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Isolated central nervous system aspergillosis in the acquired immunodeficiency syndrome
Isolated central nervous system aspergillosis in the acquired immunodeficiency syndrome E n r i q u e J. Carrazana*, E u g e n e Rossitch Jr.* *, and James Morris* * *
Introduction A significant proportion of cases diagnosed with the acquired immunodeficiency syndrome (AIDS) initially present with infections of the central nervous system (CNS). Among the many microorganisms responsible for these infections, Toxoplasma gondii, Cryptococcus neoformans, and Mycobacterium species are the most common 2. However, unusual pathogens are to be expected in the immunocompromised host. The large number of possible microorganisms to account for CNS infections in AIDS, makes succesful intervention, ie. rapid establishment of the diagnosis and prompt initiation of specific antimicrobial therapy, a difficult task. To our knowledge, only a handful of CNS aspergillosis cases in AIDS patients have been reported in the literature 3-6. The majority of these patients developed focal neurologic signs secondary to an aspergillus brain abscess. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis.
Case Report The patient was forty four year old bisexual male with a prior history of Pneumocystis carnii pneumonia, and human immunodeficiency vi-
Summary Aspergillus infection involving the central nervous system are unusual, but should be included in the differential diagnosis in patients with the acquired immunodeficiency syndrome and neurologic signs and symptoms. Of the few reported AIDS cases with central nervous system aspergillosis, the majority have had focal brain abscesses. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis. Key words: Acquired immunodeficiency syndrome (AIDS), central nervous system (CNS), aspergillus
rus (HIV)-related cardiomyopathy, who was admitted for evaluation of a one week history of exacerbation of a chronic headache (negative studies in the past, including magnetic resonance imaging and cerebrospinal fluid analysis), accompanied by nausea, fever, and difficulty walking. On physical examination, he had a low grade fever, benign fundi, mild nuchal rigidity, a systolic murmur with gallop, hepatomegaly, and a subtle right hemiparesis and right extensor plantar response. A computerized tomography (CT) study of the head revealed slight increased left sphenoid sinus opacification. CSF analysis showed a lymphocytic pleocytosis (196 cells/
* Divisions of Neurology* and Neurosurgery,** Department of Pathology***, Brighamand Women'sHospital, 75 Francis Street, Boston,MA 02115, USA. Address for correspondence and reprint requests: Enrique J. Carrazana, M.D., Baptist Medical Art Building, Office nr. 501, 8950 North Kendall Drive, Miami, Florida 33176, USA. Accepted 7-6-90 Clin Neurol Neurosurg 1991. Vol. 93-3
227
mm3), increased protein (96 mg/dl) and decreased glucose (28 mg/dl). Because of the possibility of bacterial meningitis the patient was placed on broad-spectrum antibiotics; however, the cerebrospinal fluid cultures were sterile. His neurological status progressively deteriorated with worsening of the right-sided hemiparesis, seizures, and eventual coma with decerebrate posturing. Repeat head CT revealed a left sphenoid sinusitis with rupture of the sinus into the suprasellar area. The patient expired of a cardiac arrest prior to diagnostic intervention. At autopsy there was turbid, purulent exudate mainly along the suprasellar region, and erosion of the roof of the left sphenoid sinus. Coalescent nodular thickening of the sphenoid sinus mucosa was noted. The leptomeninges showed mild diffuse thickening, particularly along the brainstem with multiple whitish nodular lesions over the basis pontis, measuring ap-
proximately 0.3 cm in diameter on the average (figure 1). Transverse sectioning through the brainstem showed extensive recent anaemic infarction of the pons. No other focal lesions were evident in sectioning of the cerebral hemipheres and cerebellum. There was neither pulmonary nor cardiac involvement by Aspergillus. Microscopic sections through the sella tursica and sphenoid sinuses revealed abundant fungal hyphae in colonies involving the wall of the sinuses and penetrating through the mucosa. Clusters of hyphae were also seen bordering the adjacent cavernous sinuses with no evidence of vasculitis nor invasion within the latter. Microscopic sections of the pons showed extension acute, anaemic infarction with florid overlying meningeal infiltration with branched septated hyphal forms and fungal arteritis and thrombosis of the basilar artery as well as several of the penetrating arteries (figure 2). The morphology
Figure 1: A view of the brainstem at autopsy showing thickening of the leptomeninges with multiple whitish nodular lesions measuring approximately 0.3 cm in diameter on the average, covering the basis pontis. The course of the basilar artery and its branches is obscured by the leptomeningeal deposits.
Figure 2: Microscopic section of the basilar artery showing branched septated hyphal forms of AspergiUus fumigatus invading the arterial wall. Haematoxylin and Eosin (x 40).
228
of the fungal hyphae was consistent with Aspergillus species and culture of the cerebrospinal fluid at the time of autopsy grew A. fumigatus. Discussion
Aspergillus species are common saprophytes, particularly abundant in soil and decaying vegetation. Few, however, are pathogenic for man 7. A. fumigatus and A. flavus are the most common offenders in reported cases of Aspergillosis8. Pathogenic aspergilli produce large numbers of aerially dispersed spores which gain access to the host's respiratory and gastrointestinal tracts. Invasion of the CNS occurs either by the hematogenous route from a pulmonary orgastrointestinal focus, by clinical extension from an anatomically adjacent site, or by direct infection after head trauma or surgical procedures 9. Direct bloodstream innoculation with viable fungal spores may also be an entry route. Aspergillus spores are known contaminants of illicit drugs, particularly heroin 1~ This parenteral drug abusers, a high risk group for AIDS, are also susceptible to the introduction of spores into the bloodstream. In reference to Aspergillus sinus involvement, two basic forms have been described: 1. a benign non-infiltrative aspergillus fungus ball, that usually presents like bacterial sinusitis; and 2. an invasive sinusitis which extends into bone and orbital tissues, often eroding into the CNS 12'13. Aspergillus most often involves the ethmoid sinuses ~3, and isolated sphenoid sinus involvement is unusual 14. Erosion of the roof of the sphenoid sinus was the entry point that lead to subsequent Aspergillus meningoencephalitis in our case. Clinical presentations of aspergillus CNS infection is variable, including meningitis ~5, meningeoencephalitis 16, abscess formation 17, granulomatous reactions TM,and arachnoiditis 19. Single Aspergillum brain abscesses are more commonly located in the frontal and temporal lobes, perhaps due to their anatomical location in relation to the paranasal sinuses. In contrast, the posterior circulation is favored by the hematogenous spread, and multiple lesions are often found 7. Granulomatous reactions are rare and generally seen in those patients who have had aspergillosis for a prolonged period of time 7.
This case is unusual in that Aspergillus rarely produces meningitis in the absence of brain abscess 15. Perhaps, the severely immunocompromised status of AIDS patients favors more aggressive presentations. Of the few AIDS cases reported with CNS aspergillosis, cerebral lesions predominate 36, with one case of spinal cord involvement 6. The majority of AIDS cases with aspergillus brain abscesses initially presented with fever and headaches as the initial complaint, with focal neurological signs and mental status changes developing weeks later. This is in contrast to our case of Aspergillus meningitis in AIDS, in which the onset of meningeal signs was rapidly followed by progressing neurological deficits and death; due to the organism's affinity for blood vessels. Aspergillus is typically vasocentric and necrotizing vasculitis is a typical finding on autopsy in cases of CNS aspergillosis 2~ Moreover, due to vascular occlusions, infarcts, either bland or septic, are common; subarachnoid hemorrhage may also occur s. Our patient's demise was the result of mycotic involvement of the basilar artery and its pontine penetrating branches, and an anaemic infarction of the pons. The diagnosis of CNS aspergillosis is difficult to establish. In most reported cases it was made late in the illness course or at autopsy. The experience with cerebrospinal fluid (CSF) examination is variable 6~ The CSF in our patient showed a lymphocytic pleocytosis, increased protein, hypoglycorrhachia, and sterile cultures. Aspergillus is difficult to recover from pre-mortem specimens of CSF 7,9. Our CSF findings contrast with those of other AIDS-related CNS aspergillosis cases, in which normal CSF or slight elevation of protein have been reported. The pathologic form of aspergillus CNS infection accounts for this difference. Cerebral abscess or granulomas have little or no accompanying meningeal involvement 7-9. Serologic tests for aspergillus are available 21, but their usefulness remains to be proven. Isolation of Aspergillus organisms from sites outside of the nervous system might obviate the need from brain biopsy. In this respect, radiological studies will be useful by disclosing pulmonary infiltrates or paranasal sinus involvement. The prognosis of CNS aspergillosis in AIDS patients is dismal, even if the diagnosis is estab229
lished ante mortem 6. In part this is due to the low efficacy of antifungal drugs, such as amphotericin B in combination with 5-fluorocytosine against Aspergillus. Also, the refractory nature of CNS infections to antibiotic therapy has been observed in AIDS patients, suggesting that the immunocompromised status hinders therpeutic response to antimicrobial medication 22. Surgical resection of single aspergillus cerebral lesions in addition to medical therapy has been reported to be of some success in the immuno-competent patient s,23. Isolated CNS aspergillosis is a difficult to diagnose, in part because of its rare occurrence. An awareness by clinicians of alternative and unusual CNS pathogens in AIDS patients is crucial in establishing the diagnosis.
2
3
4
5
6
7
8
LEVY RM, BREDESEN DE, ROSENBLUM ML.
Neurological
manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg. 1985; 62:475-495. C A R R AZ AN A E3~ ROSS1TCH E JR, SAMUELS MA. Cerebral toxoplasmosis in the acquired immune deficiency syndrome. Clin Neuro Neurosurg. 1989; 91:291-301. BERGER JR~ MOSKOWITZ L~ F1SCHL M, KELLEY RE. The neurologic complications of AIDS: frequently the initial manifestation. Neurology 1984; 34 (Suppl 1): 134. NIEDT GW, SCHINELLA RA. Acquired immunodeficiency syndrome: clinicopathologic study of 56 autopsies. Arch Pathol Lab Med, 1985; 109:727-734, LAULUND S, VISFELDT J, KLINKEN L. Patho-anatomical studies in patients dying of AIDS. Acta Pathol Microbiol Immunol Scand A. 1986; 94:201-221. WOODS GL, GOLDSMITH JC. Aspergillus infection of the central nervous system in patients with AIDS. Arch Neurol. 1990; 47:181-184. SALAKI JS, LOURIA DB, CAMEL H. Fungal and yeast infections of the central nervous system-a clinical review. Medicine. 1984; 63:108-132. WILES CM, MACKENZIE DWR. Fungal diseases of the cen-
230
10
11
12 13 14
15 t6
17
References 1
9
18
19
tral nervous system. In: KENNEDYPGE, JOHNSONRT, eds. Infections of the Nervous System. London, UK: Butterworths; 1987:99-102. YOUNG RC, BENNETI" JE, V O G E L CL, et al. Aspergillosis: the spectrum of the disease in 98 patients. Medicine. 1970; 49:147-173. T U A Z O N CV, HILL R, SHEAJREN JL. Microbiologic study of street heroin and injection paraphernalia. J Infect Dis. 1974; 129:327-329. MORROW R, WONG B, FINKELSTEIN WE, et al. Aspergillosis of the cerebral ventricles in a heroin abuser. Arch Intern Med. 1983; 143:161-164. HORA JF. Primary aspergillosis of the paranasal sinuses and associated areas. Laryngoscope. 1965; 75:768-73. RINALDI MG. Invasive aspergillosis. Reviews of Infectious Diseases. 1983; 5:1061-1077. SOOD, VP, GOYAL NK, ALEROL BM. Aspergillosis of sphenoid sinus. Eye Ear Nose Throat Monthly. 1975; 54:454457. GORDONMA, HOLZMANRS, SENTER H, et al. Aspergillus oryzae meningitis. JAMA. 1976; 235:2122-2123. UYERS, DODGE PR, ADAMSRD. TWO cases of aspergillus infection of the central nervous system. J Neurol Neurosurg Psychiat. 1952; 15:152. MUKOYAMA M, GIMPLE K, POSER CM. Aspergillosis of the CNS. Report of a brain abscess due to A. fumigatus and review of the literature. Neurology. 1969; 19:967-974. LINARESS G , MCGARRY PA, BAKER RD. Solid solitary Aspergillotic granuloma of the brain. Report of a case due to A. candidus and review of the literature. Neurology. 1971; 21:177-184. STEIN SC~ CORRADO ML~ FRIEDLANDER M~ FARMER P.
Chronic mycotic meningitis with spinal involvement (arachnoiditis): a report of five cases. An Neurol. 1982; 11:519-524. 20
21
22
MCCORMICK WF~ SCHOCHET SS, WEAVER PR~ MCCRARY JA
nl. Disseminated Aspergillosis: Aspergiilus endophthalmitis, optic nerve infarction and carotid artery thrombosis. Arch Pathol. 1975; 99:353-359. FISHER BD~ ARMSTRONG D, YU B, GOLD JWM. Invasive aspergillosis: progress in early diagnosis and treatment. An J Med. 1981; 71:571-577. LEVY RM, PONS VG, ROSENBLUM ML. I N T RA CE RE BRA L MASS LESIONS IN T H E ACQUIRED IMMUNODEFICIENCY SYN-
(AIDS). N ENGL J MED. 1983; 309:1954-1955. Primary pituitary aspergillosis responding to transphenoidal surgery and combined therapy with amphoteriein B and 5-Fluorocytosine. J Neurosurg. 1981; 54:839-841. DROME
23
RAMOS-GABATIN A, JORDAN RM.
Introduction A significant proportion of cases diagnosed with the acquired immunodeficiency syndrome (AIDS) initially present with infections of the central nervous system (CNS). Among the many microorganisms responsible for these infections, Toxoplasma gondii, Cryptococcus neoformans, and Mycobacterium species are the most common 2. However, unusual pathogens are to be expected in the immunocompromised host. The large number of possible microorganisms to account for CNS infections in AIDS, makes succesful intervention, ie. rapid establishment of the diagnosis and prompt initiation of specific antimicrobial therapy, a difficult task. To our knowledge, only a handful of CNS aspergillosis cases in AIDS patients have been reported in the literature 3-6. The majority of these patients developed focal neurologic signs secondary to an aspergillus brain abscess. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis.
Case Report The patient was forty four year old bisexual male with a prior history of Pneumocystis carnii pneumonia, and human immunodeficiency vi-
Summary Aspergillus infection involving the central nervous system are unusual, but should be included in the differential diagnosis in patients with the acquired immunodeficiency syndrome and neurologic signs and symptoms. Of the few reported AIDS cases with central nervous system aspergillosis, the majority have had focal brain abscesses. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis. Key words: Acquired immunodeficiency syndrome (AIDS), central nervous system (CNS), aspergillus
rus (HIV)-related cardiomyopathy, who was admitted for evaluation of a one week history of exacerbation of a chronic headache (negative studies in the past, including magnetic resonance imaging and cerebrospinal fluid analysis), accompanied by nausea, fever, and difficulty walking. On physical examination, he had a low grade fever, benign fundi, mild nuchal rigidity, a systolic murmur with gallop, hepatomegaly, and a subtle right hemiparesis and right extensor plantar response. A computerized tomography (CT) study of the head revealed slight increased left sphenoid sinus opacification. CSF analysis showed a lymphocytic pleocytosis (196 cells/
* Divisions of Neurology* and Neurosurgery,** Department of Pathology***, Brighamand Women'sHospital, 75 Francis Street, Boston,MA 02115, USA. Address for correspondence and reprint requests: Enrique J. Carrazana, M.D., Baptist Medical Art Building, Office nr. 501, 8950 North Kendall Drive, Miami, Florida 33176, USA. Accepted 7-6-90 Clin Neurol Neurosurg 1991. Vol. 93-3
227
mm3), increased protein (96 mg/dl) and decreased glucose (28 mg/dl). Because of the possibility of bacterial meningitis the patient was placed on broad-spectrum antibiotics; however, the cerebrospinal fluid cultures were sterile. His neurological status progressively deteriorated with worsening of the right-sided hemiparesis, seizures, and eventual coma with decerebrate posturing. Repeat head CT revealed a left sphenoid sinusitis with rupture of the sinus into the suprasellar area. The patient expired of a cardiac arrest prior to diagnostic intervention. At autopsy there was turbid, purulent exudate mainly along the suprasellar region, and erosion of the roof of the left sphenoid sinus. Coalescent nodular thickening of the sphenoid sinus mucosa was noted. The leptomeninges showed mild diffuse thickening, particularly along the brainstem with multiple whitish nodular lesions over the basis pontis, measuring ap-
proximately 0.3 cm in diameter on the average (figure 1). Transverse sectioning through the brainstem showed extensive recent anaemic infarction of the pons. No other focal lesions were evident in sectioning of the cerebral hemipheres and cerebellum. There was neither pulmonary nor cardiac involvement by Aspergillus. Microscopic sections through the sella tursica and sphenoid sinuses revealed abundant fungal hyphae in colonies involving the wall of the sinuses and penetrating through the mucosa. Clusters of hyphae were also seen bordering the adjacent cavernous sinuses with no evidence of vasculitis nor invasion within the latter. Microscopic sections of the pons showed extension acute, anaemic infarction with florid overlying meningeal infiltration with branched septated hyphal forms and fungal arteritis and thrombosis of the basilar artery as well as several of the penetrating arteries (figure 2). The morphology
Figure 1: A view of the brainstem at autopsy showing thickening of the leptomeninges with multiple whitish nodular lesions measuring approximately 0.3 cm in diameter on the average, covering the basis pontis. The course of the basilar artery and its branches is obscured by the leptomeningeal deposits.
Figure 2: Microscopic section of the basilar artery showing branched septated hyphal forms of AspergiUus fumigatus invading the arterial wall. Haematoxylin and Eosin (x 40).
228
of the fungal hyphae was consistent with Aspergillus species and culture of the cerebrospinal fluid at the time of autopsy grew A. fumigatus. Discussion
Aspergillus species are common saprophytes, particularly abundant in soil and decaying vegetation. Few, however, are pathogenic for man 7. A. fumigatus and A. flavus are the most common offenders in reported cases of Aspergillosis8. Pathogenic aspergilli produce large numbers of aerially dispersed spores which gain access to the host's respiratory and gastrointestinal tracts. Invasion of the CNS occurs either by the hematogenous route from a pulmonary orgastrointestinal focus, by clinical extension from an anatomically adjacent site, or by direct infection after head trauma or surgical procedures 9. Direct bloodstream innoculation with viable fungal spores may also be an entry route. Aspergillus spores are known contaminants of illicit drugs, particularly heroin 1~ This parenteral drug abusers, a high risk group for AIDS, are also susceptible to the introduction of spores into the bloodstream. In reference to Aspergillus sinus involvement, two basic forms have been described: 1. a benign non-infiltrative aspergillus fungus ball, that usually presents like bacterial sinusitis; and 2. an invasive sinusitis which extends into bone and orbital tissues, often eroding into the CNS 12'13. Aspergillus most often involves the ethmoid sinuses ~3, and isolated sphenoid sinus involvement is unusual 14. Erosion of the roof of the sphenoid sinus was the entry point that lead to subsequent Aspergillus meningoencephalitis in our case. Clinical presentations of aspergillus CNS infection is variable, including meningitis ~5, meningeoencephalitis 16, abscess formation 17, granulomatous reactions TM,and arachnoiditis 19. Single Aspergillum brain abscesses are more commonly located in the frontal and temporal lobes, perhaps due to their anatomical location in relation to the paranasal sinuses. In contrast, the posterior circulation is favored by the hematogenous spread, and multiple lesions are often found 7. Granulomatous reactions are rare and generally seen in those patients who have had aspergillosis for a prolonged period of time 7.
This case is unusual in that Aspergillus rarely produces meningitis in the absence of brain abscess 15. Perhaps, the severely immunocompromised status of AIDS patients favors more aggressive presentations. Of the few AIDS cases reported with CNS aspergillosis, cerebral lesions predominate 36, with one case of spinal cord involvement 6. The majority of AIDS cases with aspergillus brain abscesses initially presented with fever and headaches as the initial complaint, with focal neurological signs and mental status changes developing weeks later. This is in contrast to our case of Aspergillus meningitis in AIDS, in which the onset of meningeal signs was rapidly followed by progressing neurological deficits and death; due to the organism's affinity for blood vessels. Aspergillus is typically vasocentric and necrotizing vasculitis is a typical finding on autopsy in cases of CNS aspergillosis 2~ Moreover, due to vascular occlusions, infarcts, either bland or septic, are common; subarachnoid hemorrhage may also occur s. Our patient's demise was the result of mycotic involvement of the basilar artery and its pontine penetrating branches, and an anaemic infarction of the pons. The diagnosis of CNS aspergillosis is difficult to establish. In most reported cases it was made late in the illness course or at autopsy. The experience with cerebrospinal fluid (CSF) examination is variable 6~ The CSF in our patient showed a lymphocytic pleocytosis, increased protein, hypoglycorrhachia, and sterile cultures. Aspergillus is difficult to recover from pre-mortem specimens of CSF 7,9. Our CSF findings contrast with those of other AIDS-related CNS aspergillosis cases, in which normal CSF or slight elevation of protein have been reported. The pathologic form of aspergillus CNS infection accounts for this difference. Cerebral abscess or granulomas have little or no accompanying meningeal involvement 7-9. Serologic tests for aspergillus are available 21, but their usefulness remains to be proven. Isolation of Aspergillus organisms from sites outside of the nervous system might obviate the need from brain biopsy. In this respect, radiological studies will be useful by disclosing pulmonary infiltrates or paranasal sinus involvement. The prognosis of CNS aspergillosis in AIDS patients is dismal, even if the diagnosis is estab229
lished ante mortem 6. In part this is due to the low efficacy of antifungal drugs, such as amphotericin B in combination with 5-fluorocytosine against Aspergillus. Also, the refractory nature of CNS infections to antibiotic therapy has been observed in AIDS patients, suggesting that the immunocompromised status hinders therpeutic response to antimicrobial medication 22. Surgical resection of single aspergillus cerebral lesions in addition to medical therapy has been reported to be of some success in the immuno-competent patient s,23. Isolated CNS aspergillosis is a difficult to diagnose, in part because of its rare occurrence. An awareness by clinicians of alternative and unusual CNS pathogens in AIDS patients is crucial in establishing the diagnosis.
2
3
4
5
6
7
8
LEVY RM, BREDESEN DE, ROSENBLUM ML.
Neurological
manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg. 1985; 62:475-495. C A R R AZ AN A E3~ ROSS1TCH E JR, SAMUELS MA. Cerebral toxoplasmosis in the acquired immune deficiency syndrome. Clin Neuro Neurosurg. 1989; 91:291-301. BERGER JR~ MOSKOWITZ L~ F1SCHL M, KELLEY RE. The neurologic complications of AIDS: frequently the initial manifestation. Neurology 1984; 34 (Suppl 1): 134. NIEDT GW, SCHINELLA RA. Acquired immunodeficiency syndrome: clinicopathologic study of 56 autopsies. Arch Pathol Lab Med, 1985; 109:727-734, LAULUND S, VISFELDT J, KLINKEN L. Patho-anatomical studies in patients dying of AIDS. Acta Pathol Microbiol Immunol Scand A. 1986; 94:201-221. WOODS GL, GOLDSMITH JC. Aspergillus infection of the central nervous system in patients with AIDS. Arch Neurol. 1990; 47:181-184. SALAKI JS, LOURIA DB, CAMEL H. Fungal and yeast infections of the central nervous system-a clinical review. Medicine. 1984; 63:108-132. WILES CM, MACKENZIE DWR. Fungal diseases of the cen-
230
10
11
12 13 14
15 t6
17
References 1
9
18
19
tral nervous system. In: KENNEDYPGE, JOHNSONRT, eds. Infections of the Nervous System. London, UK: Butterworths; 1987:99-102. YOUNG RC, BENNETI" JE, V O G E L CL, et al. Aspergillosis: the spectrum of the disease in 98 patients. Medicine. 1970; 49:147-173. T U A Z O N CV, HILL R, SHEAJREN JL. Microbiologic study of street heroin and injection paraphernalia. J Infect Dis. 1974; 129:327-329. MORROW R, WONG B, FINKELSTEIN WE, et al. Aspergillosis of the cerebral ventricles in a heroin abuser. Arch Intern Med. 1983; 143:161-164. HORA JF. Primary aspergillosis of the paranasal sinuses and associated areas. Laryngoscope. 1965; 75:768-73. RINALDI MG. Invasive aspergillosis. Reviews of Infectious Diseases. 1983; 5:1061-1077. SOOD, VP, GOYAL NK, ALEROL BM. Aspergillosis of sphenoid sinus. Eye Ear Nose Throat Monthly. 1975; 54:454457. GORDONMA, HOLZMANRS, SENTER H, et al. Aspergillus oryzae meningitis. JAMA. 1976; 235:2122-2123. UYERS, DODGE PR, ADAMSRD. TWO cases of aspergillus infection of the central nervous system. J Neurol Neurosurg Psychiat. 1952; 15:152. MUKOYAMA M, GIMPLE K, POSER CM. Aspergillosis of the CNS. Report of a brain abscess due to A. fumigatus and review of the literature. Neurology. 1969; 19:967-974. LINARESS G , MCGARRY PA, BAKER RD. Solid solitary Aspergillotic granuloma of the brain. Report of a case due to A. candidus and review of the literature. Neurology. 1971; 21:177-184. STEIN SC~ CORRADO ML~ FRIEDLANDER M~ FARMER P.
Chronic mycotic meningitis with spinal involvement (arachnoiditis): a report of five cases. An Neurol. 1982; 11:519-524. 20
21
22
MCCORMICK WF~ SCHOCHET SS, WEAVER PR~ MCCRARY JA
nl. Disseminated Aspergillosis: Aspergiilus endophthalmitis, optic nerve infarction and carotid artery thrombosis. Arch Pathol. 1975; 99:353-359. FISHER BD~ ARMSTRONG D, YU B, GOLD JWM. Invasive aspergillosis: progress in early diagnosis and treatment. An J Med. 1981; 71:571-577. LEVY RM, PONS VG, ROSENBLUM ML. I N T RA CE RE BRA L MASS LESIONS IN T H E ACQUIRED IMMUNODEFICIENCY SYN-
(AIDS). N ENGL J MED. 1983; 309:1954-1955. Primary pituitary aspergillosis responding to transphenoidal surgery and combined therapy with amphoteriein B and 5-Fluorocytosine. J Neurosurg. 1981; 54:839-841. DROME
23
RAMOS-GABATIN A, JORDAN RM.