Case 3 -

Mycotic Cerebral Aneurysm Sidney E. Croul University of Toronto and Toronto General Hospital Toronto, Ontario, Canada

Virtual Slides as well as Still Images are displayed below.
For the fastest viewing of virtual slides, click:



under each thumbnail image below. You must have Aperio ImageScope installed on your PC.

If you do not already have Aperio ImageScope, Windows users with administrator privileges may download and install a free version in order to view USCAP Virtual Slides. Click the icon on the right to get your free copy:

Or, click on slide thumbnail images to view each slide
in a Web-based slide viewer, which is somewhat slower.

If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137.

Clinical History: The patient was a 54 year old man with a history of multiple cerebral aneurysms who in the spring of 2009 had a complex multilobated aneurysm in the left carotid circulation successfully treated with interventional coiling. He return in the fall of 2009 and received two interventional pipeline stents as treatment for multiple right sided internal carotid aneurysms. Five days after the procedure, he experienced significant blood loss from the catheterization site, hypotension, and new weakness of his left leg. He was readmitted to hospital and a subsequent CT angiogram documented a new occlusion of his right anterior cerebral artery just distal to the pipeline stents. Workup of the right femoral catheterization site identified an infected pseudoaneurysm which required resection. Despite aggressive therapy, within one week CT angiography revealed both new cerebral aneurysms and intracerebral hemorrhage. History and Clinical findings: This 54 year old man presented with multiple, bilateral cerebral aneurysms in the anterior circle of Willis. In the spring of 2009, a complex multi-lobated aneurysm in the left carotid circulation was successfully treated at Toronto Western Hospital by interventional coiling. He returned to Toronto Western in the fall of 2009 and received two interventional pipeline stents as treatment for multiple right sided internal carotid aneurysms. The day following that procedure, a pseudo aneurysm was noted at his right femoral puncture site and was treated with sand bag pressure. Discharge was on the third post-procedure day. Eight days after the procedure, he experienced significant blood loss from the catheterization site, hypotension, and new weakness of his left leg. He was readmitted to hospital and a subsequent CT angiogram documented a new occlusion of his right anterior cerebral artery just distal to the pipeline stents. The right femoral pseudo aneurysm was treated with thrombin injection at readmission. However, 14 days after the initial procedure, signs of infection were noted. These included positive blood cultures for gram positive cocci and distal embolization. They necessitated resection of the infected arterial segment. Nonetheless, the patient remained septic with positive blood cultures for staphylococcus aureus on the 16th post procedure day. Despite aggressive therapy, CT angiography on the 21st post procedure day revealed new cerebral aneurysms just distal to the anterior cerebral artery occlusion with an associated intracerebral hemorrhage. Over the ensuing 10 days, he became progressively hemodynamically unstable and lost brainstem reflexes. Life support measures were withdrawn on day 31 post procedure. Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Pathology: The surgically resected femoral artery was invaded by an acute and chronic inflammatory process with partial destruction of both the muscular and elastic layers. Gram stains demonstrated groups of cocci. At autopsy, following removal of the brain, the coils in the left supra-clinoid aneurysms and the residual right carotid artery were visible. Examination of the circle of Willis demonstrated more of the multi-lobated, previously coiled, aneurysm found in proximity to the left internal carotid artery. Unfortunately, both the left and right A1 portions of the anterior cerebral artery as well as the anterior communicating artery were fragmented beyond recognition by the initial brain removal. The brain itself was discolored and softened. The right frontal lobe was swollen and enlarged. The right uncus as well as the cerebellar tonsils were discolored and the left tonsil appears soft and necrotic. Coronal sections demonstrated a zone of hemorrhage and tissue softening extending from the base at the level of the corpus striatum into the lateral ventricle. This was contiguous with hemorrhage within the lateral ventricle. The right frontal lobe, inferior frontal lobe and parietal cortex contained areas with marked softening and discoloration. There was clot within the 4th ventricle. The dorsal surface of the spinal cord was layered with a cream-colored material. An area of grey-brown discoloration 1-2 cm in length was found in the high thoracic leptomeninges. Microscopic examination of the clot within the two pipeline stents demonstrated minimal organization and no signs of infection. The endothelium of the right intra-cavernous carotid artery demonstrated modest thickening, probably due to stent placement. The medial frontal cortex from the right hemisphere showed a healing infarction. The right superior temporal cortex demonstrated multiple microglial nodules within cortex and superficial white matter with surrounding gemistocytic astrocytes. At the base of the brain, there was a focus of acute inflammation in the basal ganglia intermixed with the acute hemorrhage which penetrated the brain at that point. The surrounding tissue demonstrated severe necrosis and edema. There was severe acute inflammation engulfing the left internal carotid system with necrosis and dilatation of vessel walls. This inflammatory process was also found along the leptomeninges of the cerebellum and pons and accumulated in the spinal leptomeninges. Sections of right parietal and occipital lobes as well as left frontal and temporal lobes showed minimal pathologic changes. Gross pathology of the other organs was unrevealing. Microscopically, foci of acute and chronic inflammation were found in the myocardium at the base of the tricuspid and aortic valves as well as in the renal cortices. Foci of acute and chronic pneumonia were also noted in the middle and lower lobes of the right lung. Final diagnosis in this case was a mycotic aneurysm of the femoral artery and a secondary mycotic aneurysm of the circle of Willis. The cerebral mycotic aneurysm was due to septic embolization to the region of pipeline stent placement in the right carotid artery. The right hemispheric healing infarction, microglial nodules, and astrocytosis were felt to represent vascular events in the right carotid circulation noted on post-procedure day eight. Meningitis reflected dissemination from the cerebral mycotic aneurysm. Hemorrhage at the base of brain and into ventricular system was secondary to rupture of the cerebral mycotic aneurysm. Differential Diagnoses: Mycotic Aneurysm Embolic Infarction Bacterial Meningitis Final Diagnosis: Mycotic Cerebral Aneurysm Case Discussion: Features of particular interest in this case were the post angiographic femoral mycotic aneurysm and the complications surrounding use of the pipeline stents. The majority of femoral pseudo aneurysms and their infected kin are associated with intravenous drug abuse. However, the incidence of femoral pseudo aneurysms following angiography has been increasing since the advent of more extended endovascular techniques with rates a different centers ranging from 2-8% [2, 34]. Although infection of these iatrogenic aneurysms is rare, our review of the literature found six reports documenting eight cases [4, 11, 13, 17, 33, 36]. Given the frequency of post-angiographic pseudo aneurysms, that number may grow in coming years. Review of Literature: A ruptured intracerebral mycotic aneurysm was described in 1869 by Church in a boy with mitral valve endocarditis [10]. Osler [28, 29, 30] described a patient with sub-acute bacterial endocarditis who at autopsy had a ruptured aortic aneurysm secondary to "mycotic endarteritis". During that part of the 19th century, the term "mycotic" was used to describe all microorganisms. Although the majority of these aneurysms are due to bacteria and not fungi, the term mycotic aneurysm has persisted despite attempts to supplant it with a more correct terminology such as infectious aneurysm [27]. The majority of intracranial mycotic aneurysms develop in the setting of left-sided bacterial endocarditis [3, 5, 8, 9, 18, 27, 31]. This suggests that these aneurysms result from the embolization of infected material [7]. The predominance of mycotic aneurysms in the distal middle cerebral circulation supports this pathophysiology. This contrast with classical berry aneurysms of the brain which have a predilection for the more proximal branch points of the circle of Willis. Because of the primary involvement of the muscular layer, infectious aneurysms are actually pseudo-aneurysms. Multiple aneurysms occur in up to 25% of cases [1, 8, 9, 12, 31]. Less frequently, they develop from intracranial bacterial infections such as meningitis, cavernous thrombophlebitis, and post-neurosurgical infections which spread by contiguous infection to create the aneurysms [3, 5]. The incidence of bacterial endocarditis over the last several decades has remained stable at two to six cases per 100 000 people per year in the developed world. The traditional risk factor of rheumatic heart disease has been replaced by prosthetic valves, elderly sclerotic valve disease, nosocomial hematogenous infections, and intravenous drug use [26]. The frequency of neurologic complications with mycotic aneurysms remains high. This is probably because the incidence of the disease is relatively low and patients come to attention only after neurologic signs and symptoms are reported. Although the incidence of mycotic aneurysms is reported to be 2-4% in cases of infective endocarditis, it is probably higher due to undiagnosed cases of asymptomatic disease [1, 12]. Streptococcus viridans and Staphylococcus aureus are responsible for the vast majority of mycotic aneurysms. Other bacteria implicated include coagulase-negative staphylococci, enterococci, and beta-haemolytic streptococci. Fungi are rare causative agents [3, 6, 12, 16]. The septic embolization which usually precedes aneurysm formation is probably clinically silent in the majority of cases. However, the most common sign is a focal neurologic deficit. In the absence of a deficit, severe localizing headache in a patient at risk is a correlate of the embolization [32, 35] Since most mycotic aneurysms are not diagnosed prior to rupture, any neurologic sign or symptom in patients at risk should lead to diagnostic work up. CT scanning will reveal intracranial hemorrhage as well as abscess or infarction. However, CT or MR angiography adds significant value to this evaluation [6, 21, 24]. Treatment remains somewhat controversial due small numbers of patients and lack of randomization in the literature. Noninvasive imaging modalities and minimally invasive interventional techniques have improved the accuracy of diagnosis and expanded the therapeutic options. The most important factor in planning treatment is whether the aneurysm has ruptured. Unruptured mycotic aneurysms of up to 10 mm diameter have been shown to resolve on antibiotic therapy alone [1, 20, 23, 25]. Although ruptured aneurysms carry a worse prognosis, a combination of surgery and antibiotics improves outcome over antibiotics alone [1, 3, 6, 9, 12, 16, 27, 31]. Despite the fact that interventional techniques leave the patient with foreign material within the circulation, they have shown promise as a treatment modality in this setting [8, 9]. Conclusion(s): The pipeline stent used in this patient represents a relatively new endoluminal device designed to occlude saccular aneurysms without causing compromise or compromise of the parent artery or adjacent, small branch arteries. The braided design is formulated to allow flow through branching vessels but to encourage thrombosis of the trapped aneurysm [19]. Three reports in the past year comprising the treatment of 56 patients show excellent results [14, 15, 22]. Nonetheless, it seems reasonable to conclude that in this case the right sided infarction eight days post procedure involved the pipeline stents and created a fertile field for the subsequent cerebral mycotic aneurysm. Experience at our centers in Toronto is limited to 15 cases to date. The success and failure rate of this device as well as any propensity for intravascular infectious complications will only be determined over time. References: Ahmadi J, Tung H, Giannotta SL, Destian S. Monitoring of infectious intracranial aneurysms by sequential computed tomographic/magnetic resonance imaging studies. Neurosurgery 1993; 32: 45-49. Aytekin C, Firat A, Yildirim E, Kirbas I, Boyvat F. Ultrasound-guided glue injection as alternative treatment of femoral pseudoaneurysms. Cardiovasc Intervent Radiol. 2004 Nov-Dec;27(6):612-5. Barrow DL, Prats AR. Infectious intracranial aneurysms: comparison of groups with and without endocarditis. Neurosurgery 1990; 27: 562-72. Berry MC, Van Schil PE, Vanmaele RG, De Vries DP. Infected false aneurysm after puncture of an aneurysm of the deep femoral artery Eur J Vasc Surg. 1994 May;8(3):372-4. Bohmfalk GL, Story JL, Wissinger JP, Brown WE Jr. Bacterial intracranial aneurysm. J Neurosurg 1978; 48: 369-82. Brust JC, Dickinson PC, Hughes JE, Holtzman RN. The diagnosis and treatment of cerebral mycotic aneurysms. Ann Neurol 1990; 27: 238-46. Cavassini M, Meuli R, Francioli P. Complications of infectious endocarditis. In: Scheld WM, Whitley RJ, Marra CM, eds. Infections of the central nervous system, 3rd edn. Philadelphia, PA: Lippincott, Williams, & Wilkins, 2004: 537-68. Chapot R, Houdart E, Saint-Maurice JP, et al. Endovascular treatment of cerebral mycotic aneurysms. Radiology 2002; 222: 389-96. Chun JY, Smith W, Halbach VV, Higashida RT, Wilson CB, Lawton MT. Current multimodality management of infectious intracranial aneurysms. Neurosurgery 2001; 48: 1203-13. Church W. Aneurysm of the right cerebral artery in a boy of thirteen. Trans Pathol Soc Lond 1869; 20: 109. Cleveland KO, Gelfand MS. Invasive staphylococcal infections complicating percutaneous transluminal coronary angioplasty: three cases and review. Clin Infect Dis. 1995 Jul;21(1):93-6. Corr P, Wright M, Handler LC. Endocarditis-related cerebral aneurysms: radiologic changes with treatment. AJNR Am J Neuroradiol 1995; 16: 745-48. Culver DA, Chua J, Rehm SJ, Whitlow P, Hertzer NR. Arterial infection and staphylococcus aureus bacteremia after transfemoral cannulation for percutaneous carotid angioplasty and stenting. J Vasc Surg. 2002 Mar;35(3):576-9. Fiorella D, Kelly ME, Albuquerque FC, Nelson PK. Curative reconstruction of a giant midbasilar trunk aneurysm with the pipeline embolization device. Neurosurgery. 2009 Feb;64(2):212-7; discussion 217. Fiorella D, Woo HH, Albuquerque FC, Nelson PK. Definitive reconstruction of circumferential, fusiform intracranial aneurysms with the pipeline embolization device. Neurosurgery. 2008 May;62(5):1115-20 Frazee JG Cahan LD, Winter J. Bacterial intracranial aneurysms. J Neurosurg 1980; 53: 633-41. Herchline TE, Carey D. Infected pseudoaneurysm complicating percutaneous transluminal coronary angioplasty.Clin Infect Dis. 1996 Mar;22(3):602. Johansen K, Devin J. Mycotic aortic aneurysms. A reappraisal. Arch Surg 1983; 118: 583-88. Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A new endoluminal, flow-disrupting device for treatment of saccular aneurysms. Stroke. 2007 Aug;38(8):2346-52. Kovoor JM, Jayakumar PN, Srikanth SG, Sampath S. Intracranial infective aneurysms: angiographic evaluation with treatment. Neurol India 2001; 49: 262-66. Lee WK, Mossop PJ, Little AF, Fitt GJ, Vrazas JI, Hoang JK, Hennessy OF. Infected (mycotic) aneurysms: spectrum of imaging appearances and management. Radiographics. 2008 Nov-Dec;28(7):1853-68. Lylyk P, Miranda C, Ceratto R, Ferrario A, Scrivano E, Luna HR, Berez AL, Tran Q, Nelson PK, Fiorella Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experienceNeurosurgery. 2009 Apr;64(4):632-42 Meena AK, Sitajayalakshmi S, Prasad VS, Murthy JM. Mycotic aneurysm on posterior cerebral artery: resolution with medical therapy. Neurol India 2000; 48: 276-78. Metens T, Rio F, Baleriaux D, Roger T, David P, Rodesch G. Intracranial aneurysms: detection with gadolinium-enhanced dynamic three-dimensional MR angiography-initial results. Radiology 2000; 216: 39-46. Morawetz RB, Karp RB. Evolution and resolution of intracranial bacterial (mycotic) aneurysms. Neurosurgery 1984; 15: 43-49. Moreillon P, Que YA. Infective endocarditis. Lancet 2004; 363: 139-49. Ojemann R. Infectious intracranial aneurysms. In: Fein J,Flamm E, eds. Cerebrovascular surgery. New York: Springer-Verlag, 1984: 1047-60. Osler W. Malignant endocarditis. Lecture I. Lancet 1885; 1: 415-18. Osler W. Malignant endocarditis. Lecture II. Lancet 1885; 1: 459-64. Osler W. Malignant endocarditis. Lecture III. Lancet 1885; 1: 505-08. Phuong LK, Link M, Wijdicks E. Management of intracranial infectious aneurysms: a series of 16 cases. Neurosurgery 2002; 51: 1145-51 Pruitt AA, Rubin RH, Karchmer AW, Duncan GW. Neurologic complications of bacterial endocarditis. Medicine (Baltimore) 1978;57: 329-43. Sharp MA, Gilling-Smith GL, al-Kutoubi A, Mansfield AO. Infected false aneurysm at the site of peripheral balloon angioplasty. Eur J Vasc Endovasc Surg. 1995 May;9(4):494-7. Tresukosol D, Schalij MJ, Savalle LH, Jukema JW, Buis B, Reiber JH, Bruschke AV Micro stent, quantitative coronary angiography, and procedural results. Cathet Cardiovasc Diagn. 1996 Jun;38(2):135-43. Tunkel AR, Kaye D. Neurologic complications of infective endocarditis. Neurol Clin 1993; 11: 419-40. Weinberg DJ, Cronin DW, Baker AG Jr. Infected iliac pseudoaneurysm after uncomplicated percutaneous balloon angioplasty and (Palmaz) stent insertion: a case report and literature review. J Vasc Surg. 1996 Jan;23(1):162-6.