Neurologic complications of infective endocarditis

Introduction

Despite modern advances in the diagnosis and management of infective endocarditis (IE), inpatient mortality rate for patients with IE remains high at 15%–20% [ ]. In IE patients with neurologic complications, mortality has been reported to be as high as 45% [ ]. In literature, the prevalence of neurologic complications in patients with left-sided IE ranges from 20% to 80% in literature as the definition of “neurologic complication” varies from study to study [ ]. Nonetheless, when they do occur, neurologic complications have major implications for the management of IE.

Cerebral emboli/ischemic stroke

Embolic cerebral infarction is by far the most common neurologic complication of left-sided IE. Well-recognized predictors of cerebral embolism are vegetations located on the anterior mitral valve leaflet, left-sided vegetation >10 mm in length, and severe vegetation mobility [ ]. Staphylococcus aureus is not only the most common causative organism of native-valve IE, but also of IE-associated cerebral infarction [ , , ]. Fungi and beta-hemolytic streptococcal species are rare pathogens that give rise to large vegetations and therefore increase cerebral embolism risk [ , , ].

Large cohort studies observed increased stroke risk in patients with IE as early as 40 days before their IE diagnosis [ , , ]. Contemporary data indicate that 29%–47% of IE patients initially presented with stroke symptoms [ , , ]. It has been postulated that the pathogenesis of stroke in these patients is related to systemic inflammation, which creates a proinflammatory milieu for accelerated atherosclerosis and thromboembolic events [ , ]. Initiating the appropriate antimicrobial treatment is by far the most beneficial medical therapy for reducing septic embolism [ , ]. In one prospective cohort study, antimicrobial therapy decreased the incidence of embolic stroke from 4.82 per 1000 patient days in the first week of therapy to 1.71 per 1000 patient days in the second week [ ]. Antiplatelets were studied as an adjunctive therapy to antibiotics in mitigating the risk of septic embolism. Promising data from animal models of IE suggested that acetylsalicylic acid may facilitate the resolution of valve vegetations [ , ]. However, in a double-blinded randomized control trial (RCT) of 115 IE patients, frequencies of embolic cerebral infarcts were similar in patients who received aspirin 325 mg for 4 weeks after their IE diagnosis and those taking a placebo. Although no difference was observed in rates of intracranial hemorrhage (ICH), the aspirin arm had more bleeding complications overall compared to placebo [ ]. A subsequent retrospective study assessed the effect of long-term antiplatelet therapy on embolization and found that embolism was lower in IE patients who had been on continuous antiplatelet therapy daily for at least 6 months prior to their IE diagnosis [ ]. While this study demonstrated an association between long-term daily antiplatelet therapy and reduced frequency of embolism, it did not provide any data on the risk of ICH in IE patients on continuous antiplatelet therapy. The decision to continue antiplatelet therapy therefore rests on each patient's unique risk–benefit profile.

Ischemic infarcts associated with IE resemble other causes of cardioembolic infarction with regard to imaging patterns. The majority of embolic infarcts associated with IE are clinically asymptomatic and appear as a single punctate lesion with restricted diffusion or multiple tiny foci scattered throughout the brain parenchyma ( Fig. 10.1 ) [ , , ]. A distinction is made between symptomatic embolic stroke (including transient episodes of neurologic deficits) and silent infarcts. Embolic stroke occurs in 20%–40% of patients with IE [ , , ], whereas 48%–82% of IE patients have silent infarcts on magnetic resonance imaging (MRI) [ , , , , ]. Silent infarcts, although clinically asymptomatic by definition, have implications for the urgency and safety of valve surgery as well as long-term neurologic outcome. Septic embolization can occlude large intracranial vessels and cause not only debilitating symptoms but also delay in surgical planning. In one of the largest brain MRI studies of patients with acute IE, 25% of the cohort (33/130 patients) had a considerably large infarct as a result of a large-vessel occlusion (LVO) [ ].