J Neurosurg 81:614-616, 1994 Coccidioidomycosis brain abscess Case report EHUD MENDEL, M.D., Ertc N. MILEFCHIK, M.D., JAMSHID AMADI, M.D., AND PETER GRUEN, M.D. Departments of Neurosurgery and Radiology, and the Division of Infectious Disease, Department of Internal Medicine, University of Southern California, School of Medicine, Los Angeles, California Coccidioidomycosis is an infection originating in the San Joaquin Valley of southern California, but is now seen with increasing frequency throughout southern California and the southwestern United States. A central nervous system involvement is usually manifested as meningitis. The authors present the case of a young man with pulmonary coccidiaidomycosis who developed a brain lesion that proved to be a coccidioidal abscess. This manifestation may now be more frequently seen and therefore should be included in the differential diagnosis of any patient presenting with a brain mass who is from an area in which this disease is endemic. Key Worps + coccidioidomycosis southwestern United States, with the highest incidence in California’s Central Valley and parts of Arizona. Recently the incidence in California has risen dramatically.? This disease is acquired by inhalation of the airborne arthroconidia of the organism, which reside in the soil of lower life zones of the Sonoran Desert. Pulmonary manifestations are most common and are usually self- limited. Extrapulmonary dissemination occurs infre- quently (less than 1% in whites), and most commonly manifests as skin lesions, osteomyelitis, or meningitis.’ The most common central nervous system (CNS) manifestation of coccidioidomycosis is meningitis. Re- ports of parenchymal CNS lesions are extremely rare.** Content is endemic in areas of the Case Report This 19-year-old right-handed Latino man, a resident of Los Angeles, was admitted to the hospital after a generalized tonic-clonic seizure. The patient denied prior headaches, localized weakness, memory difficul- ties, recent cough, fever, or weight loss. He had not used drugs or alcohol since undergoing treatment for polysubstance abuse 6 months prior to admission. At that time, the patient had been incarcerated at a mini- mum security prison farm in the northern San Fernando Valley where his duties included field work. There was no history of intravenous drug use. 614 brain abscess Examination and Treatment. A general physical ex- amination was unremarkable, and the patient appeared healthy. A neurological examination found no deficits. Achest roentgenogram demonstrated several scattered small nodular densities bilaterally in the midlung fields and a2 X 2-cm thin-walled cavitary lesion in the right midlung field. A gadolinium-enhanced magnetic reso- nance (MR) image of the brain revealed a 2 X 3-cm intra-axial multiloculated cystic lesion in the medial and upper portion of the right frontal lobe with marked edema adjacent to the lesion (Fig. 1A). Intravenous ad- ministration of gadopentetate dimeglumine showed a confluence of multiple ring-enhancing areas contigu- ous and adjacent to the falx cerebri with minimal en- hancement to the adjacent falx (Fig. 1B). A lumbar puncture was performed with a normal opening pressure, and cerebrospinal fluid (CSF) was obtained and found to be normal; bacterial and fungal cultures yielded negative results. Coccidioidal comple- ment fixation antibody was negative in CSF but posi- tive in serum at a 1:8 ratio. Bronchoscopy with bron- choalveolar lavage was performed, and the cultures obtained eventually grew Coccidioides immitis. A test for human immunodeficiency virus was negative. A three-phase, whole-body bone scan revealed multiple sites of abnormal uptake including the right parietal calvaria. The patient was treated with fluconazole after the fungal culture results were obtained. Amphotericin was added after 1 week. J. Neurosurg. / Volume 81 / October, 1994 Coccidioidomycosis brain abscess Fic. 1. Preoperative T,-weighted magnetic resonance im- ages, axial (A) and coronal (B). A: Gadolinium-enhanced image showing marked brain edema and a multiloculated le- sion in the medial and upper portion of the right frontal lobe adjacent to the falx cerebri. B: Postcontrast image showing a confluence of multiple parafalcine abscesses with associated minimal focal dural (falcine) enhancement. Despite the rarity of intraparenchymal lesions due to coccidioidomycosis, the lesion seen on the MR im- age indicated that surgical drainage and/or resection of- fered the best prospect for definitive diagnosis and cure. Operation. The patient underwent a right frontopa- rietal craniotomy. The lesion was localized using in- traoperative ultrasonography. The capsule of the lesion was identified and incised through a corticectomy. Once opened, white purulent material issued from the capsule’s center; C. immitis ultimately grew from this intraoperative pus specimen. Pathological specimens showed brain necrosis and inflammation. Discussion This case of a patient with coccidioidal brain abscess without meningitis is the first known case of an intra- parenchymal mass lesion caused by this organism in anonimmunocompromised person. Since the advent of computerized tomography (CT), only two cases of in- tracranial coccidioidal mass lesions have been de- scribed, One case involved a 68-year-old woman pre- senting with unilateral ophthalmoplegia who had a primary intrasellar coccidioidal granuloma simulating pituitary adenoma.* Another case involved a patient with acquired immunodeficiency syndrome who, after a prolonged illness,* was found at autopsy to have a 5-mm lesion containing spherules of C. immitis. In one large series of coccidioidal meningitis cases, paren- chymal lesions were rare and there was no mention of abscess.” There were no apparent underlying causes to explain why the patient manifested this rare form of dissemi- nated coccidioidomycosis. Despite bone scan evidence of involvement of the skull, there was no contiguous spread of disease from bone. It is probable that the le- sion formed from hematogenous seeding of brain pa- renchyma. The frontal location of the lesion allowed it to attain a large size prior to causing a generalized seizure. In 1991 and 1992 there were threefold and 10-fold increases, respectively, in the number of cases discov- J. Neurosurg. / Volume 81 / October, 1994 ered by serological testing in California which were reported to the Centers for Disease Control and Pre- vention compared with the annual number of cases re- ported since 1986." The rising incidence is believed to be caused by drought followed by rain and summertime winds, which promote the growth and spread of the infective form of the organism.’ It is therefore not sur- prising that unusual expressions of this disease may now be seen. The patient’s major risk factor for acquisition of coc- cidioidomycosis was field work at the prison farm in the northern San Fernando Valley 6 months prior to presentation. Latino ethnicity is a possible risk factor for dissemination. The absence of respiratory symp- toms despite evidence of active pulmonary disease may not be unusual as it is estimated that 60% of initially acquired infections are asymptomatic.® Treatment Considerations Traditionally, intravenous amphotericin B is used for the treatment of disseminated coccidioidomycosis. In- trathecal administration of amphotericin B is usually employed for treatment of meningitis because very poor CSF levels of the drug are attained with intra- venous use alone, and failure rates are high.> The re- cently introduced azole class of antifungal agents is a promising alternative treatment. Ketoconazole is inef- fective for CNS disease but some encouraging results have been obtained with fluconazole, especially in doses over 400 mg per day.® Fluconazole is well ab- sorbed and attains high CSF levels.’ Clinical experience in the use of fluconazole is ex- tremely limited, and there is almost no experience with it in the treatment of coccidioidal brain abscesses; how- ever, it was thought that fluconazole might provide the best achievable parenchymal level of an effective an- tifungal agent. Other factors included the concern that the patient might not comply with the outpatient am- photericin B treatment, and that the surgery might seed the meninges and lead to meningitis (serial CSF ex- aminations failed to reveal evidence of this). Intrathecal amphotericin B was considered but deemed unlikely to contribute in the treatment of intraparenchymal dis- ease. Even with optimum antifungal therapy, coccid- ioidal infection is extremely difficult to eradicate. In our patient, a complete surgical resection was at- tempted to enhance the likelihood of cure. Follow-up MR imaging demonstrated that, while most of the lesion was gone, a small area of enhance- ment persisted, suggesting residual infection. Repeat serial CT scans have demonstrated apparent gradual resolution of the lesion. Although this is the first documented case of a coc- cidioidal brain abscess in an immune-competent pa- tient, one consequence of the present epidemic of coc- cidioidomycosis may be that this manifestation of the infection is more frequently seen. Acknowledgments The authors thank Janice Scott and Sandra Mendel for pre- paring this manuscript. 615 References . Bouza E, Dreyer JS, Hewitt WL, et al: Coccidioidal men- ingitis: an analysis of thirty-one cases and review of the literature. Medicine 60:139-172, 1981 . CDC: Coccidioidomycosis — United States, 1991-1992, MMWR 42:21-24, 1993 . Einstein HE, Johnson RH: Coccidioidomycosis: new as- pects of epidemiology and therapy. Clin Infect Dis 16: 349-354, 1993 . Jarvik JG, Hesselink JR, Wiley C, et al: Coccidioidomycotic brain abscess in an HIV-infected man. West J Med 149: 83-86, 1988 . Pappagianis D: Epidemiology of coccidioidomycosis, in Stevens DA (ed): Coccidioidomycosis: A Text. New York: Plenum Medical, 1980, p 63 616 E. Mendel, et al. 6. Scanarini M, Rotilio A, Rigobello L, et al: Primary intra- sellar coccidioidomycosis simulating a pituitary adenoma, Neurosurgery 28:748-751, 1991 7. Tucker RM, Williams PL, Arathoon EG, et al: Pharmaco- kinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Che- mother 32:369--373, 1988 Manuscript received May 20, 1993. Accepted in final form July 14, 1993, Address reprint requests to: Ehud Mendel, M.D, Depart- ment of Neurosurgery, University of Southern California, Los Angeles, California 90033. J. Neurosurg. / Volume 81 / October, 1994