neurology

1. FUNGAL DISEASES OF CNS
Dr. Sunil Kumar Sharma
Senior Resident
Dept. of Neurology
GMC Kota

2. INTRODUCTION
▪ Eukaryotic organisms
▪ Develop from spores.
Yeast
• Candida,
• Cryptococcus
• Trichosporon
Filamentous
• Aspergillus
• Rhizopus,
• Mucor
Dimorphic Fungi
• Blastomyces
• Histoplasma,
• Coccidoides
• Paracoccidoides

3. INTRODUCTION …
▪ Only a small group is pathogenic.
▪ CNS infections - rare .
▪ Immunocompromised pt. - higher risk .
▪ Some fungi can infect immunocompetent hosts as well
(e.g.-Coccidioidomycosis and Aspergillosis)
(Antinori et al., 2013)

4. PREDISPOSING FACTORS
▪ Prolonged use of broad-spectrum antibiotics
▪ Steroids
▪ Immunosuppressive drugs
▪ Transplant patients
▪ Diabetes mellitus
▪ Renal failure

5. PREDISPOSING FACTORS…
▪ Malnutrition
▪ HIV / AIDS
▪ Lymphoproliferative malignancies
▪ Living in endemic areas.
▪ Aging

6. FUNGAL INFECTIONS OF THE
CNS-RED FLAGS
▪ Immunocompromised host and diabetes
mellitus
▪ HIV infection
▪ Transplant patient
▪ Paranasal sinus infection

7. PATHOPHYSIOLOGY
• Neurotropism,
• Altered defence
mechanisms in the host.
The
pathogenicity
of fungi is
attributed to
• Hematogenous spread
• Direct inoculation
• Adjacent contiguous spread
Mode of
infection

8. CLINICAL SPECTRUM
▪ Sub-acute or chronic meningitis / Meningoencephalitis.
▪ ICSOL-Parenchymal brain abscesses or granulomas.
▪ Skull base syndrome
▪ Vasculitis.
▪ Vascular thrombosis leading to infarction or ICH or
SAH
▪ Spinal syndrome

9. CLINICAL SPECTRUM…
▪ Clinical syndromes -either alone or in combination
Most frequent manifestations –
▪ Brain abscesses
▪ Meningitis.

10. INVESTIGATIONS
CSF
▪ Cell
▪ Proteins
▪ Sugar
▪ Cytological examination--‐India ink
▪ Cultures
▪ Immunoassay
▪ PCR

11. INVESTIGATIONS…
▪ Blood cultures
▪ Imaging
▪ MRI
▪ CT SCAN
▪ Biopsies
▪ Evidence of infection elsewhere

12. DIAGNOSIS
▪ Suspicion of CNS mycosis - most important initial step.
▪ Cerebrospinal Fluid Examination-
▪ Protein ↑
▪ Glucose ↓
▪ A mononuclear pleocytosis 20 - 500 cells/mm3
(except candidiasis and zygomycosis- PMN ↑)

13. DIAGNOSIS…
▪ Cytological examination - e.g. India ink preparation
for cryptococcal meningitis .
(sens.=75% in AIDS pt.,50% in non-AIDS pt.
▪ Positive cultures confirm the diagnosis but may be
difficult to obtain or take a long time.
▪ In cryptococcal meningitis, the CRAG latex
agglutination test - > 90%.

14. DIAGNOSIS…
▪ CT or MR scan may reveal features of meningitis,
granulomas, hydrocephalus, infarction or spinal cord
compression.
▪ In rhino-orbital syndromes, CT or MR is especially
helpful.
▪ The granulomas appear as irregular hypodense lesions
with irregular and minimal contrast enhancement and
disproportionate perilesional oedema.

15. CT SCAN
15
(A) Noncontrast, (B) contrast CT, (C) MRI gadolinium images showing
cerebral aspergillosis close to the frontal sinus

16. DIAGNOSIS…MRI
▪ MRI -very useful for ocular muscle and PNS involvement
▪ T2* GRE: May accentuate Ca++ or presence of blood
products
▪ DWI: Slightly bright ,no/low restricted diffusion on ADC.
▪ Tl C+- Meningeal enhancement
▪ Brain -Areas of non-specific appearing enhancement,
may be ring-like, solitary-to-multiple.

17. Dx.
▪ Spinal cord - Enhancement of disc, vertebrae and epidural
space - discitis/osteomyelitis
▪ MRA: Vessel irregularities (vasculitis), occlusions, mycotic
aneurysms
▪ MRV: Sinus thrombosis
▪ MRS: Mildly ↑ Cho,↓NAA, ↑ lactate

18. Dx.
▪ PET: ↓Meta. and ↓blood flow.
Imaging Recommendations
▪ Best imaging tool: MRI with contrast.
Protocol advice
▪ Contrast-enhanced MRI needed in all patients
▪ MRS may be helpful to differentiate infectious from
neoplastic processes

19. CLINICAL SPECTRUM

20. MENINGITIS
▪ Meningitis and meningoencephalitis can be the
presenting clinical syndrome with most of the
yeasts.
▪ They have access to the microcirculation from
which they seed the subarachnoid space.

21. MENINGITIS…
▪ Predominant presenting clinical syndrome of
cryptococcal infection.
▪ ≈ 5-10% of HIV pt.,AIDS-defining illness.
▪ ≈ 40% initial manifestation of HIV infection.
Fessler RD, Sobel J, Guyot L, Crane L, Vazquez J, Szuba MJ, et al. Management of elevated intracranial pressure in patients with cryptococcal meningitis. J
Acquir Immune Defic Syndr Hum Retrovirol 1998;17:137-42

22. MENINGITIS…
▪ Meningitis may be a manifestation of widely disseminated
histoplasmosis or an isolated illness.
▪ CNS involvement -in 5-10% of cases of progressive
disseminated histoplasmosis.
▪ The most significant complication of Coccidioides
infection is meningitis.
▪ Meningitis caused by Aspergillus spp. is very rare.
-Wright D, Schneider A, Berger JR. Central nervous system opportunistic infections. Neuroimaging Clin North Am 1997;7:513-25
-Crum NF, Lederman ER, Stafford CM, Parrish JS, Wallace MR. Coccidioidomycosis: A descriptive survey of a reemerging disease. Clinical characteristics and
current controversies. Medicine (Baltimore) 2004;83:149-75

23. MENINGITIS…
Clinical pres.-
▪ Subacute or chronic
▪ May be as lethal as bacterial meningitis if untreated.
(mortality-30-70% despite treatment)
▪ Fever less common (30%)
▪ Headache (70%)
▪ Meningoencephalitis -altered mental status and
seizures.
▪ Meningeal vasculitis with vessel thrombosis and
localized brain infarctions.
- Bouza E, Dreyer JS, Hewitt WL, Meyer RD. Coccidioidal Meningitis. An analysis of thirty-one cases and review of the literature. Medicine
(Baltimore) 1981;60:139-72.
-Prasad KN, Agarwal J, Nag VL, Verma AK, Dixit AK, Ayyagari A. Cryptococcal infection in patients with clinically diagnosed meningitis in a tertiary care center. Neurol India 2003;51:364-6.
-Miszkiel KA, Hall-Craggs MA, Miller RG, Kendall BE, Wilkinson ID, Paley MN, et al. The spectrum of MRI findings in CNS cryptococcosis in AIDS. Clin Radiol 1996;51:842-50.
Mischel PS, Vinters HV. Coccidioidomycosis of the central nervous system: Neuropathological and vasculopathic manifestation and clinical correlates. Clin Infect Dis 1995;20:400-5.

24. MENINGITIS…
▪ Complications-Hydrocephalus and elevated ICP.
▪ Elevated ICP is reported in ≈ 50% of HIV-1 infected
patients with cryptococcal meningitis without
accompanying hydropcephalus or cerebral edema.
Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practical guidelines in the management of cryptococcal disease. Clin Infect Dis
2000;30:710-8.

25. MENINGITIS…
Diagnosis –
▪ CSF profile resembles that of TBM .
▪ Elevated protein concentration,
▪ Mononuclear pleocytosis
▪ Recent report of Aspergillus meningitis, had shown a
neutrophil predominance (>60%) in the CSF of
immunocompromised (14/20) and immunocompetent
(25/37) patients (Antinori et al., 2013).
▪ The CSF glucose concentration - moderately
decreased.

26. MENINGITIS…
Certain CSF findings suggest specific
etiologies.
▪ Neutrophilic pleocytosis in a patient from the
Mississippi and Ohio River basins suggests
Blastomyces dermatitidis meningitis.
▪ Eosinophilic meningitis in Coccidioides immitis
(Bariola et al., 2010; Drake and Adam, 2009).

27. MENINGITIS…
▪ Imaging - basilar meningitis with contrast
enhancement or unexplained hydrocephalus.
▪ Determining the exact fungal etiology is highly
dependent on the suspected fungal species.
▪ For Cryptococcus spp., a serum and/or CSF
cryptococcal antigen test is recommended.

28. MENINGITIS…
▪ Lateral flow assay (LFA)-a new tool for the
diagnosis of cryptococcal meningitis in resource-
poor settings (Antinori, 2013).
▪ The LFA is a dipstick test that detect cryptococcal
antigen in CSF, serum, and urine.
▪ A point-of-care assay
▪ Rapid
▪ Inexpensive (US$1.5–2.5) (Antinori, 2013).

29. Multisite Validation of Cryptococcal Antigen Lateral
Flow Assay and Quantification by Laser Thermal
Contrast
David R. Boulware, Melissa A. Rolfes, Radha Rajasingham, Maximilian von Hohenberg, henpeng
Qin, Kabanda Taseera, Charlotte Schutz, Richard Kwizera, Elissa K. Butler, Graeme Meintjes,
Conrad Muzoora, John C. Bischof, and David B. Meya
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 20, No. 1, January 2014

30. MENINGITIS…
▪ LFA - allow earlier diagnosis -improve outcomes
although not yet proven.
▪ For Coccidioides immitis, serum and CSF ELISA
and CSF complement fixation test are
recommended.
▪ For H. capsulatum, a CSF histoplasma
polysaccharide antigen test is the test of choice
(Chayakulkeeree and Perfect, 2006; Kauffman,
2006).

31. MENINGITIS…
▪ For demonstration of the organism large volumes
(20–30 mL) of CSF from the lumbar space are
needed.
▪ If negative, CSF from a high cervical puncture will
have the highest yield.
▪ Newer tests for invasive fungal infection such as β-
glucan and galactomannan or nucleic acid detection
are being tested (Perfect, 2013), but the utility for
CNS disease remains unproven.

33. ▪ Axial T1W-C shows typical
cryptococcal meningitis
with ventricular wall
enhancement and subtle
frontal and occipital
leptomeningeal
enhancement.

34. INTRACRANIAL MASS LESIONS
▪ Abscess or granuloma.
▪ Abscess -common with certain fungi, Candida ,
Aspergillus ,Phaeohypomycosis and Zygomycetes
spp.
▪ Candida and Aspergillus spp. are commonest.
(Leventakos et al., 2010).
▪ ~20%–30% of patients with CNS Aspergillosis had
no associated immunosuppression (Kourkoumpetis
et al., 2012).
▪ Candidal abscesses are usually secondary to
disseminated disease.
Sundaram C, Umabala P, Laxmi V, Purohit AK, Prasad VS, Panigrahi M, et al. Histopathology of fungal infections of central nervous system: A seventeen years
experience from south India. Histopathology 2006;49:396-405.

35. INTRACRANIAL MASS LESIONS…
▪ CNS Aspergillosis -hematogenous dissemination or
direct extension from the PNS.
▪ Zygomycetes (Rhizopus spp., Mucor) generally
involve the CNS by direct extension from PNS.
▪ Diabetes mellitus is the most common risk factor.

36. INTRACRANIAL MASS LESIONS…
Clinical Presentation –
▪ Fever +/-.
▪ Headache is common
▪ FND and ↑ ICT
▪ May invade blood vessels -thrombosis, Aspergillus
infections can present with strokes.
▪ Pt. may have very little manifestation of disease
until they are morbid.

37. INTRACRANIAL MASS LESIONS…
DIAGNOSIS –
▪ High degree of clinical suspicion.
▪ Brain contrast imaging with MRI or CT .
▪ Etiology depend on concomitant risk factors and
previous or ongoing infection in extra-CNS organs.
▪ A brain biopsy with cultures may be required.

38. COMMON ENTITIES THAT HAVE A SIMILAR
APPEARANCE TO FUNGAL INFECTION AND
THEIR DIFFERENTIAL DIAGNOSTIC FEATURES
▪ Brain metastasis- Thicker ring enhancement. Usually no
reduced diffusion in the necrotic center
▪ Infarction- Gyral enhancement or no enhancement.
Distribution conforms to a vascular territory
▪ Bacterial abscess -Thicker ring enhancement. Reduced
diffusion in the necrotic center

39. COMMON ENTITIES THAT HAVE A SIMILAR
APPEARANCE TO FUNGAL INFECTION AND
THEIR DIFFERENTIAL DIAGNOSTIC FEATURES…
▪ Toxoplasmosis- Thicker ring enhancement. Usually
no reduced diffusion in the necrotic center
▪ Demyelinating lesion- Incomplete ring
enhancement. Usually no reduced diffusion .
▪ Enlarged perivascular space- No enhancement,
characteristic distribution

40. a.Typical thick ring of bacterial (top) and weak ring of fungal enhancement
(bottom).
b Post-contrast T1 image shows thick ring enhancement more typical of
bacterial abscess in a relatively healthy patient with presumably relatively preserved
immune function who developed aspergillosis while on corticosteroid taper for acute
alcoholic hepatitis
c. typical weak ring enhancement in a patient with leukemia who developed
aspergillosis while receiving corticosteroids.

45. ▪ multifocal angioinvasive
aspergillosis at the gray–
white junction

46. INTRACRANIAL MASS LESIONS…
▪ Aspergillus granulomas are more frontal and
temporal in location and rarely parietal.
▪ In general, these infections are extremely
difficult to treat

47. INTRACRANIAL MASS LESIONS…
Management-
▪ The suspected organism determines the
definitive antimicrobial agent used.
▪ Azoles and liposomal amphotericin B are the
most common agents.
▪ Voriconazole- DOC for CNS aspergillosis, not
effective against zygomycetes.
▪ Rhinocerebral disease, empirical treatment
with amphotericin is appropriate.
▪ NSx. Better outcome
▪ Mortality of CNS fungal abscesses remains
high

48. SKULL-BASE SYNDROMES

49. SKULL-BASE SYNDROMES…
▪ Cranial and intracranial extension- is frequent in
Aspergillus sinusitis.
▪ Basifrontal and basitemporal aspergillus granulomas.
▪ 13/21 patients with CNS aspergillosis studied by
Murthy et al., presented with skull-base syndromes:
cavernous sinus syndrome in five, orbital apex
syndrome in three, proptosis with associated limitation
of ocular movements in two and cranial neuropathy with
or without meningeal signs in three.
Murthy JM, Sundaram C, Prasad VS, Purohit AK, Rammurti S, Laxmi V. Sinocranial aspergillosis: A form of central nervous system aspergillosis in south India.
Mycoses 2001;44:141-5.

50. ▪ Of the 89 patients with CNS aspergillosis
reported by Sundaram et al., 64 patients
presented with skull-base syndromes: sino-cranial
in 47, sino-orbito-cranial in nine and sino-orbital in
eight.
Sundaram C, Umabala P, Laxmi V, Purohit AK, Prasad VS, Panigrahi M, et al. Histopathology of fungal infections of central nervous system: A seventeen years
experience from south India. Histopathology 2006;49:396-405.

54. STROKE SYNDROME

55. STROKE SYNDROMES
▪ Fungal infections known to cause cerebrovascular
involvement include
1. Aspergillosis,
2. Candidiasis,
3. Zygomycosis,
4. Coccidiodomycosis,
5. Cryptococcosis
6. Histoplasmosis

56. STROKE SYNDROMES…
▪ Large vessel vasculitis by invasion or embolization.
▪ Hemorrhage, thrombosis and large infarcts is extremely
uncommon.
▪ Very rarely- subarachnoid hemorrhage
-Somer T, Finegold SM. Vasculitides associated with infections, immunization and antimicrobial drugs. Clin Infect Dis 1993;20:1010-46.
-Kalita J, Bansal R, Ayagiri A, Misra UK. Midbrain infarction: A rare presentation of cryptococcal meningitis. Clin Neurol Neurosurg 1999;101:23-5
-McKee EE. Mycotic infection of the brain with arteritis and subarachanoid hemorrhage: Report of case. Am J Clin Pathol 1950;20:381-

58. ▪ Cardioembolic stroke - fungal endocarditis.
▪ Fungal endocarditis accounted for 1.3-6% of
infective edocarditis.
▪ Candida is the most common causative organism
in both normal and immunocompromised hosts.
-Bayer A, Scheld M. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell Douglas and Bennett.s principles and
practice of infectious diseases. Churchill Livingstone: Philadelphia, PA; 2000. p. 857-902.
-Karchmer AM. Infection on prosthetic valves and intravascular devices. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell Douglas and Bennett.s principles
and practice of infectious diseases. Churchill Livingstone: Philadelphia, PA; 2000. p. 903-17

59. ▪ Aspergillus is the second most common cause.
▪ Subarachnoid hemorrhage secondary to fungal
mycotic intracranial aneurysm is an extremely
rare complication.
▪ Fungal mycotic intracranial aneurysms are
usually found in the setting of disseminated
hematogenous infection and fungal
endocarditis.
Pierrotti LC, Baddour L. Fungal endocarditis, 1995-2000. Chest 2002;122:302-10.

61. ▪ The majority fungal mycotic aneurysms are in the
proximal portion of the major arteries at the base of
the brain and have been described with Aspergillus
spp., Candida spp. and Zygomycetes spp.
infections.
▪ Fungal mycotic aneurismal SAH is often
associated with very poor outcomes.
Horten BC, Abbort GF, Porro RS. Fungal aneurysms of intracranial vessels. Arch Neurol 1976;33:577-9.

63. SPINAL INFECTIONS

64. SPINAL SYNDROMES
▪ Can rarely present as myelopathy and
myeloradiculopathy.
Infectious processes –
▪ Intramedullary granuloma or abscess,
▪ Epidural abscess
▪ Focal spinal meningitis
▪ Fungal myelitis.

65. ▪ Spinal cord involvement -very rare with aspergillosis.
▪ Upper thoracic level –MC site -contiguous spread from
lung.
▪ Koh et al. reported three children with myelopathy
resulting from invasive aspergillosis.
▪ Spinal arachnoiditis -Aspergillosis and C. neoformans.
-Koh S, Ross LA, Gilles FH, Nelson MD Jr, Mitchell WG. Myelopathy resulting from invasive aspergillosis. Pediatr Neurol 1998;19:135-8.
- Woodall WC 3rd, Bertorini TE, Bakhtian BJ, Gelfand MS. Spinal arachnoiditis with Cryptococcus neoformans in a nonimmunocompromized child. Pediatr
Neurol 1990;6:206-8.

66. ▪ Spondylitis secondary to Candida and Aspergillus -
characterized by intervening disc involvement.
▪ The bone marrow in the affected vertebral bodies may
show low signal intensity on both T1WI and T2WI .
▪ Skeletal coccidioidomycosis is frequently multicentric.
▪ MR screening of the entire vertebral column.

67. T2W MRI of thoracic
spine shows anterior
compression with
disc involvement with
marrow changes and
abnormal cord signal

68. ▪ Spinal cord disease -rare presentation of cryptococcosis.
▪ Bony involvement -5% of disseminated cryptococcosis.
▪ Imaging findings are not specific and simulate spinal
tuberculosis (except relative preservation of the disc).

70. TREATMENT

71. CRYPTOCOCCOSIS
HIV patients
1. Induction: amphotericin B(0.5-1 mg/kg)/Lipo.
AMB,4-6 mg /kg + flucytosine,100mg/kg/day QID ×
2 weeks (minimum)
2. Consolidation: oral fluconazole 400 mg/day × 8
weeks (minimum)
3. Maintenance: oral fluconazole 200 mg/day × 1 year
(minimum)
(until CD4 count >200 cells/μL for 6 months)

72. Organ transplant patients
1. Induction: lipid-formulation amphotericin +
flucytosine × 2 weeks (minimum)
2. Consolidation: oral fluconazole 400-800 mg/day × 8
weeks
3. Maintenance: oral fluconazole 200-400 mg × 6–12
months

73. Immunocompetent patients
1. Induction: amphotericin B + flucytosine × 4
weeks
2. Consolidation: oral fluconazole 400-800
mg/day × 8 weeks
3. Maintenance: oral fluconazole 200-400 mg ×
6–12 months

74. Increased intracranial pressure (ICP) (any group)
1. If ICP ≥ 250 mm H2O and symptomatic-remove
CSF via LP to closing pressure of ≤ 200 mm H2O or
≤ 50% of opening pressure (OP) if OP very high.
2. Recheck OP daily until stable × 2 days
3. Consider temporary ventriculostomy or lumbar drain
if requiring daily LP of ICP management

75. ASPERGILLOSIS
▪ Primary: voriconazole – IV → oral
▪ 6 mg/kg BD on day1 then 3-4 mg/kg
maintanance.
▪ Secondary/salvage therapies: liposomal
amphotericin, posaconazole; echinocandins .
▪ Consider surgical resection if possible.

76. ZYGOMYCOSIS
▪ Aggressive surgical débridement
▪ Standard or lipid-formulation amphotericin
▪ Some experts advocate addition of
echinocandin or posaconazole.

77. COCCIDIOIDOMYCOSIS
▪ Oral fluconazole or itraconazole ± intrathecal
amphotericin B
▪ Salvage: Intrathecal amphotericin B ± oral azole
▪ Recommendation after CSF normalized is lifelong azole
therapy
▪ If patient has hydrocephalus: likely to need an external
ventricular drain.

78. BLASTOMYCOSIS
▪ Induction: Intravenous liposomal or standard
amphotericin × 4–6 weeks
▪ Consolidation/maintenance: Oral azole therapy
(fluconazole, itraconazole, or voriconazole) × >12
months and resolution of CSF abnormalities.

79. HISTOPLASMOSIS
▪ Induction: intravenous lipid-formulation
amphotericin × 4–6 weeks
▪ Consolidation/maintenance: itraconazole ≥ 12
months and resolution of CSF abnormalities
including Histoplasma antigen.

80. SPOROTRICHOSIS
▪ Induction: Intravenous lipid-formulation
amphotericin × 4–6 weeks
▪ Consolidation/maintenance: Itraconazole 200
mg bid ≥ 12 months and resolution of CSF
abnormalities.

81. CANDIDIASIS
▪ Induction: Intravenous lipid-formulation
amphotericin ± flucytosine for several weeks
▪ Consolidation/maintenance: Fluconazole 400–800
mg until CSF and radiologic abnormalities resolve.
▪ If possible, remove any associated intraventricular
device.

82. CONCLUSION
▪ Incidence of CNS mycoses increasing worldwide.
▪ Most common source - paranasal and the mastoid
sinuses.
▪ Suspicion is the key to diagnosis.
▪ Amphotericin B remains the mainstay of therapy.
▪ Voriconazole is DOC for CNS Aspergillosis.
▪ Surgical total excision f/b aggressive systemic
antifungal therapy offers the best outcomes.

83. Thank you

84. REFERNCES
▪ Fungal infections of the central nervous system: The
clinical syndromes; J. M. K. Murthy; Neurology India |
July-September 2007 | Vol 55 | Issue 3.
▪ MRI of CNS Fungal Infections: Review of Aspergillosis to
Histoplasmosis and Everything in Between ;J. Starkey ·
T. Moritani · P. Kirby; Clin Neuroradiol DOI
10.1007/s00062-014-0305-7.
▪ Fungal Infections Of The Central Nervous System;salwa
Shabbir Sheikh* And Samir Sami Amr; February 2011
;DOI: 10.1007/978-90-481-3713-8_5
▪ Central nervous system fungal infections; a review
article ;Majid Zarrin1, Ali Zarei Mahmoudabadi;
Jundishapur Journal of Microbiology (2010); 3(2): 41-47

85. REFERNCES
▪ Bradley’s –Neurology in clinical practice;7 th edi.
▪ Multisite Validation of Cryptococcal Antigen Lateral Flow Assay
and Quantification by Laser Thermal Contrast ;David R.
Boulware; DOI: http://dx.doi.org/10.3201/eid2001.130906
▪ Diagnostic Imaging-brain; Anne G. Osborn, MD, FACR et. Al.
▪ Mycotic Aneurysm Accompanied by Aspergillotic Granuloma: A
Case Report; Masahito Kurino, M.D. et. al.; 0090.1019/94/$7;
1994 by Elsevier Science Inc
▪ Epidural Mass Due To Aspergillus Flavus Causing Spinal Cord
Compression - A Case Report And Brief Update;*U Tendolkar et.
al.; Indian Journal of Medical Microbiology, (2005) 23 (3):200-203
▪ Harrison’s textbook of internal medicine 19 th edi.