Abstract
Fungal infections of the central nervous system (CNS) represent a wide spectrum of diseases with some common magnetic resonance imaging (MRI) features. Risk factors include immunocompromise of any cause and living in endemic areas. CNS infection occurs through hematogenous spread, cerebrospinal fluid seeding, or direct extension. MRI features include heterogeneous or ring reduced diffusion and weak ring enhancement. Angioinvasive aspergillosis is characterized by multifocal hemorrhagic lesions with reduced diffusion. Cryptococcosis results in gelatinous pseudocyst formation in the basal ganglia. Mucormycosis is characterized by frontal lobe lesions with markedly reduced diffusion. Candidiasis is usually manifest by numerous microabscesses of less than 3 mm occurring at the corticomedullary junction, basal ganglia, or cerebellum. Coccidioidomycosis often results in meningitis with contrast enhancement of the basal cisterns. Blastomycosis and histoplasmosis are rare infections with parenchymal abscesses or meningitis. Recognizing the imaging features of CNS infections allows for early, aggressive treatment of these otherwise rapidly fatal infections.
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Introduction
Fungal central nervous system (CNS) infections are relatively rare and occur almost exclusively in immunocompromised hosts [1]. Aspergillosis, cryptococcosis, mucormycosis, and candidiasis are among the most common ones [2, 3]. Intracranial fungal infections occur through hematogenous spread, infection of cerebrospinal fluid (CSF), or direct extension from sinonasal disease, each route with typical imaging features. Additionally, each organism has typical imaging features that help refine the differential diagnosis, and in some cases, allow specific diagnosis.
Potentially curative treatments for fungal infection include administration of amphotericin B, voriconazole, or other newer agents at high enough doses to cross the blood–brain barrier, correction of any underlying predisposing conditions where possible, and surgical debridement [4–6]. Understanding the imaging appearance of CNS fungal infections is imperative because early diagnosis facilitates early treatment of these otherwise rapidly fatal infections [7]. In this article, we review the magnetic resonance imaging (MRI) appearance of fungal CNS infections.
Clinical Risk Factors
Immunocompromise is the main risk factor for development of CNS fungal infection, and as such, highly virulent fungal infection should be suspected in any immunocompromised patient with neurologic symptoms and signs, especially when acute in onset [1].
Often the immunocompromise is treatment related. Chemotherapy can cause profound neutropenia and immunocompromise. Immunosuppressive therapy in post-transplant patients is also a common cause of immunocompromise. Corticosteroid treatment in patients with autoimmune diseases like inflammatory bowel disease, rheumatoid arthritis, or multiple sclerosis is a commonly overlooked cause of immunosuppression. Other times, reduced immunity is related to intrinsic or extrinsic illness, such as in patients with primary immunodeficiency, lymphoma/leukemia, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), or diabetes. Because immunocompromise may not be a prominent feature of the clinical presentation prompting imaging and may be omitted from the referral indication, evidence of immunocompromise should be specifically sought in any patient with new intracranial lesions that may be infectious.
Aside from immunocompromise, the other major risk factor for specific fungal infections is living in endemic areas. In the USA, the Southwest, Midwest, and Northeast are associated with coccidioidomycosis, blastomycosis, and histoplasmosis, respectively.
Routes of Infection
Fungal infection of the brain occurs most commonly through hematogenous spread, CSF seeding, or direct extension (Fig. 1).
All virulent fungi can hematogenously seed the CNS [7]. Early on, hematogenous spread produces radiologically invisible cerebritis with lack of abscess formation, mostly adjacent to blood vessels, followed by frank abscess formation with reduced diffusion being common. In the disseminated type of infection, mycotic vasculopathy/vasculitis-mediated septic infarction occurs predominately at the gray–white junction (Fig. 1a) or perforating arterial locations with subtle enhancement and heterogeneous reduced diffusion. This anatomic distribution is different from other infarcts, cerebritis, or abscess [8]. Consequently, while the differential diagnosis of single or multiple brain lesions in an immunocompromised patient must include fungal infection along with bacterial infection, septic emboli, multiple infarcts, metastatic disease, and lymphoma, fungal infection can be specifically suggested when lesions occur at the gray–white junction and perforating arterial zones.
Infectious seeding of the CSF is less common and typically occurs with Cryptococcus (Fig. 1b) or Aspergillus. These infections produce variable imaging appearances: enhancing or non-enhancing lesions of the meninges, choroid plexus, or ependyma, hydrocephalus, and/or white matter edema.
Direct intracranial extension from the sinuses occurs with Zygomycetes/Phycomycetes or Aspergillus infection, producing characteristic lesions at the inferior frontal lobes adjacent to the posterior sinuses (Fig. 1c), usually with enhancement and reduced diffusion.
General MRI Features: Heterogenous or Ring Reduced Diffusion and Weak Ring Enhancement
The high viscosity and cellularity of fungal pus leads to reduced diffusion and is often the earliest diagnostic imaging clue to fungal infection, even preceding enhancement (Fig. 2). The reduced diffusion pattern is frequently heterogeneous (Fig. 3a) but may also be ring-like and peripheral, mirroring the post-gadolinium enhancement pattern in larger lesions (Fig. 3b). In smaller lesions, reduced diffusion may be punctate (Fig. 3c). In contrast, bacterial abscesses tend to have a more homogeneous, highly restricting center. Diffusion-weighted imaging (DWI) has important limitations because it cannot reliably differentiate (1) fungal from pyogenic abscess, (2) early cerebritis with edema from late cerebritis with necrosis, or (3) focal infection from small infarct lesions as sequelae of cerebral thromboembolism [9].
In contrast to their often striking reduced diffusion, fungal lesions often demonstrate only a thin rim of peripheral “weak ring” enhancement (Fig. 4a). Pathologic correlation shows marked absence of inflammatory response, which may explain this weak ring appearance (Fig. 4b, c). In our case series, in contrast to weak or absent enhancement in most patients, one patient with recent initiation of short-term steroid treatment and likely little immunocompromise showed relatively robust enhancement more typical of bacterial infections (Fig. 4a) with brisk inflammatory response at the microscopic level (Fig. 4b), supporting the idea that an intact immune system leads to relatively robust enhancement, while the lack of a host response and inflammation may lead to weaker enhancement [10]. In some cases, enhancement may be absent altogether despite large, aggressive lesions (Fig. 2).
Differential Diagnostic MRI Features of Non-fungal Entities
Many entities can have a similar appearance to fungal infection. Table 1 summarizes major differential diagnostic features that may suggest non-fungal entities.
Review of Specific Infections
Aspergillosis
Aspergillus is a saprophytic opportunistic fungus found in soil and on plants. It is a mold on decaying organic material [11]. It has septate (cross-walled) branching hyphae that show dichotomous (i.e., “Y” shaped) branching, and irregular, non-parallel cell walls (Fig. 4b, c). It produces numerous spores. It is not dimorphic. Infections are usually caused by Aspergillus fumigatus.
Risk factors include immunosuppression of any form, although fungal infection in HIV patients is somewhat uncommon because of relative sparing of polymorphonuclear cell function [9]. Patient presentation is variable, but can include altered mental status (AMS), weakness, and seizures. Fevers may or may not be present [12–14]. Mortality rates were near 100 % regardless of therapy in the past but have greatly improved with early aggressive antifungal therapy and surgical resection [2, 3, 9, 13, 15–21]. Voriconazole and amphotericin B are first-line agents, while caspofungin is second line.
Hematogenous spread from the lungs is common [22], but less than half of patients have documented co-existing lung lesions [23].
Aspergillus has a characteristic intermediate to low peripheral T2 signal intensity with central hyperintensity in a target-like pattern (Fig. 5b), likely reflecting increased iron related to peripheral fungal elements, hemorrhage, and possibly due to ferromagnetic elements related to fungal metabolism, including calcium and manganese [10, 24–26].
Aspergillus species are angioinvasive [22]. They produce the enzyme elastase and digest the internal elastic lamina of arteries (all sizes), leading to focal microhemorrhage [27]. Digested, weakened walls also allow mycotic aneurysm formation and subarachnoid hemorrhage, which are common in aspergillosis; their presence should prompt institution of antifungal therapy in immunocompromised patient populations when the clinical picture suggests infection. Fungal elements can also fill vessels, leading to occlusive thrombosis, embolism, and infarction with hemorrhagic transformation (Fig. 5). Likely owing to a predilection for perforating arteries, aspergillosis commonly involves the basal ganglia, thalamus, and corpus callosum. Aspergillus elements at these sites block the origins of small perforating arteries and cause sterile infarction [8]. Because infarction of the corpus callosum is not typically seen in thromboembolic infarction or pyogenic infection, when present, it suggests aspergillosis (Fig. 3c) [8], though this finding is present in a minority of cases [28]. Breakdown of brain tissue at sites of infarction leads to direct fungal extension into surrounding brain [9, 14, 16, 22, 29, 30]. Thus, aspergillus vasculopathy/vasculitis-mediated septic infarction often leads to hemorrhage and rapid extension of infection into the surrounding tissues with associated cerebritis and abscess formation.
The high viscosity and cellularity of Aspergillus pus can lead to reduced diffusion, although infarcted tissue and cerebritis can also contribute to reduced diffusion seen in aspergillosis. Often the lesion center is hypointense on DWI surrounded by hyperintense tissue on DWI with low ADC values, giving a typical ring pattern of reduced diffusion (Fig. 3b). Weak ring or no enhancement is most common [8], and this is an important diagnostic clue [30]. When present, ring enhancement can correlate with capsule formation from chronic inflammation and production of granulation tissue on pathologic examination [7].
Meningitis and ventriculitis are also common though often radiographically occult and only seen with pathologic examination on autopsy [8]. Ependymal enhancement is distinctly uncharacteristic, and often the only clue to meningitis/ventriculitis is hydrocephalus or ventricular asymmetry (Fig. 3c) [8].
Aspergillosis also affects the sinuses and is the most common cause of fungal sinus infection. Like the peripheral low T2 hyperintensity of intracranial lesions, fungal sinusitis has a characteristic low T2 hyperintensity, but diffuse rather than peripheral [10, 24–26]. Intracranial extension (invasive sinus aspergillosis) is often not visible or subtle on MRI in the early stages [3, 13, 19, 31, 32]. When present, intracranial granuloma formation affords poor antifungal penetration because of dense fibrosis [27].
Cryptococcosis
Cryptococcus neoformans is an encapsulated, yeast-like fungus that is found in animal droppings, notably from pigeons and other birds, but also some mammals [11]. Outside of an animal host, C. neoformans forms sexual spores or yeast cells that become dehydrated and weakly encapsulated. The capsule is composed of a high-molecular-weight polysaccharide that, when rehydrated within a host, thickens and gives rise to its macroscopic gelatinous features (Fig. 6) [33].
The strongest risk factor for infection is T-cell dysfunction, namely HIV. However, up to a third of patients have no identifiable pre-existing illness [34]. Patients typically present with AMS, headache, lethargy, or seizures. While untreated infection is always fatal, with treatment, mortality is relatively low compared with other fungal infections, limited to 15–30 % with modern antifungal therapies [33].
The C. neoformans spores in the dehydrated state are small enough to be inhaled and cause an asymptomatic lung infection followed by meningitis. The CNS is thought to be a preferred site of infection because anticryptococcal antibodies are absent there [35].
The brain regions most commonly affected are the basal ganglia and meninges [27, 36]. While meningitis is more common overall, in the basal ganglia, localized pockets of organisms up to several millimeters in size may develop with a pathognomonic appearance of gelatinous pseudocyst formation, known as a cryptococcoma [36, 37]. Gelatinous pseudocysts are T1 hypointense. T2 imaging shows a hypointense ring surrounding a hyperintense center (Fig. 6b). The outer hypointense ring likely represents methemoglobin blood products in the capsule wall or activated macrophages producing free radicals and paramagnetic susceptibility artifact [38]. The pseudocyst center often lacks enhancement owing to its avascular nature (Fig. 6c) and may or may not cause reduced diffusion (Fig. 6d). A large pseudocyst may convert into a frank abscess with enhancement and reduced diffusion.
Mucormycosis
Mucormycosis is caused by molds belonging to the Mucor, Rhizopus, and Absidia genera [39]. These ubiquitous pathogens infect humans through spore inhalation. Within tissue, they grow as non-septate molds and have right-angle branching and irregular, non-parallel cell walls (Fig. 7a) [3, 40]. Like Aspergillus, they are monomorphic.
Risk factors for mucormycosis include diabetes, acidosis, steroid use, hematologic malignancy, solid organ transplantation, neutropenia, and renal failure [40, 41]. Rhino-orbital-cerebral mucormycosis develops when inhaled spores infect the paranasal sinuses and extend into the orbits, optic nerves, oral cavity, and cranium. With CNS involvement, mortality rates are greater than 70 % [40, 41], but early initiation of antifungal agents combined with aggressive surgical resection can improve outcomes [6].
CNS infection almost always involves the frontal lobes (Fig. 7b–d); any lesion of the frontal lobes in an immunocompromised patient, especially in an inferior location, should raise suspicion of mucormycosis (along with aspergillosis). Although lesions may be bilateral, unilateral lesions are also seen. As with aspergillosis, blood vessels become infected with a tendency to cause infarction [27]. Bony erosion is also common.
Lesions have a variable appearance on T2-weighted imaging and can be hypo- to hyperintense (Fig. 8b) [42]. Contrast enhancement of the involved sinuses and orbits is common (Fig. 8c). DWI often shows markedly reduced diffusion (Fig. 7d) [43–46].
Candidiasis
Candida species are small, round to oval, thin-walled, yeast-like fungi that lack a sexual cycle and reproduce by budding or fusion (Fig. 8a) [47]. Pseuodohyphae predominate, but occasionally true hyphae are also seen. While candidal infections are most commonly caused by the albicans species overall, roughly half of infections are caused by other species including Candida glabrata and Candida parasilosis [48].
Risk factors for candidiasis include treatment for bacterial sepsis, intravenous hyperalimentation, HIV infection with low CD4 count (< 135/mm3), immunosuppression, hematologic malignancy, and prematurity [48, 49]. The clinical presentation is variable but generally includes lethargy and AMS with insidious onset. Infection of the CNS is almost always caused by hematogenous spread with disseminated systemic infection. Mortality rates for cerebral candidiasis are unknown but likely high given the high mortality rates for candidal sepsis in general [48, 49, 50].
While frank abscess formation and meningitis do occur [51], numerous microabscesses of less than 3 mm occurring at the corticomedullary junction, basal ganglia, or cerebellum are most common, often with enhancement (Fig. 8b, c) and less often with associated hemorrhage or infarction [52]. The lesions are T1 hypointense and T2 variable. Reduced diffusion is also variable but may be more prominent than enhancement (Fig. 8d). Diagnosis is usually not a dilemma because the patient will usually develop the microabscesses in the setting of known candidal fungemia.
Coccidioidomycosis
Coccidioides immitis is a fungus found in the soil and endemic to the southwestern USA and northern Mexico. It produces spores (Fig. 9a) and is dimorphic [53].
Because the C. immitis is geographically limited to the southwest USA, the strongest risk factor is living in an endemic area. Pulmonary infection is common, while CNS involvement is distinctly uncommon, and only a few cases of CNS infection are reported in the literature [54–56]. Patients usually present with headaches, lethargy, and fevers. CNS involvement is usually secondary to hematogenous dissemination from the lungs.
The meninges is the most common site of infection [53], but parenchymal infection is also seen (Fig. 9b, c). Approximately 4–5 % of symptomatic patients may develop disseminated disease with high morbidity and mortality, with dissemination more common in immunocompromised patients [53].
Contrast enhancement of the basal cisterns is typical in coccidioidomycosis meningitis [54]. DWI with peripheral lesion restriction has been reported [55].
Blastomycosis
Blastomycosis is caused by the dimorphic fungus Blastomyces dermatitidis. It exists as a mold in the environment and a yeast at body temperatures (Fig. 10a) [57].
Infections are usually sporadic. The only recognized risk factor is living in endemic areas of the midwestern USA, classically near the states surrounding the Ohio or Mississippi river [57]. Presentation is non-specific with headache, AMS, fever, vision changes, and seizures. The lungs are affected most often following introduction of spores by inhalation. However, the organism can infect the skin, genitourinary system, and CNS, and isolated CNS infection can be seen in patients with diabetes or immunosuppression [58].
The few available case reports suggest that leptomeningeal enhancement and enhancing mass lesions are common (Fig. 10b) [58, 59]. Reduced diffusion may be central (Fig. 10c).
Histoplasmosis
Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum. Like Blastomycoses, Histoplasma exists as a mold in the environment and yeast at body temperatures (Fig. 11a) [57].
As with Blastomycoses, Histoplasma infections are usually sporadic, and the only consistent risk factor is living in endemic areas of the midwestern USA. Patients with AIDS are prone to developing disseminated histoplasmosis [57], with 5–10 % of cases progressing to CNS involvement. Patients may present with confusion, lethargy, weakness, and fevers [60].
Lesions, also known as “histoplasmomas,” tend to be small (< 2 cm) and round with peripheral ring enhancement (Fig. 11b) [60–63]. Lesions can be singular but are more often multifocal (cerebral histoplasmosis) and may occur in subcortical gray matter structures, the gray–white junction, the cerebellum, the brain stem, or the spinal cord. The lesions are T1 hypointense and T2 variable. Reduced diffusion may show various signals depending on the presence of inflammatory cells and the type of necrosis (e.g., coagulative or liquefactive; Fig. 11c). Diffuse meningitis has also been described [64].
Conclusions
Fungal CNS infections are relatively rare infections that occur almost exclusively in immunocompromised patients. MRI findings such as weak ring enhancement and reduced diffusion can help suggest the diagnosis, with additional features like lesion distribution sometimes enabling specific diagnosis. Recognition of characteristic imaging findings is imperative to enable early treatment of these otherwise rapidly fatal infections.
Conflict of Interest
The authors declare that there are no actual or potential conflicts of interest in relation to this article.
References
de Medeiros BC, de Medeiros CR, Werner B, Neto JZ, Loddo G, Pasquini R, et al. Central nervous system infections following bone marrow transplantation: an autopsy report of 27 cases. J Hematother Stem Cell Res. 2000;9(4):535–40.
Cox J, Murtagh FR, Wilfong A, Brenner J. Cerebral aspergillosis: MR imaging and histopathologic correlation. AJNR Am J Neuroradiol. 1992;13(5):1489–92.
Epstein NE, Hollingsworth R, Black K, Farmer P. Fungal brain abscesses (aspergillosis/mucormycosis) in two immunosuppressed patients. Surg Neurol. 1991;35(4):286–9.
Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med. 1994;330(4):263–72. doi:10.1056/NEJM199401273300407.
Ehrmann S, Bastides F, Gissot V, Mercier E, Magro P, Bailly E, et al. Cerebral aspergillosis in the critically ill: two cases of successful medical treatment. Intensive Care Med. 2005;31(5):738–42. doi:10.1007/s00134-005-2605-5.
Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards J, Jr, Ibrahim AS. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis. 2009;48(12):1743–51. doi:10.1086/599105.
Gaviani P, Schwartz RB, Hedley-Whyte ET, Ligon KL, Robicsek A, Schaefer P, et al. Diffusion-weighted imaging of fungal cerebral infection. AJNR Am J Neuroradiol. 2005;26(5):1115–21. doi:26/5/1115 [pii].
DeLone DR, Goldstein RA, Petermann G, Salamat MS, Miles JM, Knechtle SJ, et al. Disseminated aspergillosis involving the brain: distribution and imaging characteristics. AJNR Am J Neuroradiol. 1999;20(9):1597–604.
Gabelmann A, Klein S, Kern W, Kruger S, Brambs HJ, Rieber-Brambs A, et al. Relevant imaging findings of cerebral aspergillosis on MRI: a retrospective case-based study in immunocompromised patients. Eur J Neurol. 2007;14(5):548–55. doi:10.1111/j.1468-1331.2007.01755.x.
Yamada K, Zoarski GH, Rothman MI, Zagardo MT, Nishimura T, Sun CC. An intracranial aspergilloma with low signal on T2-weighted images corresponding to iron accumulation. Neuroradiology. 2001;43(7):559–61.
Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 7th ed. Philadelphia: Churchill Livingstone; 2010.
Beal MF, O’Carroll CP, Kleinman GM, Grossman RI. Aspergillosis of the nervous system. Neurology. 1982;32(5):473–9.
Jinkins JR, Siqueira E, Al-Kawi MZ. Cranial manifestations of aspergillosis. Neuroradiology. 1987;29(2):181–5.
Walsh TJ, Hier DB, Caplan LR. Aspergillosis of the central nervous system: clinicopathological analysis of 17 patients. Ann Neurol. 1985;18(5):574–82. doi:10.1002/ana.410180511.
Adler CH, Stern MB, Brooks ML. Parkinsonism secondary to bilateral striatal fungal abscesses. Mov Disord. 1989;4(4):333–7. doi:10.1002/mds.870040407.
Ashdown BC, Tien RD, Felsberg GJ. Aspergillosis of the brain and paranasal sinuses in immunocompromised patients: CT and MR imaging findings. AJR Am J Roentgenol. 1994;162(1):155–9.
Goodman ML, Coffey RJ. Stereotactic drainage of Aspergillus brain abscess with long-term survival: case report and review. Neurosurgery. 1989;24(1):96–9.
van der Knaap MS, Valk J, Jansen GH, Kappelle LJ, van Nieuwenhuizen O. Mycotic encephalitis: predilection for grey matter. Neuroradiology. 1993;35(8):567–72.
Shuper A, Levitsky HI, Cornblath DR. Early invasive CNS aspergillosis. An easily missed diagnosis. Neuroradiology. 1991;33(2):183–5.
Miaux Y, Guermazi A, Bourrier P, Singer B, Leder S. MR of cerebral aspergillosis: different patterns in the same patient. AJNR Am J Neuroradiol. 1994;15(6):1193–5.
Coulthard A, Gholkar A, Sengupta RP. Case report: frontal aspergilloma-a complication of paranasal aspergillosis. Clin Radiol. 1991;44(6):425–7.
Miaux Y, Ribaud P, Williams M, Guermazi A, Gluckman E, Brocheriou C, et al. MR of cerebral aspergillosis in patients who have had bone marrow transplantation. AJNR Am J Neuroradiol. 1995;16(3):555–62.
Hagensee ME, Bauwens JE, Kjos B, Bowden RA. Brain abscess following marrow transplantation: experience at the Fred Hutchinson Cancer Research Center, 1984-1992. Clin Infect Dis. 1994;19(3):402–8.
Tempkin AD, Sobonya RE, Seeger JF, Oh ES. Cerebral aspergillosis: radiologic and pathologic findings. Radiographics. 2006;26(4):1239–42. doi:10.1148/rg.264055152.
Breadmore R, Desmond P, Opeskin K. Intracranial aspergillosis producing cavernous sinus syndrome and rupture of internal carotid artery. Australas Radiol. 1994;38(1):72–5.
Zinreich SJ, Kennedy DW, Malat J, Curtin HD, Epstein JI, Huff LC, et al. Fungal sinusitis: diagnosis with CT and MR imaging. Radiology. 1988;169(2):439–44.
Sundaram C, Umabala P, Laxmi V, Purohit AK, Prasad VS, Panigrahi M, et al. Pathology of fungal infections of the central nervous system: 17 years’ experience from Southern India. Histopathology. 2006;49(4):396–405. doi:10.1111/j.1365-2559.2006.02515.x.
da Rocha AJ, Maia AC, Jr, Ferreira NP, do Amaral LL. Granulomatous diseases of the central nervous system. Top Magn Reson Imaging. 2005;16(2):155–87. doi:00002142-200504000-00004 [pii].
Hurst RW, Judkins A, Bolger W, Chu A, Loevner LA. Mycotic aneurysm and cerebral infarction resulting from fungal sinusitis: imaging and pathologic correlation. AJNR Am J Neuroradiol. 2001;22(5):858–63.
Charlot M, Pialat JB, Obadia N, Boibieux A, Streichenberger N, Meyronnet D, et al. Diffusion-weighted imaging in brain aspergillosis. Eur J Neurol. 2007;14(8):912–6. doi:10.1111/j.1468-1331.2007.01874.x.
Hartwick RW, Batsakis JG. Sinus aspergillosis and allergic fungal sinusitis. Ann Otol Rhinol Laryngol. 1991;100(5 Pt. 1):427–30.
Schwartz S, Thiel E. Update on the treatment of cerebral aspergillosis. Ann Hematol. 2004;83(Suppl. 1):S42–4. doi:10.1007/s00277-004-0849-8.
Buchanan KL, Murphy JW. What makes Cryptococcus neoformans a pathogen? Emerg Infect Dis. 1998;4(1):71–83. doi:10.3201/eid0401.980109.
Aharon-Peretz J, Kliot D, Finkelstein R, Ben Hayun R, Yarnitsky D, Goldsher D. Cryptococcal meningitis mimicking vascular dementia. Neurology. 2004;62(11):2135.
Igel HJ, Bolande RP. Humoral defense mechanisms in cryptococcosis: substances in normal human serum, saliva, and cerebrospinal fluid affecting the growth of Cryptococcus neoformans. J Infect Dis. 1966;116(1):75–83.
Caldemeyer KS, Mathews VP, Edwards-Brown MK, Smith RR. Central nervous system cryptococcosis: parenchymal calcification and large gelatinous pseudocysts. AJNR Am J Neuroradiol. 1997;18(1):107–9.
Garcia CA, Weisberg LA, Lacorte WS. Cryptococcal intracerebral mass lesions: CT-pathologic considerations. Neurology. 1985;35(5):731–4.
Haimes AB, Zimmerman RD, Morgello S, Weingarten K, Becker RD, Jennis R, et al. MR imaging of brain abscesses. AJR Am J Roentgenol. 1989;152(5):1073–85.
Ibrahim AS, Edwards JE, Filler SG, Spellberg B. Mucormycosis and entomophthoramycosis (zygomycosis). In: Kauffman CA, Pappas PG, Sobel JD, Dismukes WE, editors. Essentials of clinical mycology. New York: Springer; 2011. pp. 265–80.
Almyroudis NG, Sutton DA, Linden P, Rinaldi MG, Fung J, Kusne S. Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature. Am J Transplant. 2006;6(10):2365–74. doi:10.1111/j.1600-6143.2006.01496.x.
Sun HY, Forrest G, Gupta KL, Aguado JM, Lortholary O, Julia MB, et al. Rhino-orbital-cerebral zygomycosis in solid organ transplant recipients. Transplantation. 2010;90(1):85–92.
Chan LL, Singh S, Jones D, Diaz EM, Jr, Ginsberg LE. Imaging of mucormycosis skull base osteomyelitis. AJNR Am J Neuroradiol. 2000;21(5):828–31.
Safder S, Carpenter JS, Roberts TD, Bailey N. The “Black Turbinate” sign: an early MR imaging finding of nasal mucormycosis. AJNR Am J Neuroradiol. 2010;31(4):771–4. doi:10.3174/ajnr.A1808.
Mathur S, Karimi A, Mafee MF. Acute optic nerve infarction demonstrated by diffusion-weighted imaging in a case of rhinocerebral mucormycosis. AJNR Am J Neuroradiol. 2007;28(3):489–90.
Hatipoglu HG, Gurbuz MO, Yuksel E. Restricted diffusion in the optic nerve and retina demonstrated by MRI in rhino-orbital mucormycosis. J Neuroophthalmol. 2009;29(1):13–5. doi:10.1097/WNO.0b013e318183bde4.
Horger M, Hebart H, Schimmel H, Vogel M, Brodoefel H, Oechsle K, et al. Disseminated mucormycosis in haematological patients: CT and MRI findings with pathological correlation. Br J Radiol. 2006;79(945):e88–95. doi:79/945/e88.
Vazquez JA, Sobel JD. Candidiasis. In: Kauffman CA, Pappas PG, Sobel JD, Dismukes WE, editors. Essentials of clinical mycology. New York: Springer; 2011. pp. 167–206.
Horn DL, Neofytos D, Anaissie EJ, Fishman JA, Steinbach WJ, Olyaei AJ, et al. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis. 2009;48(12):1695–703. doi:10.1086/599039.
Parker JC, Jr, McCloskey JJ, Lee RS. Human cerebral candidosis-a postmortem evaluation of 19 patients. Hum Pathol. 1981;12(1):23–8.
Benjamin DK, Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD, et al. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics. 2006;117(1):84–92. doi:10.1542/peds.2004-2292.
Pendlebury WW, Perl DP, Munoz DG. Multiple microabscesses in the central nervous system: a clinicopathologic study. J Neuropathol Exp Neurol. 1989;48(3):290–300.
Lai PH, Lin SM, Pan HB, Yang CF. Disseminated miliary cerebral candidiasis. AJNR Am J Neuroradiol. 1997;18(7):1303–6.
Ampel NM. Coccidioidomycosis. In: Kauffman CA, Pappas PG, Sobel JD, Dismukes WE, editors. Essentials of clinical mycology. New York: Springer; 2011. pp. 349–66.
Banuelos AF, Williams PL, Johnson RH, Bibi S, Fredricks DN, Gilroy SA, et al. Central nervous system abscesses due to Coccidioides species. Clin Infect Dis. 1996;22(2):240–50.
Castro S, Bernardes I. Coccidioidal cerebral abscess with peripheral restricted diffusion. J Neuroradiol. 2009;36(3):162–4. doi:10.1016/j.neurad.2008.12.003.
Mendel E, Milefchik EN, Amadi J, Gruen P. Coccidioidomycosis brain abscess. Case report. J Neurosurg. 1994;81(4):614–6. doi:10.3171/jns.1994.81.4.0614.
Bradsher RW, Bariola JR. Blastomycosis. In: Kauffman CA, Pappas PG, Sobel JD, Dismukes WE, editors. Essentials of clinical mycology. New York: Springer; 2011. pp. 337–48.
Bariola JR, Perry P, Pappas PG, Proia L, Shealey W, Wright PW, et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis. 2010;50(6):797–804. doi:10.1086/650579.
Szeder V, Ortega-Gutierrez S, Frank M, Jaradeh SS. CNS blastomycosis in a young man working in fields after Hurricane Katrina. Neurology. 2007;68(20):1746–7. doi:10.1212/01.wnl.0000265229.31844.45.
Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis. 2005;40(6):844–52. doi:10.1086/427880.
Tabbal SD, Harik SI. Images in clinical medicine. Cerebral histoplasmosis. N Engl J Med. 1999;340(15):1176. doi:10.1056/NEJM199904153401506.
Saccente M, McDonnell RW, Baddour LM, Mathis MJ, Bradsher RW. Cerebral histoplasmosis in the azole era: report of four cases and review. South Med J. 2003;96(4):410–6.
Vos MJ, Debets-Ossenkopp YJ, Claessen FA, Hazenberg GJ, Heimans JJ. Cerebellar and medullar histoplasmosis. Neurology. 2000;54(7):1441.
Levi GC, Pozzi CM, Hirschheimer SM, Chahade WH, Gomes HR, Granato C. [Central nervous system involvement by histoplasmosis as the unique manifestation of this disease in immunocompetent patients: presentation of two cases]. Arq Neuropsiquiatr. 2003;61(3B):859–63.
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Starkey, J., Moritani, T. & Kirby, P. MRI of CNS Fungal Infections: Review of Aspergillosis to Histoplasmosis and Everything in Between. Clin Neuroradiol 24, 217–230 (2014). https://doi.org/10.1007/s00062-014-0305-7
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DOI: https://doi.org/10.1007/s00062-014-0305-7