**3. Head and neck**

#### **3.1. Brain**

It is well known that there are many different central nervous system (CNS) manifestations of SE [37]. However, proving direct cause-and-effect relationship has been more challenging. Evidence suggests that septic cerebral embolic events may complicate as many as 40% of cases of IE, with recurrence rates for SE reaching 50% [38]. Cumulatively, manifestations of SE within the cerebral circulation can be divided into cerebral infarction (purely ischemic, purely hemorrhagic, or combined), CNS infection (encephalitis, meningitis, and abscess formation); and vasculopathy (vasculitis, mycotic aneurysm formation), with widely varied clinical presentations [38]. Summary of potential CNS manifestations of IE is provided in **Table 1**.

Involvement of SE within the CNS can be broadly categorized into cerebrovascular and noncerebrovascular event types. Given that approximately 20% of cardiac output is dedicated to supplying the cerebrovascular system, it is no surprise that the brain is among the most commonly involved organs in IE. In fact, it is not uncommon for a cerebrovascular event to precede the formal diagnosis of IE, and to be the trigger for subsequent cardiac work-up [39]. Consistent with the above information, the greatest risk factor for a cerebral SE is left-sided IE, especially when due to *Staphylococcus aureus* infection. For embolic strokes, symptomatology heavily depends on the final resting point of the embolus. In one extreme case, complete cortical blindness followed the rupture of bilateral occipital mycotic aneurysms [40]. Even among patients with a limited duration of initial clinical symptoms, the risk of recurrent brain infarction may be as high as 80% [41]. **Figure 2** demonstrates septic embolism to the brain originating from mitral valve endocarditis.

between intracerebral hemorrhage and ischemic infarction based on clinical symptoms alone, and importantly, the American Stroke Association recommends against the use of intravenous Alteplase in cases of suspected ischemic stroke due to SE because of elevated potential for hemorrhagic conversion [23]. At the time of this publication there is no specific recommendation for or against intra-arterial intervention (e.g., thrombectomy) in the setting of SE causing large vessel occlusion and cerebral infarction, and cases should be evaluated on an

**Figure 2.** An example of septic embolization to the brain (circled) originating from an infected vegetation on the mitral valve (arrow) (source: Ref. [29]. Image used under the terms of the Creative Commons Attribution-Noncommercial-

Septic Embolism in Endocarditis: Anatomic and Pathophysiologic Considerations

http://dx.doi.org/10.5772/intechopen.76766

153

Risk factors for mortality in stroke caused by SE include MRSA infection, older patient age, and larger vegetation size [44]. Patients with right-sided IE can also experience cerebral SE although it is very uncommon and occurs through the so-called "paradoxical embolus" pathway [45, 46]. Prompt evaluation for cerebral SE is critical in any patient presenting with focal neurologic symptoms, and usually starts with computed tomography (CT) of the brain to rule out bleeding, and potentially CT-Angiography to evaluate the cerebral circulation for patency. One must keep in mind that, regardless of clinical symptoms, the majority of patients with IE

Patients with cerebral SE have elevated mortality rates compared to patients presenting with stroke from other etiologies. In fact, baseline mortality of approximately 8–9% may reach nearly 40% in the presence of meningitis, hemorrhage, or brain abscess [39]. In the setting of mild cerebral ischemia, immediate antibiotic therapy combined with valve surgery within 48 h results in improved outcomes, including fewer systemic embolic events and more favorable mortality profile [49]. Recent studies also suggest that an ischemic stroke secondary to IE is unlikely to transform into a hemorrhagic stroke [50]. Primary indications for surgery in the setting of IE include the emergence of heart failure, uncontrolled infection, and embolism prevention [49]. Note that antithrombotic therapy is somewhat controversial in this setting. The American Heart Association guidelines for surgical intervention state that in the absence of severe neurological deficits, cardiac surgery should be considered urgently [50, 51]. In cases

have some evidence of cerebral SE on magnetic resonance imaging (MRI) [47, 48].

individual basis.

Share Alike 3.0 Unported license).

Among patients experiencing CNS complications due to SE, approximately 50–60% have ischemic lesions, with the middle cerebral artery distribution being most commonly affected [42, 43]. Associated symptoms may include contralateral hemiplegia, homonymous hemianopia, dysarthric or aphasic speech, neglect, and sensory loss. It is difficult to differentiate


Adopted from Ref. [6].

**Table 1.** Central nervous system manifestations of infective endocarditis.

**3. Head and neck**

152 Advanced Concepts in Endocarditis

originating from mitral valve endocarditis.

Ischemic stroke Meningoencephalitis Toxic-metabolic

**Table 1.** Central nervous system manifestations of infective endocarditis.

It is well known that there are many different central nervous system (CNS) manifestations of SE [37]. However, proving direct cause-and-effect relationship has been more challenging. Evidence suggests that septic cerebral embolic events may complicate as many as 40% of cases of IE, with recurrence rates for SE reaching 50% [38]. Cumulatively, manifestations of SE within the cerebral circulation can be divided into cerebral infarction (purely ischemic, purely hemorrhagic, or combined), CNS infection (encephalitis, meningitis, and abscess formation); and vasculopathy (vasculitis, mycotic aneurysm formation), with widely varied clinical presentations [38]. Summary of potential CNS manifestations of IE is provided in **Table 1**.

Involvement of SE within the CNS can be broadly categorized into cerebrovascular and noncerebrovascular event types. Given that approximately 20% of cardiac output is dedicated to supplying the cerebrovascular system, it is no surprise that the brain is among the most commonly involved organs in IE. In fact, it is not uncommon for a cerebrovascular event to precede the formal diagnosis of IE, and to be the trigger for subsequent cardiac work-up [39]. Consistent with the above information, the greatest risk factor for a cerebral SE is left-sided IE, especially when due to *Staphylococcus aureus* infection. For embolic strokes, symptomatology heavily depends on the final resting point of the embolus. In one extreme case, complete cortical blindness followed the rupture of bilateral occipital mycotic aneurysms [40]. Even among patients with a limited duration of initial clinical symptoms, the risk of recurrent brain infarction may be as high as 80% [41]. **Figure 2** demonstrates septic embolism to the brain

Among patients experiencing CNS complications due to SE, approximately 50–60% have ischemic lesions, with the middle cerebral artery distribution being most commonly affected [42, 43]. Associated symptoms may include contralateral hemiplegia, homonymous hemianopia, dysarthric or aphasic speech, neglect, and sensory loss. It is difficult to differentiate

encephalopathy

Cerebritis Seizure Spinal cord infarction

Abscess formation Headache Discitis/osteomyelitis

Ventriculitis Cranial neuropathies

Ependymitis Mononeuritis multiplex

Myeloradiculitis

Myalgia

**Cerebrovascular Infections Secondary complications Rare complications**

**3.1. Brain**

Intracerebral hemorrhage

Subarachnoid hemorrhage

Mycotic aneurysm formation

Adopted from Ref. [6].

**Figure 2.** An example of septic embolization to the brain (circled) originating from an infected vegetation on the mitral valve (arrow) (source: Ref. [29]. Image used under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license).

between intracerebral hemorrhage and ischemic infarction based on clinical symptoms alone, and importantly, the American Stroke Association recommends against the use of intravenous Alteplase in cases of suspected ischemic stroke due to SE because of elevated potential for hemorrhagic conversion [23]. At the time of this publication there is no specific recommendation for or against intra-arterial intervention (e.g., thrombectomy) in the setting of SE causing large vessel occlusion and cerebral infarction, and cases should be evaluated on an individual basis.

Risk factors for mortality in stroke caused by SE include MRSA infection, older patient age, and larger vegetation size [44]. Patients with right-sided IE can also experience cerebral SE although it is very uncommon and occurs through the so-called "paradoxical embolus" pathway [45, 46]. Prompt evaluation for cerebral SE is critical in any patient presenting with focal neurologic symptoms, and usually starts with computed tomography (CT) of the brain to rule out bleeding, and potentially CT-Angiography to evaluate the cerebral circulation for patency. One must keep in mind that, regardless of clinical symptoms, the majority of patients with IE have some evidence of cerebral SE on magnetic resonance imaging (MRI) [47, 48].

Patients with cerebral SE have elevated mortality rates compared to patients presenting with stroke from other etiologies. In fact, baseline mortality of approximately 8–9% may reach nearly 40% in the presence of meningitis, hemorrhage, or brain abscess [39]. In the setting of mild cerebral ischemia, immediate antibiotic therapy combined with valve surgery within 48 h results in improved outcomes, including fewer systemic embolic events and more favorable mortality profile [49]. Recent studies also suggest that an ischemic stroke secondary to IE is unlikely to transform into a hemorrhagic stroke [50]. Primary indications for surgery in the setting of IE include the emergence of heart failure, uncontrolled infection, and embolism prevention [49]. Note that antithrombotic therapy is somewhat controversial in this setting. The American Heart Association guidelines for surgical intervention state that in the absence of severe neurological deficits, cardiac surgery should be considered urgently [50, 51]. In cases of severe ischemic stroke, it is recommended to delay surgery by at least 4 weeks, and with hemorrhagic stroke (usually a more severe complication) at least 4 weeks are recommended prior to proceeding with cardiac surgery [50].

**4.2. Thoracic aorta**

**4.3. Pulmonary artery**

**4.4. Pulmonary circulation**

aortotracheobronchial fistula [66, 67].

Mycotic aneurysms of the aorta have been described as a consequence of septic emboli from infective endocarditis [64]. Clinical management of these lesions is challenging, partly due to the presence of active infection within the aneurysm itself, and partly due to the associated inflammatory changes and altered (e.g., diminished) structural integrity of the involved aorta [65]. Mycotic aortic aneurysms are associated with significant mortality and complications, including the potential for the development of aortoesophageal or

Septic Embolism in Endocarditis: Anatomic and Pathophysiologic Considerations

http://dx.doi.org/10.5772/intechopen.76766

155

Pulmonary artery aneurysms (PAA) of infectious etiology are among less frequently seen complications of endocarditis [68, 69]. They are similar to mycotic aneurysms, with the main difference being the location of occurrence [70]. PAAs (also referred to as Rasmussen's aneurysms) can be seen in patients with tuberculosis. However, there have been recent cases with PAAs being associated with endocarditis [70, 71]. These aneurysms require prompt surgical treatment given published mortality rates of approximately 50% [72]. Patients with aneurysms that are symptomatic or >6 centimeters in size are candidates for surgery [73]. Data regarding surgical treatment are limited; however, recent studies have shown that steel coil embolization may be applicable in this setting [70, 74–76]. While PAAs are uncommon in endocarditis, they

Pulmonary SE are relatively common complications of right-sided IE (RSIE). As outlined in previous sections, any areas through which large volume of blood transits will be inherently susceptible to SE. The pulmonary arterial circuit is no exception in this regard. From an anatomic standpoint, evidence suggests that septic pulmonary emboli (SPE) involve both upper and lower lobes, with bilateral upper lobes involved in >70% of patients, and peripheral or subpleural zones involved in >90% of cases [58]. Centrally located lesions were noted in only about 25% of instances [58]. SPE are distinct from other types of pulmonary emboli because of their tendency to form cavitary lesions with air-fluid levels [77]. A significant proportion of patients with RSIE are intravenous drug users [78, 79], although there is an increasing number of patients with SPE who present with IE due to implanted cardiac devices [80, 81]. SPE in intravenous drug users can manifest with empyema, and is most likely to be associated with endocarditis due to *S. aureus* infection [82]. Other common complications of SPE include pulmonary abscess and pulmonary nodules [77]. If patients with either empyema or a pulmonary abscess are identified, it is crucial to continue intravenous antibiotics and preform an incision and drainage prior to any required valve surgery [83]. Waiting is not recommended as a strategy in these patients, mainly because of the risk of further complications associated with therapeutic delays [83, 84]. Pulmonary and perivalvular abscess should be suspected in

should be considered in patients with IE that present with pulmonary symptoms.

intravenous drug users who fail to respond to antibiotic administration [84].

#### **3.2. Eyes**

Septic embolization involving ocular and facial structures is extremely rare. There is, however, fragmentary case-based evidence for such occurrences. In one example, Dadu et al. [52], described SE involving the ophthalmic artery and the inferior muscular artery, resulting in diplopia due to medial rectus muscle paralysis. In that particular case, IE of the mitral valve was causative. In another rare occurrence, Cumurcu et al. [53], describe a case of a septic metastasis to the iris, resulting in iris abscess and endophthalmitis.

## **3.3. Thyroid**

The possibility of SE to the thyroid has been proposed in 1959 by Richie while describing acute suppurative thyroiditis in a child [54]. Cabizuca et al. [55], reported an unusual case of IE leading to acute thyroiditis, presumably due to septic embolization. Although undoubtedly uncommon, the paucity of literature reports in this area is likely due to limited awareness and under-recognition of similar clinical presentations.
