Anticoagulation has established benefit in reducing the risk of stroke in persons with atrial fibrillation. Consensus supports the use of long-term oral warfarin therapy for atrial fibrillation in most cases. Risk stratification systems are helpful in deciding whether anticoagulation is warranted (Gage et al., 2001). Aspirin (325 mg/day) is the recommended agent when warfarin is contraindicated. Recent studies suggest that addition of clopidogrel (75 mg/day) is also worthwhile (Connolly et al., 2009). Standard practice is to start warfarin at least 3 weeks before elective cardioversion in patients with atrial fibrillation of more than 2 days’ duration. Warfarin therapy is continued at least until a normal rhythm has been maintained for 4 weeks. Myocardial infarcts, especially apical, anterolateral, or large infarcts, carry a risk of embolic stroke. In most cases, infarction occurs within a week, but the risk persists for approximately 2 months. Therefore, it is recommended to use heparin for those patients not on thrombolytic therapy after MI, and to continue warfarin for 3 months if they have an increased risk of embolism. The groups with increased risk are those with congestive heart failure, previous emboli, a mural thrombus, left ventricular dysfunction, substantial wall motion abnormalities, or atrial fibrillation.

Emboli are an important cause of death in people with rheumatic valvular disease. The risk of embolism increases in the presence of atrial fibrillation or intraatrial thrombus or in patients with a history of emboli; long-term warfarin treatment is the recommended treatment. Addition of low-dose aspirin (50-100 mg/day) is recommended for recurrent systemic emboli or left atrial thrombus despite adequate warfarin therapy.

Mitral valve prolapse is a common anomaly, especially in young women, and is a recognized source of cerebral emboli. The risk of embolism is relatively small, and long-term warfarin therapy is the recommended treatment for persons who have had previous embolic phenomena or are in atrial fibrillation. Aspirin therapy (50-325 mg/day) is the recommended treatment for patients with mitral valve prolapse and transient cerebral ischemic attacks of uncertain nature.

Patent foramen ovale is common in asymptomatic subjects and does not seem to be a risk factor with cryptogenic ischemic stroke or transient ischemic attacks (TIAs), especially when small or occurring as an isolated cardiac abnormality. Those that are large or associated with an atrial septal aneurysm are at higher risk of stroke, but whether to choose treatment with aspirin, warfarin, or surgical or percutaneous closure for stroke prophylaxis is unclear.

Among patients with a history of cardiogenic emboli, recurrent stroke is more likely in those with cardiac valve disease and congestive heart failure. Nevertheless, the main cause of death in such patients is from the heart disease itself rather than neurological complications. The conversion of a cerebral infarct into a hemorrhage is a concern when patients with stroke from cardiogenic emboli are anticoagulated. The concern is especially justified in patients with large infarcts or when imaging studies suggest preexisting hemorrhagic transformation. With small infarcts, it is good practice to initiate anticoagulation therapy only if initial computed tomography (CT) shows no evidence of major hemorrhagic transformation. With large infarcts, delay anticoagulation for 3 to 7 days, and when indicated, begin with warfarin alone without bridging heparinoids.

Syncope

Transitory global cerebral ischemia secondary to cardiac arrhythmia often causes syncope. Most normal people have fainted at least once. Nonspecific premonitory symptoms such as visual disturbances, paresthesias, and lightheadedness may precede the syncope (Soteriades et al., 2002). Syncope usually is associated with loss of muscle tone, but prolonged ischemia causes tonic posturing and irregular jerking movements that are easily mistaken for seizures (Stokes-Adams attacks). The syncopal patient is pale, and postictal confusion is absent or short lived, usually lasting less than 30 seconds. Obstructed outflow from aortic stenosis or left atrial tumor or thrombus is one cardiac cause of syncope. Other causes are arrhythmias, especially from ventricular tachycardia or fibrillation, chronic sinoatrial disorder or sick sinus syndrome, and paroxysmal tachycardia. Placement of implantable loop recorders allows the recording of electrocardiographic data during spontaneous syncopal events. This strategy increases the diagnostic rate and permits appropriate treatment to be instituted (Farwell et al., 2006). Arrhythmia is detectable in 25% to 46% of patients with syncope, and another 24% to 42% will be in sinus rhythm during a clinical event, which is therefore not attributable to a disturbance of cardiac rhythm (McKeon et al., 2006). Additional causes of syncope are central and peripheral dysautonomias, postural hypotension, and endocrine and metabolic disorders. (Discussions of vasovagal syncope and the prolonged QT-interval syndrome are in Chapter 49B.)

Cardiac Arrest

Brain function is critically dependent on the cerebral circulation. The brain receives approximately 15% of the total cardiac output. Ventricular fibrillation or asystole leads to circulatory failure, which can cause irreversible anoxic-ischemic brain damage if it lasts for more than a critical time. The prognosis generally depends on age, the duration of the arrest before institution of cardiopulmonary resuscitation, and the interval before initiation of defibrillating procedures. The prognosis is better when the cause of circulatory arrest is ventricular fibrillation rather than asystole.

The pathophysiology of neurological damage secondary to transitory interruption of cerebral blood flow is unclear. Suspected mechanisms are the accumulation of intracellular calcium, increased extracellular concentrations of glutamate and aspartate, and increased concentrations of free radicals.

In the mature brain, gray matter generally is more sensitive to ischemia than white matter, and the cerebral cortex is more sensitive than the brainstem. (The premature brain has the reverse pattern of sensitivity; see Chapter 60.) Cerebral or spinal regions lying between the territories supplied by the major arteries (watershed areas) are especially vulnerable to ischemic injury.

The severity of neurological complications of circulatory arrest correlates with the duration of the arrest. Brief arrests (<5 minutes in duration) cause temporary loss of consciousness and impaired cognitive function. A demyelinating encephalopathy may occur to 10 days later. Characteristic of the encephalopathy are increasing cerebral dysfunction with cognitive disturbances and pyramidal or extrapyramidal abnormalities that may lead to a fatal outcome. Thus, some patients regain consciousness after several hours, with the subsequent development of progressive neurological deficits affecting cognitive and cortical function: intellectual decline, seizures, visual agnosia, cortical blindness, amnestic syndromes, and personality changes. Less common residua are the locked-in syndrome, parkinsonism and other extrapyramidal syndromes, abnormal ocular movements, bilateral brachial paresis, and action myoclonus. Spinal cord dysfunction is uncommon and usually involves the watershed region at T5; flaccid paraplegia with sensory loss, areflexia, and sphincter dysfunction are the immediate findings.

Prolonged cardiac arrest causes widespread and irreversible brain damage characterized by prolonged coma leading to a persistent vegetative state. Prolonged coma and loss of brainstem reflexes indicate a poor prognosis for survival or useful recovery. Therapeutic hypothermia initiated rapidly after the arrest improves neurological outcome (Bernard et al., 2002). Absence of the pupillary response to light and absence of motor recovery better than extensor posturing at 72 hours are perhaps the most useful clinical guides to prognosis (see Chapter 5 for further discussion). These features of the clinical examination, along with measurement of neuron-specific enolase and recording of median-derived somatosensory evoked potentials (to determine whether the N20 component is absent bilaterally), can be helpful in prognostication, although recent data question whether these same tests and time frames apply in patients treated with hypothermia (Rossetti et al., 2010).

Complications of Cardiac Catheterization and Surgery

Cardiac catheterization in adults causes large cerebral emboli in less than 1% of cases; for unexplained reasons, these more often involve the posterior than the anterior circulation. The frequency of large cerebral emboli after percutaneous transluminal coronary angioplasty is less than 1% and may involve either the carotid or vertebral circulation. The risk of stroke, however, is greater in patients with acute MI treated by angioplasty.

Hypoxia and emboli are the usual causes of “post-pump” encephalopathy, seizures, and cerebral infarction after cardiac surgery. Type of surgery, symptomatic cerebrovascular disease, diabetes mellitus, and advanced age are important risk factors for neurological complications (Boeken et al., 2005). Ascertaining the degree of functionally significant cerebrovascular disease is an essential part of the preoperative evaluation (McKhann et al., 2006). The causes of postoperative psychoses or encephalopathy are metabolic disturbances, medication, infection, and multiorgan failure. Intracranial infection should be suspected when behavioral disturbances develop several weeks postoperatively in patients receiving immunosuppressive agents. The usual causes of postoperative seizures are focal or generalized cerebral ischemia, electrolyte or metabolic disturbances, and multiorgan failure. Intracranial hemorrhage is a rare complication of cardiopulmonary bypass. Cognitive changes after cardiac bypass surgery are detectable in 53% of patients at discharge, some of which persist. However, the previously described late cognitive decline that occurs years following cardiac bypass surgery is similar to that found in age-matched patients with coronary artery disease managed without surgery (Selnes et al., 2008). Compression or traction injuries to the brachial plexus, especially the lower trunk, and the phrenic and recurrent laryngeal nerves may occur during cardiac surgery. Other common early complications of cardiac transplantation are organ rejection followed by cardiac failure and the side effects of immunosuppressive drugs. Cerebral air embolism may require hyperbaric oxygen therapy combined with aggressive resuscitation (Hinkle et al., 2001). Infection (meningitis, meningoencephalitis, or cerebral abscess) secondary to immunosuppressive therapy is the most important late complication. The infecting organisms include Aspergillus, Toxoplasma, Cryptococcus, Candida, Nocardia, and viruses including JC virus. An increased risk of lymphoma and reticulum cell sarcoma has been observed in patients on long-term immunosuppressive agents. Primary central nervous system (CNS) lymphoma may be difficult to distinguish clinically or radiologically from infection, and biopsy may be necessary (see Chapters 33A and 52C).

Stroke occurs in approximately 5% of patients undergoing coronary artery bypass surgery. The risk is increasing because of the increasing number of procedures in older patients with more severe vascular disease, and in complicated combined procedures such as bypass surgery plus valve replacement (Nussmeier, 2002). Other risk factors include proximal aortic atherosclerosis, hypertension, diabetes, and female gender. The mechanism is either embolic or, less commonly, a watershed infarction from hypoperfusion. A history of previous stroke also increases the risk, but a carotid bruit or radiological evidence of atherosclerotic disease of the carotid artery does not. Carotid endarterectomy preceding cardiac surgery is not justified.

A few patients who fail to recover consciousness after surgery, despite the absence of any metabolic cause, probably have suffered diffuse cerebral ischemia or hypoxia. Hemispheric or multifocal infarction (Fig. 49A.1) is responsible in some cases. In evaluating patients with postoperative neurological deficits, diffusion-weighted magnetic resonance imaging (MRI) is more sensitive than CT to ischemic change and may reveal multiple small embolic infarcts (Wityk et al., 2001).

Fig. 49A.1 A, Noncontrast computed tomographic (CT) scan of brain performed to evaluate confusion and left-sided weakness in a 76-year-old man 3 days post coronary artery bypass. B, Multiple bilateral ischemic lesions can be seen on diffusion-weighted magnetic resonance imaging (MRI) that are not conspicuous on CT scan.

Neurological Complications of Medication

Infectious and neoplastic complications of immunosuppressive agents have already been discussed in previous sections. Other adverse effects associated with corticosteroid treatment are behavioral disturbances, psychoses, postural tremor, cataracts, osteoporotic fractures, and proximal weakness with type II muscle fiber atrophy. Benign intracranial hypertension may occur during treatment with or on withdrawal of corticosteroids. Neurological complications of cyclosporine and other calcineurin inhibitors include tremor, seizures, focal deficits, paresthesias, encephalopathy, and ataxia. Sirolimus is an alternative immunosuppressant in solid-organ transplant and appears to have less neurotoxicity than the calcineurin inhibitors.

Among antiarrhythmic agents, amiodarone causes tremor, sensorimotor peripheral neuropathy, myopathy, ataxia, optic neuropathy, and pseudotumor cerebri. Procainamide may unmask latent myasthenia gravis or precipitate a lupus-like syndrome with secondary vascular occlusive complications that probably are associated with lupus anticoagulant and antiphospholipid antibodies. Quinidine has neurological side effects similar to those of procainamide and causes headache, tinnitus, and syncope.

Lidocaine and related agents may cause seizures, tremor, paresthesias, and confusional states. Calcium channel–blocking agents occasionally cause encephalopathy. Beta-blockers are associated with mental changes, paresthesias, and disturbances of neuromuscular transmission, and digoxin and thiazide diuretics with an encephalopathy and disturbances of color vision.

Infective Endocarditis

The incidence of infective endocarditis has been increasing because of intravenous substance abuse and the increasing use of prosthetic cardiac valves. The overall incidence of neurological complications of infective endocarditis is approximately 25% to 35% but varies with the infecting organism. Such complications are the initial sign or major complaint in 25% to 50% of patients and are associated with a significantly higher mortality rate. Neurological manifestations are especially common in patients with mitral valve abnormalities and consist of embolic or hemorrhagic stroke and infections such as meningitis or brain abscess.

Cerebral mycotic aneurysms (Fig. 49A.2) are recognized complications of infective endocarditis and may result in intracranial hemorrhage. They are generally more distally located than congenital berry aneurysms. The pathogenesis of mycotic aneurysms is unclear. The most likely cause is impaction of infected material in the vasa vasorum, with resulting destruction of the wall of an artery. Intraluminal occlusion of the vessel by infected material, with subsequent aneurysmal formation, is less likely but has been documented in some cases. Mycotic aneurysms may be clinically silent and sometimes resolve with antibiotic therapy. They are less common but occur earlier in acute than in subacute bacterial endocarditis. Their natural history is unknown.

Fig. 49A.2 Carotid angiogram, lateral view with subtraction. Patient was a 48-year-old man with multiple peripheral mycotic aneurysms (arrows) verified at autopsy.

Intracranial hemorrhage is also caused by septic arteritis that destroys the vessel wall without causing aneurysm and by hemorrhagic transformation of cerebral infarcts. Arteriography distinguishes intracranial hemorrhage from mycotic aneurysm from septic arteritis.

Intracranial bleeding from a ruptured mycotic aneurysm can be the initial feature of an underlying cardiac disorder or may occur during the management of a recognized infective endocarditis. Every patient with infective endocarditis who has a subarachnoid hemorrhage requires four-vessel arteriography. Arteriography should be performed before initiation of anticoagulation therapy unless the neurological symptoms developed after an appropriate course of antibiotics.

Embolization of infected material causes cerebral microabscesses and meningitis. Multiple septic emboli may cause meningoencephalitis or a diffuse encephalopathy characterized by a confusional state, headache, meningismus, and a cerebrospinal fluid (CSF) profile suggesting an aseptic process. The basis of these symptoms probably is multifactorial: infection, vascular occlusion, metabolic abnormalities, and mycotic aneurysms.

Antibiotic therapy to resolve the cardiac infection is the mainstay of treatment and is important in preventing neurological complications (Heiro et al., 2000). Neurological abnormalities usually resolve. Patients with progressive or persistent neurological deficits or abnormalities on CSF examination require imaging studies. MRI findings suggestive of mycotic aneurysm necessitate arteriography. Once mycotic aneurysms have ruptured, curative surgical or endovascular treatment is necessary to prevent re-rupture. Management of unruptured mycotic aneurysms is less clear, and many advocate conservative management with antibiotics and serial imaging. Anticoagulants are usually withheld from patients with infective endocarditis and cerebral embolism until after appropriate antibiotic therapy, owing to the risk of rupture of an unrecognized mycotic aneurysm. Anticoagulation also may increase the risk of hemorrhagic transformation of embolic infarcts.