Section I Hemorrhagic Stroke

Lorenzo Rinaldo and Leonardo Rangel Castillo

Abstract

Mycotic aneurysms (MA) are rare entities that present daunting clinical challenges due to the medical complexity of the harboring patient population. The morbidity and mortality associated with the presence and rupture of these lesions are significant, though favorable neurologic outcomes are achievable in patients who are not moribund from a disseminated infection. Understanding the indications for screening and treatment of MAs is essential to obtaining a successful outcome. Herein, available evidence on the incidence, natural history, and treatment outcomes of MAs is reviewed to detail the basis for management algorithms of these complex vascular lesions.

Key words

angiography – infective endocarditis – intracranial hemorrhage – mycotic aneurysm – screening

4 Mycotic Aneurysms: Incidence, Natural History, and Treatment Strategies

4.1 Goals

Review the literature detailing the incidence of and risk factors for MA formation.
Review the literature describing the natural history of MAs.
Review the literature detailing the risks of cardiac surgery in the setting of a known MA.
Review the literature forming the basis of treatment algorithms for MAs.

4.2 Case Example

4.2.1 History of Present Illness

A 30-year-old male with a history of a bicuspid aortic valve and associated aortic regurgitation presented to the emergency department with transient episodes of left-sided face and arm sensory disturbances. The patient’s symptoms were characterized by tingling of the mouth and tongue as well as his left arm. These episodes lasted for approximately 10 seconds, during which he also experienced difficulty speaking. He denied any alteration in consciousness or upper or lower extremity weakness. Computed tomography (CT) of the head demonstrated a small focus of traumatic subarachnoid hemorrhage in the posterior right temporal lobe (Fig. 4.1a), with CT angiography (CTA) demonstrating a 4- to 5-mm likely aneurysm along the right frontal convexity (Fig. 4.2a). Follow-up magnetic resonance imaging (MRI) revealed multifocal punctate infarcts in the right posterior temporal and frontal lobes (Fig. 4.1b, c). The patient was also noted to have multiple renal and splenic infarcts on abdominal imaging. Subsequent cardiac ultrasound demonstrated 1.0- and 1.6-cm vegetation on his aortic and mitral valves, respectively, and severe aortic regurgitation with associated heart failure. Blood cultures were obtained and found to be positive for Cardiobacterium hominis.

Past medical history: Anemia, bicuspid aortic valve, aortic regurgitation.

Past surgical history: None.

Family history: Uncle with bicuspid aortic valve.

Social history: Endorses use of chewing tobacco and denies intravenous drug use, recent foreign travel, or sick contacts.

Review of systems: Endorses fatigue, night sweats, and 15-lb weight loss over the 3 months preceding presentation.

Neurologic examination: Mild dysarthria, otherwise unremarkable.

Imaging studies: See figures.

**Fig. 4.1** Initial computed tomography (CT) and magnetic resonance (MR) imaging. Initial head CT demonstrates a subtle focus of subarachnoid blood in the right posterior temporal lobe (a). Follow-up MRI demonstrates areas of restricted diffusion in the right posterior temporal **(b)** and frontal **(c)** lobes, consistent with embolic infarction.

**Fig. 4.2** Initial vascular imaging. Computed tomography (CT) angiography demonstrates a focus of enhancement in the right frontal lobe (a). Formal angiography revealed an aneurysm located on the branch of the middle cerebral artery **(b)** that filled well into the venous phase (c).

4.2.2 Treatment Plan

The patient’s clinical presentation was consistent with infective endocarditis (IE) complicated by septic cerebrovascular throm-boemboli causing multifocal infarctions and formation of a distal right middle cerebral artery (MCA) mycotic aneurysm (MA). The patient was started on a third-generation cephalosporin, ceftriaxone, administered intravenously. The patient’s sensory episodes were indicative of partial seizures; he was initiated on an antiepileptic medication and experienced no further recurrence of his spells. He was evaluated by cardiovascular surgery and deemed to require urgent aortic valve replacement. Prior to surgery, a cerebral angiogram was obtained, which demonstrated the previously seen distal right MCA aneurysm (Fig. 4.2a). Aneurysm filling was seen well into the venous phase, suggestive of intra-aneurysmal stasis (Fig. 4.2b, c). Given the aneurysm’s unruptured status, it was determined to continue medical management with antibiotics and proceed with aortic valve replacement on day 5 after initial presentation.

4.2.3 Follow-up

The patient’s aortic valve replacement proceeded uneventfully. He was given intravenous heparin intraoperatively and subsequently reversed with protamine sulfate at the conclusion of the procedure. Postoperatively, he was noted to be at his neurologic baseline but soon developed a dense left-sided hemiplegia and right-sided gaze deviation. A head CT demonstrated a right frontal intraparenchymal hemorrhage (IPH) with intraventricular extension (Fig. 4.3a). Due to early hydrocephalus, a left-sided ventriculostomy was placed. Shortly after placement of the ventriculostomy, the patient became acutely comatose and was found to have a fixed and dilated left pupil. He was taken emer-gently for a repeat CT scan, which demonstrated expansion of the patient’s IPH and IVH, now with complete casting of the right lateral ventricle (Fig. 4.3b, c). Significant right-to-left midline shift was noted; thus, the patient was taken for a decompressive right-sided hemicraniectomy, hematoma evacuation, and resection of the known MA. Intraoperatively, the aneurysm was localized via ultrasound and found to be thrombosed; it was resected using microsurgical technique. Postoperative CT/CTA demonstrated partial intraparenchymal and intraventricular hematoma evacuation and a de novo aneurysm off the distal anterior cerebral artery (Fig. 4.3d); given the relative locations of the aneurysm and hematoma, this new aneurysm was deemed responsible for the patient’s postoperative hemorrhage. The patient was subsequently taken for endovascular Onyx embolization of the ACA aneurysm with good angiographic result (Fig. 4.4a-d).

After an initial recovery period, the patient returned to his preoperative cognitive baseline, though he remained with a dense left-sided hemiplegia. He was initiated on anticoagulation for his aortic valve without adverse effects. A cranioplasty was performed approximately 2 months after his decompressive surgery that proceeded without complication. Serial blood cultures after initiation of antibiotics remained negative for growth. Prior to dismissal, an echocardiogram was performed that demonstrated good functioning of his prosthetic valve. The patient was ultimately dismissed to an inpatient rehabilitation facility.

4.3 Case Summary

Which predisposing risk factor for MA formation was present in this patient?

MAs are rare entities that occur most frequently in the setting of IE, with less common etiologies including meningitis, sinusitis, skull osteomyelitis, sepsis, and general immunocompromised state. ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ Causative microbial organisms are generally bacterial, usually Streptococcus or Staphylococcus species, though viral and fungal etiologies are not uncommon. ¹ ^, ² ^, ⁴ ^, ⁵ ^, ⁶ ^, ⁷ MAs have a predilection for distal branches of the anterior or posterior circulation, ¹ ^, ⁶ ^, ⁸ ^, ⁹ though aneurysms resulting from meningitis or other local infections may occur more frequently at proximal locations. ⁴ ^, ⁵ In a large series of patients with IE undergoing cerebral angiography, the reported incidence of MAs ranges from 2.0 to 8.9% (Mean: 4.5%, Standard Deviation: 3.2%). ⁷ ^, ¹⁰ ^, ¹¹ ^, ¹² Criteria for screening patients with

IE are not well-defined. Though MAs may be present in a minority of patients with intracranial hemorrhage, ¹³ intraparenchymal or subarachnoid hemorrhage is predictive of MAs and should prompt vascular imaging. ⁴ ^, ¹⁰ ^, ¹² The utility of screening in patients with IE and focal neurologic deficits is less clear, given the similar frequency of neurologic deficits noted in patients with and without MAs, yet may nevertheless be warranted given the morbidity associated with MA rupture. ¹² Screening neurologically asymptomatic patients is likely to be of low yield and to have an unfavorable risk-to-benefit ratio. ⁷ Both CT and MR angiography have limited sensitivity for MAs; thus, all patients in whom the diagnosis of MA is suspected should undergo formal angiography. ¹⁰ ^, ¹⁴
What is the natural history of patients with MAs treated with appropriate antibiotics?

In the presented case, the patient’s distal MCA aneurysm was unruptured, with his neurologic symptoms on presentation instead attributable to multifocal cerebral infarctions resulting from septic thromboemboli. Given the unruptured status and prolonged filling of the aneurysm visualized on initial angiography (Fig. 4.2b, c), this aneurysm was deemed likely to spontaneously thrombose and was not treated. The patient unfortunately experienced an intracranial hemorrhage from rupture of a de novo aneurysm forming sometime between initial angiography and cardiac surgery. In general, available evidence suggests that conservative management of unruptured MAs is reasonable, with multiple series describing no instances of rupture and high frequency of spontaneous resolution in patients with unruptured MAs treated with antibiotics alone, ¹ ^, ³ ^, ⁵ ^, ⁸ ^, ¹⁵ though rupture of initially unruptured MAs despite medical therapy has been reported. ² ^, ⁶ Unruptured MAs should nevertheless be monitored with serial imaging to ensure stability or resolution as aneurysm growth during medical therapy can occur ³ ^, ⁶ ^, ⁸ and has preceded fatal hemorrhage. ⁶ In contrast to noninfectious aneurysms, ruptured MAs typically present with IPH. ⁴ ^, ⁵ ^, ⁹ Ruptured MAs have a high rate of rebleeding with significant associated morbidity and mortality and thus should be treated if technically feasible. ⁴ ^, ⁶ ^, ⁹ Data on the rate of de novo aneurysm formation while on antibiotic therapy is limited, though available literature suggests it is uncommon. ⁸ ^, ¹⁶
How wouldyou counsel the patient regarding the risks of cardiac surgery in the setting of a known MA? Cardiac surgery for valve replacement is often necessary in patients with IE complicated by heart failure. ¹⁷ Reported mortality rates after valve replacement in the setting of known cerebrovascular complications are high but also variable, ranging from 0.0 to 25.0% in available case series (Mean: 9.7%, SD: 8.4%). ¹⁸ ^, ¹⁹ ^, ²⁰ ^, ²¹ ^, ²² ^, ²³ Shorter interval between onset of neurologic symptoms and cardiac surgery is strongly associated with higher rates of neurologic morbidity and mortality, with respective rates of 43.8 and 31.3% observed in a large case series when valve replacement was performed within 7 days of initial neurologic injury. ¹⁸ Valve replacement should thus be delayed in patients with intracranial hemorrhage, with a suggested time interval of 4 weeks between presentation and surgery. ¹⁸ ^, ²² As was the case in our patient, however, such delays are not always feasible in the presence of decompensated heart failure. In patients requiring urgent surgery, the risk of morbidity and mortality with valve replacement is exceedingly high and patients should be counseled as such. Data specific to the management of MAs in the setting of IE requiring valve replacement are limited, but available evidence suggests that treatment of MAs, if warranted, can be safely performed in the interval between presentation and cardiac surgery ²⁰ ^, ²³ ^, ²⁴ ^, ²⁵ ^, ²⁶ if cardiac surgery must precede aneurysm treatment, the risk of rehemorrhage from an unsecured ruptured MA is likely substantial. ²²
What are the treatment options for MAs and how do they compare in terms of efficacy and outcome?

As evidenced in the presented case, MAs can be amenable to either surgical or endovascular therapy. Previously reported surgical treatment options include clipping, wrapping, or trapping with either subsequent resection or bypass. ³ ^, ²⁷ Endovascular options include parent vessel occlusion, saccular occlusion with coils or liquid embolic agents, or stenting with or without coil embolization. ²⁸ ^, ²⁹ ^, ³⁰ ^, ³¹ Distal aneurysms located in noneloquent cortex can be safely treated with trapping and resection, while direct clipping or bypass after trapping may be necessary for aneurysms in eloquent cortex. ³ Similarly, simple parent vessel occlusion with either coils or liquid embolic agents is an effective and durable endovascular option for distal aneurysms in noneloquent cortex. ²⁸ ^, ³⁰ ^, ³¹ In eloquent cortex, direct aneurysmal embolization is preferable if feasible, but not always possible in instances of fusiform or dissecting morphology. ³ Treatment-related morbidity, as well as recurrence and rebleeding rates, appears to be low after surgical therapy, though data are limited to small case series. ³ ^, ⁶ ^, ⁸ ^, ⁹ , A systematic review analyzing the outcomes of endovascular treatment of 86 MAs quoted procedure-related morbidity and mortality rates of 12.6 and 6.1%, respectively, with recurrence and rebleeding rates after treatment of 7.9 and 5.8%, respectively. ³² Comparative studies of surgical versus endovascular therapies would be of interest; however, these are likely to be technically difficult, given the rarity of MAs and medical complexity of the patient population. Several authors advocate a multimodal approach to treatment of MAs, with selection of medical, surgical, or endovascular therapy dependent on both clinical circumstances and aneurysm characteristics. For example, for unruptured aneurysms, Chun and colleagues advocate medical treatment with appropriate antibiotics followed by serial angiography. For ruptured aneurysms in noneloquent cortex, endovascular treatment is recommended and if unsuccessful followed by microsurgery. Finally, ruptured aneurysms in eloquent cortex are treated initially with microsurgery. If a hematoma is present causing elevated intracranial pressure, microsurgery is favored regardless of aneurysm location. ³