Fungal Aneurysms of

Intracranial Vessels

Bruce C. \s=b\ Intracranial fungal aneurysms arise from major cerebral arteries. Fungi directly invade vessel walls from the luminal surface (fungal emboli) or from the adventitia (fungal meningitis). The vasa vasorum are free of fungi. Aneurysmal rupture is common with extensive hemorrhagic necrosis of the surrounding brain. Aspergillus is the usual causative agent; its sources are nasal sinusitis or endocarditis. (Aren A/euro/ 33:577-579, 1976)

blood vessel produced by an infectious agent is termed a mycotic aneurysm. Osier1-2 and Eppinger3 introduced this term and provided early clinical4 and patho¬


dilation of


logic descriptions. However, in 1852, Kirkes3 had already noted the associa¬ tion of ruptured aneurysms with bacterial endocarditis. Throughout

the next 100 years the association of intracranial mycotic aneurysms with bacteria was the rule. Although the

designation "mycotic" encompassed not only bacteria but also fungi, no such fungal intracranial aneurysm

described until 1968."7 the present case, four such intracranial aneurysms have now been documented.''" In size, shape, and angiographie presentation, these saccular aneurysms closely resemble the common berry aneurysm. With the remarkable increase in fungal infection among hospitalized patients over the past 15 years, one may antic¬ ipate a corresponding increase in true mycotic intracranial aneurysms. was



for publication April 5, 1976. Department of Pathology, New York Hospital-Cornell Medical Center, New York. Dr Horten is now with the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York. Dr Abbott is now with the Department of Neuroradiology, New York Hospital. From the

\s=d\DrPorro died Feb 26, 1975. Reprint requests to Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (Dr Horten).

Horten, MD; Gerald F. Abbott, MD; Robert S. Porro, MD\s=d\


History A 3-week-old girl was noted to have a harsh systolic murmur. When she was 3 years old, cardiac catheterization revealed a patent ductus arteriosus, a ventricular septal defect, aortic stenosis, and possible mitral stenosis. The patent ductus arterio¬ sus was ligated. She had increasing dyspnea during the following 12 years, and at age 15 a subvalvular aortic fibrous band was excised. Dyspnea and fatigue per¬ sisted, and at age 17 open heart surgery was again performed with removal of subaortic scar. Recovery was uneventful. One and a half months later, she complained of poorly localized headache. Two weeks later, she awoke with incoordi¬ nation and right-sided numbness. She developed a severe generalized headache and then suffered a right-sided focal motor seizure, after which she was unrespon¬



Following hospital admission, the pa¬ tient gradually awoke. There was a right hemiplegia with right central facial pare¬ sis. The cerebrospinal fluid was grossly bloody. Three days later, bilateral carotid arteriograms (Fig 1) showed an aneurysm 7 mm in diameter arising from a branch of


right middle cerebral artery within the


fissure. A second aneurysm, 3 mm in diameter, arose from a callosomarginal branch of the right anterior cerebral artery. The clinical impression was rup¬ tured mycotic aneurysm, and antibiotic therapy was instituted. However, on the ninth hospital day the patient became unresponsive and died. A cerebrospinal fluid culture submitted two days ante-

mortem subsequently yielded Aspergillus fumigatus.

Pathologic Findings Firmly

adherent to an endothelialized suture line in the anteromedial wall of the ascending aorta was a mass of friable nodules embedded in thrombus. The mass, measuring 1 cm in diameter and 5.5 cm in

length extended proximally

into the noncoronary cusp of the aortic valve and distally into the arch of the aorta. Portions of suture material were embedded within the nodular areas. Microscopically, these nodules consisted of radiating hyphae with dichotomous branching and true septations. Postmortem culture of the mass yielded A fumigatus. There were recent infarcts of the spleen and both kidneys.

Microscopically, fungal emboli occluded splenic and renal interlobular arteries, with formation of a fungal aneurysm in one kidney.

Fig 1 .—Subtraction right carotid arteriogram. Large aneurysm (white arrow) arises from middle cerebral artery. Second aneurysm (black arrow) arises from anterior cerebral artery.

Fig 2.—Ruptured fungal aneurysm of right middle cerebral artery with extruded mass of Aspergillus hyphae (solid arrow) seen adjacent to point of rupture (open arrows). Remainder of aneurysmal sac extends as attenuated fibrous tissue (star) to encom¬ pass laminated thrombus (asterisk) (methenamine silver, original magnification

Fig 3.—Detail of hyphae illustrated in Fig 2. Note septation and branching characteristic of Aspergillus (methenamine silver, orig¬ inal magnification X480).


Fungal Intracranial Aneurysms Source & Spock,6 Morriss & Spock7


Case/Age, yr/Sex 1/11/M

Prior Illness Tooth extraction; maxillary sinusitis and orbital cellulitla

Davidson & Robertson»


Hereditary hemorrhagic telangiectasia; chronic




Site of Aneurysm Internal carotid

artery at origin ophthalmic artery Basilar artery of




Subaortic stenosis;


by histology

Aspergillus by histology

Probable sinusitis— with hematogenous extension

Basilar artery


Trifurcation of middle cerebral

Aspergillus fumigatus by

Unknown; perhaps operative Massive fungal


et al»

Source of Fungus Orbit by direct extension

Organism Pénicillium

by histology



artery _

The brain weighed 1,350 gm. Extensive subarachnoid hemorrhage encased the in¬ ferior surface. There was bilateral tonsillar herniation and softening of the right temporal lobe. Dissection of the circle of Willis and its immediate branches revealed a ruptured saccular aneurysm, 6 mm in length, protruding from a proximal Sylvian branch of the right middle cerebral artery. Coronal brain sections demonstrated hemorrhagic necrosis of the right frontal lobe with right temporal intraventricular hemorrhage. The cerebral hemispheres elsewhere were congested but otherwise unremarkable except for central hernia¬ tion. Duret hemorrhages were present in the brain stem. The cerebellum and pitui¬ tary gland were unremarkable.

ruptured aneurysm paraffin. Serial sections were sequen¬ tially stained with hematoxylin-eosin, The




PAS, Masson trichrome, and Gomori methenamine silver. At the point of rupture (Fig 2), the vessel wall was infil¬ trated by dichotomously branching hyphae with true septations (Fig 3) identical to the fungi present within the aortotomy inci¬ sion. The remainder of the aneurysmal sac was composed of attenuated fibrous tissue. The vasa vasorum were free of fungi. Proximal to the rupture, minute hyphae and many giant cells were adherent to the arterial wall and focally embedded within proliferating intima. Rare hyphae ex¬ tended through the intima up to small clefts in the fibrillated elastica; on occa-

sion, a hypha penetrated the elastica to protrude into the adventitia. Here also the vasa vasorum were

free of


COMMENT Bacteria are the most common pathogenic agent of intracranial my¬ cotic aneurysms, and it is from the study of these bacterial aneurysms that virtually all our present knowl¬ edge of mycotic aneurysms is derived. The intracranial bacterial aneurysm is usually small (1 to 2 mm in diameter) and is located within the peripheral branches of the middle cerebral

artery.1"-'3 Characteristically, there are

many such aneurysms within


single arterial distribution. Because

most of these aneurysms are so small and so rarely prone to rupture, the adjacent cerebral cortex is usually free of infarcì or hemorrhagic necro¬ sis. The most common organism iso¬ lated from intracranial bacterial aneurysms is Streptococcus viridans." Second most frequent are the staphylococci. The source of such bacteria in 80% to 90% of cases is bacterial endo¬ carditis, and the route of spread, hematogenous dissemination." The most common agents of endocarditis are Str viridans (35%) and Staphylococcus aureus (17%).I3 Thus the most frequent agent of endocarditis is also the most common pathogen recovered from intracranial bacterial aneu¬ rysms. Several pathogenetic mechanisms have been proposed to explain bacte¬ rial aneurysms: (1) embolie occlusion of vasa vasorum; (2) direct invasion of the arterial wall from within the lumen (emboli) or from without (men¬ ingitis); and (3) vascular injury via deposition of immune complexes.1 In order to evaluate the first of these proposals, Molinari and colleagues13-"1 incubated minute silicone cylinders with bacteria and then injected them into the cerebral circulation where they lodged within vasa vasorum, initiating an inflammatory lesion that extended from adventitia through media to intima. The more virulent Staphylococcus produced an aneurysm whereas the less virulent Str viridans produced a brain abscess, although the reverse seems to be true clinically. In the past 50 years, the percentage of intracranial aneurysms attribut¬ able to bacteria has decreased. In 1916, of 50 intracranial aneurysms at London Hospital, 30% were mycotic.17 By 1939, McDonald and Korb1" found 6% among 1,125 intracranial aneu¬ rysms, and in 1965, Roach and Drake1" noted 2.6% among 191 such cases. By contrast, the decline of these bacterial :

lesions has been paralleled by the rise of opportunistic fungal infections. It was in this clinical setting that the first report of a fungal intracranial aneurysm appeared in 1968."7 Includ¬ ing the present report, four cases have now been documented."-*'


Table, which summarizes these reports, emphasizes features of the intracranial fungal aneurysm that set it apart from the bacterial variety. The fungal aneurysm arises from major cerebral arteries and is large (5 to 10 mm); the bacterial aneurysm protrudes from peripheral arterial branches and is small (1 to 2 mm).

Occasionally, large bacterial aneu¬ rysms are reported,"' but in general most are minute. The predominant organism of the intracranial fungal aneurysm is Aspergillus. Sources in¬ clude adjacent sinusitis or surgical contamination of either meninges or endocardium with subsequent fungal emboli. The most common fungi of sinusitis are Mucor and Aspergillus,-'' and the fungus isolated in 70% of fungal endocarditis is Candida.-''-' Despite this prevalance of Mucor and Candida, there seems to be a peculiar predisposition of Aspergillus to cause intracranial aneurysms. Although there is as yet no experimental model to establish the pathogenesis of the fungal aneurysm, the primary mecha¬ nism seems to be direct invasion of the arterial wall from an intraluminal embolus that extends its hyphae outward, or from fungal meningitis (secondary to sinusitis) that pene¬ trates into the adventitia. The vasa vasorum play little part in this process, which therefore contrasts with Molinari's model of bacterial aneurysms. The resulting fungal arteritis follows one of three courses. Most commonly, there is thrombosis of the inflammed vessel with hemorinfarcts or ill-defined rhagic cerebral abscesses.33 -7 Occasionally, there is immediate vessel rupture with mas¬ sive hemorrhage." Last, there may be focal necrosis of the elastica with a diffuse expansion of the vessel3" or, as in the present series, a saccular intra¬ cranial fungal aneurysm. -"

References 1. Osier W: The Gulstonian lectures on malignant endocarditis: Lecture I. Br Med J 1:467-470,


2. Osier W: Gulstonian lectures on malignant endocarditis. Lancet 1:415-418, 459-464, 505-508, 1885. 3. Eppinger H: Pathogenesis (Histogenesis und Aetiologie) der Aneurysmen einschliesslich des Aneurysma equi verminosum. Arch Klin Chir 35(suppl):1-553, 1887.

4. Osier W: The Principles and Practice of Medicine. New York, D Appleton & Co, 1892, p 707. 5. Kirkes WS: On some of the principal effects resulting from the detachment of fibrinous deposits from the interior of the heart, and their mixture with the circulating blood. Med Chir Tr 35:281-324, 1852. 6. Mahaley MS, Spock A: An unusual case of intracranial aneurysm, in Smith JL (ed): Neuroophthalmology. St Louis, CV Mosby Co, 1968, vol 4, pp 158-166. 7. Morriss FH, Spock A: Intracranial aneurysm secondary to mycotic orbital and sinus infection. Am J Dis Child 119:357-362, 1970. 8. Davidson P, Robertson D: A true mycotic (Aspergillus) aneurysm leading to fatal subarachnoid hemorrhage in a patient with heredi-

tary hemorrhagic telangiectasia. J Neurosurg 35:71-76, 1971. 9. Visudhiphan P, Bunyaratavej S, Khantana-


S: Cerebral

aspergillosis. J Neurosurg

38:472-476, 1973. 10. Roach MR, Drake CG: Ruptured cerebral aneurysms caused by micro-organisms. N Engl J Med 273:240-244, 1965. 11. Housepian EM, Pool JL: A systematic analysis of intracranial aneurysms from the autopsy

file of the Presbyterian Hospital 1914 to 1956. J Neuropathol Exp Neurol 17:409-423, 1958. 12. Hourihane JB: Ruptured mycotic intracranial aneurysm. Vasc Surg 4:21-29, 1970. 13. Weinstein L, Rubin RH: Infective endocarditis\p=m-\1973. Prog Cardiovasc Dis 16:239-274, 1973. 14. Goadby HK, McSwiney RR, Rob CG: Mycotic aneurysms. St Thomas's Reports 5(series 2):44-52, 1949. 15. Molinari GF: Septic cerebral embolism. Stroke 3:117-122, 1972. 16. Molinari GF, Smith L. Goldstein MN, et al: Pathogenesis of cerebral mycotic aneurysms. Neurology 23:325-332, 1973. 17. Fearnsides EG: Intracranial aneurysms. Brain 39:224-296, 1916. 18. McDonald CA, Korb M: Intracranial aneurysms. Arch Neurol Psychiatry 42:298-328, 1939. 19. Shibuya S. Igarashi S, Amo T, et al: Mycotic aneurysms of the internal carotid artery. J Neurosurg 44:105-108, 1976. 20. Douek E: Acute sinusitis, in Ballantyne J, Groves J (eds): Scott-Brown's Diseases of the Ear, Nose and Throat, ed 3. Philadelphia, JB Lippincott Co, 1971, pp 183-214. 21. Ostermiller WE, Dye WS, Weinberg M: Fungal endocarditis following cardiovascular surgery. J Thorac Cardiovasc Surg 61:670-675, 1971. 22. The spectrum of fungal endocarditis, Medical Staff Conference, University of California, San Francisco. Calif Med 115:34-40, October 1971. 23. Dismukes WE, Karchmer AW, Buckley MJ, et al: Prosthetic valve endocarditis. Circulation 48:365-377, 1973. 24. Zimmerman LE: Candida and Aspergillus endocarditis. Arch Pathol 50:591-605, 1950. 25. Young RC, Bennett JE, Vogel CL, et al: Aspergillosis. Medicine 49:147-173, 1970. 26. Meyer RD, Young LS, Armstrong D, et al: Aspergillosis complicating neoplastic disease. Am J Med 54:6-15, 1973. 27. Chernik NL, Armstrong D, Posner JB: Central nervous system infections in patients with cancer. Medicine 52:563-581, 1973. 28. McKee EE: Mycotic infection of brain with arteritis and subarachnoid hemorrhage. Am J Clin Pathol 20:381-384, 1950. 29. Baker RD: Mucormycosis, in Baker RD (ed): The Pathologic Anatomy of Mycoses. Berlin, Springer-Verlag, 1971, pp 832-918.

Fungal aneurysms of intracranial vessels.

Fungal Aneurysms of Intracranial Vessels Bruce C. \s=b\ Intracranial fungal aneurysms arise from major cerebral arteries. Fungi directly invade vess...
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