Cardiovascular intervention neurologic complications …

Sarah Horn MD

Stroke & Vascular Disorders

Updated 04.25.2024
Released 12.18.2007
Expires For CME 04.25.2027

Cardiovascular intervention: neurologic complications

Author: Sarah Horn MD

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Editor: Steven R Levine MD

Cardiovascular intervention: neurologic complications

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Introduction

Overview

Since the introduction of coronary artery bypass graft (CABG) surgery in the 1960s, it has become the most common cardiac surgical procedure performed worldwide (143). Because of this, it is important to review not only the proper diagnosis of associated neurologic complications, but also the strategies that are used to reduce the occurrence of these events. This comprehensive review addresses the central and peripheral nervous system complications of cardiovascular intervention, including coronary artery bypass grafting, aortic surgery, heart valve replacement, cardiac transplantation, ventricular assist device implantation, cardiac catheterization, percutaneous coronary interventions, electrophysiological studies, surgery for congenital heart disease, extracorporeal membrane oxygenation (ECMO), and issues pertaining to pregnancy.

Key points

	• Stroke complicates up to 5% of cardiac surgical procedures.
	• Neurologic complications after cardiac procedures can affect any part of the central or peripheral nervous system
	• Patients with acute stroke after a cardiac procedure may be eligible for acute stroke treatment including mechanical thrombectomy.

Historical note and terminology

There have been dramatic technological advances in therapeutic interventions in the field of cardiology over the past several decades. As a result, the number of patients undergoing cardiac procedures has continued to increase particularly to include the further aging population with significant comorbidities.

Through improvements in technology, along with advances in surgical and anesthetic techniques, there has been a reduction in mortality related to cardiovascular procedures; neurologic complications continue to be recognized as important factors in postoperative morbidity from these procedures. Strokes complicate 1% to 5% of cardiac surgical procedures (76; 173; 13; 85; 57) and seizures complicate 0.5% to 1% (164). Neurologic complication, such as stroke or seizure, is a strong independent predictor of neurologic morbidity and mortality, which can be increased almost tenfold (85).

Cardiac procedures are being performed on an increasingly aged population, often with significant medical comorbidities, such as aging, depression, mild cognitive, carotid artery stenosis, or heart failure that place them at higher risk for neurologic complication (42). Thus, it is important to discuss not only the proper diagnosis of neurologic events, but also the strategies that are used to reduce the occurrence of these events.

This review will address the neurologic complications of cardiac procedures including CABG, ventricular assist device implantation, aortic surgery, heart valve replacement, cardiac transplantation, cardiac catheterization, percutaneous coronary interventions, electrophysiological studies, surgery for congenital heart disease, and issues pertaining to pregnancy.

Clinical manifestations

Presentation and course

The clinical manifestation of neurologic complications after cardiac surgery depends on the level of involvement of the nervous system. Neurologic complications of cardiac procedures can involve any part of the central and peripheral nervous systems (see Table 1).

Table 1. Neurologic Complications Associated with Cardiac Procedures

Procedure	Level of Neurologic Involvement	Complication	Neurologic Findings
CABG	Cerebral cortex	Infarction	Variable depending on the site of the lesion.
	Cerebral cortices or brainstem	Coma	Brainstem or bihemispheric signs. Evidence of hypoxic-ischemic injury, including abnormal brainstem reflexes and abnormal motor response to pain, respiratory disturbances, myoclonic jerks, and seizures.
	Cerebral cortices or brainstem	Cognitive dysfunction	Disturbances in learning, memory, attention, concentration, psychomotor function, language, and other areas of higher cortical functioning.
	Cerebral white matter	Periventricular leukomalacia	Spastic diplegia
	Basal ganglia	Infarction, transient T2 hyperintensities in the caudate and putamen	Movement disorders, including “post pump chorea”
	Pituitary gland	Apoplexy	Headache, visual acuity, field deficits, and cranial nerve palsies
	Optic nerve	Ischemia: anterior ischemic optic neuropathy (AION), posterior ischemic optic neuropathy (PION)	Sudden painless visual loss, loss of visual acuity, optic disc swelling involving mainly the lower part of the visual field in one eye (AION), unilateral or bilateral loss of visual acuity, visual fields or blindness without disc swelling (PION).
	Pupillary changes	Infarction: bilateral anteromedial midbrain	Fixed, dilated pupils
	Retina	Central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO)	Acute, unilateral, painless visual loss (CRAO); Acute, unilateral, painless partial visual loss (BRAO).
	Spinal cord	Infarction	Paraplegia
	Cervical sympathetic chain	Injury	Horner syndrome (miosis, ptosis, anhidrosis)
	Brachial plexus	Brachial plexopathy (Usually lower trunk)	Sensory loss in an ulnar distribution is most common. May have weakness of all intrinsic hand muscles, all ulnar-innervated muscles, and index finger extension. Brachial monoparesis if complete injury.
	Peripheral nerve	Phrenic nerve injury	Minimal symptoms with unilateral diaphragmatic paralysis unless underlying lung disease. May have nocturnal orthopnea or dyspnea with exertion. Ventilatory dependence with bilateral diaphragmatic paralysis.
	Peripheral nerve	Ulnar nerve injury	Medial hand numbness and weakness of intrinsic hand muscles; other signs depend on whether the nerve is injured at the elbow, wrist, or hand.
	Peripheral nerve	Recurrent laryngeal nerve	Respiratory insufficiency, ineffective cough, hoarseness. May have dysphagia.
	Peripheral nerve	Saphenous nerve	Saphenous neuralgia with anesthesia, hyperesthesia, and pain along the medial calf and foot to the great toe.
	Peripheral nerve	Common peroneal nerve	Foot drop with impaired dorsiflexion and eversion of the ankle and extension of the toes.

Ventricular assist device implantation	Cerebral cortex, subcortical structures, cerebellum, brainstem	Hemorrhage, ischemia, air embolism, infectious emboli, posterior reversible encephalopathy syndrome (PRES)	Variable depending on site of lesion.
Extracorporeal membrane oxygenation	Cerebral cortex, subcortical structures, cerebellum, brainstem, brachial plexus, peripheral nerve, muscle	Hemorrhage, ischemia, air embolism, plexopathy, critical illness neuromyopathy	Variable depending on the site of the lesion
Aortic surgery	Cerebral cortex	Seizures	Loss of consciousness +/- tonic-clonic movements.
	Neuromuscular junction	Weakness due to neuromuscular block. Ventilatory dependency	Generalized weakness may be present. Difficulty weaning from ventilator.
	Cerebral cortex, subcortical structures, cerebellum, brainstem	Ischemia	Variable depending on the site of the lesion.
	Spinal cord	Ischemia	Paraparesis or paraplegia
	Peripheral nerve	Recurrent laryngeal nerve	Hoarseness, low-pitched voice
Valve replacement surgery	Cerebral cortex, subcortical, cerebellum, brainstem	Stroke, ischemic, intracranial hemorrhage, subarachnoid hemorrhage, PRES	Variable depending on level of lesion.
	Brachial plexus	Brachial plexopathy (usually lower trunk)	Sensory loss in an ulnar distribution is most common. May have weakness of all intrinsic hand muscles, all ulnar-innervated muscles, and index finger extension. Brachial monoparesis if complete injury.
	Peripheral nerve	See above with CABG	See above with CABG
Cardiac transplantation	Cerebral cortex, subcortical structures, cerebellum, brainstem	Infarction or hemorrhage	Variable depending on the site of the lesion
	Cerebral cortex	Seizures	Usually loss of consciousness and generalized tonic-clonic movements.
	Cerebral cortex	Encephalitis	May have fever, meningismus, headache, altered mental status, weakness or paralysis, and seizures
	Cerebral cortex	Abscess	May have fever, headache, meningismus, altered mental status, focal neurologic signs, seizures.
	Cerebral cortex, subcortical structures, cerebellum, brainstem	PRES	Encephalopathy, seizures, visual field defects, and other focal neurologic deficits.
	Meninges	Meningitis	May have fever, altered consciousness, confusion, headache, nausea, vomiting, and seizures.
	Central nervous system (CNS)	Post-transplant lymphoproliferative disorder	Altered mental status with or without focal neurologic findings.
	Muscle	Acute myopathy	Muscle weakness, difficulty weaning from ventilator.
Cardiac catheterization	Cerebral cortex, subcortical regions, cerebellum, brainstem	Stroke, ischemic or hemorrhagic	Variable depending on the site of the lesion.
	Cerebral cortex	Seizure	Focal motor or generalized tonic-clonic movements
	Cerebral cortex	Contrast-induced encephalopathy	Cortical blindness, seizures, focal neurologic deficits, migrainous phenomena
	Brachial plexus	Brachial plexus injury with axillary artery approach	Abnormal motor and sensory function in one arm. May have associated pain.
	Lumbar plexus	Lumbar plexus compressed by retroperitoneal hematoma	Pain in groin, flank, abdomen with radiation to the anterior thigh. Numbness of the anterior thigh and medial calf with reduced or absent patellar reflex.
	Peripheral nerve	Lateral femoral cutaneous nerve injury	Meralgia paresthetica with paresthesias and hypesthesias over the upper lateral thigh.
	Peripheral nerve	Femoral nerve (direct injury or compression by an arteriovenous fistula or pseudoaneurysm)	Weakness of the quadriceps muscle and decreased patellar reflex. May have acute severe pain in the groin, thigh, and/or lower abdomen.
	Peripheral nerve	Median nerve injury with brachial artery catheterization	Paralysis of flexor pollicis longus and flexor digitorum profundus of the second digit (orator’s hand posture).
Congenital heart disease surgery	Cerebral cortex, subcortical structures, cerebellum or brainstem	Cerebral infarction, ischemic	Variable depending on the site of the lesion.
	Cerebral cortex, subcortical structures, cerebellum or brainstem; subarachnoid, subdural, or epidural spaces	Intracerebral hemorrhage (subarachnoid hemorrhage, subdural hematoma, epidural hematoma)	Variable depending on the site of the lesion.
	Cerebral cortex	Seizures	Generalized or partial seizures
	Cerebral cortex	Cerebral abscess	May have fever, headache, meningismus, altered mental status, focal neurologic signs, seizures.
	Cerebral cortex	Coma	Brainstem or bihemispheric signs. Evidence of hypoxic-ischemic injury including brain death or coma with fixed pupils and respiratory disturbances including apnea, myoclonic jerks, and seizures.
	Basal ganglia	Biochemical or microembolic phenomena	Post-pump chorea
	Cervical sympathetic chain	Injury	Horner syndrome (miosis, ptosis, anhidrosis)
	Cerebral venous system	Thrombosis	Variable spectrum of signs and symptoms. May have seizures, papilledema, headache, altered consciousness, lethargy, and focal neurologic deficits.
	Spinal cord	Ischemia	Paraplegia
	Peripheral nerve	Recurrent laryngeal nerve paralysis	Respiratory insufficiency, ineffective cough, hoarseness. May have dysphagia.
	Peripheral nerve	Phrenic nerve paralysis	Minimal symptoms with unilateral diaphragmatic paralysis unless underlying lung disease. May have nocturnal orthopnea or dyspnea with exertion. Ventilatory dependence with bilateral diaphragmatic paralysis.
Atrial myxoma surgery	Cerebral cortex, subcortical structures, cerebellum or brainstem	Ischemic or hemorrhagic stroke; delayed intracerebral or subarachnoid hemorrhage from tumor recurrence	Variable signs and symptoms. May have seizures, altered consciousness, and focal neurologic deficits depending on location of lesion.

Coronary artery bypass grafting. Coronary artery bypass grafting (CABG) is the most common surgical procedure performed in the United States. On average, over one million coronary artery bypass grafting procedures are performed in the world every year with over half of these performed in the United States. This number of surgeries performed on patients with advanced age (ie, the octogenarian population), who often have several comorbid diseases making them high risk for cerebrovascular disease, will continue to rise.

After coronary artery bypass grafting, patients may present with signs and symptoms of dysfunction in four general categories: (1) cerebrovascular events, (2) encephalopathy or coma, (3) early or delayed cognitive impairment, and (4) other neurologic events.

Cerebrovascular events. The incidence of clinically detectable stroke after CABG varies from 0.8% to 5.0% (199; 13; 47; 43; 227). The incidence varies depending on a number of factors including whether the study was retrospective or prospective, the type of operation, age of the patient population, and the sensitivity of the tests performed. Using highly sensitive diffusion-weighted MRI increases the incidence of cerebral infarctions to 18%. However, about two thirds of these infarcts are asymptomatic (73). Most patients (61%) present with clinical evidence of stroke within the first 2 days after coronary artery bypass grafting, with the majority being intraoperatively (124; 135). Less commonly, strokes can occur after a few days of delay, often related to cardiac arrhythmias such as atrial fibrillation.

The largest and most significant independent risk factors for stroke after CABG include advanced age, prior stroke, prior peripheral arterial disease including carotid artery stenosis, and prolonged cardiopulmonary bypass time (135). Having a history of stroke or transient ischemic attack appears to portend a higher risk of postoperative cerebral ischemia (47).

Atheromatous aorta and carotid artery disease are known predictors for stroke after CABG. In patients with carotid occlusion or stenosis of greater than 75%, prophylactic cerebrovascular interventions and the selective use of aorta no-touch, off-pump coronary artery bypass can significantly reduce the incidence of perioperative stroke (156). A meta-analysis of 11,398 cases from eight studies corroborated the finding that avoidance of aortic manipulation during off-pump CABG decreases neurologic complications (144). This advantage of off-pump over the use of cardiopulmonary bypass, on-pump, CABG is likely to be more evident in those at highest risk, such as the elderly (75). Whether the routine use of cardiopulmonary bypass has a significant impact on the incidence of ischemic events is unclear. However, multiple systemic reviews have not found a significant benefit of off-pump compared with on-pump CABG with regard to incidence of stroke (148; 187).

Another controversial question is the timing of operative interventions for patients with concurrent carotid and coronary artery disease. It has not been proven that the benefit of either STAGED or SYNC CEA-CABG procedures outweigh the risks in asymptomatic patients; however, carotid revascularization may be justified in symptomatic or high-risk patients such as those with contralateral carotid occlusion or bilateral high-grade stenosis. Gopaldas and colleagues compared outcome data from a nationwide database of 6153 patients who underwent carotid endarterectomy (CEA) before or after CABG during the same hospital admission but not on the same day (STAGED) and 16,639 patients who underwent both procedures on the same day (SYNC) (82). They found no significant difference in mortality or neurologic complications between STAGED and SYNC approaches. On-pump CABG was associated with higher stroke rates in SYNC patients.

The clinical picture of cerebrovascular events following CABG varies, and it depends on the location, number, and extent of lesions affecting the brain. In a study of strokes after CABG, embolic strokes accounted for 62.1%, followed by multiple other etiologies (10.1%), including: hypoperfusion (8.8%), lacunar (3.1%), thrombotic (1.0%), and hemorrhage (1.0%). Nearly 14% of strokes after CABG were of unknown etiology. Nearly 45% (105 of 235) of the embolic, and 56% (18 of 32) of hypoperfusion strokes occurred within the first postoperative day, and an additional 20% occurred by day 2 (126). Further information about embolic cerebral infarctions, watershed (border-zone infarctions), and lacunar infarctions associated with CABG is discussed below.

Embolic cerebral infarctions. Embolic infarctions are the most common type of infarction occurring in the perioperative period with CABG.

Embolic cerebral infarctions after CABG (MRI)

This brain MRI shows new scattered infarcts involving both cerebral hemispheres predominantly in a watershed distribution. There is also a more confluent area of infarct involving the left parietal-occipital region, which is also ...

Clinical manifestations of embolic infarctions may include a decreased level of consciousness at onset of stroke, a sudden onset of symptoms and signs that are maximal at onset, and symptoms reflecting involvement of different vascular territories of the brain due to multiple emboli. However, such a clear history may be difficult to obtain in cases of perioperative strokes. Cortical deficits, such as aphasia, visual field deficits, and neglect, commonly reflect involvement of the territories of the middle and posterior cerebral arteries and their branches. Multiple bilateral infarctions in the cerebral white matter may lead to spastic diplegia. Other, rare presentations have been reported, such as fixed, dilated pupils after cardiac surgery due to bilateral anteromedial midbrain infarctions (38; 29). On the general examination, there may be evidence of cardiac dysrhythmias such as atrial fibrillation or, rarely, other signs of systemic embolism.

In cases of arterial air embolism, clinical features include headaches, dizziness, visual manifestations, focal motor/sensory neurologic deficits, changes in sensorium, coma, seizures, and status epilepticus.

Watershed (border-zone) cerebral infarctions. Watershed (border-zone) infarctions typically occur in the setting of prolonged hypotension, but they can also occur in patients without documented hemodynamic instability. The cause in such situations is possibly secondary to sustained showers of microemboli that lodge in the terminal portions of the circulation. This results in a clinical and radiological picture resembling territories with perfusion failure (98).

In situations of generalized hypoperfusion, the vulnerable watershed regions are most commonly encountered in areas between the arterial distributions of the anterior and middle cerebral arteries. In addition, there is a boundary zone between the three major cerebral arteries, located in the posterior parietal lobe, and a similar boundary zone between the territories of supply of the superior cerebellar and posterior inferior cerebellar arteries. In general, these types of infarcts result in bilateral and symmetric lesions.

Watershed infarctions can produce distinctive clinical manifestations. Infarctions that occur in the regions between the middle and posterior cerebral arteries may result in Balint syndrome. Balint syndrome is characterized by visual or spatial disorientation, apraxia of gaze, optic ataxia, and simultanagnosia. Simultanagnosia is a rare condition when an individual is not capable of perceiving more than one object at a time. The syndrome may also initially result in cortical blindness that improves but leaves a residual of dyslexia, dyscalculia, dysgraphia, and memory defect of verbal and nonverbal material. Watershed ischemia of anterior, middle, and posterior cerebral arteries may result in bilateral lower altitudinal visual field defects and difficulty in judging size, distance, and movements. Bilateral ischemia between the anterior and middle cerebral arteries can result in bilateral arm sensory and motor impairments, which is also known as man-in-the-barrel syndrome. Watershed cerebellar ischemia can present as dizziness, vertigo, and ataxia.

Lacunar infarctions. A small number of patients (about 16%) will have evidence of lacunar infarctions involving the small subcortical territories after cardiac surgery (124). The clinical manifestations are similar to the traditional lacunar syndromes. However, unlike the traditional lacunar syndromes, the mechanism may be different. It has been suggested in animal models and in clinical studies that the mechanism of lacunar infarction in this population is due to microembolization of the terminal vessels. Lacunar infarction in this population is often due to small emboli that occlude single perforating arteries (22; 131; 124).

Encephalopathy or coma. Patients may present with signs and symptoms of encephalopathy. Often in the literature, terms “encephalopathy” and “delirium” are used interchangeably for the same phenomenon. Patients may emerge from anesthesia with persistent agitation or confusion, or they may simply remain in a state of reduced consciousness for longer than anticipated, but generally do not have evidence of focal motor or sensory deficits. Encephalopathy is usually evident after extubation and is a strong independent predictor of mortality up to 10 years postoperatively, especially in younger individuals and in those without prior stroke (84). Although metabolic and drug-related causes need to be ruled out, there is evidence that encephalopathy after CABG may be due to showers of microemboli. There may be evidence of multifocal small areas of brain ischemia on diffusion-weighted MRI after surgery. It has been suggested that encephalopathy, stroke, and coma represent a continuum of conditions with the same underlying mechanism of showers of embolic material to the brain (81; 141). In a prospective series of over 8000 patients undergoing CABG, postoperative delirium was present in 5.8% of patients. This independently predicted perioperative stroke and was associated with long-term risk of death and stroke (136).

Coma can occur in patients with brainstem or significant bilateral hemispheric ischemia. Severe global hypoperfusion can lead to severe brain injury, coma, or death.

Early and delayed cognitive impairment. Neuropsychological dysfunction or cognitive decline is a well-described complication of CABG. Neurocognitive decline is common after cardiac surgery, varying from 7% to 49% at 3 months and up to 33% after 1 year (173; 157; 214). This discrepancy in the frequency of its occurrence is likely due to differences in patient selection, the definition of neuropsychological decline, the timing and type of neuropsychological testing, and multiple other factors (70).

One of the most frequently described causes of neuropsychological decline after CABG is that related to showers of microemboli to the brain, as observed in autopsy studies and as documented by transcranial Doppler monitoring during cardiopulmonary bypass. Although there is little dispute that microembolism occurs, assessing the impact of this phenomena on short- and long-term cognitive functioning is more difficult for the reasons alluded to above. A significant relationship between intraoperative cerebral oxygen desaturation and early postoperative cognitive decline has also been described (196).

Newman and colleagues evaluated 261 patients undergoing CABG using cardiopulmonary bypass with a battery of cognitive tests before surgery and at intervals up to 5 years after surgery (157). The incidence of cognitive decline at discharge, 6 weeks, 6 months, and 5 years was 53%, 36%, 24%, and 42%, respectively. Cognitive function at discharge was a strong predictor of long-term function. The reason for the increase in cognitive decline at 5 years that was observed in this study is not known.

A study evaluating late progressive decline in memory and neurocognitive function after CABG done with a well-matched control group has failed to demonstrate significant cognitive decline, suggesting that the decline in cognition observed was likely related to preexisting vascular disease, new neurologic events, or other coexistent neurodegenerative disease, but not related to the cardiac bypass procedure (185; 142). Supporting this finding are the results of a longitudinal study of 170 patients who underwent neuropsychological testing at baseline and at 1 year following surgery (60). Although postoperative cognitive decline was observed in 18.2% of patients at 6 weeks, only half of those demonstrated the impairment at 1 year. An additional 15.8% of those who did not have cognitive impairment at 6 weeks developed it by 1-year follow-up, suggesting that factors other than the surgery are responsible for the majority of delayed cognitive impairment.

Minimally invasive endoscopic CABG (Endo-CABG) is a newer surgical technique that avoids medial sternotomy and allows for faster recovery. Rates of stroke, delirium, and postoperative cognitive dysfunction after Endo-CABG are 1.72%, 8.6%, and 13%, respectively (200). Rates of stroke and postoperative cognitive dysfunction were similar to percutaneous cardiac intervention, though a head-to-head comparison of neurologic outcomes after Endo-CABG versus traditional CABG has not been done.

Other neurologic events. Infarction of the spinal cord has rarely been described after CABG (218). Symptoms typically reflect involvement at the mid-thoracic spinal cord level, between the circulatory areas of the descending spinal arteries and the areas of the artery of Adamkiewicz. Patients may present with an anterior spinal artery syndrome with acute urinary retention, flaccid paraparesis, and a dissociated sensory loss, typically with a sensory level to pinprick and temperature sensations with intact position and vibration sense. There has been a case report of a modified Brown-Sequard syndrome secondary to CABG (83). Etiology is poorly understood, though hypotheses include hypoperfusion and embolism of atherosclerotic plaque. Certain surgical techniques may increase the risk of spinal cord ischemia, including manipulation of the aorta and interruption of collateral blood supply, by harvesting the internal mammary arteries.

Pituitary apoplexy is a rare phenomenon following CABG and is characterized by headache, nausea and vomiting, diplopia and changes in vision or visual fields, and cranial nerve palsies (09). Postulated mechanisms relate primarily to changes in physiology resulting from cardiopulmonary bypass, leading Levy and colleagues to recommend operating on patients with pituitary adenoma who need a CABG off pump in order to prevent pituitary apoplexy (122).

Central retinal artery occlusion or branch retinal artery occlusion may occur with CABG, most commonly due to embolism. Patients are noted to have acute onset of complete visual loss in one eye (with central retinal artery occlusion) or acute onset of partial visual loss in one eye (with branch retinal artery occlusion).

Ischemic optic neuropathy is an extremely rare event after cardiac surgery, with an overall frequency of 0.06% (159). Anterior ischemic optic neuropathy is characterized by sudden painless visual loss involving mainly the lower part of the visual field in one eye with optic disc swelling. Posterior ischemic optic neuropathy is characterized by unilateral or bilateral loss of visual acuity, visual fields or blindness without disc swelling. Factors associated with visual loss after cardiopulmonary bypass include anemia, history of clinically severe vascular disease, and preoperative coronary angiogram within 48 hours of surgery (159).

An uncommon cause of transient ischemic attack is the coronary-subclavian steal syndrome caused by atherosclerotic disease or the proximal left subclavian artery in the post-coronary artery bypass graft patient. This can present with angina or with lightheadedness, left arm numbness or weakness, and a difference in systolic blood pressure between the right and the left arm (178).

Peripheral nerve dysfunction. The most common nerves to be injured in cardiac surgery are the lower trunk of the brachial plexus and the phrenic nerve. Other nerves that may be damaged include the ulnar nerve, the recurrent laryngeal nerve, the saphenous nerve, the common peroneal nerve, and the cervical sympathetic chain.

Brachial plexopathy may occur when the brachial plexus is stretched during a median sternotomy. At the time of median sternotomy, it may be disrupted by the use of sternal retractors or when there may be direct trauma to the brachial plexus from first rib fracture fragments or an associated fracture hematoma directly compressing the nerves (188; 35). Clinically, patients with a lower trunk brachial plexopathy may present with sensory loss on the dorsal and palmar surfaces of the fifth digit and medial half of the fourth digit and the ulnar part of the wrist to the hand. There may be paresis or paralysis of all intrinsic hand muscles and a “claw hand” deformity. Patients with injured nerves tend to be older and to have had longer operation times. Also, an ulnar neuropathy can occur due to compression at the elbow or at the wrist and hand.

Phrenic nerve injury, resulting in unilateral or bilateral diaphragmatic paralysis, may result from direct manipulation of the nerve, trauma to the nerve during internal mammary artery dissection, ischemia, or topical hypothermia (58; 106; 188).

The left recurrent laryngeal nerve may be injured during internal mammary artery dissection and may be affected by ice water that is introduced to the pleural cavity. Other mechanisms of damage may occur during endotracheal intubation, central venous catheter placement, or surgical dissection (188).

The saphenous nerve may be injured during harvesting of the long saphenous vein. Patients present with a saphenous neuralgia, which is characterized by anesthesia, hyperesthesia, and pain along the medial calf and foot to the great toe.

Very rarely (in 0.19% of patients), the common peroneal nerve may be affected during CABG with damage to the nerve at the fibular head due to nerve ischemia from compression or stretching (215).

Finally, the cervical sympathetic chain, which lies medial to the inferior trunk of the brachial plexus, may be injured during sternal retraction with a posterior first rib fracture (188). Clinical findings are Horner syndrome with ptosis, miosis, and anhidrosis.

Ventricular assist devices. Ventricular assist devices (VADs) are implanted continuous flow pumps that assist and support circulation. Due to the growing prevalence of end-stage heart failure, ventricular assist devices are being inserted into an increasing number of patients with advanced heart failure. These devices improve survival and quality of life (197). Most patients (> 90%) receive a left ventricular assist device (LVAD). Others receive biventricular support, otherwise known as a biventricular devices (BiVAD), which includes a right ventricular assist device (RVAD) in addition to the left, an isolated RVAD, or a total artificial heart (189; 147). Neurologic complications are the second most common cause of death of LVADs after multisystem organ failure and include ischemic stroke, intracerebral hemorrhage, and air embolism (147). Risk factors for the development of neurologic complications beyond the presence of the device itself and the need for systemic anticoagulation include previous stroke, persistent malnutrition and inflammation, severity of heart failure, post-LVAD infections, atrial fibrillation, and mechanical factors associated with the device itself, including deposition of fibrin/protein material throughout the assembly (105; 222).

Ischemic or hemorrhagic stroke is the most common neurologic complication in patients with LVADs (192). Causes include inadequate anticoagulation, septic emboli from infected thrombus in the device, heparin-induced thrombocytopenia, and comorbid atrial fibrillation (206). In a series of 173 consecutive patients undergoing VAD implantation, 2.3% experienced a hemorrhagic stroke and 5.2% an ischemic stroke (114). Neurologic complications are more common in total artificial heart (TAH) implantation. Copeland and colleagues reported on a series of 101 patients who underwent TAH implantation (46). Of these, 7.9% experienced embolic strokes, of which five occurred within 9 days after device implantation. During 24 years of patient follow-up, only three strokes occurred while on chronic support, suggesting that the highest risk is in the perioperative period. One patient in this series experienced severe cerebral air embolism.

These implanted mechanical devices require systemic anticoagulation to an INR of 2.5 to 3.5 in addition to antiplatelet therapy in order to prevent stasis or thrombosis of the device components. This, along with the effects of being on cardiopulmonary bypass, including platelet dysfunction, platelet consumption, and hemodilution of clotting factors, may increase the risk of bleeding complications. Intracerebral hemorrhage occurs in 13% to 14% of patients with VADs (56). The design of left ventricular assist devices continues to advance as technology improves, leading to a lower incidence of stroke with the newer devices (192).

Extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation (ECMO) is increasingly used as a last resort to maintain oxygenation when other treatment options for cardiopulmonary failure have failed. Neurologic complications have been reported to occur in up to half of patients, though the rate has declined over time, with recent reports of such complications in 13% of adults and 21.3% of children (128; 226). Reported neurologic complications include cognitive impairment, seizures, strokes, intracerebral hemorrhage, ischemic encephalopathy, brain death, foot drop, deafness, and paraplegia (225). Brachial plexus injury has also been reported and is postulated to result from axillary artery cannulation resulting in hematoma formation (145). In a series of 15 patients undergoing ECMO as a bridge to lung transplantation, 10 (66%) developed critical illness polyneuropathy (48).

Aortic surgery. According to The Society of Thoracic Surgeons Adult Cardiac Surgery Database, approximately over 14,000 surgeries for aortic aneurysms are performed each year, with the majority of these involving the ascending aorta (25). Complications related to surgery on the aorta are highlighted here.

Cerebral and brainstem ischemia. Rates of stroke following open surgery for thoracic aortic disease have been reported at 6% to 11% (151; 203). The report incidence of stroke after thoracic endovascular aortic repairs (TEVAR) ranges from 3.2% to 6.2% (212). Risk factors for cerebral ischemia included obesity, significant intraoperative blood loss, and evidence of peripheral vascular thrombosis. Severe atheromatous disease involving the aortic arch was strongly associated with perioperative stroke (88). Manipulation of the aorta has resulted in embolization of neo-endothelium to the vertebral artery and cerebellar infarction, as was reported in the case of a patient undergoing redilation of an aortic stent (23). In a retrospective review of patients who underwent TEVAR, all strokes were embolic, and patients with posterior circulation strokes were less likely to achieve a full neurologic recovery than those with anterior circulation strokes (211).

Seizures. A prospective database of 2578 consecutive patients undergoing cardiac surgeries, of which 290 were aortic, reported a 5% seizure incidence in aortic surgeries. The increased incidence of seizure in aortic surgeries is likely related to the requirement for deep hypothermic circulatory arrest. The OR for postoperative seizures among those undergoing deep hypothermic circulatory arrest among all cardiac surgeries was 7.4, representing the strongest predictor of seizures among this population, greater than extensive aortic calcification or atheroma (OR 3.1) (80).

Spinal cord ischemia. Spinal cord ischemia following endovascular procedures of the thoracic aorta can occur due to left subclavian artery coverage. Based on European Collaborators on Stent/Graft Techniques for Aortic Aneurysm Repair (EUROSTAR) registry data, rates of spinal cord ischemia range from 0% in patients who underwent prophylactic left subclavian artery revascularization to 8.4% when there was left subclavian artery coverage without revascularization (32). This is contrasted with reported rates for paraplegia following open surgery for thoracic aortic disease of 3% to 19% (151). Risk factors for SCI include older age, chronic obstructive pulmonary disease, chronic renal insufficiency, hypertension, aneurysm as an underlying pathology, the use of an iliac conduit, and coverage of the hypogastric artery (110; 181).

Peripheral nerve dysfunction. Peripheral nerve ischemia has been reported after internal iliac artery ligation, which may also be injured during endovascular repair. Likewise, ischemic injuries to the spinal cord, nerve roots, or lumbosacral plexus as well as chronic ischemic monomelic neuropathies may complicate emergent and reoperative abdominal aortic reconstruction or critical limb ischemia (168; 190; 220). The most common procedure-related complication for open traumatic thoracic aortic transactions is recurrent laryngeal nerve injury (204). The left recurrent laryngeal nerve wraps around the aortic arch with the vagus nerve; thus, surgery on the aortic arch may compress the nerve. These patients present with hoarseness and a low-pitched voice.

Other neurologic events. Several other neurologic syndromes have been described as occurring after surgery on the ascending aorta with or without aortic valve replacement. Mokri syndrome presents as a triad of supranuclear gaze palsy, dysarthria, and gait disturbance resembling progressive supranuclear palsy (146; 209). The disorder is biphasic, consisting of some symptoms acutely after anesthesia wears off, followed a latent progressive phase weeks to months later. Neuroimaging is largely normal in these patients.

A variety of isolated eye movement abnormalities following aortic surgery have been reported, with brain imaging in some patients revealing lesions in the dorsomedial pons, cerebellum, or cerebral hemispheres; mesial temporal sclerosis; or hippocampal atrophy (228; 65).

Cardiac valve surgery. Cardiac valve surgeries are performed in 99,000 patients each year in the United States (158). The most common valve surgery is isolated aortic valve replacement, and there are over 25,000 isolated aortic valve replacement surgeries each year (25). There are a number of variables in these surgeries, including whether the valve is repaired or replaced, whether open heart surgery, balloon valvuloplasty, or transcatheter placement is used, whether the prosthetic valve is mechanical or bioprosthetic, whether the valve is in the mitral or aortic position, whether concomitant procedures (eg, left atrial appendage closure, CABG, etc.) are performed, and whether adequate anticoagulation is used. In addition, outcomes are affected by the underlying pathology, the type of procedure, and the experience of the surgeon. These variables make it very difficult to make a comparison between studies and to compare stroke statistics.

Stroke. Stroke is the most common neurologic complication of these surgeries. Some generalizations can be made about the risk of stroke. First of all, stroke is more common with surgeries at the mitral position than the aortic position, with all valve types. The higher rates of stroke at the mitral position are attributed to an increased likelihood of atrial fibrillation, left atrial enlargement, and possible endocardial damage from rheumatic mitral valve disease (39). Second, the rate of stroke is considered to be equal between bioprosthetic and mechanical valves. One 11-year study showed a similar incidence of thromboembolism, endocarditis, and valve thrombosis comparing anticoagulated patients with mechanical valves and non-anticoagulated patients with bioprosthetic valves (90). Another study showed that there was no significant difference in the occurrence of embolism over a 12-year follow-up period when comparing mechanical and bioprosthetic valve surgery (21). If cardiac valve surgery is combined with CABG, repair of other cardiac abnormalities, or carotid endarterectomy, the risk of stroke is higher (224; 71).

Several studies will be reviewed to give a general estimate of the incidence of stroke with cardiac valve surgery. In a large cardiac database from Emory University of patients undergoing mitral valve surgery, there was a 4.2% incidence of postoperative strokes among 1250 patients (208). There was no difference between the mitral repair group and the mitral replacement group. In elderly patients undergoing mitral valve surgery, the risk of postoperative stroke was comparable at 5%, although the overall mortality was higher (79). Another prospective study found a lower risk of 1.3% for mitral bioprostheses and 2.3% for mitral mechanical valves (176). In long-term studies of the risk of thromboembolism with bioprosthetic valves, the risk was 0.2% to 2.3% per year for the aortic position and 0.7% to 2.6% per year for the mitral position (96). The incidence of thromboembolism after aortic valve replacement varies in the literature from 1.4% to 4.4% (06; 116). Another prospective study found that the risk was 1.3% per year for aortic bioprostheses, and 1.4% for aortic mechanical valves (176).

Transcatheter aortic valve replacement (TAVR) surgery is being increasingly used, especially in those who are higher risk for surgery (121). Previously the risk of stroke was higher in transcatheter aortic valve implantation (TAVI) than with surgical replacement (182). As the operator experience and the catheter systems have improved, the outcomes including incidence of stroke have decreased compared to the surgical procedure per the aforementioned trial. In comparing the primary end points of death and disabling stroke at 2 years, there was no significant difference between the two groups.

The autograft procedure for aortic valve replacement, also known as the Ross procedure, utilizes the patient’s own pulmonary valve to replace the diseased aortic valve, and then uses a pulmonary allograft to replace the pulmonary valve. Although the operation is complex and necessitates replacement of two valves, there is a lower risk of endocarditis, avoidance of anticoagulant therapy, and lower thrombogenicity. In a series of 347 patients who underwent this procedure, only two strokes occurred, both in patients with new-onset atrial fibrillation (193). In patients undergoing percutaneous mitral valvuloplasty for mitral stenosis, the rate of systemic embolization is 0.5% to 3.0%, with most of these representing symptomatic embolisms to the brain (62). Since the introduction of transesophageal echocardiography to detect atrial thrombi and with the use of the Inoue technique, which requires less left atrial manipulation, the incidence of systemic embolism has been lower with percutaneous mitral valvuloplasty (87).

Strokes can occur during either the intraoperative or postoperative period (see Table 2). During surgery, emboli and hypoperfusion are the most common causes of stroke. In the postoperative period, valve thrombosis, left-atrial thrombi secondary to atrial fibrillation, and endocarditis are most common. Patients with intraoperative strokes may be noted to have a failure to awaken from anesthesia as quickly as expected with the presence of encephalopathy or coma due to multifocal infarction. There may be evidence of a focal neurologic deficit such as speech deficit, visual field abnormality, or motor or sensory deficit. Patients who have a stroke after surgery will usually have a sudden onset of visual, speech, motor, or sensory deficits or multiple deficits in more than one vascular territory due to embolism.

Tranexamic acid is an antifibrinolytic used for bleeding during cardiac surgery. In dose-dependent fashion, it has been associated with an increased incidence of generalized seizures postoperatively (137; 07).

Table 2. Mechanism of Stroke During or After Valve Replacement Surgery

Intraoperative stroke
	Cerebral hypoperfusion
		Intraoperative hypotension Decreased cardiac output
	Procedural-related
		Bypass Vessel clamping
	Emboli
		Air embolism Atherosclerotic emboli Fat emboli (01)
Postoperative stroke
	Embolism
		Valve thrombosis Left atrial thrombus/atrial fibrillation Septic embolism

Important causes of stroke after valvular surgery include valve thrombosis, atrial fibrillation and left atrial thrombosis, and endocarditis. Also, issues related to anticoagulation will be discussed briefly.

Valve thrombosis. Both mechanical and bioprosthetic valves are associated with valve thrombosis. In patients with adequate anticoagulation, the rate of thrombotic events is equal with mechanical and bioprosthetic valves (90). Approximately 15% of patients with valvular thrombosis will have a stroke (175). The risk of stroke persists for a person’s lifetime after the valve surgery. Approximately 20% of patients with valve prostheses have an embolic stroke by 15 years after valve replacement (176).

Atrial fibrillation and left-atrial thrombus. Atrial fibrillation is the most significant risk factor for delayed stroke after surgery, specifically mitral valve replacement (18). It more commonly occurs in patients who are older and have a larger preoperative left atrial size (112). Approximately 90% of patients with late-onset stroke had atrial fibrillation in one study (18). There was a significant difference in the stroke-free survival 15 years after valve surgery between those in normal sinus rhythm (90.7%) and those in chronic atrial fibrillation (73.8%) (18). One autopsy study of early death (between 1 and 60 days) found a 61% rate of left-atrial thrombus formation (186). Percutaneous closure of the left atrial appendage is an effective alternative to chronic oral anticoagulation for stroke prevention in patients with atrial fibrillation, though it is indicated in people with nonvalvular atrial fibrillation (210). Procedural complications include stroke and device and air embolism (172).

Endocarditis. The development of endocarditis after prosthetic valve surgery is a major complication, with significant morbidity and a high mortality rate (55). Stroke is a major predictor of mortality in this condition.

Prosthetic valve endocarditis accounts for 7% to 25% of cases of infective endocarditis (153). The incidence of prosthetic valve endocarditis is reported to be 1% to 3% during the postoperative period. Up to 65% of embolic events in infective endocarditis involve the central nervous system. The incidence of neurologic complications is 20% to 40% in all cases of infective endocarditis (66; 93). Mechanical heart valves are probably at higher risk for infection than are bioprostheses during the first 3 months after surgery, but the rates of infection are similar at 5 years (100; 33; 15; 153). The cumulative risk of prosthetic valve endocarditis is approximately 1% at 12 months and 2% to 3% at 60 months (05; 216; 153).

Prosthetic valve endocarditis with onset before 60 days after surgery is called early prosthetic valve endocarditis. Early prosthetic valve endocarditis is usually hospital-acquired with the most common organisms being Staphylococcus aureus (35.9%), coagulase-negative staphylococci (17%) and culture-negative cases (17%) (219). Infections that occur more than 60 days after surgery are called late prosthetic valve endocarditis. The most common causes are coagulase-negative staphylococci (19.9%), S aureus (18.4%), Enterococcus (12.7%) and culture-negative cases (12.4%) (219).

Neurologic manifestations are usually consistent with ischemic stroke with events in the history that may indicate an embolic source (as previously described). Other clinical manifestations include fever in nearly all patients and a new or changing murmur as the disease progresses in over 50% of patients. The classic signs of native valve endocarditis (petechia, Roth spots, Janeway lesions, and Osler nodes) are often absent. Splenomegaly is present in 25% of patients in the early stages and 40% of patients in the later stages. Peripheral embolization may be evident in the extremities.

Rarely, patients with endocarditis may be found to have intracerebral hemorrhage, subarachnoid hemorrhage, cerebral abscess, or mycotic aneurysms. Overall, patients with prosthetic valve endocarditis have a 30-day mortality of 13%, compared with 5.6% in patients with native valve endocarditis (134). Both entities have similar long-term survivals.

Anticoagulation. The issue of anticoagulation in cardiac surgery patients is a debated topic. In general, patients with mechanical valves receive long-term anticoagulation whereas patients with bioprosthetic valves receive a 3-month course of warfarin (target INR 2.5), and then only antiplatelet therapy, such as aspirin. The recommended INR value ranges for various cardiac valve replacements (ie, bileaflet, aortic; tilting-disc, aortic; bileaflet, mitral; tilting-disc, mitral, caged-ball disc; etc.), are beyond the scope of this review. However, suffice it to say that anticoagulation control has a dramatic and significant influence on stroke risk and survival after valve replacement surgery (31).

Anticoagulation-related hemorrhages are a dreaded complication of oral anticoagulant therapy in patients with valve replacements. The incidence of intracranial and spinal bleeding was 0.57 per 100 patient-years on oral anticoagulation in patients with mechanical heart valves (36). Spontaneous intracranial hemorrhages have been reported in patients without supratherapeutic levels of anticoagulation following open heart surgery for valve replacement (155; 14; 160). The appropriate use and recommendations regarding anticoagulant therapy in patients with bioprosthetic and mechanical valve replacements are reviewed elsewhere (161).

Other neurologic complications. Peripheral nerve injuries can occur with cardiac valve surgery and are similar to those with CABG, as discussed previously.

Several studies have suggested, by different methods of evaluation, that there is cognitive decline after cardiac valve surgery. Altered cognition was demonstrated by delayed P-300 auditory evoked responses at 7 days after valve replacement surgery (230). Transcranial Doppler has demonstrated high intensity transient signals after valve replacement surgery and has been correlated with neurocognitive deficits in some studies (54), but others have questioned these findings (154). Subcortical brain abnormalities like those described with CABG, have been described in patients undergoing valve replacement surgery. These lesions were located subcortically and were associated with alterations in memory, attention, and speed of information processing. The neurocognitive symptoms resolved after 4 months (113).

Migrainous-like phenomena have been seen after insertion of prosthetic cardiac valves. This was first described by Caplan and colleagues in 1976 in two patients who satisfied criteria for “classic migraine” (37). The mechanism remains unclear. As these headaches can be associated with manifestations suggestive of transient central nervous system dysfunction, they can mimic recurrent cerebral emboli.

Cardiac transplantation. Cardiac transplantation is the treatment of choice for patients with advanced heart failure (49). Although major advances have been made since the early days of cardiac transplantation, there is still a 4% risk of death from all neurologic causes and a need to reduce neurologic morbidity associated with the procedure (24).

The incidence of neurologic complications with cardiac transplant is 19.5%, with noninfectious causes predominating (152). Neurologic complications can be divided into cerebrovascular complications (stroke, intracerebral hemorrhage), CNS infections, metabolic encephalopathy, seizures, drug toxicities, and neoplasms (78). Cerebrovascular events occurring in the immediate post-transplantation period are similar to those seen after valvular or coronary revascularization surgery. However, the overall incidence of complications is higher than with elective CABG or elective valve replacement surgery (99).

Cerebrovascular complications.

Ischemic stroke. Ischemic stroke occurs in 2% to14% of patients undergoing cardiac transplantation (97; Andrews al 1990; 02; 103; 139; 78). Strokes are the cause of early death (0 to 30 days) after transplantation in 6.7% of patients (205), and the 5-year stroke rate after the perioperative period is 4.1% (08). The etiology of stroke in the perioperative period includes cardioembolism of fibrin and platelet microthrombi, embolization of atherosclerotic debris during cross-clamping and cannulation of the aorta, air embolism during cardiectomy, and embolization of material from bacterial endocarditis from the donor patient (03; 02; 139; 78). Stroke occurring later may be related to diagnostic procedures such as cardiac catheterizations and right heart biopsy, acute rejection, and arrhythmias (78).

Intracerebral hemorrhage. Intracerebral hemorrhage has been reported in 5% of early transplant recipients (194). The etiologies of the hemorrhages may be secondary to systemic anticoagulation, disseminated intravascular coagulation, relative cerebral hyperperfusion in the presence of impaired cerebral autoregulation (“breakthrough cerebral hemorrhage”), and angioinvasive opportunistic infections, such as aspergillosis, and herpes encephalitis (194; 78).

CNS infections. CNS infections occur in approximately 3% of patients in adult cardiac transplant patients (139; 213). The types of CNS infections include meningitis, encephalitis, meningoencephalitis, and abscess. One study from the Mayo Clinic indicated that all of their patients with CNS infections presented within the first 4 years of cardiac transplant (213). Clinically, patients presented with acute or subacute confusion or headache 88% of the time, often without fever or meningismus. The number of possible infective agents causing CNS infection after cardiac transplant is staggering and has been described elsewhere, and may include phycomycosis, coccidioides, aspergillus, candida, cryptococcus, cytomegalovirus, herpes simplex virus, varicella-zoster virus, JC virus, nocardia, listeria, and toxoplasma (78). In the series from the Mayo Clinic, cryptococcal meningitis was the most common CNS infection (213).

In cases of meningoencephalitis or CNS mass lesions in cardiac transplant patients, the differential includes a broad spectrum of potential pathogens based on timing from the transplant date. In early cases (less than 1 month after transplant), the most common offending agents are aspergillus, candida, and cytomegalovirus. From 1 to 6 months after transplant, the most common infecting agents are aspergillus, cytomegalovirus, cryptococcus, Epstein-Barr virus, human herpes virus 6, toxoplasmosis, and varicella-zoster virus. In late cases (more than 6 months after transplant), aspergillus, cryptococcus, Epstein-Barr virus-associated lymphoma, molds, nocardia, and toxoplasmosis are the most common infecting agents (51). Progressive multifocal leukoencephalopathy, an opportunistic infection of the JC virus in the CNS, has also been described in transplant recipients (89; 72; 123; 213). Patients with progressive multifocal leukoencephalopathy presented with progressive neurologic deterioration at 15 and 36 months after cardiac transplant. Those who experience graft rejection are at higher risk for all types of infection due to the increased administration of immunosuppressant drugs.

Metabolic encephalopathy. Encephalopathy occurring after cardiac transplantation can be related to a global hypoxic-ischemic insult, metabolic abnormalities, hepatic or renal dysfunction, multiple organ failure, sepsis, or drug toxicity (194). Delirium or mental status changes often are the first signs of opportunistic CNS infections. Other common etiologic factors to consider as a cause for encephalopathy in the posttransplant patient are general anesthesia side effects, volume and electrolyte shifts, posterior reversible encephalopathy syndrome (PRES), drug toxicity (corticosteroids, cyclosporine, tacrolimus), fever, coagulopathy, infection, and psychoactive drug withdrawal (63; 195).

Seizures. Seizures, either generalized tonic-clonic or complex partial seizures, are reported in as many as 40% of patients in some series (149). The most common causes of seizures in this population are those related to drug toxicity and abnormal metabolic parameters. Medications that can cause seizures include cyclosporine, tacrolimus, and OKT3. Other etiologies include cerebral ischemia, anoxic brain injury, PRES, CNS infection, and tumor (78).

Drug toxicities. There are a number of drugs given to cardiac transplant patients that can cause neurologic symptoms. These include the maintenance immunosuppression of steroids, calcineurin inhibitors, mTOR inhibitors, steroids, and mycophenolate mofetil or azathioprine. Therapy may also often include induction therapy with polyclonal or monoclonal antibodies. These biological agents induce lysis of lymphocytes. The proinflammatory cytokine release may result in several symptoms including fever, headache, serum sickness, and anaphylaxis. Up to 10% of people may experience symptoms of aseptic meningitis (167). Steroids can cause proximal myopathy. Cyclosporine and tacrolimus can cause a number of neurologic syndromes (see Table 3). Immunosuppressive neurotoxicity is usually seen as an acute postoperative complication but can be seen months after transplantation. It may be a direct drug effect that is unrelated to dosing versus associated with elevated therapeutic drug levels. Reversible cerebral vasoconstriction (Call-Fleming syndrome) has rarely been described with the use of cyclosporine and tacrolimus (see clinical vignette, case 2). Patients may present with sudden onset of thunderclap headaches and focal neurologic deficits. Cyclosporine and tacrolimus are postulated to have a direct toxic effect on the vascular endothelial cells in the CNS, resulting in the release of endothelin, prostacyclin, and thromboxane, with resulting uncontrolled vasoconstriction and vasospasm in the cerebral vessels (111). Neuroimaging studies may reveal changes consistent with PRES. Angiography in the patient described in vignette case 2 revealed extensive multifocal narrowing and dilation of the intracranial vessels.

Table 3. Neurologic Complications Associated with Organ Transplantation and Immune Suppression with Cyclosporine and Tacrolimus

Delirium Isolated visual hallucinations Dementia-like syndrome Frontal lobe syndromes Secondary mood, anxiety, thought disorders Movement disorders Central pontine myelinolysis Impaired taste sensation Incontinence Sexual dysfunction Posterior reversible encephalopathy syndrome
	• Encephalopathy • Seizures • Headaches • Cortical blindness • Hemiparesis • Aphasia
Source: (195)

Posttransplant lymphoproliferative disorder occurs in 0.75% of cardiac transplant patients and is detected only in the CNS in 85% of patients (207). Patients present with mental status changes with or without a focal neurologic deficit associated with CT showing multicentric, symmetric, ring-enhancing lesions around the subependymal white matter and perivascular spaces (165).

Peripheral nerve injuries occur with cardiac transplant surgery and are similar to those described with CABG. Critical illness neuromyopathy occurs more frequently after cardiac transplantation than after other cardiac surgeries and procedures.

Cardiac catheterization. In the United States, about 1.5 million cardiac catheterization procedures are performed per year. The neurologic complications with cardiac catheterization include stroke, seizures, and peripheral nerve complications. Stroke among patients with acute coronary syndromes enrolled in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) I and II studies were associated with six-month mortality rates of 27% (50).

Clinically relevant embolic events during diagnostic cardiac catheterization occur in 0.1% to 0.4% of adult patients (184). In one 2-year study, the incidence of strokes after 3494 cardiac catheterization procedures was 0.4% (101). Interestingly, asymptomatic cerebral infarction is described in 15% of patients as detected by diffusion-weighted MRI in a study that included diagnostic and interventional cardiac catheterization (30).

Stroke with cardiac catheterization may occur during the procedure, immediately after the procedure while the femoral artery sheath is still intact or up to 36 hours after the procedure (184; 180).

Stroke in association with cardiac catheterization is approximately evenly split between the carotid circulation and the vertebrobasilar circulation. There is a suggestion that posterior circulation strokes are more common with the brachial artery approach and anterior circulation events are more common with the femoral artery approach (53; 115; 107; 120).

There are a number of factors that can predispose to cerebrovascular complications with cardiac catheterization (see Table 4) (45; 180). Cerebral microemboli are predominantly detected during catheter advancement, catheter flushing, contrast injection, and ventriculography (130). There is also a significant correlation between the number of microemboli and the volume of contrast used (130). There has been no definitive evidence to determine whether transradial catheterization is superior to femoral catheterization in terms of lesser incidence of stroke.

Table 4. Risk Factors for Cerebrovascular Complications with Cardiac Catheterization

Patient-related
	Age over 60 Worsening New York Heart Association functional class Lower ejection fraction Greater risk with 3-vessel or left main disease Left ventricular hypertrophy Over 50% stenosis of any coronary artery Female gender Atherosclerotic peripheral vascular disease Atheromas or extensive plaques of the aorta, especially mobile ones, on transesophageal echocardiogram Hypertension Diabetes mellitus Renal insufficiency Prior stroke
Procedure-related
	Longer fluoroscopic time Use of large-caliber catheters Introduction of air emboli from catheter, sheath, or line during contrast or saline injection Introduction of microemboli during catheter advancement, catheter flushing, contrast injection, and ventriculography Large volume of contrast

Table 5 lists the etiologies of stroke with cardiac catheterization.

Table 5. Potential Etiologies of Cerebrovascular Complications during Cardiac Catheterization

Thromboembolism Atherosclerosis Air embolism Bleeding
	Spontaneous Iatrogenic
		Secondary to pharmacotherapy Antiplatelet therapy Anticoagulant therapy Secondary to vascular injury
			Vessel dissection Vessel perforation Vessel spasm
Contrast reaction Systemic
	Hypoxia Hypotension
Source: (45)

Transient cortical blindness has been described extremely rarely with coronary angiography, and the condition may be related to direct neurotoxicity of the contrast media (201). In the cases described, the symptoms and signs resolved after 48 hours.

Seizures occur extremely rarely with cardiac catheterization in the adult population. However, in the pediatric population, seizures are a more common presenting symptom, usually representing a manifestation of stroke. In one 12-year prospective study, 0.24% of children had neurologic events during diagnostic cardiac catheterization and 1% of children undergoing percutaneous coronary intervention had neurologic complications (127). The majority of these events manifested as a seizure. However, stroke was determined to be the cause of neurologic symptoms in 57% of cases. Another 4-year study involving 1362 cardiac catheterization procedures in children less than 15 years of age revealed that 18 (1.3%) of children, without prior nervous system disease, developed neurologic sequelae within 24 hours of cardiac catheterization (221). Three presented with seizures only, 10 with neurologic deficits, and 5 with both focal seizures and stroke.

Peripheral nervous system complications can occur with cardiac catheterization. Peripheral nerve injuries can be divided into femoral nerve injuries, lumbosacral plexopathy, and median nerve injuries. The femoral nerve can be lacerated or compromised by a hematoma with groin puncture and can present with pain and paresthesias over the anterior thigh and medial calf, weakness of hip flexion and knee extension, and an absent patellar reflex. The severity of postcatheterization femoral neuropathy can range from mild transient sensory neuropathy to disabling paralysis. Average delay from catheterization to recognition of symptoms is 37 hours. Although initially disabling, the neuropathy usually resolves completely. Surgery is only recommended when there are coexisting complications (eg, development of a large hematoma) (108).

The lumbar plexus (primarily involving the femoral and obturator nerves) can be compressed by a retroperitoneal hematoma. Patients present with variable symptoms, depending on the rate of expansion of the hematoma and the structures that are compressed. Patients may have groin, flank, or abdominal pain that radiates to the anterior thigh associated with numbness of the anterior thigh and medial calf with a reduced or absent patellar reflex. The size of the retroperitoneal hematoma does not correlate well with the severity of the sensory or motor deficits. The lateral femoral cutaneous nerve can be injured from tight compression bandages, resulting in meralgia paresthetica.

Other rare conditions that can compress the femoral nerve include pseudo-aneurysm formation of the femoral profunda artery, presenting with a painful pulsatile groin mass and sometimes with a systolic bruit, and arteriovenous fistula with a continuous groin bruit or thrill. Superficial or common femoral artery occlusion may present as ischemic monomelic neuropathy of the lower extremity.

Median neuropathy is a rare complication of brachial artery catheterization. Nerve compromise due to direct injury in the antecubital region or secondary to hematoma formation has been described. Brachial plexopathy has been described after axillary angiography and may be secondary to hematoma, pseudoaneurysm formation, or direct compression (162).

Percutaneous coronary interventions. Coronary intervention procedures including balloon angioplasty and stent placement are performed very commonly, with over 1 million procedures performed annually in the United States.

The etiologies of cerebrovascular complications from percutaneous coronary intervention are numerous, and they overlap somewhat with those of cardiac catheterization (see Table 6).

Table 6. Etiologies of Cerebrovascular Complications during Percutaneous Coronary Intervention

	Embolism Thrombus Air embolism Atheroma Vasospasm Medication reaction Vessel trauma Bleeding secondary to pharmacotherapy
Source: (26; 44)

In a retrospective study from a large database, unspecified neurologic complications occurred in 0.1% of patients undergoing percutaneous coronary interventions (132). Others have reported a higher incidence of complications. The incidence of stroke has been reported to be 0.08% to 0.4% for percutaneous coronary intervention (26; 74; 64; 132; 180).

Another study of approximately 6500 patients who underwent invasive cardiac procedures such as left heart catheterization, balloon angioplasty, and valvuloplasty described an overall 0.4% incidence of neurologic complications. The most common symptoms were visual disturbances (26%), hemiparesis (26%), and facial droop (26%). Deficits were localizable to the posterior circulation in 36% of patients and anterior circulation in 64%. Most of the embolic strokes during catheterization procedures are associated with an embolus located in either the common carotid bifurcation or the proximal middle cerebral artery (10). One study reported a posterior circulation predominance with up to 70% of patients presenting with confusion, visual field deficits, and brainstem signs. The remainder present with hemiparesis, hemisensory deficits, dysphasia, and retinal ischemia secondary to carotid distribution events (26; 44). In another study of strokes complicating 20,900 cardiac catheterization procedures, the posterior circulation was affected in 21 of the 39 infarcts (184).

The risk factors for stroke with percutaneous coronary interventions are similar to those with cardiac catheterization and are detailed in Table 7 (44; 94). In one study, stroke was significantly associated with the severity of coronary artery disease and the duration of the procedure (132). In patients undergoing percutaneous interventions, stiff, large-bore guiding catheters are used. These design characteristics can be more traumatic to the aorta than diagnostic catheters, which are more flexible and have smaller lumens and tapered tips (180).

Table 7. Major Risk Factors for Stroke with Percutaneous Coronary Intervention

Use of more catheters
Multiple catheter manipulation
Greater contrast volumes
Presence of atheroma
Age
Peripheral vascular disease
Gender
Poor ejection fraction
Left ventricular hypertrophy

Invasive electrophysiological procedures. The neurologic complications that can occur with invasive electrophysiological studies include TIA and stroke. Fortunately, the incidence of these events is extremely low. Table 8 lists the mechanisms of stroke with invasive electrophysiological procedures (104).

Table 8. Mechanisms of Stroke with Invasive Electrophysiological Procedures

Thromboembolism
	From catheter and sheaths From left atrial appendage thrombi From mechanical damage to the cardiac endothelium From mechanical disruption of clot from left ventricle or left ventricular aneurysm
Air embolism during transseptal catheterization Food embolism due to transesophageal fistula development Direct embolism during radiofrequency energy delivery Hypoxic-anoxic injury secondary to hypoperfusion from anesthetic complications

Congenital heart disease. Children with congenital heart disease represent a diverse group. In this review, neurologic complications of pediatric cardiac surgery in general will be discussed rather than reviewing specific cardiac defects and procedures. The specific procedure of closure of a patent foramen ovale is discussed in detail separately.

The incidence of neurologic complications with pediatric cardiac surgery is reported to be from 0.54% to 25% (69; 68; 16; 12; 61). Disappointingly, stroke accounts for greater than 20% of the noncardiac causes of death in this population (166). Age, duration of bypass, and reoperation may be associated with stroke risk (61). A retrospective series of 900 children undergoing cardiac surgery reported a 4.2% incidence of neurologic complications (17). Central nervous system complications were associated with higher morbidity and longer hospitalization times.

The most common postoperative neurologic sequela of open heart surgery in children is seizures (17). Other neurologic findings that have been reported with cardiac surgeries include Horner syndrome due to interruption of preganglionic sympathetic fibers during aortic arch surgery (eg, Blalock-Taussig shunts), vocal cord paralysis during extensive aortic arch manipulation, spinal ischemia and injury with aortic arch surgery, subclavian steal syndrome with Blalock-Taussig shunt procedures for tetralogy of Fallot, superior vena cava syndrome with intracranial venous hypertension with the Mustard procedure to correct transpositions (125), and diaphragmatic paralysis after ventricular septal defect repair (3.9%), Glenn anastomosis (8.6%), Tetralogy of Fallot repair (4.3%), Senning operation (10%), arterial switch operation (3.2%), Fontan procedure (33%), coarctation of the aorta repair (7%), and pulmonary artery banding (6.4%) (67). Children with coarctation of the aorta have a 7% incidence of cerebral aneurysms, predisposing them to intracranial or subarachnoid hemorrhages. Other described neurologic complications include intracranial hemorrhages (intracerebral hemorrhages, subarachnoid hemorrhages, subdural hematomas, and epidural hematomas), arterial ischemic strokes, cerebral venous gas embolism (28), venous thrombosis, cerebral abscess, spinal cord ischemia, encephalopathy and coma, hypoxic-ischemic injury, cerebral atrophy, postpump choreoathetosis, and peripheral nervous system injuries (recurrent laryngeal nerve and phrenic nerves).

The causes of neurologic complication are multifactorial and include preoperative brain malformations, perioperative hypoxemia and low cardiac output states, sequelae of cardiopulmonary bypass, deep hypothermic circulatory arrest, and postoperative arrhythmias (12). It should also be noted that children with congenital heart disease undergoing surgery may have underlying genetic abnormalities (eg, genetic polymorphisms mediating inflammatory response to cardiopulmonary bypass) or acquired abnormalities (eg, hemoglobinopathies, coagulation disturbances) that predispose them to thrombosis (34). For example, patients with Smith-Magenis syndrome, who are known to have a high incidence of congenital heart disease, may have gene deletions that affect cholesterol homeostasis. A patient with this syndrome experienced a stroke after cardiac surgery presumably due to premature intracerebral atherosclerosis (41). There may be preoperative factors that have produced baseline neuropsychological deficits due to marginal cerebral blood flow and oxygen delivery from uncorrected heart defects prior to surgery. Long-term sequelae may include language and learning disorders, anxiety and depression, intellectual disability, epilepsy, and cerebral palsy (69; 95).

Invasive diagnostic tests such as cardiac catheterization and other procedures predispose these children to thrombosis and stroke (34; 91). Neurologic complications occur in 0.24% of diagnostic catheterizations in children (127). Stroke accounts for greater than half of the neurologic complications. However, two thirds of these children have no neurologic sequelae on long-term follow-up (127). The risk of complications increases with interventional procedures during the catheterization, with prolonged duration of the procedure and with the presence of a right-to-left shunt (127).

Surgery for tumors. Myxomas account for 40% to 50% of primary cardiac tumors, and they typically arise from left-sided cardiac structures, predominantly the left atrium. The most common neurologic manifestation of atrial myxoma is cerebral ischemia secondary to embolism of myxomatous material or thrombus. Intracerebral or subarachnoid hemorrhage can occur as can delayed complications from tumor recurrence with embolization, progressive vascular stenosis, aneurysm formation and rupture, or parenchymal metastasis (217). Neurologic sequelae after resection are rare and may occur without recurrence of the myxoma. Aneurysms may enlarge after tumor resection or they may appear for the first time (174). Fragments of tumor that have metastasized to vessel walls may enlarge, occluding the vessel and resulting in delayed cerebral ischemia (171). Scrofani and colleagues reported a series of 38 patients who underwent surgical resection of a cardiac myxoma and found that 7.9% of these developed postoperative neurologic complications including transient ischemic attacks and stroke (183). Recurrence of myxoma after resection is rare (2% to 3%) (140; 19), suggests incomplete resection at the initial operation, and has been reported to occur from 6 months to 11 years after the initial resection. Recurrence of tumor has been associated with recurrent cerebral infarctions and cerebral fusiform aneurysms (117). Intra-arterial (77) and intravenous (202) thrombolysis have been used safely in single case reports of cerebral embolic infarction due to atrial myxoma.

Closure of patent foramen ovale. The prevalence of patent foramen ovale in the general population is as high as 30%. It is estimated that about 70,000 strokes per year are associated with patent foramen ovale; however, this association is controversial. The prevalence of atrial septal aneurysms is estimated to be 1% based on necropsies. There is an association of atrial septal aneurysms and the presence of patent foramen ovale. The risk of stroke is higher if there is a patent foramen ovale associated with an atrial septal aneurysm (177). In clinical trials, closure of the patent foramen ovale is associated with a lower rate of recurrent ischemic strokes when compared to medical therapy alone (138). Of note, there was a higher risk of atrial fibrillation in those that had patent foramen ovale closure.

Table 9 outlines the reported complications of percutaneous patent foramen ovale closure. Periprocedural complications of patent foramen ovale closure that may increase stroke risk include the development of atrioventricular block and atrial fibrillation (129).

Table 9. Complications of Percutaneous PFO Closure

• Venous access complications
	- Femoral arteriovenous fistula - Aneurysm of femoral artery
• Air embolism • Device embolism • Atrial wall perforation • Atrial fibrillation • Sinus node dysfunction • Infective endocarditis • Frame fracture and deformity • Thrombus formation around device

Prognosis and complications

The impact of stroke on early outcomes after cardiac surgery is significant with ICU stays that are twice as long, postoperative hospital lengths of stay that are 2.5 times longer, a doubling of the total hospital charges, and an increase in hospital mortality from between 4% to 5% for those without stroke to 19% to 33% for those with a stroke (179; 13). Patients with stroke after CABG have a 3-fold higher risk of dying in the 10-year period after the CABG when compared to those without a stroke (52). In a series of 100 patients having cardiac valve procedures, 24 had focal deficits. Of those 24, 13 (54%) had completely recovered in 2 months, and 22 (92%) had completely recovered in 5 months. The remaining two patients (8%) continued to have persistent disability throughout a 5-year follow-up period (198). Patients with neurologic complications after cardiac transplantation had longer ventilation times, longer stays in the ICU, and a higher incidence of pneumonia and sepsis when compared with patients without neurologic events (229). Also, there was a trend toward higher in-hospital mortality in the neurologic complication group (15%) when compared to those without neurologic complications (6%). Surprisingly, there was no difference in long-term survival (65% vs. 78%) (229). In most patients, neurologic complications were not the actual cause of death, but they significantly contributed to increased morbidity. The majority of patients who had a stroke following cardiac catheterization had an unfavorable outcome with a Rankin score of 3 to 6, ie, moderate disability to coma, with a high inpatient mortality rate (184).

Clinical vignette

Case 1. A 68-year-old man was admitted with prolonged substernal chest pain. He had a history of hypertension, diabetes mellitus, and hypercholesterolemia. EKG demonstrated an acute, non-ST elevation myocardial infarction. Coronary arteriography demonstrated severe 3-vessel coronary artery disease. The man underwent a CABG, and on awakening from anesthesia, he was noted to be less responsive than expected. He also could not move his right arm and leg as well as he could move the left. Neurologic examination was notable for right arm and leg paresis. A head CT scan showed subtle hypodensity in the left frontal and parietal regions consistent with ischemic stroke.

Case 2. A 41-year-old woman had a heart transplant because of a genetic dilated cardiomyopathy, not associated with muscular dystrophy or sensorineural hearing loss. Her father had died at the age of 35 years and her brother at the age of 38 years due to an apparent similar condition. She presented to the emergency department with new onset of excruciating headaches previously labeled as migraines. Her headaches were associated with confusion, disorientation, polyopia (she saw multiple images of her arms and legs), visual distortions described as “feeling something surreal,” and weakness of her limbs as if “my bones are leaving my body.” She had no history suggestive of palinopsia. Her immunosuppressant medications following heart transplant included mycophenolate 1500 mg twice daily and cyclosporine 125 mg twice daily.

Examination was noteworthy for cortical blindness, asymmetric quadriparesis, and a right Babinski sign. She underwent an unenhanced CT that showed no acute changes. MRI/MRA was not done due to remnant pacemaker leads. Cerebrospinal fluid examination was unremarkable. CT angiogram was performed.

Multifocal narrowing and dilation of intracranial vessels (initial presentation)

In this initial CT angiogram of the extra and intracranial circulation, extensive multifocal narrowing and dilation of the intracranial vessels are apparent predominantly on the posterior circulation (basilar artery and posterior ...

The cyclosporine and mycophenolate were discontinued. Approximately 1 month later, she underwent repeat CTA with demonstrated improvement.

Multifocal narrowing and dilation of intracranial vessels (1-month follow-up)

One month after initial presentation, there is irregularity of multiple intracranial branches including the distal internal carotid arteries, distal vertebral arteries, basilar artery, and proximal segments of the anterior, middle...

Another CTA 3 months after the initial scan revealed further improvement with nearly normal appearance of the cerebral vasculature.

Multifocal narrowing and dilation of intracranial vessels (3-month follow-up)

Three months after initial presentation, there is significant improvement in the appearance of the multifocal abnormalities previously noted in the intracranial arteries. The intracranial arteries are now almost normal in appearan...

The clinical impression was that she had clinical manifestations suggestive of possible PRES, as well as reversible segmental cerebral vasoconstriction (Call-Fleming syndrome) possibly due to treatment with cyclosporine. In this patient, the clinical and CTA findings were reversible. Another case is described in the literature of tacrolimus encephalopathy with MRI findings consistent with posterior leukoencephalopathy (111).

Case 3. A 69-year-old man underwent quadruple aortocoronary artery bypass graft, aortic valve replacement, and myomectomy for hypertrophic cardiomyopathy with idiopathic hypertrophic subaortic stenosis. When he awoke from surgery, he felt his vision was blurred. Examination showed optic disc pallor, decreased visual acuity, and afferent papillary defect in the left eye. He had suffered a nonarteritic anterior optic neuropathy, presumably due to intraoperative hypotension. MRI of the brain showed no abnormalities. At follow-up 3 years after his surgery, he reported that he only noticed his visual deficit when driving. Examination showed visual acuity of 20/40 in the left eye and 20/25 in the right, red desaturation, Marcus Gunn pupil, and temporal disc pallor in the left eye.

Case 4. A 55-year-old man presented with an acute myocardial infarction of several days’ duration and cardiogenic shock. An intra-aortic balloon pump was inserted in the cardiac cath lab. During the procedure he coded, requiring one round of epinephrine and chest compressions. He remained in cardiogenic shock despite the balloon pump. Because of the continued cardiogenic shock and the hypotension, he underwent emergency placement of a left ventricular assist device. Following surgery, he was started on dopamine, abciximab for 12 hours, aspirin, and clopidogrel and was continued on heparin drip. Within several days of the procedure, he awoke with complete loss of vision. Onset was abrupt, bilateral, painless, and nonprogressive. He had no light perception with either eye. Motility was full and painless. There was significant optic nerve pallor bilaterally. CT of the head was unremarkable, and MRI could not be performed because of his ventricular assist device. There were no symptoms to suggest temporal arteritis; however, given an elevated ESR of 69 mm/hr and CRP of 3.1 mg/dl, rheumatology was consulted, and he did undergo biopsy of the right temporal artery, which showed no evidence of arteritis. No visual-evoked responses were recorded in either eye following flash (strobe) monocular stimulation. He was evaluated by neurology and neuroopthalmology, and it was determined that the etiology of his vision loss was postoperative bilateral posterior ischemic optic neuropathy, most likely due to profound hypotension. Photographs of the fundi taken several weeks later showed pallor of the optic discs bilaterally.

Optic disc pallor in postoperative bilateral posterior ischemic optic neuropathy

Fundus photograph of the right eye (A) shows a flat macula, pale optic nerve and retinal vessels of normal caliber. Fundus photograph of the left eye (B) shows a flat macula, some hypopigmented spots just nasal to the fovea, optic...

Biological basis

Etiology and pathogenesis

The most common underlying pathophysiologic mechanisms producing stroke with cardiac surgery include preexisting cerebrovascular disease, emboli, hypoperfusion, and atrial fibrillation (141).

It is not surprising that patients undergoing cardiac surgery for atherosclerotic cardiac disease would have concomitant cerebrovascular disease. Factors that increase the risk of neurologic complications after cardiac surgery include a history of previous stroke, hypertension, diabetes, age, and the presence of a carotid bruit (141).

Emboli occurring during cardiac surgery can vary in size and come from a number of different potential sources (see Tables 10 and 11). These emboli may be divided into macroemboli (those occluding flow in arteries 200 microns or greater) or microemboli (those occluding smaller vessels) (20). The extracorporeal circulatory pump system can be a source of microembolism. In addition, microembolism can occur during aortic cannulation or aortic clamping/unclamping. MRI using diffusion-weighted imaging in the postoperative period after CABG can detect acute ischemic events related to microemboli and may demonstrate multiple lesions in a "watershed" pattern of distribution (223). Acute brain swelling on MRI in the immediate postoperative period may involve the cerebral cortex primarily, which correlates with the pathologic finding of small capillary and arteriolar dilatations in the cortex and deep gray matter (92).

Table 10. Embolic Material Produced During Cardiopulmonary Bypass and Open Heart Surgery

Fibrin
Fat (free fat, denatured lipoproteins, chylomicrons)
Denatured protein
Platelet aggregates
Red cell debris
Gas (nitrogen, oxygen)
Foreign material (calcium, tissue debris, suture material)
Other material (primarily roller pumps)

Table 11. Nongaseous Microemboli Reported During Cardiopulmonary Bypass

Microthrombi (eg, fibrin)
Platelet aggregates
Neutrophil aggregates
Red cell aggregates
Denatured protein
Fat or lipids
Cold-reacting antibodies
Bone fragments
Muscle fragments
Calcium particles
Plastic particles
Filter material
Tubing fragments
Metal
Talc
Thread
Bone wax
Microfibrillar collagen
Silicone antifoam
Cotton fibers

Hypoperfusion is another mechanism producing stroke during cardiac surgery. It is not clear what duration or degree of hypoperfusion can be tolerated intraoperatively, because other factors, such as comorbid diseases affecting cerebral autoregulation, play a role.

Atrial fibrillation occurs in approximately one third of patients in the early postoperative period after cardiac surgery and is the etiology of the stroke in 36% of patients with stroke (118).

Hematologic disturbances may result from cardiopulmonary bypass. There may be consumption of platelets and coagulation factors, decreased platelet adhesiveness, and abnormal activation of the coagulation cascade (04; 109).

Prevention

There are a number of risk factors associated with CABG (see Table 12) (70). Many of these risk factors are risk factors for ischemic stroke in general. If CABG is combined with other procedures, such as cardiac valve surgery, repair of other cardiac abnormalities, or carotid endarterectomy, the risk of stroke is higher (224; 71).

Table 12. Risk Factors for Stroke Associated with CABG

Patient-related
	Increasing age Female gender Previous TIA, stroke, or cerebrovascular disease Carotid artery disease or carotid bruit History of neurologic disease Proximal aortic atherosclerosis or calcified aorta Previous cardiac surgery Preoperative infection Recent myocardial infarction Poor left ventricular ejection fraction Cardiac mural thrombus Peripheral vascular disease Arterial hypertension Diabetes mellitus Chronic obstructive pulmonary disease Cigarette smoking Renal failure
Procedure-related
	Urgent operation Longer duration of cardiopulmonary bypass Use of alpha-adrenergic drugs after bypass High transfusion requirement Need for intraoperative hemofiltration Postoperative arrhythmias Intraaortic balloon pump
Source: (70)

Risk factors associated with an increased risk of perioperative neurologic complications in cardiac transplant patients include a prior history of stroke, catecholamine dependence preoperatively, intraaortic balloon pump or ventricular assist device usage in the preoperative period, and known coronary artery disease (78).

Risk factors for postoperative delirium include a prior history of cerebrovascular disease, peripheral vascular disease, atrial fibrillation, diabetes, ejection fraction less than 30%, urgent operation, need for massive blood transfusion, and operation time more than 3 hours (27).

Risks associated with cardiac valve surgery are detailed in Table 13. In general, early onset postoperative stroke is usually due to embolization of atheromatous debris, while delayed (after 24 hours) stroke is usually due to cardiogenic embolism (39).

Table 13. Risk Factors for Stroke with Valve Replacement Surgery

Patient-related
	Age over 65 years Female gender Prior TIA or stroke Notable atherosclerosis of the proximal aorta, carotid arteries, intracranial arteries Coronary artery disease Peripheral vascular disease Hypertension Tobacco use Postoperative atrial fibrillation
Procedure-related
	Clamp time longer than 60 minutes Pump time longer than 120 minutes Aortic calcification Simultaneous CABG and valvular surgery
Source: (124; 18; 176)

Table 4 reviews the risk factors associated with cardiac catheterization and Table 7 reviews the major risk factors for stroke with percutaneous coronary interventions.

Attention should be focused on methods to prevent stroke. McKhann and colleagues have proposed methods to prevent stroke with cardiac surgery before, during, and after the procedure is performed (141). Table 14 outlines these potential strategies.

Other strategies have been explored but have not had positive results. One study sought to determine whether epiaortic ultrasound scanning reduces cerebral emboli before or during cardiopulmonary bypass. The study randomized patients to transcranial Doppler ultrasound of the middle cerebral arteries to continuously before, during, and after aortic manipulation compared to control. Although epiaortic scanning did lead to modifications in intraoperative surgical management in 29% of patients, including adjustments of the cannulation site and avoidance of aortic cross-clamping, these interventions did not lead to a reduced number of cerebral emboli (59).

To date, there are no approved pharmacologic therapies for the prevention or treatment of cardiac surgery-associated cerebral injury. Despite numerous studies with negative results, studies continue to be undertaken looking at new compounds as neuroprotective agents in the setting of cardiac surgery (86; 119).

Table 14. Neuroprotective Strategies for Cardiac Surgery

Time	Issue	Suggestions
Before surgery	Identification of patients at high risk using established “risk models”	Alternative surgical procedures (off-pump). Use of percutaneous coronary intervention therapy
	Identification of carotid artery stenosis	Use of carotid endarterectomy or stenting
	Preexisting cerebrovascular disease and ischemic lesions identified on imaging (MRI)	Alteration of surgical procedures, eg, blood pressure management
	Atrial fibrillation	Pretreatment with drug therapy
During surgery	Aortic atheroma	Use of epiaortic/transesophageal echocardiogram ultrasound to identify ascending and arch aortic disease
		Modifications to surgical procedure: minimization of aortic manipulation, use of single aortic cross clamp for proximal grafts, no-touch aortic technique, altered cannula placement
		Use of higher blood pressures during cardiopulmonary bypass
		Increase hematocrit to 30%
		Use of alpha-stat pH management (for adults)
		Prevent rewarming temperature over 37ºC
		Prevent hyperglycemia by having a structured glucose management protocol in place
		Use of arterial line filters
		Avoid use of cardiotomy suction
After surgery	Prevention of atrial fibrillation	Early intervention for arrhythmias
After surgery	Diagnosis and identification of ischemic brain lesions and brain perfusion mismatch	Early blood pressure intervention to minimize infarction size. Use of diffusion-weighted MRI/perfusion-weighted imaging.
Source: (141)

Diagnostic workup

When evaluating patients with a suspected stroke during or after cardiac surgery, it is necessary to review important information from the preoperative history, including vascular risk factors and prior history of stroke. Next, information about the intraoperative course should be obtained, including, when applicable, the duration of cardiopulmonary bypass and intraoperative and postoperative arterial blood pressures and ECG to evaluate for periods of hypotension and cardiac rhythm disturbances. Patients with stroke after a diagnostic or interventional procedure should have a review of preprocedural risk factors and a review of intraprocedural vital signs and cardiac rhythm to evaluate for hypotension or cardiac arrhythmias. A thorough general examination should be performed, with attention given to vital signs, including temperature, whether there is a cardiac rhythm disturbance, and whether there is evidence of peripheral embolization. Neurologic examination should focus on determining if there are alterations in mental status, evaluating for focal motor or sensory deficits, and determining whether any deficit is due to central or peripheral nervous system involvement.

Laboratory data should be reviewed and appropriate tests ordered to rule out a metabolic cause of encephalopathy or coma. Initial tests to evaluate for stroke should include a head CT without contrast or an MRI of the brain with diffusion-weighted images. The most common pattern encountered is multiple embolic infarcts, located in the cortex of the hemispheres and in the cerebellar hemispheres. Lesions can occur in either hemisphere, as well in the anterior and posterior circulations. An EEG is appropriate in patients suspected of having seizures. Vigilant evaluation for infection is indicated in the cardiac transplant population, including, when appropriate, blood cultures, chest x-ray, CSF analysis, and head CT or MRI of the brain.

In the patient who has an ischemic stroke after cardiac transplant, general diagnostic tests as discussed above are applicable. For those suspected of having a posttransplant CNS infection, appropriate testing may include head CT without and with contrast, CSF analysis, blood cultures, blood serologies specific for suspected infectious agents, and in some cases, stereotactic brain biopsy. Those with seizures should be evaluated for a stroke and PRES. Thorough metabolic screening should be undertaken, including evaluating for hypomagnesemia, which in combination with cyclosporine toxicity may be an etiology for seizures. Levels of calcineurin inhibitors should be obtained. Patients should be evaluated for CNS infection as a cause of seizures. Seizures can be managed acutely with benzodiazepines. If long-term treatment is deemed necessary, antiseizure medications that do not induce hepatic enzymes that metabolize cyclosporine should be used (consider valproic acid, felbamate, lamotrigine, gabapentin, levetiracetam, or pregabalin).

In patients with ischemic stroke after cardiac valve surgery, diagnostic testing is similar to that described for stroke after CABG. Patients presenting with delayed stroke after mitral valve replacement should be evaluated for the presence of atrial fibrillation and left-atrial thrombus. In a patient with suspected prosthetic valve endocarditis, head CT or brain MRI, blood cultures, and transesophageal echocardiography should be obtained.

Management

A stroke involving occlusion of the proximal vessel in the anterior circulation can often lead to catastrophic outcomes including death and inability to have a functional quality of life even with standard therapy. In patients with stroke after cardiac surgery, use of intravenous tissue plasminogen activator (tPA) in select patients may be considered, but the potential increased risk of surgical-site hemorrhage should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits in each patient (170). Since multiple landmark trials were published in 2015 establishing the superiority of endovascular thrombectomy over medical management alone in patients with acute stroke due to large vessel occlusions, mechanical thrombectomy has become standard of care for the treatment of acute stroke and should be considered in eligible patients who present with stroke after a cardiac procedure (170; 102). A detailed discussion of patient eligibility for tPA and thrombectomy is beyond the scope of this review, and further information can be found in the Guidelines for the Early Management of Patients with Acute Ischemic Stroke from the American Heart Association/American Stroke Association (170).

Treatment of patients after ischemic stroke should include careful attention to maintaining normal body temperature, maintaining adequate oxygenation, avoiding hypotension/brain hypoperfusion, maintaining normal serum glucose, avoiding hypotonic intravenous fluids, preventing deep venous thrombosis, and avoiding aspiration pneumonia by evaluating swallowing capacities (70). If the etiology of the stroke is an air embolism, patients should be placed on 100% oxygen until they are transferred to a hyperbaric chamber facility (150).

Media

References

01: Abend NS, Levine JM. Hypodense middle cerebral artery with fat embolus. Neurocrit Care 2007;6(2):147-8. PMID 17522799
02: Adair JC, Call GK, O’Connell JB, Baringer JR. Cerebrovascular syndromes following cardiac transplantation. Neurology 1992;42(4):819-23. PMID 1565236
03: Adair JC, Woodley SL, O’Connell JB, Call GK, Baringer JR. Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen. Neurology 1991;41(2 (Pt 1)):249-52. PMID 1899475
04: Addonizio VP Jr, Smith JB, Strauss JF 3rd, Colman RW, Edmunds LH Jr. Thromboxane synthesis and platelet secretion during cardiopulmonary bypass with bubble oxygenator. J Thorac Cardiovasc Surg 1980;79(1):91-6. PMID 7350392
05: Agnihotri AK, McGiffin DC, Galbraith AJ, O'Brien MF. The prevalence of infective endocarditis after aortic valve replacement. J Thorac Cardiovasc Surg 1995;110(6):1708-20. PMID 8523884
06: Akins CW. Results with mechanical cardiac valvular prostheses. Ann Thorac Surg 1995;60(6):1836-44. PMID 8787503
07: Alaifan T, Alenazy A, Xiang Wang D, et al. Tranexamic acid in cardiac surgery: a systematic review and meta-analysis (protocol). BMJ Open 2019;9(9):e028585. PMID 31530593
08: Alejaldre A, Delgado-Mederos R, Santos MÁ, Martí-Fàbregas J. Cerebrovascular complications after heart transplantation. Curr Cardiol Rev 2010;6(3):214-7. PMID 21804780
09: Alkhaibary A, Alsubaie N, Alharbi A, et al. Oculomotor nerve palsy following coronary artery bypass graft surgery: can pituitary apoplexy complicate the post-operative course of cardiac surgery? J Surg Case Rep 2021;2021(7):rjab312. PMID 34345402
10: Al-Mubarak N, Vitek JJ, Mousa I, et al. Immediate catheter-based neurovascular rescue for acute stroke complicating coronary procedures. Am J Cardiol 2002;90(2):173-6. PMID 12106853
11: Andrews BT, Hershon JJ, Calanchini P, Avery GJ 2nd, Hill JD. Neurologic complications of cardiac transplantation. West J Med 1990;153(2):146-8. PMID 2219870
12: Andropoulos DB, Stayer SA, Diaz LK, Ramamoorthy C. Neurological monitoring for congenital heart surgery. Anesth Analg 2004;99(5):1365-75. PMID 15502032
13: Anyanwu AC, Filsoufi F, Salzberg SP, Bronster DJ, Adams DH. Epidemiology of stroke after cardiac surgery in the current era. J Thorac Cardiovasc Surg 2007;134(5):1121-7. PMID 17976438
14: Aoyagi S, Kosuga T, Fukunaga S, Tayama E, Ueda T. Subdural hematoma after open-heart surgery. J Heart Valve Dis 2007;16(4):450-3. PMID 17702373
15: Arvay A, Lengyel M. Incidence and risk factors of prosthetic valve endocarditis. Eur J Cardiothorac Surg 1988;2(5):340-6. PMID 3272238
16: Austin EH 3rd, Edmonds HL Jr, Auden SM, et al. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg 1997;114(5):707-17. PMID 9375600
17: Avila-Alvarez A, Gonzalez-Rivera I, Ferrer-Barba A, et al. [Acute neurological complications after pediatric cardiac surgery: still a long way to go.]. An Pediatr (Barc) 2012;76(4):192-8. PMID 22056311
18: Bando K, Kobayashi J, Hirata M, et al. Early and late stroke after mitral valve replacement with a mechanical prosthesis: risk factor analysis of a 24-year experience. J Thorac Cardiovasc Surg 2003;126(2):358-64. PMID 12928631
19: Bjessmo S, Ivert T. Cardiac myxoma: 40 years’ experience in 63 patients. Ann Thorac Surg 1997;63:697-700. PMID 9066386
20: Blauth CI. Macroemboli and microemboli during cardiopulmonary bypass. Ann Thorac Surg 1995;59(5):1300-3. PMID 7733756
21: Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med 1991;324(9):573-9. PMID 1992318
22: Bogousslavsky J. The plurality of subcortical infarction. Stroke 1992;23(5):629-31. PMID 1579957
23: Boshoff DE, Eyskens B, Gewillig M. Late redilation of a stent in the aorta crossing the subclavian artery complicated with a cerebellar infarction. Acta Cardiol 2007;62(3):295-7. PMID 17608105
24: Bourge RC, Kirklin JK, Thomas K, et al. The emergence of co-morbid diseases impacting survival after cardiac transplantation, a ten year multi-institutional experience. J Heart Lung Transplant 2001;20(2):167-8. PMID 11250259
25: Bowdish ME, D'Agostino RS, Thourani VH, et al. The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2020 update on outcomes and research. Ann Thorac Surg 2020;109(6):1646-55. PMID 32247780
26: Brown DL, Topol EJ. Stroke complicating percutaneous coronary revascularization. Am J Cardiol 1993;72(15):1207-9. PMID 8237818
27: Bucerius J, Gummert JF, Borger MA, et al. Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery. J Thorac Cardiovasc Surg 2004;127(1):57-64. PMID 14752413
28: Buompadre MC, Arroyo HA. Accidental cerebral venous gas embolism in a young patient with congenital heart disease. J Child Neurol 2008;23(1):121-3. PMID 18184947
29: Burns JD, Manno EM, Wijdicks EF. An unusual cause of fixed dilated pupils after cardiac surgery. Neurocrit Care 2008;9(3):370-3. PMID 18521761
30: Busing KA, Schulte-Sasse C, Flüchter S, et al. Cerebral infarction: incidence and risk factors after diagnostic and interventional cardiac catheterization--prospective evaluation at diffusion-weighted MR imaging. Radiology 2005;235:177–183. PMID 15731373
31: Butchart EG, Payne N, Li HH, Buchan K, Mandana K, Grunkemeier GL. Better anticoagulation control improves survival after valve replacement. J Thorac Cardiovasc Surg 2002;123(4):715-23. PMID 11986600
32: Buth J, Harris PL, Hobo R, et al. Neurologic complications associated with endovascular repair of thoracic aortic pathology: incidence and risk factors. A study from the European Collaborators on Stent/Graft Techniques for Aortic Aneurysm Repair (EUROSTAR) registry. J Vasc Surg 2007;46(6):1103-11. PMID 18154984
33: Calderwood SB, Swinski LA, Waternaux CM, Karchmer AW, Buckley MJ. Risk factors for the development of prosthetic valve endocarditis. Circulation 1985;72(1):31-7. PMID 4006134
34: Caldwell RL. Stroke and congenital heart disease in infants and children. Sem Cerebrovasc Dis Stroke 2003;3(4):200-6.
35: Canbaz S, Turgut N, Halici U, Sunar H, Balci K, Duran E. Brachial plexus injury during open heart surgery--controlled prospective study. Thorac Cardiovasc Surg 2005;53(5):295-9. PMID 16208616
36: Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJ, Vandenbroucke JP, Briët E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995;333(1):11-7. PMID 7776988
37: Caplan LR, Weiner H, Weintraub RM, Austen WG. “Migrainous” neurologic dysfunction in patients with prosthetic cardiac valves. Headache 1976;16(5):218-21. PMID 977326
38: Carter CA, Weston GA. Fixed dilated pupils following cardiac surgery. Anaesthesia 1987;42(11):1231-2. PMID 3434749
39: Caswell J, O’Brien B, Schneck M. Risk of stroke following valve replacement surgery. Sem Cerebrovasc Dis Stroke 2003;3:214-8.
40: Chandrasekhar S, Cook C, Collard C. Cardiac surgery in the parturient. Anesth Analg 2009;108(3):777-85. PMID 19224782
41: Chaudhry AP, Schwartz C, Singh AK. Stroke after cardiac surgery in a patient with Smith-Magenis syndrome. Tex Heart Inst J 2007;34(2):247-9. PMID 17622381
42: Chen H, Mo L, Hu H, Ou Y, Luo J. Risk factors of postoperative delirium after cardiac surgery: a meta-analysis. J Cardiothorac Surg 2021;16(1):113. PMID 33902644
43: Chen JW, Lin CH, Hsu RB. Mechanisms of early and delayed stroke after systematic off-pump coronary artery bypass. J Formos Med Assoc 2015;114(10):988-94. PMID 21621423
44: Cho L. Cerebrovascular complications in interventional cardiology. Sem Cerebrovasc Dis Stroke 2003;3(4):228-32.
45: Cline SL, Kalaria VG, Von Der Lohe E, Breall JA. Cerebrovascular complications of cardiac catheterization. Sem Cerebrovasc Dis Stroke 2003;3(4):194-9.
46: Copeland JG, Copeland H, Gustafson M, et al. Experience with more than 100 total artificial heart implants. J Thorac Cardiovasc Surg 2012;143(3):727-34. PMID 22245242
47: Coskun I, Colkesen Y, Demirturk OS, Tunel HA, Giray S, Gulcan O. Pre- and perioperative risk factors predicting neurologic outcomes after coronary artery bypass surgery in patients with pre-existing neurologic events. J Stroke Cerebrovasc Dis 2013;22(8):1340-9. PMID 23422349
48: Cottini SR, Wenger U, Sailer S, et al. Extracorporeal membrane oxygenation: beneficial strategy for lung transplant recipients. J Extra Corpor Technol 2013;45(1):16-20. PMID 23691779
49: Crespo-Leiro MG, Metra M, Lund LH, et al. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2018;20(11):1505-35. PMID 29806100
50: Cronin L, Mehta SR, Zhao F, et al. Stroke in relation to cardiac procedures in patients with non-ST-elevation acute coronary syndrome: a study involving >18,000 patients. Circulation 2001;104(3):269-74. PMID 11457743
51: Czartoski T. Central nervous system complications in transplant recipients. Continuum 2006;12(2):95-110.
52: Dacey LJ, Likosky DS, Leavitt BJ, et al. Perioperative stroke and long-term survival after coronary bypass graft surgery. Ann Thorac Surg 2005;79(2):532-6. PMID 15680829
53: Dawson DM, Fischer EG. Neurologic complications of cardiac catheterization. Neurology 1977;27(5):496-7. PMID 558558
54: Deklunder G, Roussel M, Lecroart JL, Prat A, Gautier C. Microemboli in cerebral circulation and alteration of cognitive abilities in patients with mechanical prosthetic heart valves. Stroke 1998;29(9):1821-6. PMID 9731602
55: Del Val D, Panagides V, Mestres CA, Miró JM, Rodés-Cabau J. Infective endocarditis after transcatheter aortic valve replacement: JACC state-of-the-art review. J Am Coll Cardiol 2023;81(4):394-412. PMID 36697140
56: Deng MC, Edwards LB, Hertz MI, et al. Mechanical circulatory support device database of the International Society for Heart and Lung Transplantation: third annual report—2005. J Heart Lung Transplant 2005;24(9):1182-7. PMID 16143231
57: Devgun JK, Gul S, Mohananey D, et al. Cerebrovascular events after cardiovascular procedures: risk factors, recognition, and prevention strategies. J Am Coll Cardiol 2018;71(17):1910-20. PMID 29699618
58: Dimopoulou I, Daganou M, Dafni U, et al. Phrenic nerve dysfunction after cardiac operations: electrophysiologic evaluation of risk factors. Chest 1998;113(1):8-14. PMID 9440560
59: Djaiani G, Ali M, Borger MA, et al. Epiaortic scanning modifies planned intraoperative surgical management but not cerebral embolic load during coronary artery bypass surgery. Anesth Analg 2008;106(6):1611-8. PMID 18499587
60: Djaiani G, Katznelson R, Fedorko L, et al. Early benefit of preserved cognitive function is not sustained at one-year after cardiac surgery: a longitudinal follow-up of the randomized controlled trial. Can J Anaesth 2012;59(5):449-55. PMID 22290354
61: Domi T, Edgell DS, McCrindle BW, et al. Frequency, predictors, and neurologic outcomes of vaso-occlusive strokes associated with cardiac surgery in children. Pediatrics 2008;122(6):1292-8. PMID 19047248
62: Drobinski G, Montalescot G, Evans J, Nivet M, Thomas D, Grosgogeat Y. Systemic embolism as a complication of percutaneous mitral valvuloplasty. Cathet Cardiovasc Diagn 1992;25(4):327-30. PMID 1571998
63: Dubin WR, Field HL, Gastfriend DR. Postcardiotomy delirium: a critical review. J Thorac Cardiovasc Surg 1979;77(4):586-94. PMID 370460
64: Dukkipati S, O'Neill WW, Harjai KJ, et al. Characteristics of cerebrovascular accidents after percutaneous coronary interventions. J Am Coll Cardiol 2004;43(7):1161-7. PMID 15063423
65: Eggers S, Moster ML, Cranmer K. Selective saccadic palsy after cardiac surgery. Neurology 2008;70:318-20. PMID 18057315
66: Eishi K, Kawazoe K, Kuriyama Y, Kitoh Y, Kawashima Y, Omae T. Surgical management of infective endocarditis associated with cerebral complications. Multi-center retrospective study in Japan. J Thorac Cardiovasc Surg 1995;110(6):1745-55. PMID 8523887
67: El Tantawy AE, Imam S, Shawky H, Salah T. Diaphragmatic nerve palsy after cardiac surgery in children in Egypt: outcome and debate in management. World J Pediatr Congenit Heart Surg 2013;4(1):19-23. PMID 23799750
68: Fallon P, Aparício JM, Elliott MJ, Kirkham FJ. Incidence of neurological complications of surgery for congenital heart disease. Arch Dis Child 1995;72(5):418-22. PMID 7618908
69: Ferry PC. Neurologic sequelae of cardiac surgery in children. Am J Dis Child 1987;141(3):309-12. PMID 3544810
70: Fleck JD, Biller J. Cerebrovascular complications of cardiovascular interventions: Coronary artery bypass graft procedures. Sem Cerebrovasc Dis Stroke 2003;3(4):207-13.
71: Fleck JD, O’Donnell JA, Biller J. Cardiac evaluation of patient with carotid artery stenosis and treatment strategies for coexisting disease. In: Loftus CM, Kresowik TF, editors. Carotid Artery Surgery. New York: Thieme, 2000:121-9.
72: Flomenbaum MA, Jarcho JA, Schoen FJ. Progressive multifocal leukoencephalopathy fifty-seven months after heart transplantation. J Heart Lung Transplant 1991;10(6):888-93. PMID 1756153
73: Floyd TF, Shah PN, Price CC, et al. Clinically silent cerebral ischemic events after cardiac surgery: their incidence, regional vascular occurrence, and procedural dependence. Ann Thorac Surg 2006;81(6):2160-6. PMID 16731147
74: Fuchs S, Stabile E, Kinnaird TD, et al. Stroke complicating percutaneous coronary interventions: incidence, predictors, and prognostic implications. Circulation 2002;106(1):86-91. PMID 12093775
75: Fudulu D, Benedetto U, Pechhinenda GG, et al. Current outcomes of off-pump versus on-pump coronary artery bypass grafting: evidence from randomized control trials. J Thorac Dis 2016;8(Suppl 10):S758-71. PMID 27942394
76: Gardner TJ, Horneffer PJ, Manolio TA, et al. Stroke following coronary artery bypass grafting: a ten-year study. Ann Thorac Surg 1985;40(6):574-81. PMID 3878134
77: Gassanov N, Nia AM, Dahlem KM, et al. Local thrombolysis for successful treatment of acute stroke in an adolescent with cardiac myxoma. ScientificWorldJournal 2011;11:891-3. PMID 21516285
78: Gill WJ, O’Donnell J. Cerebrovascular complications of cardiac transplantation. Sem Cerebrovasc Diseases and Stroke 2003;3(4): 219-24.
79: Goldsmith I, Lip GY, Kaukuntla H, Patel RL. Hospital morbidity and mortality and changes in quality of life following mitral valve surgery in the elderly. J Heart Valve Dis 1999;8(6):702-7. PMID 10616251
80: Goldstone AB, Bronster DJ, Anyanwu AC, et al. Predictors and outcomes of seizures after cardiac surgery: a multivariable analysis of 2,578 patients. Ann Thorac Surg 2011;91(2):514-8. PMID 21256303
81: Gootjes EC, Wijdicks EF, McClelland RL. Postoperative stupor and coma. Mayo Clin Proc 2005;80(3):350-4. PMID 15757016
82: Gopaldas RR, Chu D, Dao TK, et al. Staged versus synchronous carotid endarterectomy and coronary artery bypass grafting: analysis of 10-year nationwide outcomes. Ann Thorac Surg 2011;91(5):1323-9. PMID 21457941
83: Gottesman MH, Saraya I, Tenti F. Modified Brown-Séquard syndrome following coronary artery bypass graft: case report. Paraplegia 1992;30(3):178-80. PMID 1630844
84: Gottesman RF, Grega MA, Bailey MM, et al. Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol 2010;67(3):338-44. PMID 20373345
85: Gottesman RF, McKhann GM, Hogue CW. Neurological complications of cardiac surgery. Semin Neurol 2008;28(5):703-15. PMID 19115176
86: Grocott H. Pharmacologic neuroprotection: the search continues. J Extra Corpor Technol 2007;39:296-301. PMID 18293824
87: Guerios EE, Bueno R, Nercolini D, et al. Mitral stenosis and percutaneous mitral valvuloplasty (part 1). J Invasive Cardiol 2005;17(7):382-6. PMID 16003027
88: Gutsche JT, Cheung AT, McGarvey ML, et al. Risk factors for perioperative stroke after thoracic endovascular aortic repair. Ann Thorac Surg 2007;84(4):1195-200. PMID 17888969
89: Hall WA, Martinez AJ, Dummer JS. Progressive multifocal leukoencephalopathy after cardiac transplantation. Neurology 1988;38(6):995-6. PMID 3285241
90: Hammermeister KE, Sethi GK, Henderson WG, Oprian C, Kim T, Rahimtoola S. A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veteran Affairs Cooperative Study on Valvular Heart Disease. N Engl J Med 1993;328(18):1289-96. PMID 8469251
91: Harrar DB, Salussolia CL, Vittner P, et al. Stroke after cardiac catheterization in children. Pediatr Neurol 2019;100:42-8. PMID 31481331
92: Harris DN, Bailey SM, Smith PL, Taylor KM, Oatridge A, Bydder GM. Brain swelling in first hour after coronary artery bypass surgery. Lancet 1993;342(8871):586-7. PMID 8102722
93: Heiro M, Nikoskelainen J, Engblom E, Kotilainen E, Marttila R, Kotilainen P. Neurologic manifestations of infective endocarditis: a 17-year experience in a teaching hospital in Finland. Arch Intern Med 2000;160(18):2781-7 PMID 11025788
94: Hoffman SJ, Routledge HC, Lennon RJ, et al. Procedural factors associated with percutaneous coronary intervention-related ischemic stroke. JACC Cardiovasc Interv 2012;5(2):200-6. PMID 22361605
95: Horner T, Liberthson R, Jellinek MS. Psychosocial profile of adults with complex congenital heart disease. Mayo Clin Proc 2000;75(1):31-6. PMID 10630755
96: Horstkotte D, Scharf RE, Schultheiss HP. Intracardiac thrombosis: patient-related and device-related factors. J Heart Valve Dis 1995;4(2):114-20. PMID 8556170
97: Hotson JR, Pedley TA. The neurological complications of cardiac transplantation. Brain 1976;99(4):673-94. PMID 192413
98: Hupperts R, Wetzelaer W, Heuts-van Raak L, Lodder J. Is haemodynamical compromise a specific cause of border zone brain infarcts following cardiac surgery. Eur Neurol 1995;35(5):276-80. PMID 8542916
99: Inoue K, Lüth JU, Pottkämper D, Strauss KM, Minami K, Reichelt W. Incidence and risk factors of perioperative cerebral complications. Heart transplantation compared to coronary artery bypass grafting and valve surgery. J Cardiovasc Surg (Torino) 1998;39:(2):201-8. PMID 9639005
100: Ivert TS, Dismukes WE, Cobbs CG, Blackstone EH, Kirklin JW, Bergdahl LA. Prosthetic valve endocarditis. Circulation 1984;69(2):223-32. PMID 6690095
101: Jackson JL, Meyer GS, Pettit T. Complications from cardiac catheterization: analysis of a military database. Mil Med 2000;165(4):298-301. PMID 10803005
102: Jadhav AP, Desai SM, Jovin TG. Indications for mechanical thrombectomy for acute ischemic stroke: current guidelines and beyond. Neurology 2021;97(20 Suppl 2):S126-S136. PMID 34785611
103: Jarquin-Valdivia AA, Wijdicks EF, McGregor C. Neurologic complications following heart transplantation in the modern era: decreased incidence, but postoperative stroke remains prevalent. Transplant Proc 1999;31(5):2161-2. PMID 10456001
104: Jayachandran JV. Cerebrovascular complications of invasive electrophysiologic procedures. Sem Cerebrovasc Dis and Stroke 2003;3(4):225-7.
105: Kato TS, Schulze PC, Yang J, et al. Pre-operative and post-operative risk factors associated with neurologic complications in patients with advanced heart failure supported by a left ventricular assist device. J Heart Lung Transplant 2012;31(1):1-8. PMID 21986099
106: Katz MG, Katz R, Schachner A, Cohen AJ. Phrenic nerve injury after coronary artery bypass grafting: will it go away. Ann Thorac Surg 1998;65(1):32-5. PMID 9456091
107: Keilson GR, Schwartz WJ, Recht LD: The preponderance of posterior circulatory events is independent of the route of cardiac catheterization. Stroke 1992;23(9):1358-9.
108: Kent KC, Moscucci M, Gallagher SG, DiMattia ST, Skillman JJ. Neuropathy after cardiac catheterization: incidence, clinical patterns, and long-term outcome. J Vasc Surg 1994;19(6):1008-13. PMID 8201701
109: Kestin AS, Valeri CR, Khuri SF, et al. The platelet function defect of cardiopulmonary bypass. Blood 1993;82(1):107-17. PMID 7686785
110: Khoynezhad A, Donayre CE, Bui H, Kopchok GE, Walot I, White RA. Risk factors of neurologic deficit after thoracic aortic endografting. Ann Thorac Surg 2007;83(2):S882-9; discussion S890-2. PMID 17257946
111: Kiemeneij IM, de Leeuw FE, Ramos LM, van Gijn J. Acute headache as a presenting symptom of tacrolimus encephalopathy. J Neurol Neurosurg Psychiatry 2003;74(8):1126-7. PMID 12876250
112: Kim JB, Yun TJ, Chung CH, Choo SJ, Song H, Lee JW. Long-term outcome of modified maze procedure combined with mitral valve surgery: analysis of outcomes according to type of mitral valve surgery. J Thorac Cardiovasc Surg 2010;139(1):111-7. PMID 19740489
113: Knipp SC, Matatko N, Schlamann M, et al. Small ischemic brain lesions after cardiac valve replacement detected by diffusion-weighted magnetic resonance imaging: relation to neurocognitive function. Eur J Cardiothorac Surg 2005;28(1):88-96. PMID 15922616
114: Koene RJ, Win S, Naksuk N, et al. HAS-BLED and CHA2DS2-VASc scores as predictors of bleeding and thrombotic risk after continuous-low ventricular assist device implantation. J Card Fail 2014;20(11):800-7. PMID 25152496
115: Kosmorsky G, Hanson MR, Tomsak RL. Neuro-ophthalmologic complications of cardiac catheterization. Neurology 1988;38(3):483-5. PMID 3347353
116: Kvidal P, Bergström R, Malm T, Ståhle E. Long-term follow-up of morbidity and mortality after aortic valve replacement with a mechanical valve prosthesis. Eur Heart J 2000;21(13):1099-111. PMID 10843828
117: Kvitting JE, Engvall J, Broqvist M, et al. Recurrence of myxoma in the left ventricle with concurrent cerebral fusiform aneurysms after previous atrial myxoma surgery. J Thorac Cardiovasc Surg 2008;135(5)1172-3. PMID 18455603
118: Lahtinen J, Biancari F, Salmela E, et al. Postoperative atrial fibrillation is a major cause of stroke after on-pump coronary artery bypass surgery. Ann Thorac Surg 2004;77(4):1241-4. PMID 15063244
119: Lakic N, Surlan K, Jerin A, Meglic B, Curk N, Bunc M. Importance of erythropoietin in brain protection after cardiac surgery: a pilot study. Heart Surg Forum 2010;13(3):E185-9. PMID 20534421
120: Lazar JM, Uretsky BF, Denys BG, Reddy PS, Counihan PJ, Ragosta M. Predisposing risk factors and natural history of acute neurologic complications of left-sided cardiac catheterization. Am J Cardiol 1995;75(15):1056-60. PMID 7747689
121: Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016;374(17)1609-20. PMID 27040324
122: Levy E, Korach A, Merin G, Feinsod M, Glenville B. Pituitary apoplexy and CABG: should we change our strategy. Ann Thorac Surg 2007;84(4):1388-90. PMID 17889010
123: Lewis AR, Kline LB, Pinkard NB. Visual loss due to progressive multifocal leukoencephalopathy in a heart transplant patient. J Clin Neuroophthalmol 1993;13(4):237-41. PMID 8113435
124: Libman RB, Wirkowski E, Neystat M, Barr W, Gelb S, Graver M. Stroke associated with cardiac surgery. Determinants, timing, and stroke subtypes. Arch Neurol 1997;54(1):83-7. PMID 9006418
125: Lichtenberg R, Anderson DC. Neurologic manifestations of congenital heart disease. In: Biller J, editor. The Interface of Neurology & Internal Medicine. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2008.
126: Likosky DS, Marrin CA, Caplan LR, et al. Determination of etiologic mechanisms of stroke secondary to coronary artery bypass graft surgery. Stroke 2003;34(12):2830-4. PMID 14605327
127: Liu XY, Wong V, Leung M. Neurologic complications due to catheterization. Pediatr Neurol 2001;24(4):270-5. PMID 11377101
128: Lorusso R, Barili F, Mauro MD, et al. In-hospital neurologic complications in adult patients undergoing venoarterial extracorporeal membrane oxygenation: results from the extracorporeal life support organization registry. Crit Care Med 2016;44(10):e964-72. PMID 27340754
129: Luermans JG, Post MC, Plokker HW, Ten Berg JM, Suttorp MJ. Complications and mid-term outcome after percutaneous patent foramen ovale closure in patients with cryptogenic stroke. Neth Heart J 2008;16(10):332-6. PMID 18958256
130: Lund C, Nes RB, Ugelstad TP, et al. Cerebral emboli during left heart catheterization may cause acute brain injury. Eur Heart J 2005;26(13):1269-75. PMID 15716287
131: Macdonald RL, Kowalczuk A, Johns L. Emboli enter penetrating arteries of monkey brain in relation to their size. Stroke 1995;26(7):1247-51. PMID 7604423
132: Mack MJ, Brown PP, Kugelmass AD, et al. Current status and outcomes of coronary revascularization 1999 to 2002: 148,396 surgical and percutaneous procedures. Ann Thorac Surg 2004;77(3):761-6; discussion 766-8. PMID 14992867
133: Mahli A, Izdes S, Coskun D. Cardiac operations during pregnancy: review of factors influencing fetal outcome. Ann Thorac Surg 2000;69:1622-26. PMID 10881866
134: Manne MB, Shrestha NK, Lytle BW, et al. Outcomes after surgical treatment of native and prosthetic valve infective endocarditis. Ann Thorac Surg 2012;93(2):489-93. PMID 22206953
135: Mao Z, Zhong X, Yin, J, Zhao Z, Hu X, Hackett ML. Predictors associated with stroke after coronary artery bypass grafting: a systematic review. J Neuro Sci 2015;357(1-2):1-7. PMID 26208801
136: Martin BJ, Buth KJ, Arora RC, Baskett RJ. Delirium: a cause for concern beyond the immediate postoperative period. Ann Thorac Surg 2012;93(4):1114-20. PMID 22200370
137: Martin K, Knorr J, Breuer T, et al. Seizures after open heart surgery: comparison of ε-aminocaproic acid and tranexamic acid. J Cardiothorac Vasc Anesth 2011;25(1):20-5. PMID 21272777
138: Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 2017;377(11):1011-21. PMID 28902593
139: Mayer TO, Biller J, O’Donnell J, Meschia JF, Sokol DK. Contrasting the neurologic complications of cardiac transplantation in adults and children. J Child Neurol 2002;17(3):195-9. PMID 12026235
140: McCarthy PM, Piehler JM, Schaff HV, et al. The significance of multiple, recurrent, and “complex” cardiac myxomas. J Thorac Cardiovasc Surg 1986;91:389-96. PMID 3951243
141: McKhann GM, Grega MA, Borowicz LM Jr, Baumgartner WA, Selnes OA. Stroke and encephalopathy after cardiac surgery: an update. Stroke 2006;37(2):562-71. PMID 16373636
142: McKhann GM, Grega MA, Borowicz LM Jr, et al. Is there cognitive decline 1 year after CABG. Comparison with surgical and nonsurgical controls. Neurology 2005;65(7):991-9. PMID 16107605
143: Melly L, Torregrossa G, Lee T, Jansens JL, Puskas JD. Fifty years of coronary artery bypass grafting. J Thorac Dis 2018;10(3):1960-7. PMID 29707352
144: Misfeld M, Brereton RJ, Sweetman EA, Doig GS. Neurologic complications after off-pump coronary artery bypass grafting with and without aortic manipulation: Meta-analysis of 11,398 cases from 8 studies. J Thorac Cardiovasc Surg 2011;142(2):e11-7. PMID 21281950
145: Mittal MK, Schears GJ, Wijdicks EF. Brachial plexus injury associated with extracorporeal membrane oxygenation. J Clin Neuromuscul Dis 2013;15(1):24-7. PMID 23965406
146: Mokri B, Ahlskog JE, Fulgham JR, Matsumoto JY. Syndrome resembling PSP after surgical repair of ascending aorta dissection or aneurysm. Neurology 2004;62:971-3. PMID 25688554
147: Molina EJ, Shah P, Kiernan MS, et al. The Society of Thoracic Surgeons Intermacs 2020 Annual Report. Ann Thorac Surg 2021;111(3):778-92. PMID 33465365
148: Moller CH, Penninga L, Wetterslev J, Steinbrüchel DA, Gluud C. Off-pump versus on-pump coronary artery bypass grafting for ischaemic heart disease. Cochrane Database Syst Rev 2012;3:CD007224. PMID 22419321
149: Montero CG, Martinez AJ. Neuropathology of heart transplantation: 23 cases. Neurology 1986;36(9):1149-54. PMID 3528916
150: Moon RE. Hyperbaric treatment of air or gas embolism: current recommendations. Undersea Hyperb Med 2019;46(5):673-83. PMID 31683367
151: Morales JP, Taylor PR, Bell RE, et al. Neurological complications following endoluminal repair of thoracic aortic disease. Cardiovasc Intervent Radiol 2007;30(5):833-9. PMID 17508247
152: Muñoz P, Valerio M, Palomo J, et al. Infectious and non-infectious neurologic complications in heart transplant recipients. Medicine (Baltimore) 2010;89(3):166-75. PMID 20453603
153: Mylonakis E, Calderwood SB. Infective endocarditis in adults. 2001;345(18):1318-30. PMID 11794152
154: Nadareishvili ZG, Beletsky V, Black SE, et al. Is cerebral microembolism in mechanical prosthetic heart valves clinically relevant. J Neuroimaging 2002;12(4):310-5. PMID 12380477
155: Nakajima M, Tsuchiya K, Kanemaru K, et al. Subdural hemorrhagic injury after open heart surgery. Ann Thorac Surg 2003;76(2):614-5. PMID 12902119
156: Nakamura M, Okamoto F, Nakanishi K, et al. Does intensive management of cerebral hemodynamics and atheromatous aorta reduce stroke after coronary artery surgery. Ann Thorac Surg 2008;85(2):513-9. PMID 18222254
157: Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neuroocognitive function after coronary-artery bypass surgery. N Engl J Med 2001;344(6):395-402. PMID 11172175
158: Nishimura RA, Otto CM, Bonow RO, et al. 2017 ACC/AHA focused update of the 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;70(2):252-89. PMID 28315732
159: Nuttall GA, Garrity JA, Dearani JA, Abel MD, Schroeder DR, Mullany CJ. Risk factors for optic neuropathy after cardiopulmonary bypass: A matched case/control study. Anesth Analg 2001;93(6):1410-6. PMID 11726415
160: Oka K, Kamota T, Satou M, et al. Subdural hematoma following cardiac surgery. Kyobu Geka 2008;61(10):868-72. PMID 18788377
161: Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Thorac Cardiovasc Surg 2021;162(2):e183-e353. PMID 33332149
162: Ozcakar L, Dinçer F, Atalay A, Kaymak B, Aksu AE, Akyürek M. Compressive injury of the brachial plexus after axillary arteriography and its further consequences. Joint Bone Spine 2004;71(4):349-51. PMID 15288865
163: Parry AJ, Westaby S. Cardiopulmonary bypass during pregnancy. Ann Thorac Surg 1996;61:1865-9. PMID 8651812
164: Pataraia E, Jung R, Aull-Watschinger S, Skhirtladze-Dworschak K, Dworschak M. Seizures after adult cardiac surgery and interventional cardiac procedures. J Cardiothorac Vasc Anesth 2018;32(5):2323-9. PMID 29398383
165: Patchell RA. Neurological complications of organ transplantation. Ann Neurol 1994;36(5):688-703. PMID 7979215
166: Perloff JK, Childs JS. Congenital Heart Disease in Adults. 2nd ed. Philadelphia: WB Saunders, 1998.
167: Pittock SJ, Rabinstein AA, Edwards BS, Wijdicks EF. OKT3 neurotoxicity presenting as akinetic mutism. Transplantation 2003;75(7):1058-60. PMID 12698102
168: Plecha EJ, Seabrook GR, Freischlag JA, Towne JB. Neurologic complications of reoperative and emergent abdominal aortic reconstruction. Ann Vasc Surg 1995;9(1):95-102. PMID 7703069
169: Pomini F, Merccogliano D, Cavaletti C, Caruso A, Pomini P. Cardiopulmonary bypass in pregnancy. Ann Thorac Surg 1996;61:259-68. PMID 8561577
170: Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019;50(12):e344-e418. PMID 31662037
171: Price DL, Harris JL, New PF, Cantu RC. Cardiac myxoma: a clinicopathologic and angiographic study. Arch Neurol 1970;23(6):558-67. PMID 5478277
172: Qiao J, Zhang B, Wang J, et al. Comparison between amplatzer and watchman left atrial appendage closure devices for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Cardiology 2022;147(3):290-7. PMID 35468598
173: Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335(225):1857-63. PMID 8948560
174: Roeltgen D, Kidwell CS. Neurologic complications of cardiac tumors. Handb Clin Neurol 2014;119:209-22. PMID 24365298
175: Roudaut R, Lafitte S, Roudaut MF, et al. Fibrinolysis of mechanical prosthetic valve thrombosis: a single-center study of 127 cases. J Am Coll Cardiol 2003;41(4):653-8. PMID 12598078
176: Ruel M, Masters RG, Rubens FD, et al. Late incidence and determinants of stroke after aortic and mitral valve replacement. Ann Thorac Surg 2004;78(1):77-83. PMID 15223407
177: Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 1989;25(4)382-90. PMID 2712533
178: Sadek MM, Ravindran A, Marcuzzi DW, Chisholm RJ. Complete occlusion of the proximal subclavian artery post-CABG: presentation and treatment. Can J Cardiol 2008;24(7):591-2. PMID 18612504
179: Salazar JD, Wityk RJ, Grega MA, et al. Stroke after cardiac surgery: short- and long-term outcomes. Ann Thor Surg 2001;72(4):1195-201. PMID 11603436
180: Sankaranarayanan R, Msairi A, Davis GK. Stroke complicating cardiac catheterization--a preventable and treatable complication. J Invasive Cardiol 2007;19(1):40-5. PMID 17297185
181: Scali ST, Wang SK, Feezor RJ, et al. Preoperative prediction of spinal cord ischemia after thoracic endovascular aortic repair. J Vasc Surg 2014;60(6):1481-90. PMID 25282701
182: Schaff HV. Transcatheter aortic-valve implantation--at what price. N Engl J Med 2011;364(23):2256-8. PMID 21639812
183: Scrofani R, Carro C, Villa L, Botta M, Antona C. Cardiac myxoma: surgical results and 15-year clinical follow-up. Ital Heart J Suppl 2002;3(7):753-8. PMID 12187636
184: Segal AZ, Abernethy WB, Palacios IF, BeLue R, Rordorf G. Stroke as a complication of cardiac catheterization: risk factors and clinical features. Neurology 2001;56(7):975-7. PMID 11294941
185: Selnes OA, Grega MA, Borowicz LM Jr, Royall RM, McKhann GM, Baumgartner WA. Cognitive changes with coronary artery disease: a prospective study of coronary artery bypass graft patients and nonsurgical controls. Ann Thorac Surg 2003;75(5):1377-84. PMID 12735550
186: Shachar GB, Vlodaver Z, Joyce LD, Edwards JE. Mural thrombosis of the left atrium following replacement of the mitral valve. J Thorac Cardiovasc Surg 1981;82(4):595-600. PMID 7278352
187: Shaefi S, Mittel A, Loberman D, Ramakrishna H. Off-pump versus on-pump coronary artery bypass grafting-a systematic review and analysis of clinical outcomes. J Cardiothorac Vasc Anesth 2019;33(1):232-44. PMID 29753665
188: Sharma AD, Parmley CL, Sreeram G, Grocott HP. Peripheral nerve injuries during cardiac surgery: risk factors, diagnosis, prognosis, and prevention. Anesth Analg 2000;91:1358-1369. PMID 11093980
189: Shehab S, Hayward CS. Choosing between left ventricular assist devices and biventricular assist devices. Card Fail Rev 2019;5(1):19-23. PMID 30847240
190: Shin RK, Stecker MM, Imbesi SG. Peripheral nerve ischaemia after internal iliac artery ligation. J Neurol Neurosurg Psych 2001;70:411-2. PMID 11181877
191: Shook LL, Barth WH Jr. Cardiac surgery during pregnancy. Clin Obstet Gynecol 2020;63(2):429-46. PMID 32282355
192: Shoskes A, Fan TH, Starling RC, Cho SM. Neurologic complications in patients with left ventricular assist devices. Can J Cardiol 2023;39(2):210-21. PMID 36400374
193: Sievers HH, Hanke T, Stierle U, et al. A critical reappraisal of the Ross operation: renaissance of the subcoronary implantation technique. Circulation 2006;114(1 Suppl):I504-11. PMID 16820628
194: Sila CA. Spectrum of neurologic events following cardiac transplantation. Stroke 1989;20(11):1586-9. PMID 2554543
195: Skotzko CE, Strouse TB. Solid organ transplantation. In: The American Psychiatric Publishing Textbook of Consultation – Liaison Psychiatry: Psychiatry in the Medically Ill, 2nd ed. Washington, DC: American Psychiatric Publishing, 2002:623-56.
196: Slater JP, Guarino T, Stack J, et al. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg 2009;87(1):36-45. PMID 19101265
197: Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 2009;361(23):2241-51. PMID 19920051
198: Sotaniemi KA. Long-term neurologic outcome after cardiac operation. Ann Thorac Surg 1995;59(5):1336-9. PMID 7733764
199: Stamou SC. Stroke and encephalopathy after cardiac surgery: the search for the holy grail. Stroke 2006;37(2):284-5. PMID 16373633
200: Stessel B, Nijs K, Pelckmans C, et al. Neurological outcome after minimally invasive coronary artery bypass surgery (NOMICS): an observational prospective cohort study. PLoS One 2020;15(12):e0242519. PMID 33362277
201: Sticherling C, Berkefeld J, Auch-Schwelk W, Lanfermann H. Transient bilateral cortical blindness after coronary angiography. Lancet 1998;351(9102):570. PMID 9492782
202: Sun MC, Tai HC, Lee CH. Intravenous thrombolysis for embolic stroke due to cardiac myxoma. Case Rep Neurol 2011;3:21-6. PMID 21468176
203: Sundt TM, Flemming MD, Oderich GS, et al. Spinal cord protection during open repair of thoracic and thoracoabdominal aortic aneurysms using profound hypothermia and circulatory arrest. J Am Coll Surg 2011;212(4):678-83; discussion 684-5. PMID 21463811
204: Tang GL, Tehrani HY, Usman A, et al. Reduced mortality, paraplegia, and stroke with stent graft repair of blunt aortic transections: a modern meta-analysis. J Vasc Surg 2008;47(3):671-5. PMID 17980541
205: Taylor DO, Edwards LB, Boucek MM, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult heart transplant report--2007. J Heart Lung Transplant 2007;26(8):769-81. PMID 17692781
206: Thomas CE, Jichici D, Petrucci R, Urrutia VC, Schwartzman RJ. Neurologic complications of the Novacor left ventricular assist device. Ann Thorac Surg 2001;72(4):1311-5. PMID 11603452
207: Thomas JA, Allday MJ, Crawford DH. Epstein-Barr virus-associated lymphoproliferative disorders in immunocompromised individuals. Adv Cancer Res 1991;57:329-80. PMID 1659123
208: Thourani VS, Weintraub WS, Guyton R A, et al. Outcomes and long-term survival for patients undergoing mitral valve repair versus replacement: effect of age and concomitant coronary artery bypass grafting. Circulation 2003;108(3):298-304. PMID 12835220
209: Tisel SM, Ahlskog JE, Duffy JR, Matsumoto JY, Josephs KA. PSP-like syndrome after aortic surgery in adults (Mokri syndrome). Neurol Clin Pract 2020;10(3):245-54. PMID 32642326
210: Turagam MK, Osmancik P, Neuzil P, Dukkipati SR, Reddy VY. Left atrial appendage closure versus oral anticoagulants in atrial fibrillation: a meta-analysis of randomized trials. J Am Coll Cardiol 2020;76(23):2795-7. PMID 33272374
211: Ullery BW, McGarvey M, Cheung AT, et al. Vascular distribution of stroke and its relationship to perioperative mortality and neurologic outcome after thoracic endovascular aortic repair. J Vasc Surg 2012;56(6):1510-7. PMID 22841287
212: Upchurch GR Jr, Escobar GA, Azizzadeh A, et al. Society for Vascular Surgery clinical practice guidelines of thoracic endovascular aortic repair for descending thoracic aortic aneurysms. J Vasc Surg 2021;73(1S):55S-83S. PMID 32628988
213: van de Beek D, Patel R, Daly RC, McGregor CG, Wijdicks EF. Central nervous system infections in heart transplant recipients. Arch Neurol 2007;64(12):1715-20. PMID 17923621
214: van Dijk D, Nierich AP, Jansen ED, et al; Octopus Study Group. Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study. Circulation 2001;104(15):1761-6. PMID 11591611
215: Vasquez-Jimenez JF, Krebs G, Schiefer J, et al. Injury of the common peroneal nerve after cardiothoracic operations. Ann Thorac Surg 2002;73(1):119-22. PMID 11833997
216: Vlessis AA, Hovaguimian H, Jaggers J, Ahmad A, Starr A. Infective endocarditis: ten-year review of medical and surgical therapy. Ann Thorac Surg 1996;61(4):1217-22. PMID 8607686
217: Walker MT, Kilani RK, Toye LR, Bird CR. Central and peripheral fusiform aneurysms six years after left atrial myxoma resection. J Neurol Neurosurg Psychiatry 2003;74(2):281-2. PMID 12531975
218: Wanat-Hawthorne A, Akorede R, Floyd T. Perioperative spinal cord ischemia after cardiac surgery not involving the aorta: a review of the literature. J Cardiothorac Vasc Anesth 2022;36(3):776-84. PMID 33451953
219: Wang A, Athan E, Pappas PA, et al; International Collaboration on Endocarditis-Prospective Cohort Study Investigators. Contemporary clinical profile and outcome of prosthetic valve endocarditis. JAMA 2007;297(12):1354-61. PMID 17392239
220: Weinberg JH, Simovic D, Isner J, Ropper AH. Chronic ischemic monomelic neuropathy from critical limb ischemia. Neurology 2001;57(6):1008-12. PMID 11571325
221: Weissman BM, Aram DM, Levinsohn MW, Ben-Shachar G. Neurologic sequelae of cardiac catheterization. Cathet Cardiovasc Diagn 1985;11(6)577-83. PMID 4092235
222: Willey JZ, Demmer RT, Takayama H, Colombo PC, Lazar RM. Cerebrovascular disease in the era of left ventricular assist devices with continuous flow: risk factors, diagnosis, and treatment. J Heart Lung Transplant 2014;33(9):878-87. PMID 24997495
223: Wityk RJ, Goldsborough MA, Hillis A, et al. Diffusion- and perfusion-weighted brain magnetic resonance imaging in patients with neurologic complications after cardiac surgery. Arch Neurol 2001;58(4):571-6. PMID 11295987
224: Wolman RL, Nussmeier NA, Aggarwal A, et al. Cerebral injury after cardiac surgery: identification of a group at extraordinary risk. Multicenter Study of Perioperative Ischemia Research Group (McSPI) and the Ischemia Research Education Foundation (IREF) Investigators. Stroke 1999;30(3):514-22. PMID 10066845
225: Xie A, Lo P, Yan TD, Forrest P. Neurologic complications of extracorporeal membrane oxygenation: a review. J Cardiothorac Vasc Anesth 2017;31(5):1836-46. PMID 28625752
226: Xiong H, Xia B, Zhu J, Li B, Huang W. Clinical outcomes in pediatric patients hospitalized with fulminant myocarditis requiring extracorporeal membrane oxygenation: a meta-analysis. Pediatr Cardiol 2017;38(2):209-14. PMID 27878629
227: Yamamoto K, Natsuaki M, Morimoto T, et al. Periprocedural stroke after coronary revascularization (from the CREDO-Kyoto PCI/CABG Registry Cohort-3). Am J Cardiol 2021;142:35-43. PMID 33279479
228: Yee RD, Purvin VA. Acquired ocular motor apraxia after aortic surgery. Trans Am Ophthalmol Soc 2007;105:152-9. PMID 18427605
229: Zierer A, Melby SJ, Voeller RK, et al. Significance of neurologic complications in the modern era of cardiac transplantation. Ann Thorac Surg 2007;83(5):1684-90. PMID 17462379
230: Zimpfer D, Kilo J, Czerny M, et al. Neurocognitive deficit following aortic valve replacement with biological/mechanical prosthesis. Eur J Cardiothorac Surg 2003;23(4):544-51. PMID 12694774

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Sarah Horn MD

Dr. Horn of UT Health San Antonio received consulting fees from CalaTrio.
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Editor

Steven R Levine MD

Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.
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Former Authors

Anjali A Joshi MD
Alain Heroux MD
Sara E Hocker MD
Jose Biller MD
James D Fleck MD, Betsy B Love MD

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: Women are more likely to have a stroke after CABG, and they have a higher mortality rate than men after CABG.
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Cardiovascular disease, unspecified: 429.2

Complications of surgical and medical care, not elsewhere classified: 996-999
ICD-10: Chronic ischemic heart disease: I25

Complications of medical and surgical care: Y40-Y84

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Cardiovascular intervention: neurologic complications

Associated Disorders

Aseptic meningitis
Border-zone infarction
Brachial plexus injury
Femoral neuropathy
Hypoxic or ischemic encephalopathy
- Lumbosacral plexopathy
- Neuromuscular disorders
- Polyneuropathy
- Posterior reversible leukoencephalopathy
- Small vessel infarction
- Watershed infarction

Differential Diagnosis

nonsurgical factors (surgical and catheter manipulations)
drugs
infection
posttransplantation lymphoproliferative disorders
metabolic derangements
- embolic stroke
- intracranial hemorrhage
- spinal cord injury
- peripheral nerve injury
- seizures

Also Relevant

Aortic atherosclerosis and stroke
Aortic diseases: neurologic complications
Atrial myxoma
Cardiovascular procedures: neurologic complications
Congenital heart disease: neurologic complications
- General anesthesia: neurologic complications
- Infective endocarditis

Clinical Categories

Stroke & Vascular Disorders

Cardiovascular intervention: neurologic complications

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Neurologic Complications Associated with Cardiac Procedures

Table 2. Mechanism of Stroke During or After Valve Replacement Surgery

Table 3. Neurologic Complications Associated with Organ Transplantation and Immune Suppression with Cyclosporine and Tacrolimus

Table 4. Risk Factors for Cerebrovascular Complications with Cardiac Catheterization

Table 5. Potential Etiologies of Cerebrovascular Complications during Cardiac Catheterization

Table 6. Etiologies of Cerebrovascular Complications during Percutaneous Coronary Intervention

Table 7. Major Risk Factors for Stroke with Percutaneous Coronary Intervention

Table 8. Mechanisms of Stroke with Invasive Electrophysiological Procedures

Table 9. Complications of Percutaneous PFO Closure

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Table 10. Embolic Material Produced During Cardiopulmonary Bypass and Open Heart Surgery

Table 11. Nongaseous Microemboli Reported During Cardiopulmonary Bypass

Prevention

Table 12. Risk Factors for Stroke Associated with CABG

Table 13. Risk Factors for Stroke with Valve Replacement Surgery

Table 14. Neuroprotective Strategies for Cardiac Surgery

Differential diagnosis

Associated or underlying disorders

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Questions or Comment?

Also in This Category

Vein of Galen malformations

Patent foramen ovale

Neuroimaging in acute stroke

Atrial myxoma

Anterior cerebral artery stroke syndromes

Hemorrhagic transformation of ischemic stroke

Intracerebral hemorrhage due to thrombolytic therapy

White matter abnormalities in the brain

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