is an aerobic dimorphic fungus. The disease is acquired by inhalation of conideos, causing lung infection. From this primary complex, fungus can spread to the kidney, spleen, liver, bone, adrenal gland, and CNS by lymphatic or blood circulation (1315).

Paracoccidioidomycosis has been noted in all ages over 3 years old, being more common in patients between 30 and 50 years of age (1). The typical patient is a middle-aged male agricultural worker, who is malnourished, lives in contact with soil, and has a chronic lung disease (4). The most common affected organ is the lung (50%100%), followed by the skin, mucous membranes, lymph nodes, adrenal gland, liver, and bone (5,14,15). Recent studies have shown evidence of immunodeficiency secondary to paracoccidioidomycosis, with decreased humoral and cellular responses (16). This fact may explain the occurrence of associated opportunistic infections such as tuberculosis and cryptococcosis (17). Neurologic symptoms depend on the lesional site, but previous studies have reported signs of intracranial hypertension (e.g., vomiting, headache, papilledema), hemiparesis and hemiplegia, cranial nerve palsies, seizures, and gait ataxia (2,7,8). Asymptomatic patients were also reported (4).

FIG. 4. Computed tomography scan showing an irregular hypodense left parietal lesion (A) with a ring-like pattern of enhancement after contrast injection (B). Severe edema is also demonstrated.

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FIG. 5. Computed tomography scan after a contrast injection revealing two regular hyperdense lesions with ring-like enhancement and discrete edema (A). In a detail (B), an intralesional calcification (arrow) is demonstrated.

The CNS involvement for paracoccidioidomycosis was first suggested in 1919 by Pereira and Jacobs (18); however, only in the last 40 years has this presentation has been closely studied (2,4,8,19). The frequency of CNS paracoccidioidomycosis was discussed in several reports. Pla et al. (8) observed a frequency of 0%27% in a necropsy study, Colli et al. (9) noticed a variation from 10%12%, Moura et al. (10) presented a frequency of 10%27%, and Magalhaes et al. (7) suggested CNS involvement in 10% of the patients with paracoccidioidomycosis. In the CNS, P. braziliensis causes a granulomatous reaction within the parenchyma or, less commonly, chronic meningitis; however, both can be present at the same time. The intracranial paracoccidioidal granulomas, blastomycomas, or pseudotumors are spaceoccupying lesions of granulomatous tissue commonly associated with other organs or tissue involvement. The

lesion is surrounded by a thick capsule, frequently with a central necrotic area in which many parasites can usually be seen. The necrotic material is surrounded by a cellular infiltrate, which includes epithelioid cells, giant cells (Langhans cells), eosinophils, lymphocytes, and plasma cells. The lesion is circumscribed and does not infiltrate or disseminate through surrounding tissue. Reactive gliosis is observed in the neighboring parenchyma and is responsible for the thick capsule observed in CNS paracoccidioidomycosis, as was seen in all patients in the current study. This capsule does not allow free blood access, reducing natural defenses and the capacity to destroy the parasite (2,7,8). The granulomatous or pseudotumoral form is much more common (12,20,21). Granulomas are usually described as multiple and randomly distributed; however, we observed only five patients (30%) with three or more

FIG. 6. Computed tomography (CT) scan showing a hyperdense left brain stem lesion (A). In the same patient, the CT scan performed 6 months after treatment of paracoccidioidomycosis reveals a calcified left frontal lesion (B).

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TABLE 1. CT scan findings in 17 patients with central nervous system paracoccidioidomycosis

Case 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Number 1 Multiple 1 2 3 1 Multiple 1 2 1 2 Multiple 1 1 1 4 2

Sizea 40 40 32 20 28 15 22 22 14 30 20 40 30 20 45 20 12

Edema ** ** ** * * ** ** * * ** ** ** * *

Hydrocephalus ** * * * ** * **

Topography LF R CP, R P, R O, L BG, L P LP L CH, R V R TP, R CC, L PO R TH HEM R TH L CP, R O L CH L BS, L F L CH, HEM L CH L CH R CH LO, LP, RF, CC RP

Attenuation Hypo Hypo Hypo Hyper Hyper Hyper Hyper Hypo Hypo/hyper Hyper Hyper Hypo Hypo Hypo Hypo Hypo Hyper

Contrast enhancement Ring-like Ring-like Ring-like Ring-like Ring-like Ring-like Ring-like Ring-like Ring-like/ Ring-like Ring-like Ring-like Ring-like Ring-like Ring-like Ring-like

Configuration Irregular Irregular Irregular Irregular Regular Regular Irregular Irregular Regular Irregular Irregular Irregular Irregular Irregular Irregular Irregular Regular

a Size in millimeters of the largest diameter of the largest lesion. , no; *, discrete; **, severe; R, right; L, left; F, frontal; P, parietal; T, temporal; O, occipital; CP, cerebral peduncule; BG, basal ganglia; CH, cerebellum hemisphere; V, cerebellar vermis; CC, corpus callosum; TP, temporoparietal; PO, parieto-occipital; TH, thalamus; HEM, cerebral hemispheres; BS, brain stem; hyper, hyperdense; hypo, hypodense.

lesions. Although several authors described a strong predilection of CNS paracoccidioidomycosis for the supratentorial region (3,20,21), recent reports noted an equivalent distribution in supra- and infratentorial areas (2,7), which was seen in our cases. In the supratentorial region, the lesions are more common in the cerebral hemispheres, and in the infratentorial region, granulomas usually are located in cerebellar hemispheres. Cases of spinal involvement have been reported (9,10,22,23). Head CT scan findings of CNS paracoccidioidomycosis were described in case reports and small series, but it is difficult to define a pattern. In the pseudotumoral or granulomatous presentation, authors have observed single or multiple round lesions with central low signal and ring-like contrast enhancement, little perilesional edema, and obstructive hydrocephalus. In the meningeal form, leptomeningeal diffuse enhancement was demonstrated (2,4,8,24). In our study, we observed granulomas of several sizes (with a mean size of 23 mm in the largest diameter) and irregular shape. Almost all patients showed perilesional edema, and hydrocephalus was observed in 41% of the cases. In the lesions with acute presentation (less than 5 months), we noticed central low attenuation signal with ring-like contrast enhancement. When the symptoms appeared more than 5 months before the medical examination, the lesions were hyperdense with ring-like contrast enhancement. Twenty percent of cases showed intralesional calcification and septation. Paracoccidioidal granulomas can mimic primary malignant tumors, metastasis, and pyogenic and nonpyogenic (fungal and bacterial) abscesses. The diagnosis of CNS paracoccidioidomycosis is usually difficult, and most cases are discovered after surgical resection, necropsy, or lesion involution, which is clinically and radiologically observed after empiric treatment of paracocJ Comput Assist Tomogr, Vol. 27, No. 1, 2003

cidioidomycosis (2). Unfortunately, endemic paracoccidioidomycosis areas have been confined to regions of the world where there are no facilities to confirm the diagnosis except by surgical resection (1,8). Poor results with available diagnostic methods, existence of isolated neurologic lesions, absence of previous systemic lesions, and nonspecific clinical presentation are responsible for the difficulty in making an early diagnosis (2,6). CONCLUSION Although preoperative diagnosis remains difficult, findings in our patients suggest that CT scans in conjunction with clinical data, films, and laboratory findings might be useful in some cases, especially when neurologic involvement is associated with proven systemic infection. The head CT scan is especially useful in the detection of the lesions as well as determining the topography and the number of granulomas. Early diagnosis of CNS paracoccidioidomycosis is of particular importance, because early treatment may reduce the devastating effects of the disease and might lead to cure. REFERENCES
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