Journal of Neuroscience Nursing:
Infectious Intracranial Aneurysms: Triage and Management
Gulek, Bernice G.; Rapport, Richard
Richard Rapport, MD, is a neurosurgeon and a clinical professor at the University of Washington School of Medicine, and actively working with the Neurosurgical Population, Department of Neurological Surgery, Harborview Medical Center, University of Washington School of Medicine, Seattle, WA.
Questions or comments about this article may be directed to Bernice G. Gulek, MS ARNP, at email@example.com. She is an acute care nurse practitioner and is currently working at the Harborview Medical Center Department of Neurological Surgery, University of Washington, Seattle, WA.
ABSTRACT: Infectious intracranial aneurysms are a rare but serious potential complication of subacute endocarditis. Early diagnosis and treatment is essential to prevent devastating neurological deficits and mortality. Because nurse practitioners' roles expand into acute care as well as urgent care settings, they are frequently involved in the care of this population. Identifying the patients at risk, ordering appropriate studies, and initiating goal directed therapy are vital to outcomes. For nurse practitioners who are involved in care of neuroscience populations, it is important to be familiar with disease processes. This article provides a literature review of the topic, explores diagnostic methods, discusses management strategies, and presents an illustrative case.
Infectious Intracranial Aneurysms: Triage and Management
Infectious intracranial aneurysms (IIAs) are rare neurovascular lesions believed to represent 2% to 6% of all intracranial aneurysm in adults. The incidence in the pediatric population may be as high as 10%. The true incidence of intracranial infectious aneurysms is underestimated because the reported population excludes undiagnosed asymptomatic IIAs, those spontaneously resolved, and patients dead because of subarachnoid hemorrhage outside of medical attention (Kovoor, Jayakumar, Srikanth, & Sampath, 2001; Luders, Steinmetz, & Mayberg, 2005; Nakahara et al., 2006; Ojemann, 1995).
IIAs are commonly caused by subacute bacterial endocarditis (SBE) resulting in circulation of infected emboli. When such emboli lodge in the vasa vasorum of distal cerebral arteries, it causes intense inflammation in the media adventitia and subsequent weakening of the vessel wall leading to aneurysm formation (Molinari, 1972; Molinari, Smith, Goldstein, & Satran, 1973). This occurs when pulsation against the necrotic wall of an occluded or weakened recanalized vessel creates aneurysmal enlargement. Such a mechanism is suspected to be the reason for the late appearance of aneurysms even during antibiotic treatment, although they may occur as early as 24 hours. The evolution of IIAs is unpredictable; neurological sequelae may develop even after the initiation of antibiotic therapy in up to 30% of the cases. Intracranial infectious aneurysms may spontaneously resolve, decrease in size, remain unchanged, or enlarge. In addition, new aneurysms may develop or rupture (Chapot et al., 2002; Kovoor et al., 2001; Luders et al., 2005; Nakahara et al., 2006).
The presence of bacterial endocarditis predisposes the patient to IIAs. Despite the fact that the epidemiology of endocarditis in developed countries has profoundly changed in recent years, the incidence has remained stable (Peters, Harrison, & Lennox, 2006; Moreillon & Que, 2004). Traditional risk factors such as rheumatic heart disease have been replaced by the presence of prosthetic heart valves, dental procedures or tooth abscess, nosocomial bacteremia, mitral or aortic valve insufficiency or stenosis, and intravenous drug use (Luders et al., 2005; Peters et al., 2006). The age of onset for the development of intracranial aneurysms has increased from 30 to 40 years in the preantibiotic era to the current 47 to 69 years. Contributing factors to the increased age of onset are antibiotic use, prosthetic valve placement, and exposure to nosocomial bacteria. Mechanical heart valves pose a higher infection rate in the first 3 months postoperatively than biological valves; however, the infection rate for the two converges to the same rate at 5 years (Mylonakis & Calderwood, 2001).
Septic emboli from the SBE to the vascular tree promote the formation of IIAs by weakening the arterial wall. Aneurysm of extravascular origin arise because of local extension of infection followed by invasion of large arteries commonly associated with middle ear disease, cavernous sinus thrombophlebitis, meningitis, adjacent osteomyelitis of the skull, sinus infection, or postoperative infection. Bacterial aneurysms may also occur in the absence of obvious inflammatory focus elsewhere in the body. These have been termed primary or cryptogenic intracranial infectious aneurysms (Bullock, Dellen, & ven den Heever, 1981; Kojima, Saito, & Kim, 1989; Kovoor et al., 2001; Venkatesh, Phadke, Kalode, Kumar, & Jain, 2000).
IIAs may arise anywhere in the central nervous system. However, they most commonly occur in the distal branch of the middle cerebral artery (MCA), most likely because these vessels have the greatest blood flow. In contrast, congenital aneurysms tend to be located centrally in the circle of Willis. Whereas one study found that 77% of all angiographically proven infective intracranial aneurysms occurred in the distal MCA (Ojemann, 1995), another reported unusual predominance in the posterior cerebral territory (Venkatesh et al., 2000). Multiple IIAs can be found in up to 25% of cases (Bohmfalk, Story, Wissinger, & Brown, 1978; Dorsch, 1997; Luders et al., 2005).
Hemorrhage from IIAs is rare but associated with mortality reported as high as 80% in some studies (Bohmfalk et al., 1978; Chukwudelunzu, Brown, Wijdicks, & Steckelberg, 2002; Monsuez et al., 1989; Phuong, Link, & Vijdicks, 2002). Patients who have left-sided endocarditis often initially present with systemic symptoms, including malaise, fever, and weight loss. However, those who eventually are found to have IIAs may first complain of focal neurological symptoms, although aneurysmal formation itself from embolic foci is usually clinically silent. In a series of clinical studies, embolic infarction causing focal neurological deficit was the most common neurological presentation (Luders et al., 2005; Peters et al., 2006; Pruitt, Rubin, Karchmer, & Duncan, 1978; Tunkel & Kaye, 1993). In addition, patients may present with localized severe headache, confusion, seizure, meningitis, and aphasia (Cavassini, Meuli, & Crancioli, 2004; Chun et al., 2001; Dorsch, 1997; Luders et al., 2005; Peters et al., 2006; Phuong et al., 2002; Pruitt et al., 1978; Tunkel & Kaye, 1993). Mass effect from the enlarging or ruptured aneurysm may cause cranial nerve palsy or focal neurological deficits (Dorsch, 1997; Luders et al., 2005; Peters et al., 2006; Phuong et al., 2002; Pruitt et al., 1978).
The most common pathogens responsible for IIAs are Streptococcus viridans and Staphylococcus aureus. These organisms represent 51% to 91% of all cases combined. The remaining causative organisms include enterococci, beta-hemolytic streptococci, and coagulase-negative staphylococci. More infrequently reported etiologic agents include gram-negative rods and fungi (Barrow & Prats, 1990; Bullock et al., 1981; Corr, Wright, & Handler, 1995; Frazee, Cahan, & Winter, 1980). Endocarditis caused by more virulent microorganisms such as S. aureus and Enterobacteriaceae results in higher numbers of intracranial embolic events (Peters et al., 2006; Tunkel & Kaye, 1993).
Early diagnosis of IIAs is extremely critical because the rupture of an aneurysm is likely to cause serious neurological deficits. After careful physical examination, the most useful initial study in the setting of endocarditis and/or focal neurological deficit is a computed tomography (CT) of the head. CT scanning is a sensitive method for revealing intracranial blood, mass effect, hydrocephalus, infarct, and intracranial abscess formation. Vascular pathology can be assessed further by CT angiography (Peters et al., 2006) or magnetic resonance angiography (Ahmadi, Tung, Giannotta, & Destian,1993). However, a four-vessel cerebral angiography may be necessary in the event of peripheral and atypical locations as well as the fact that the abnormalities are often too small to capture by other imaging techniques (Metens et al., 2000; Figure 1).
The clinical presentation of patients with intracranial infectious aneurysms dictates evaluation and management. Those with known endocarditis accompanied by focal neurological deficit should be urgently investigated with diagnostic four-vessel cerebral angiography (Bohmfalk et al., 1978; Hourihane, 1970; Kannoth, Thomas, Nair, & Sarma, 2008; Ng, Wong, & Skene-Smith, 1975). Many patients present with neurological symptoms who are not known to have endocarditis, although they may be septic. In younger patients with otherwise unexplained hemiplegia, the presumptive diagnosis is SBE and associated IIA (Lerner & Weinstein, 1966). In addition, if a cardiac murmur is noted, cerebral angiography should be obtained for definitive diagnosis. Even patients who do not have a cardiac murmur or other suggestive symptoms of endocarditis but are found to have IIA should be considered to have SBE until proven otherwise (Bohmfalk et al., 1978).
Patients with known infective endocarditis and IIAs but who remain neurologically asymptomatic should be followed by cerebral angiography in 7- to 14-day intervals even on treatment because of the high risk of rupture and mortality rate that accompanying that lesion (Bohmfalk et al., 1978; Hourihane, 1970; Figure 2).
Treatment and Management
The current treatment modalities for IIAs remain controversial because of the lack of randomized controlled trials. The most common options include conservative management with antibiotic treatment alone or combined with surgical and/or endovascular treatment. Decisions regarding treatment should be guided by associated factors including the presence of hematoma, increased intracranial pressure, or the involvement of eloquent brain tissue (close to areas of primary motor, sensory, or speech cortex) distal to the lesion (Chun et al., 2001; Luders et al., 2005; Peters et al., 2006). The location of the aneurysm and the number of aneurysms present should also be considered.
A patient with known unruptured aneurysms on antibiotic therapy should undergo serial cerebral angiography to document improvement or resolution every 7 to 14 days, then 1 and 3 months thereafter. Some authors have recommended yearly follow-up after that (Kojima et al., 1989). If the aneurysm is stable on two consecutive studies, it is probably resolved. An aneurysm that is filling and emptying slowly at the time of angiography presents a smaller risk of rupture (Bohmfalk et al., 1978). If the aneurysm is large, not resolving, or enlarging despite antibiotic treatment, then surgical or endovascular intervention is indicated (Kojima et al., 1989).
Patients who present with ruptured infectious aneurysm and a mass effect should be considered for early intervention. Depending on the morphology and the location of the lesion, the surgical options include excision or clipping. Proximal bacterial aneurysms are more threatening than those distally located and are associated with a mortality rate up to 58% (Kovoor et al., 2001; Peters et al., 2006). These are best treated by craniotomy in the acute phase because the aneurysm wall is most often friable, and it is difficult to treat by coil embolization (Campbell & Burklund, 1953; Hara, Hosoda, Wada, Kimura, & Kohmura, 2006; Peters et al., 2006; Roach & Drake, 1965). Artery-to-artery bypass graft may be necessary to preserve perfusion of brain tissue in the affected vascular territory (Peters et al., 2006). Because the true incidence of this illness is not well known, the best timing of definitive treatment remains uncertain. One study suggested that in patients who presented with subarachnoid hemorrhage while on antibiotic treatment, the median time to bleed was 23 days, with a range between 5 and 35 days (Frazee et al., 1980).
Endovascular obliteration of intracranial aneurysms may be an option when the lesion is not in eloquent vascular territory and if the patient does not have hematoma causing mass effect or increased intracranial pressure (Chapot et al., 2002). In this situation, treatment with endovascular coiling can be accomplished with minimal manipulation and risk of rupture to the arterial wall. However, this may sometimes require parent artery sacrifice (Chun et al., 2001; Peters et al., 2006). If indicated, intra-arterial amobarbital (Amytal) testing can be done to determine eloquence of the vascular territory distal to the lesion.
The embolization of arteries with the use of coils has been an advance in the management of patients at risk for aneurysm rupture, but the introduction of foreign material into the infected vessel may theoretically lead to prolonged infection and/or abscess formation (Peters et al., 2006). There is a case report of a patient with an aneurysm of the left internal carotid artery suspected to be infectious that was coiled 3 months before being readmitted with fever, aphasia, and right hemiparesis. After the initiation of antibiotic therapy, the patient became neurologically asymptomatic within 72 hours.
A 48-year-old man presented to the emergency department with a history of pancreatic abscess secondary to pancreatitis and alcoholism. He had a splenic rupture because of a fall while intoxicated and underwent emergent splenectomy. During the hospital stay, he became septic and then developed endocarditis and focal neurological symptom, including headache, decreased mental status, and seizure activity. His blood cultures grew Enterococcus faecalis and Enterococcus durans. Transthoracic echo demonstrated anterior and posterior leaflet vegetations on the mitral valve as well as a patent foramen ovale. Subsequently, IIAs were found in both MCAs. He was placed on vancomycin and streptomycin for a total of 6 weeks assistance of infectious disease services and was discharged on home with antibiotic home infusion therapy.
He returned for follow-up in 6 weeks for a diagnostic four-vessel angiogram, which revealed bilateral MCA aneurysm enlargement. His only complaint during 6 weeks follow-up was mild intermittent headache without any neurological deficit. His repeat transthoracic echo demonstrated resolution of vegetations.
His bilateral MCA IIAs warranted surgical treatment secondary to aneurysmal enlargement while on appropriate antibiotic therapy. He was admitted for a planned two-stage craniotomy. He first underwent right frontotemporal craniotomy and superficial temporal artery to MCA bypass graft with excision of the right-sided MCA aneurysm. One week later, this operation was followed by a left frontotemporal craniotomy and radial artery bypass graft with resection of the second aneurysm. He had cerebral angiography after each surgical resection that revealed patent grafts without stenosis or residual aneurysms.
The patient remained hospitalized in the neurointensive care unit until neurologically deemed to be stable. During the neurointensive care unit stay, he was monitored by transcranial Doppler studies, which were obtained daily, and SPECT scans twice a week after his cranial bypass surgery to monitor his graft patency. He was started on a full-dose aspirin to preserve graft patency.
Although he initially did demonstrate abnormal graft velocities evidenced on cranial Doppler studies, he never developed neurological deficit or any new neurological symptoms. He was transferred to the acute care floor then to inpatient rehabilitation where he continued to recover. He was discharge to home and able to take care himself independently. He returned to clinic visit again 6 weeks after his discharge from rehabilitation. His follow-up CT angiogram and transcranial Doppler studies showed patent bypass graft and no residual of aneurysms.
Implications to Profession
Because the diagnostic studies are getting more specific and sensitive, the nurse practitioner and the nurses will encounter more patients with IIAs. Because nurse practitioners and nurses are being familiar with IIA's disease processes, performing frequent neurological examination will prevent catastrophe and expedite timely intervention. Baseline neurological examination will allow comparison and help identify change early. Nurse practitioners should follow imaging results and discuss with the team further treatment plans.
Administration of antibiotics in a timely manner will provide maximum effect. Furthermore, follow cultures and sensitivity to identify most suitable antibiotic regimen over time. Patient education plays a very important role for full recovery and should include signs and symptoms to monitor, when to seek medical attention, importance of complying with medication regimen, and keeping the follow-up appointments.
He is a young patient and should be referred to the Alcoholics Anonymous program for treatment of his alcoholism. Evidence has been shown that a combination of treatment along with involvement in the Alcoholics Anonymous program resulted in the most positive outcomes. Besides a reduction or cessation of drinking, positive outcomes have been reported in self-efficacy, social support, and improved coping skills (Seppala, DuPont, Tonigan, & Zenmore, 2005). Failure to adhere to the program is one of the major problem; this may be avoided if followed by a provider, either a nurse practitioner or a psychologist who specializes in this area.
IIAs are rare complications of infectious endocarditis; however, the cerebrovascular lesions may be associated with devastating neurological injury. The patient may present with or without neurological deficit. In the absence of randomized trials, the best management of these aneurysms is still debated, although diagnostic and therapeutic techniques have improved care. Early diagnosis and treatment may decrease morbidity and mortality. Nurse practitioners and nurses are in a position to help identify and manage those patients with IIA.
The authors thank Dr. Laligam N. Sekhar for encouraging them to write about this topic and Dr. M. Nathan Nair for his early review of this topic.
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