Technical progress has effectively lowered the cardiological adverse events of surgical and angiographic procedures of the heart and coronary arteries over the past decades, whereas the neurological complication rate has remained fairly stable. Thus, there is an increasing effort to detect and lower these events. In this article, different types of neurological adverse events following surgical and angiographic procedures will be outlined and their clinical significance will be discussed, and different diagnostic modalities to detect brain damage will be described.

Cardiac surgery, including coronary artery bypass grafting (CABG) and valve surgery, has been performed for over 30 years and is one of the most frequent surgical procedures in the United States. Perioperative morbidity and mortality are important factors in the assessment of cardiac surgery's risk-benefit ratio. In addition to cardiological and anesthesiological adverse events, neurological complications represent an important proportion of the overall complication rate.

Despite an overall reduction in perioperative mortality, the proportion of lethal neurological complications has increased significantly (Cosgrove et al., 1984). The importance of neurological complications was underlined by a study reporting a 47% five-year mortality rate in patients with perioperative stroke (Salazar et al., 2001). Neurological damage following CABG can be divided between perioperative stroke caused by thromboembolic events or hemorrhage and diffuse encephalopathy that has been poorly understood until now.

Stroke. Intraoperative stroke may be caused by ischemia due to thromboembolic vessel occlusion or hemorrhage as a potential risk of anticoagulation. Stroke occurs in about 2% to 3% of patients after cardiac surgery, with higher rates after valve replacement or other cardiac surgical procedures than after CABG (Roach et al., 1996; Wolman et al., 1999). This neurological complication rate significantly differs from other surgical procedures (Smith et al., 1986), excluding carotid endarterectomy (North American Symptomatic Carotid Endarterectomy Trial Collaborators, 1991).

Predisposing factors for perioperative stroke are previous stroke, hypertension, diabetes and duration of the extracorporeal circulation (McKhann et al., 2002). Perioperative stroke has grave socioeconomic and clinical impacts: Patients with stroke spent more than twice the number of days in the hospital and suffered a 16-fold higher mortality rate than patients without stroke (McKhann et al., 2002).

Diffuse encephalopathy. Psychopathological disturbances after cardiac surgery were first described by Fox et al. in 1954. Since then, a large number of studies have investigated these postoperative abnormalities. In particular, perception and information processing abilities are vulnerable, with attention, concentration, psychomotor speed and short-term memory being most affected. Symptoms also may include confusion, disturbances of consciousness and delirium. In one study, an incidence rate of postoperative cognitive impairment of 53% at discharge, 36% at six weeks and 24% at six months was reported (Newman et al., 2001). Some authors reported delayed impairment in cognitive test performance one year postoperatively (Selnes et al., 2001). Another study found a decline in cognitive abilities was still present five years postoperatively in 12% of the patients (Sotaniemi et al., 1986).

Risk factors for postoperative encephalopathy, which represents a severe postoperative complication with a fivefold higher mortality and a marked longer stay in the hospital, include age, past stroke, carotid bruit, diabetes, hypertension and time on cardiopulmonary bypass (McKhann et al., 2002). Possible causes of postoperative encephalopathy include the influence of anesthesia, hypothermia or diffuse ischemic brain damage, due to thromboembolism or air embolism originating from the extracorporeal circulation.

In perioperative stroke, brain imaging--including computed tomography (CT) and magnetic resonance imaging (MRI)--is usually applied to visualize the extent of brain damage and to differentiate between ischemic and hemorrhagic stroke. For the diagnosis and quantification of the more subtle changes in diffuse encephalopathy, methods such as blood tests, Doppler sonography and neuropsychological tests have been used.

Blood tests. After damage of astrocytes, blood values of the protein S100 b increase. In several studies, an increase of S100 b was reported after CABG, which correlated with the degree of postoperative cognitive impairment (Herrmann et al., 2000; Jonsson et al., 1999). Herrmann et al. also reported an increase in the neuron-specific enolase after neuronal damage. Neither substance is specific for brain damage since they may also be released from extra-cerebral tissue (Missler et al., 2002). Therefore, the relevance of increased values after cardiac surgery remains under debate.

Doppler sonography. Doppler sonography is a noninvasive ultrasound examination for blood flow measurements. Intraoperative Doppler sonography of the carotid or middle cerebral artery reveals a large number of short signals of high intensity, called high intensity transient signals (HITS), in the normal spectrum of blood flow. These HITS may be caused by air or thromboembolism that cannot be reliably differentiated by Doppler sonography. While the clinical relevance of intraoperative HITS is unknown, an increased number of HITS has been reported in patients with neurological deficits (Braekken et al., 1998). The influence of the HITS count on the diffuse encephalopathy remains under debate with studies reporting both significant (Sylivris et al., 1998) and no significant (Neville et al., 2001) relationships.

CT and MRI. In patients presenting with a perioperative stroke, CT is usually applied to exclude a space-occupying infarction or hemorrhage. In these critically ill patients, MRI is usually not feasible. However, MRI is more sensitive in detecting ischemic lesions. Recent studies have utilized MRI to examine the incidence of new lesions on T2-weighted (T2-w) images in relation to neuropsychological and clinical findings. These studies have shown highly variable results ranging from no new lesions (Schmidt et al., 1993) up to an incidence of 42% (Toner et al., 1993). The reason for this discrepancy is the insensitivity of T2-w images for detecting new lesions, especially in patients with pre-existing vascular lesions.

Diffusion-weighted MRI is a new MR technique with high sensitivity and specificity for acute ischemic lesions. In patients presenting with a new neurological deficit postoperatively, diffusion-weighted MRI is capable of demonstrating the corresponding acute ischemic lesion even in the presence of pre-existing vascular lesions (Wityk et al., 2001). Diffusion-weighted MRI can also be applied to demonstrate ischemic lesions in neurologically asymptomatic patients. In a recent study, a 26% incidence of ischemic lesions was reported in the absence of neurological symptoms (Bendszus et al., 2002) (Figure). Therefore, clinically symptomatic ischemia may represent the tip of the iceberg of the overall number of ischemic lesions.

It is not only the presence, but also the location, of an ischemic lesion that causes neurological damage. Fortunately, the majority of lesions are located in brain regions that do not cause an overt neurological deficit. The presence of clinically silent ischemic lesions is not related to diffuse encephalopathy. While the lesion pattern is predominantly embolic, a hemodynamic pattern may be present as well, especially in symptomatic patients (Wityk et al., 2001).

Perfusion-weighted MRI is another new MR technique that allows for demonstration of relative hemodynamic parameters including regional cerebral blood volume, regional blood flow and mean transit time through the brain tissue. Perfusion-weighted MRI enables the differentiation of hemodynamic from embolic ischemic lesions postoperatively (Wityk et al., 2001), which has an impact on the therapeutic strategy.

Another MR technique for in vivo detection of cerebral metabolites is MR-spectroscopy. N-acetyl-aspartate (NAA) is the most prominent metabolic peak that represents integrity and function of neurons, and NAA reveals a transient decline postoperatively that can be attributed to a temporary functional disturbance of cerebral neurons (Bendszus et al., 2002). The NAA decrease is correlated with the presence of a postoperative encephalopathy, which indicates the patient's symptoms are caused by a temporary metabolic disturbance of neurons.

Neuropsychological tests. Neuropsychological test performance can characterize and quantify diffuse encephalopathy. However, the neuropsychological data reported in the literature on the prevalence and severity of the encephalopathy reveal a wide range. This may be caused by methodological differences and different patient selection. In the majority of studies, concentration, attention and psychomotor speed have been reported to be most affected.

In a consensus paper, a combination of the Rey Auditory Verbal Learning Test, the Trail-Making Test A and B, and the Grooved Pegboard Test were suggested as a minimal solution for pre- and postoperative testing (Murkin et al., 1995). However, a number of other factors, including anxiousness, depression and learning effects, may strongly influence the test performance.

Neurological complications--most frequently stroke--after diagnostic and interventional procedures have been reported to occur in <1% of cases (Krone et al., 1996). However, using Doppler sonography, a large number of HITS was detected during the angiographic procedure despite the absence of neurological symptoms (Leclercq et al., 2001). Since the HITS mainly occurred during injection of contrast medium, Leclercq et al. speculated that they are of gaseous origin. The clinical relevance of these asymptomatic HITS remains unknown. Histopathologically, focal capillary dilatations that may be caused by microscopic air embolism have been described in patients after aortography (Moody et al., 1990). Therefore, there may be subtle structural brain damage even in the absence of overt neurological symptoms.

Until recently, there were no studies available on the frequency of silent ischemic lesions after coronary angiography using diffusion-weighted MRI. However, following cerebral angiography, a 23% incidence of new ischemic lesions has been demonstrated in the absence of neurological symptoms (Bendszus et al., 1999). Thus, it can be assumed that after coronary angiography the overall incidence of new ischemic lesions is also higher than the apparent neurological complication rate.

Neurological symptoms substantially contribute to the overall complication rate following cardiac surgery. Angiographic procedures of the heart and coronary arteries are associated with a relatively low risk for neurological deficits; although the relevance of clinically silent brain damage, which is more frequent than the apparent neurological complication rate, has not been sufficiently studied.

New diagnostic modalities including diffusion- and perfusion-weighted MRI, as well as MR- spectroscopy, enable the demonstration and quantification of subtle structural, functional and metabolic changes. They may, therefore, be used as tools to assess the efficacy of procedural changes and to lower the clinically apparent neurological complication rate.

Dr. Bendszus is a consultant and university lecturer in the department of neuroradiology at the University of Wuerzburg in Germany. His main scientific focus in on MR spectroscopy and diffusion-weighted MRI.

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Brain Damage After Surgical and Angiographic Heart Procedures