Infectious Intracranial Aneurysms

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CHAPTER 379 Infectious Intracranial Aneurysms

The first description of an aneurysm of infectious etiology arising within the intracranial circulation was provided by Church in 1869, when he described an aneurysm in a 13-year-old boy with mitral valve endocarditis.¹ Osler then coined the term mycotic aneurysm during his “Gulstonian Lectures on Malignant Endocarditis” in 1885, when he described an aortic aneurysm that developed in a patient with bacterial endocarditis.² Eppinger acknowledged the significance of infected emboli in the development of these lesions by calling them mycotic-embolic aneurysms.³ The term mycotic aneurysm came to describe all aneurysms of infectious origin and is the terminology that has persisted until recently in the literature to describe aneurysms of infectious etiology. In one of the larger earlier series, Stengel and Wolforth reviewed 34 reported cases of infectious aneurysm in 1923.⁴ Bohmfalk and colleagues replaced mycotic aneurysm with bacterial aneurysm because the underlying infectious cause is most commonly bacterial and not fungal as mycotic would suggest.⁵ They described 85 cases from 1954 to 1978, which remains the largest series to date. Hospital series include those of Frazee and associates,⁶ Monsuez and coworkers,⁷ and Barrow and Prats,⁸ with 13, 12, and 12 patients, respectively. More recently Kannoth and colleagues described 25 cases spanning from 1976 to 2003.⁹ Chun and coauthors reported on 20 cases over a 10-year period.¹⁰ As evidenced by the small number of patients in these series, infectious aneurysms are a rare entity.

Terminology

There is much debate in the literature on what constitutes the appropriate terminology to refer to intracranial aneurysms of infectious etiology. The term mycotic aneurysm has been used historically to describe aneurysms of infectious etiology, but the terminology is misleading because it implies a fungal source, which can be the case but excludes bacteria, viruses, and tuberculous bacilli as possible causative agents. The term infectious aneurysm has replaced mycotic aneurysm as the most frequently used term. However, some object to use of the term infectious because it implies that the aneurysm itself acts as a source of further infection, and therefore other terminology has been suggested, such as infected or inflammatory.¹¹ Because there does not currently appear to be a consensus on the appropriate terminology, infectious aneurysm will be used as an all-encompassing term. An attempt will be made to be specific whenever possible, and fungal aneurysm and bacterial aneurysm will be used to describe an aneurysm of fungal or bacterial etiology, respectively, when the distinction is important.

Epidemiology

Intracranial aneurysms of infectious etiology are rare and represent approximately 2% to 6% of all intracranial aneurysms.¹²^–¹⁴ The incidence may be higher in children, in whom they account for as many as 10% of all intracranial aneurysms.¹⁵ In one series, aneurysms of infectious origin were found in 2% of children with bacterial endocarditis and accounted for 43% of the neurological complications related to endocarditis.¹⁶ A meta-analysis of cerebral aneurysms in children younger than 1 year found aneurysms of infectious etiology to represent 10% of intracranial aneurysms in that age group.¹⁷ Others have found a lower incidence of infectious aneurysms in the pediatric population, with an estimated incidence of less than 5%.¹⁸ The true incidence of these lesions in both the pediatric and adult population is difficult to ascertain because of their rarity. Their propensity to grow or regress rapidly and asymptomatically suggests that they are often undetected and that reported rates probably underestimate the true incidence. In 1916, Fearnsides’ autopsy review reported that 30% of all intracranial aneurysms were infectious.¹⁹ Subsequently, McDonald and Korb reported an incidence of 6.2% based on autopsies.¹⁴ This relative decline has been attributed to the introduction of antibiotic therapy. However, antibiotic therapy can select for more virulent organisms and thus alter the natural history of infectious aneurysms and the effectiveness of current antibiotics. In addition, improved survival of immunocompromised patients may also contribute to the relative increase in the number of fungal aneurysms.

Endocarditis, particularly left-sided valve disease, predisposes patient to infectious aneurysms and neurological complications. More than 80% of patients with intracranial infectious aneurysms carry an underlying diagnosis of endocarditis.⁵ Twenty percent to 40% of patients with endocarditis suffer neurological sequelae. Cerebral infarction is most common and afflicts up to 31% of patients.²⁰ Intracranial hemorrhage occurs in 5%.²¹ Overall, in 1% to 4% of patients with infective endocarditis, an infectious intracranial aneurysm is clinically diagnosed.^6,^7,^12,^22,²³

Intracranial infectious aneurysms may also develop in the absence of endocarditis or intravascular infection. Extravascular infection such as meningitis,²⁴^–²⁶ cavernous sinus thrombophlebitis,^27,²⁸ cerebral abscess,²⁹^–³² subdural empyema,³³ osteomyelitis of the skull,³⁴ and sinus infections^9,^28,³⁵ can potentially extend into the arterial wall and induce arteritis and aneurysm formation. Infectious aneurysms from an extravascular source such as meningitis tend to occur proximally, whereas embolic infectious aneurysms associated with infective endocarditis occur predominantly in distal cerebral arterial regions.⁹ The difference in location and incidence of fungal aneurysms requires a different management approach.

Fungal or “true” mycotic aneurysms are rare. However, the incidence of these lesions has recently increased as a result of more patients with immunocompromised states. Prolonged steroid use, immunosuppressive therapy, immunodeficient states, and exposure to broad-spectrum antibiotics have been implicated in their development.^8,^35,³⁶ In addition, fungal aneurysms can occur secondary to contiguous spread of postoperative fungal infection.³⁷ More aggressive use of immunosuppressive therapy and broad-spectrum antibiotics, along with an increasing population of immunocompromised patients, may explain the resurgence of fungal intracranial aneurysms.

Pathophysiology

The pathophysiology of infectious aneurysms is dependent on the causative agent, mechanism of spread, and the timeliness of diagnosis and initiation of appropriate therapy. Infectious agents can spread by several different mechanisms. There can be endovascular spread with infectious intracranial aneurysms occurring as a result of septic emboli, as is seen with bacterial endocarditis. As described previously, infectious intracranial aneurysms can be divided into those derived from intravascular infection and those that find their infectious origin in the extravascular space. Intravascularly derived infectious aneurysms are usually bacterial but may rarely be fungal.³⁸ Because of their embolic etiology, intravascularly derived infectious aneurysms tend to form in locations where blood flow is maximal and the vascular anatomy favors the lodging of embolic particles, such as vessel branch points in the distal vasculature. The most common location is the distal middle cerebral artery (MCA), where more than 60% of emboli lodge.^34,³⁹ This contrasts with classic berry aneurysms, which tend to form on large basal vessels as solitary lesions. Because the origin of infectious aneurysms is most commonly mitral valve septic vegetations, numerous emboli can lead to multiple aneurysms in as many as 30% of patients.⁴⁰

Unlike infectious aneurysms originating from an intravascular source, infectious aneurysms from an extravascular source are more likely to occur in the proximal intracranial arteries from contiguous infectious spread at the base of the brain. Usual locations include the intracavernous internal carotid artery, the midbasilar artery, and the vertebral artery. Although most bacterial aneurysms arise as a result of intravascular embolism, nearly all fungal aneurysms find their origin in the extravascular space. These “true” mycotic aneurysms tend to be larger and more fusiform in shape with a higher association of occlusion of the vessel than occurs with bacterial aneurysms.^36,^37,^41,⁴²

The precise mechanism of aneurysm formation probably varies depending on the infectious agent, immune status of the host, and time course of initiation of antibiotic therapy. Some animal models have shed light on the possible pathogenesis. Nakata and associates introduced bacteria into a canine aorta that had been isolated by clamps to demonstrate the role of stasis and sepsis in vascular destruction of the vasa vasorum.⁴³ However, this theory has been questioned because of the relative absence of vasa vasorum in cerebral arteries, particularly in the most distal segments, where infectious aneurysms are prone to form.^44,⁴⁵ Molinari designed a study to evaluate the exact role of septic emboli in the cerebral circulation by injecting bacteria-coated silicone rubber particles into the internal carotid artery. They found that the entire process, including embolization, arteritis, aneurysm formation, and hemorrhage, occurred within a couple of days. Interestingly, they also found that the inflammatory process involved the adventitia and muscularis primarily despite delivery of the bacteria to the intimal surface. The elastica and intima were the last to be affected, thereby supporting stasis and sepsis of the vasa vasorum and perhaps leakage into the Virchow-Robin spaces.⁴⁴

The pathologic changes produced by either septic embolization or contiguous spread are similar. Infiltration of the adventitia and media by polymorphonuclear leukocytes is accompanied by marked intimal proliferation. Thrombosis of the involved vessel may occur but is not necessary for the formation of an aneurysm. Some fungal infections such as aspergillosis and mucormycosis have a tendency to directly invade blood vessel walls. The angioinvasive nature of Aspergillus is directly related to its capacity to digest elastic tissue through production of the enzyme elastase.^35,⁴⁶ The tendency of Aspergillus for intramural growth is directly related to the fusiform shape seen with fungal aneurysms, as opposed to the more saccular shape seen with bacterial aneurysms.³⁵ Focal arteritis, whether bacterial or fungal, gives rise to a severely weakened and necrotic vessel wall, with aneurysmal dilation or frank vessel wall disintegration leading to hemorrhage. Thus, hemorrhage can occur as a result of necrotic vasculitis and does not necessarily indicate the presence of an infectious aneurysm. Intracranial infectious aneurysms are typically friable and often not separable from the surrounding parenchyma, which plays an important role in surgical planning. Antibiotic treatment may reverse this damage by inducing reparative fibrosis of the aneurysmal wall and parent artery,⁴⁵ but it does not necessarily preclude rupture of the aneurysm.

Intracranial aneurysms of infectious etiology demonstrate dynamic cycles of formation, enlargement, regression, and resolution. In his canine model, Molinari demonstrated that although there was a decrease in the rate of rupture in the first week, aneurysms were still present in dogs euthanized at 7 days. This suggests that the natural course of an infectious aneurysm is altered by antibiotic treatment. In addition, antibiotic therapy changed the nature of the aneurysms so that they were tough, fibrotic, and less likely to rupture.⁴⁵ Clinical studies have further underscored the dynamic manner in which infectious aneurysms develop and resolve.^47,⁴⁸ The behavior of an infectious aneurysm can range from abrupt rupture despite appropriate antibiotics to spontaneous resolution with appropriate therapy, thus making it difficult to stereotype the natural history.

Microbiology

Streptococcus viridans and Staphylococcus aureus are responsible for 57% to 91% of infectious intracranial aneurysms.⁴⁹ Other bacterial organisms have also been cultured, including enterococci, coagulase-negative staphylococci, Haemophilus, Actinobacillus, Cardiobacterium hominis, Acinetobacter, Eikenella corrodens, Kingella, Pseudomonas, Neisseria, and Corynebacterium.^{6–8,26,49–54} Multiple organisms are found in less than 5% of patients.⁵⁵ Despite multiple blood or cerebrospinal fluid (CSF) cultures, at least 12% to 19% of patients fail to grow an organism.^55,⁵⁶

Extravascular infections that predispose to intracranial aneurysms include meningitis, cavernous sinus thrombophlebitis, osteomyelitis, tonsillitis, pharyngitis, sinusitis, and wound infection, as well as drug abuse. Bacterial organisms cultured from these infections include S. aureus, Mycobacterium tuberculosis, pneumococci, Pseudomonas, Brucella, Neisseria, and other species that inhabit potential portals to the intracranial space.

As mentioned previously, aneurysms of fungal etiology usually occur in immunocompromised hosts. Aspergillus is the most common fungus cultured, followed by Phycomycetes and Candida albicans. Intracranial fungal aneurysms attributable to Cryptococcus, Coccidioides, Petriellidium boydii, Pseudallescheria boydii, Nocardia asteroides, and fungi causing chromoblastomycosis have also been reported.^35,^36,^41,^42,⁵⁷^–⁵⁹ Aspergillosis of the central nervous system usually occurs as a result of direct infection via the paranasal sinus or indirectly by hematogenous infectious spread, most commonly from the lungs.⁵⁸ Direct spread of a fungal infection associated with an aneurysm after craniofacial and other neurosurgical procedures has also been described.^60,⁶¹

Clinical Findings

The signs and symptoms in patients with infectious aneurysm are highly variable. A high index of suspicion is required in those with risk factors for infectious intracranial aneurysms and new neurological symptoms or signs. Patients may have clinical manifestations referable to numerous underlying disease processes, but it is the combination of the underlying disease process and new neurological findings that should raise suspicion. However, infectious intracranial aneurysms can be asymptomatic and the diagnosis can be challenging.

The majority of patients with infectious intracranial aneurysms also have left-sided subacute bacterial endocarditis. The overall incidence of infectious intracranial aneurysms has remained stable at 2 to 6 cases per 100,000 people per year despite changes in therapy and underlying conditions. Classically, rheumatic heart disease and related valvular abnormalities were an important predisposing factor. Recently, new risk factors such as prosthetic valves, elderly sclerotic valve disease, nosocomially acquired bloodstream infections, and intravenous drug abuse have become the most important predisposing factors.^49,⁶² The most common manifestation is a focal neurological deficit, which occurred in 48% of patients in one larger series.⁹ This finding is in contrast to other intracranial aneurysms, which are much less likely to be accompanied by focal signs or symptoms.⁶³ Not all neurological complaints signify the presence of an aneurysm. In fact, neurological manifestations are common in patients with endocarditis, with only a minority ultimately referable to an infectious aneurysm. Signs of subarachnoid or intracranial hemorrhage in the setting of endocarditis should raise strong suspicion of an infectious aneurysm. The signs and symptoms of hemorrhage are present in 57% of patients with infectious aneurysms and are otherwise uncommon in those with endocarditis.⁵⁹ However, intracranial hemorrhage can occur in the setting of bacterial endocarditis in the absence of a demonstrable aneurysm.²¹ Symptoms may include focal neurological deficit, headache, meningismus, seizure, or change in mental status.

Patients with intracranial aneurysms caused by extravascular infection are initially seen with a wide array of symptoms and signs referable to the site of infection. Patients are often immunocompromised. Underlying disease processes include systemic lupus erythematosus, near drowning, Burkitt’s lymphoma, meningitis, sinusitis, tonsillitis, pharyngitis, osteomyelitis, and infection from previous intracranial surgery. Intracavernous internal carotid aneurysms associated with cavernous sinus thrombophlebitis can cause exophthalmos, ophthalmoplegia, and ocular pain.

Natural History

No definitive information exists regarding the natural history of infectious intracranial aneurysms. The natural history is uncertain, with the information being gleaned from retrospective cohorts in relatively small case series with no clear standardization of antibiotic regimens. The discrepancy in reported incidence rates between autopsy and clinical series indicates that many infectious aneurysms remain clinically dormant and undiscovered. Routine screening of patients with endocarditis for infectious aneurysms would lead to a higher incidence of aneurysms in those with endocarditis than in clinical series because angiography is not universally performed in the absence of neurological signs or symptoms. In the absence of histopathologic confirmation of an infectious etiology of an aneurysm, even digital subtraction angiography (DSA) can be misleading, with uncertainty about whether an identified asymptomatic aneurysm can be clearly defined as infectious.⁶⁴ Dynamic cycles of growth and regression further hinder efforts to obtain reliable incidence rates and limit the reliability of clinical prediction. Clinical series in which serial angiographic imaging of infectious aneurysms reveals unpredictable cycles of growth and regression confirm these findings. Ojemann retrospectively reviewed 27 patients who underwent follow-up angiography while being treated medically: 30% of the aneurysms resolved, 19% decreased in size, 15% did not change, 22% enlarged, and 15% of patients were found to have a new aneurysm.⁵⁵ Bohmfalk and coauthors reported similar figures in their review of 25 patients who were treated conservatively and underwent repeat angiography.⁵ Phuong and associates reported that in the 5 patients in their series who underwent follow-up angiography after antibiotic treatment and observation, the aneurysm resolved in 2 patients, was unchanged in size in 1, was unchanged in size in 1 but a new aneurysm was found, and became enlarged and necessitated surgical treatment in 1.⁴⁰ The likelihood of prospective studies is limited by the heterogeneous nature of the clinical findings and the rarity of the disease process. Meta-analyses are also limited because they rely on case series of heterogeneous populations.

Previous reports of infectious intracranial aneurysms indicate a poor prognosis. However, the mortality associated with infectious aneurysms is highly variable, with mortality in reported series ranging from 12% to as high as 80%.⁵^–⁷ ^,22 ^,40 ^,54 The wide variability seen in the mortality associated with infectious aneurysms can be attributed in part to patient selection factors but highlights the difficulty in making treatment generalizations from the data available. The most important prognostic factor for outcome is the presence of hemorrhage. Based on Bohmfalk and colleagues’ review, mortality after rupture of an intracranial bacterial aneurysm was 80%, whereas the mortality without rupture was 30%.⁵ Many patients who suffer hemorrhage die before reaching the hospital. Of patients arriving at the hospital with evidence of subarachnoid hemorrhage from an intracranial bacterial aneurysm, 42% die.⁵ Intracranial fungal aneurysms impart an even worse prognosis, with a mortality rate greater than 90% despite medical or surgical therapy.

Diagnostic Evaluation

Diagnosis of an intracranial aneurysm of infectious etiology requires a high index of clinical suspicion accompanied by thorough clinical, laboratory, and radiographic examination. Prompt diagnosis is crucial for timely institution of appropriate medical and surgical therapy. A thorough history should document any cardiac disease and preexisting conditions that predispose to intracranial infection. As in patients with aneurysms of noninfectious etiology, a thorough neurological examination is important. In contrast to patients with aneurysms of noninfectious etiology, patients with infectious aneurysms are more likely to present with a focal neurological deficit.⁹

The diagnosis of endocarditis is often suggested by the physical examination. Information from registry data demonstrates that 90% of patients with endocarditis have fever, frequently accompanied by systemic symptoms such as chills, poor appetite, and weight loss.⁶⁵ Heart murmurs are found in up to 85% of patients.⁶⁶ Classic peripheral signs of endocarditis such as Osler’s nodes and Janeway’s lesions are becoming increasingly uncommon because of early diagnosis in developed countries. However, vasculitic phenomena such as splinter hemorrhages, Roth’s spots, and glomerulonephritis are still frequently seen.⁶⁶ Fever in the presence of a neurological deficit is also suggestive of endocarditis and mandates an evaluation for infection. Blood cultures are crucial because they may confirm the presence of bacteremia or fungemia and identify the pathogen. Current guidelines suggest that three samples should be taken an hour apart in an effort to identify the causative organism and start appropriate therapy. The first two sets of blood cultures are positive in more than 90% of patients.⁶⁶ Normocytic normochromic anemia, microhematuria, and positive serology for rheumatoid factor also corroborate the diagnosis of endocarditis. Transthoracic echocardiography can be used in patients who are at low risk for endocarditis based on clinical suspicion, but transesophageal echocardiography has higher sensitivity and specificity and should be used if clinical suspicion is high.

Computed tomography (CT) is the most useful initial diagnostic tool in evaluating a patient with a suspected intracranial aneurysm of infectious etiology. Rupture of an intracranial infectious aneurysm often causes subarachnoid or intraparenchymal hemorrhage demonstrable on CT. Other findings readily identified with non–contrast-enhanced CT include infarction, edema, and hydrocephalus. Infusion of contrast material extends the utility of CT by accentuating the cerebral vasculature and infectious processes such as abscesses. Nearly 50% of endocarditis patients with a neurological deficit demonstrate abnormalities on CT, with infarction secondary to septic embolization being the most common. Intracranial hemorrhage in the setting of endocarditis is a strong indication for cerebral angiography.²⁰ Some authors advocate cerebral infarction as an indication for angiography because of its association with subsequent aneurysm formation. Normal findings on CT do not preclude the presence of an intracranial aneurysm of infectious etiology. When performed on the day of aneurysm rupture, CT identifies 95% of cases of subarachnoid hemorrhage.⁶⁷ The sensitivity is probably higher with newer high-resolution CT. However, if imaging is delayed or the hemorrhage is mild, the findings on CT may be normal.

CT angiography (CTA) is a relatively new technique that permits imaging of the intracranial vasculature by rapid-sequence CT after a bolus of intravenous contrast material. CTA is less invasive, more rapid, and more cost-efficient than conventional DSA. Furthermore, studies have demonstrated its emerging efficacy in detecting intracranial aneurysms. However, CTA is currently limited in its ability to identify intracranial infectious aneurysms, which tend to be small and distally located. Recent work with 64-section multidetector CTA has shown good sensitivity with even smaller aneurysms, including 92.3% sensitivity for aneurysms less than 4 mm, where sensitivity has been seen to drop off in previous studies with single-section CTA.⁶⁸ Limitations still do exist with peripherally located aneurysms and blister-like aneurysms, which are commonly seen in infectious intracranial aneurysms.

Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) are also evolving techniques that have become increasingly useful in the diagnosis of aneurysms. MRI can demonstrate intracranial hemorrhage, edema, and infection. MRA is a blood flow–dependent technique that can illustrate the vascular anatomy and identify intracranial aneurysms. Three-dimensional time-of-flight phase-contrast angiography shows particular promise. Current limitations include the relative insensitivity of MRI to acute intracranial hemorrhage in comparison to CT and the inability of MRA to identify small, peripherally located aneurysms. Studies have suggested difficulty in prospectively identifying aneurysms smaller than 5 mm.⁶⁹

Lumbar puncture is performed to rule out the presence of subarachnoid hemorrhage in patients with normal findings on head CT. Sampling of CSF also permits cell count, Gram stain, and culture analysis for possible infection. CSF cultures in patients with intracranial aneurysms of infectious etiology will often fail to grow an organism, with one study finding CSF cultures positive in just 16% of patients.⁷⁰

DSA is currently the “gold standard” for the diagnosis of intracranial aneurysms. Three-dimensional rotational DSA increases the sensitivity over standard angiography for aneurysms less than 3 mm and provides additional information about ultrastructure.⁷¹ Cerebral angiography is warranted in patients with intracranial hemorrhage, infarction, or a focal neurological deficit in the setting of endocarditis or suspected intracranial infection. A complete four-vessel angiogram must be performed because of the likelihood of multiple aneurysms. Close attention should be paid to the distal vasculature, and multiple oblique views or three-dimensional rotational angiography is often necessary to rule out a small fusiform aneurysm. Intracranial infectious aneurysms display unpredictable cycles of growth and regression despite appropriate medical therapy. Consequently, serial follow-up angiography is indicated. The inherent risk associated with angiography has prompted debate about the appropriate timing, duration, and modality of follow-up angiograms. Aneurysms that are visible on CTA can be monitored by repeat CTA, with the caveat being that there is a small but definite chance that a newly developed small aneurysm could be missed. Initially, it is prudent to perform DSA and three-dimensional rotational DSA to ensure that all aneurysms are identified initially. Once correlation has been confirmed, CTA can be performed serially to monitor treatment and may permit less frequent follow-up with DSA.

Treatment

Prompt initiation of medical and surgical therapy is paramount in avoiding the potentially devastating consequences of aneurysm rupture. Nevertheless, controversy exists regarding the optimal treatment modality and timing of surgical intervention. Because of the dynamic and variable nature of these lesions, all but the most general treatment algorithm options may be presented.

Cardiac Considerations

Patients with intracranial aneurysms of infectious etiology often have compromised cardiac function. The goal of endocarditis therapy is to eradicate microorganisms from cardiac vegetations and stabilize the patient’s cardiovascular status. Occasionally, a patient’s cardiac status is so compromised that surgical intervention is warranted. Indications for cardiac surgery in patients with endocarditis are (1) hemodynamic instability secondary to valve destruction, (2) persistent fever despite appropriate antibiotic therapy, (3) development of abscesses or fistulas secondary to perivalvular spread of infection, (4) involvement of highly resistant organisms, (5) the presence of prosthetic valve endocarditis, and (6) large vegetations with high embolic potential.⁶⁶ In these situations, cardiac surgery is often performed before obliteration of the aneurysm. The principal neurological concern during cardiac surgery is perioperative stroke and hemorrhage. In some instances, an intracranial hematoma or abscess mandates emergency evacuation despite severe cardiac dysfunction. In these situations, simultaneous intracranial and cardiac surgery can be considered. However, neurosurgical decompression and obliteration of the aneurysm are complicated by the intraoperative heparinization required during cardiac valve replacement. Recent advances have made endovascular approaches more appealing in patients who are less likely to tolerate open surgery and require urgent cardiac surgery.

In the absence of acute intracranial hemorrhage or stroke, cardiac valve replacement may be undertaken before surgical or medical resolution of an infectious intracranial aneurysm. Intraoperative heparinization during cardiac surgery is not thought to increase the risk for perioperative hemorrhage from an unruptured infectious aneurysm. However, a bioprosthetic rather than synthetic cardiac replacement valve should be used to obviate the need for long-term postoperative anticoagulation.⁴⁷

Medical Treatment

The rationale behind medical management of infectious intracranial aneurysms is that some aneurysms will be obliterated with appropriate antibiotic therapy at the same time that the underlying infection is being treated.⁷ Several authors have demonstrated the effectiveness of antibiotic therapy in treating infectious aneurysms.^5,⁷² In addition, even in patients who will demonstrate further aneurysmal growth and ultimately require surgery, antibiotic therapy helps initiate reparative fibrosis. Antibiotic therapy should be initiated promptly in all patients suspected of harboring an infectious intracranial aneurysm. Three blood samples for culture should be drawn an hour apart as mentioned earlier because in the vast majority of cases the causative agent identified will be related to the bacterial endocarditis. The proliferation of more virulent and antibiotic-resistant organisms has led some to warn against empirical therapy before blood culture results are available. While awaiting the results of specific organism and sensitivity testing, antibiotics should be targeted toward the most common infectious organisms: staphylococcal and streptococcal species. Antibiotic dosages must be adequate for penetration of the blood-brain barrier and should be continued for a minimum of 4 to 6 weeks or until cultures are consistently sterile. Unruptured aneurysms should initially be treated conservatively without surgery unless there is documented enlargement during antibiotic therapy or failure to regress after a full course of antibiotics. One approach is to perform an angiogram 1 week after the initiation of appropriate antibiotic therapy to establish the trajectory of aneurysmal change.¹⁰ Additional relative indications for continued nonsurgical conservative management of ruptured or unruptured intracranial infectious aneurysms include (1) aneurysms arising from the proximal cerebral vessels and sacrifice of the parent artery is not possible, (2) aneurysms whose surgical obliteration would result in serious neurological deficits, (3) regression of aneurysms while undergoing antibiotic therapy, and (4) fungal aneurysms.⁵⁵ Despite adequate antibiotic therapy, aneurysms of infectious etiology may remain the same size, enlarge, or even rupture. Neurological complications can develop in up to 30% of patients after the initiation of antibiotic therapy.⁷³ Consequently, follow-up angiography is important to monitor intracranial infectious aneurysms during antibiotic treatment, and aneurysmal growth should prompt urgent surgical treatment.

Surgical and Endovascular Treatment

Indications for surgical intervention include (1) the presence of a symptomatic mass effect from a hematoma or the aneurysm, (2) a ruptured aneurysm, (3) enlargement of an aneurysm during appropriate antibiotic treatment, (4) failure of an aneurysm to resolve despite a full course of appropriate antibiotic therapy, and (5) neurological deterioration during antibiotic therapy. Surgical manipulation of recently ruptured or newly developed intracranial bacterial or fungal aneurysms is often difficult because of the friable and necrotic consistency of the aneurysm and parent vessel. Whenever possible, a short course of antibiotics should be given to allow reparative fibrosis of the aneurysm.

When planning surgical repair of an intracranial infectious aneurysm, the surgeon must be prepared to use a variety of techniques and alternative tactics if the planned surgical strategy is not successful. Clipping is frequently not possible because of the aneurysm’s friable nature and adherence to surrounding parenchyma. Excision of the aneurysm along with a short segment of the parent vessel is a potent treatment option but can be performed only in distal noneloquent vascular distributions. It can usually be performed with low morbidity for peripheral aneurysms. Excision has been combined successfully with revascularization techniques to treat proximal aneurysms. Examples include excision of a proximal MCA aneurysm with primary anastomosis of the parent vessel, as well as excision of a proximal MCA aneurysm with simultaneous superficial temporal artery–MCA bypass procedure. Similarly, carotid ligation with or without distal revascularization has been successful in the treatment of intracavernous infectious aneurysms. Proximal aneurysms and aneurysms supplying eloquent areas can present a management challenge because the potential morbidity associated with proximal ligation can be severe. The surgeon has to be prepared for a friable lesion that cannot be safely clipped and be ready to sacrifice the vessel with or without revascularization. Infectious intracranial aneurysms are often difficult to locate surgically because of their preference for the peripheral vasculature. Stereotaxis may be useful in the intraoperative localization of these lesions. CT and angiography-guided stereotactic techniques have been used to minimize cortical disruption and vessel dissection during surgical obliteration. Frameless MRI or MRA stereotaxis may likewise prove to be useful in the management of these lesions.

Distal selective catheterization with injection of amobarbital (Amytal) during DSA in a cooperative patient provides useful information about eloquent areas in planning treatment and whether the parent vessel can be sacrificed.⁷⁴ Alternatively, awake stereotactic craniotomy with temporary occlusion of the parent vessel has been performed to evaluate eloquent regions before occlusion of the parent vessel.⁷⁵ Balloon test occlusion of the proximal vasculature can also be performed to evaluate for collateral flow before sacrifice of the vessel.

Endovascular obliteration is a recently developed treatment modality for infectious intracranial aneurysms. The technology is advancing rapidly, and therefore treatment paradigms need to reflect the potential significant improvements in current results. Recently, multiple authors have reported success in treating infectious aneurysms with coils and occlusion of the parent artery.^10,⁷⁶^–⁷⁸ Intravascular embolization may be suited for lesions that require treatment and pose an unacceptable surgical risk. Reports have demonstrated the safety and efficacy of these methods in the treatment of intracranial infectious aneurysms.^10,⁷⁶^–⁷⁸ The friable nature of the arteritis associated with infectious aneurysms increases the risk for rupture in endovascular procedures, just as it does in open procedures. A recent meta-analysis by Chun and colleagues found that patients were more likely to undergo parent vessel sacrifice during an endovascular approach (65%) than during an open surgical approach (37%).¹⁰ Endovascular treatment before cardiac surgery may ultimately lead to more rapid treatment of the underlying valve defect.⁷⁹

Multiple intracranial infectious aneurysms are often encountered and may present a surgical dilemma. Some authors recommend a more aggressive approach to multiple aneurysms, including elective surgical obliteration of all unilateral aneurysms at one operation whenever possible or, in the case of bilateral aneurysms, elective obliteration of the largest aneurysm or the one most likely to have bled.⁶ In view of the equivalent prognosis and hemorrhage rate of patients with multiple and single aneurysms, we recommend identical treatment programs and surgical guidelines for each individual aneurysm. When surgery is indicated in the setting of multiple aneurysms, attempts should be made to obliterate the lesion most likely to have bled, as well as easily accessible aneurysms whose obliteration will not unnecessarily increase surgical morbidity. The remaining aneurysms should be treated individually based on radiographic and clinical follow-up.

Outcomes

The paucity of large series of intracranial infectious aneurysms limits the conclusions that one can make regarding the various therapeutic management options. Ojemann’s analysis of reported cases through 1980 found a 42% mortality rate after antibiotic treatment alone, whereas mortality after antibiotics and surgery was 19%.⁵⁵ Phuong and coauthors reviewed 16 cases of infectious intracranial aneurysms through 1999 and found only an 18% mortality rate.⁴⁰ Likewise, Monsuez and coworkers reported a mortality rate of 25% in their series of 12 patients.⁷ Outcomes after endovascular treatment of infectious aneurysms have recently been promising, with one study finding 35% morbidity associated with the initial hemorrhage, no mortality, and no additional permanent morbidity or mortality in 14 patients treated endovascularly.⁷⁸ The variability in studies reflects selection bias, heterogeneous patient populations, changes in management, and the relatively small number of patients. Unruptured aneurysms in patients in whom appropriate antibiotics have been started have a low associated morbidity and mortality.^5,^6,^8–10,50^,53 ^,54 ^,80 ^,81 Ruptured aneurysms have a worse prognosis with antibiotic therapy alone and an improved outcome with endovascular or surgical treatment.^5,^6,^{8–10,50,53,54,80,81} A prospective study would better elucidate the appropriate management of these patients but is unlikely because of the rarity of infectious aneurysms.