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Selection and clinical significance of neuropsychologic tests
Selection and Clinical Significance of Neuropsychologic Tests David A. Stump, PhD Departments of Anesthesia and Neurology, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina
There have been major advancements in cardiac surgery over the past two decades and a concomitant decrease in mortality and major morbidity. The improved safety in cardiac procedures permitted 330,000 operations involving cardiopulmonary bypass in 1992. However, several recent studies have demonstrated that cardiac surgery poses substantial risk of negative neurologic and neuropsychologic outcomes. Although very few patients die as a result of a cardiac operation, more than two thirds of patients demonstrate evidence of neuropsychologic dysfunction postoperatively. The mechanisms contributing to neuropsychologic deficits after cardiopulmonary by-
pass are uncertain. To characterize the incidence and severity of such deficits after cardiac operations, a concise battery of neuropsychologic tests that provides reliable evidence of subtle brain trauma is essential. With an objective, valid measure of brain injury, the etiology of neuropsychologic deficits can be identified and either eliminated or the effects ameliorated. The proper selection and use of neurobehavioral tools provides a basis to evaluate the efficacy of surgical and pharmacologic interventions to further improve neurologic outcome after cardiopulmonary bypass.
t the inception of every research p l a n to evaluate the effect of c a r d i o p u l m o n a r y b y p a s s (CPB) on the brain, one of the major areas of contention is how best to describe evidence of brain trauma. The p u r p o s e of this discussion is to explore the differences in the developm e n t of a traditional neuropsychologic battery of tests as o p p o s e d to a research battery whose variables are defined not only by the clinical question b u t by environmental a n d patient demographics. There are a variety of reasons w h y a patient m a y b e referred for a clinical neuropsychologic evaluation: (1) to d e t e r m i n e if the patient has e x p e r i e n c e d a brain trauma, (2) to d e t e r m i n e if the patient has d e v e l o p e d a psychiatric dysfunction, or (3) to d e t e r m i n e w h e t h e r the patient has both an organic a n d a psychiatric complaint. The historical p u r p o s e of the clinical neuropsychologic evaluation was localization of the lesion site, but given the advances in imaging, localization of lesions has taken a s e c o n d a r y role. Assessment, with an e m p h a s i s on d e t e r m i n i n g the level of social a n d cognitive i m p a i r m e n t , has taken precedence. The traditional a p p r o a c h for a clinical referral is to give the patient an extensive battery of tests that will survey his or her abilities a n d elicit errors that can be evaluated for clinical significance a n d diagnostic importance. The rationale for the use of an exhaustive neuropsychologic battery is to ensure that all modalities are explored for any potential deficits. A n y errors are carefully e x a m i n e d to d e t e r m i n e if they are evidence for labeling the patient
with a specific s y n d r o m e or higher cortical dysfunction. A l t h o u g h it might take only a few m o m e n t s to recognize a patient has a language disorder, it might take several hours of testing to tease out the specifics of a subcortical aphasia, for example. W h e n a s k e d to provide a battery of tests to a n s w e r a research question, experienced neuropsychologists t e n d to fall back on the familiar basic clinical examination, which covers a b r o a d s p e c t r u m of behaviors a n d takes 2 or m o r e hours to administer. However, w h e n asked to study cardiac surgical patients, these neuropsychologists are r u d e l y a w a k e n e d w h e n it b e c o m e s a p p a r e n t that they have only 45 m i n u t e s to evaluate the most complicated system in the body, the organ of behavior, the brain. The task to refine the question in line with the limited access one has to the patient b e c o m e s a series of compromises. The first level on the decision tree to provide an a b b r e v i a t e d 45-minute evaluation is to a n s w e r this question: W h a t is the research question? In other words, w h a t are we ultimately trying to accomplish with the s t u d y of p a t i e n t s u n d e r g o i n g CPB? Essentially, it is a l r e a d y k n o w n that patients experience varying levels of brain insult s e c o n d a r y to CPB. W h a t is n e e d e d is to either eliminate the source of the t r a u m a or ameliorate its effect. The question then b e c o m e s w h a t level of refinement is necessary to describe a n d define the deficit. Is it sufficient to just d e t e r m i n e that a b r a i n t r a u m a has occurred, or is a m o r e complete description of the deficits necessary? To answer the principal question of w h e t h e r or not an intervention has affected outcome, it is not necessary to exquisitely define specific n e u r o b e h a v i o r a l deficits. Reliability a n d sensitivity are m o r e key to a research evaluation than the n a m e s of specific deficits. In other words, it is m o r e i m p o r t a n t to be able to reliably d e t e r m i n e the
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Presented at the Conference on CNS DysfunctionAfter Cardiac Surgery: Defining the Problem, Fort Lauderdale, FL, Dec 10-11, 1994. Address reprint requests to Dr Stump, Department of Anesthesia, Bowman Gray School of Medicine, Medical Center Bird, Winston-Salem, NC 27157-1009. © 1995 by The Society of Thoracic Surgeons
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patient has a visual deficit than it is to label the i m p a i r m e n t a prosopagnosia. A n o t h e r highly controversial question a t t e n d a n t on the issue of CPB a n d neuropsychologic outcome is the clinical significance of the deficits exhibited b y these patients. This is the quality of life issue, that is, if the patients are not "significantly" impaired, such as after a major stroke, do we n e e d to intervene? There are two possible answers to this concern: (1) yes, the n e u r o p s y chologic deficits are i m p o r t a n t a n d should be avoided, a n d (2) it does not m a t t e r if the deficits are behaviorally i m p o r t a n t as long as they are reliable m a r k e r s of brain injury a n d can be u s e d to i m p r o v e CPB. If the research were limited to eliminating the factors associated with CPB that cause death, an impossibly large n u m b e r of patients w o u l d be n e e d e d to obtain significance. By using as an end point an objective, reliable, and valid m e a s u r e of brain trauma, such as the relative change b e t w e e n preoperative a n d postoperative neuropsychologic performance of the patient, then fewer patients, h u n d r e d s instead of thousands, are a d e q u a t e to assess the efficacy of a treatment. R e m a r k a b l y few patients die or are completely disa b l e d as a b y - p r o d u c t of CPB. However, most individuals w o u l d agree that a d e c r e m e n t in m e m o r y or coordination w o u l d be a major inconvenience. Further, it s e e m s reasonable to p r e s u m e that if it were possible to eliminate the cause of the small problems, the n u m b e r of " m a j o r " events w o u l d p r o b a b l y be r e d u c e d as well. The criteria for defining a deficit is critical. If the definition is too stringent, then few patients meet the criteria. If the definition is too broad, then most patients have some level of t r a u m a a n d the ability to evaluate an intervention is lost. However, there is not a consensus in the literature on w h a t constitutes an i m p a i r m e n t . There is little a g r e e m e n t on how " s e v e r e " a deficit m u s t be before it is considered clinically important.
A Question of Severity, or Not All Lesions Are Created Equal For the p u r p o s e s of r e d u c i n g cognitive i m p a i r m e n t after CPB, severity can be described in two ways, behaviorally a n d structurally. The first describes the h u m a n condition, m e a n i n g that a small left-hemispheric central cortical stroke resulting in an expressive dysphasia, d o m i n a n t h a n d weakness, a n d eye m o v e m e n t incoordination is a socioeconomic disaster for the patient. Conversely, a larger anterior right frontal lobe stroke m a y go u n n o ticed, although causing a greater level of tissue destruction. The second description of severity is the quantity of tissue d a m a g e d , which, we can see from the example given, does not necessarily correlate with the socioeconomic consequences of a focal stroke. W h i c h is the best a p p r o a c h to ranking severity? An analogy might be along the line of a t t e m p t i n g to stop drivers from r u n n i n g a r e d light. It is i m p o r t a n t to the victim a n d society w h e t h e r the vehicle is struck on the driver or p a s s e n g e r side but largely irrelevant to the engineer assigned to s t o p p i n g the violators. If the side on
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which the victim is struck is relatively r a n d o m , then half the time the consequences to the driver of s o m e o n e r u n n i n g the light are severe and the other half, m e r e l y inconvenient. It w o u l d be i n a p p r o p r i a t e to a t t e m p t to control only the driver-side accidents. It w o u l d be best to try to p r e v e n t all accidents, a n d p r e s u m e if you d e c r e a s e d the n u m b e r of f e n d e r - b e n d e r s , you w o u l d also p r o p o r tionally reduce the n u m b e r of socioeconomically important left-sided crashes w h e r e the driver is hospitalized. The goal of the " e n g i n e e r " is to keep the " e m b o l i c d r i v e r " from entering the intersection, t h e r e b y preventing the severe accidents b y p r e v e n t i n g all accidents. This example helps explain w h y the n u m b e r of tests on which a patient performs abnormally might possibly reflect only the socioeconomic consequences of the lesion and not its severity. A left-hemispheric stroke would cause a patient to do poorly in the following categories of function (tests) relative to preoperative performance: (1) vocabulary test; (2) verbal learning test; (3) visual-motor coordination task; (4) visual-motor, frontal lobe function; (5) motor coordination task; (6) motor coordination, visual scanning, and planning; (7) visual learning and reaction time; and (8) visual scanning, attention, and concentration. The same size stroke in the same location in the right hemisphere would cause deficits in these tests: (1) motor coordination (nondominant hand), and (2) motor coordination (nondominant hand), visual scanning, and planning. One interpretation of these results is that the first (left h e m i s p h e r e ) lesion is four times as severe as the second (right hemisphere), even though they are the s a m e size. From the patient's point of view, the first lesion is far m o r e devastating than the r i g h t - h e m i s p h e r i c stroke, certainly worse than a 4 on a severity scale, even though anatomically equal. This p r o b l e m could potentially be a d d r e s s e d using s t a n d a r d i z e d scores (Z-scores) and categories of dysfunction w h e r e a category such as m o t o r function w o u l d be the composite score of four motor and visual-motor tests using the d o m i n a n t a n d n o n d o m i n a n t hands. M e m o r y w o u l d be the composite of two tests (verbal and nonverbal} a n d p e r c e p t u a l m o t o r functioning, five tests. The composite scores w o u l d be i n d e p e n d e n t of the side of the lesion b u t w o u l d still be subject to location versus size of lesion inequalities. This is not a satisfactory solution because it is not possible to equate the a m o u n t of tissue d i s r u p t i o n with the behavioral consequences of a lesion. At best, a relative rating of the level of i m p a i r m e n t for a given behavioral domain, memory, for example, could be used, but it w o u l d be a description of i m p a i r m e n t rather than an indication of severity. Alternatively, a cutoff score could be u s e d such that a given level or change in performance is abnormal. Again, this a p p r o a c h does not actually a d d r e s s a "severity scale." Further, the social consequences of a deficit are d e p e n d e n t on individual factors such as e m p l o y m e n t , education, hobbies, a n d age. A language i m p a i r m e n t w o u l d be m o r e devastating to a lawyer than a mechanic, w h e r e a s a major left-sided weakness would be a 100% disability for the mechanic b u t not a c a r e e r - e n d i n g deficit for a lawyer or politician.
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Perhaps the most objective method of scaling the relative structural severity of a frank stroke is with neuroimaging techniques. This approach avoids the subjective social bias that ranks behavioral attributes as opposed to lesion size and tissue destruction. The problem with this approach is that it is accurate only for relatively large lesions. If the cause of the behavioral deficit is the absolute volume of small ischemic lesions, the behavioral manifestation may far exceed any radiologic evidence of structural abnormality. A similar example is the early stages of Alzheirner's disease where the patient is obviously impaired but the radiologic examination is equivocal. The preceding discussion highlights several of the dilemmas associated with the question of how to assign a level of severity to a neurobehavioral symptom. It is important to stay focused on the central goal of improving outcome after CPB and not be driven by the accountants in the study of the consequences of cardiac surgery. All brain insults should be prevented, not just those that have quantifiable monetary cost to the individual or society. However, most studies are directed toward reducing the "major" deficits. The reason is most behavioral and neurologic tests are designed to assess either the social consequences of a brain injury or its location. These tests do not determine the size or the destructiveness of a lesion, which, if the brain is to be protected, is the important issue. Currently, there is no way to selectively influence where the lesions occur. There is some possibility that the factors related to lesion site are not random. Microemboli may preferentially go to the right hemisphere. The deficits may be an expression of bilateral watershed infarctions if the lesions are ischemic in nature, secondary to hypoperfusion. Anatomic location will determine the "social relevance" of the lesions independent of their size and destructiveness. It is probably more important to determine the relative size and distribution of lesions than their exact anatomic site. Small strokes 2 cm apart can cause radically different symptoms.
Development of Neuropsychologic Assessment Battery Precise characterization of the neuropsychologic deficits occurring after cardiac operations poses a unique challenge. Although the test battery must quantify the incidence of brain dysfunction occurring after CPB, a short battery cannot be sufficiently detailed to exhaustively characterize subtle higher cortical dysfunctions. The test battery must be concise because of the n u m b e r of timeconsuming perioperative activities and because of patient fatigue, which may reduce patient cooperation and data validity. In addition, the battery must offer good interobserver and intraobserver reproducibility, good discriminative capacity, and appropriate controls for practice effects. Because of patient time constraints, the selection and the evaluation of the battery of tests described in Appendix 1 emphasized specificity and test-retest reliability.
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Tests were deleted if previous studies or personal experience proved they were insensitive and unlikely to identify any abnormalities. Such tests, including the complete Wechsler adult intelligence scale and other measures of general intelligence, show only minor changes in scores [1, 2]. Other tests were chosen to facilitate comparison between the event rates reported by other investigators [3, 4], and several tests were chosen because they had proved to be sensitive in other series. The psychometric examination requires approximately 50 to 60 minutes preoperatively and somewhat longer postoperatively because of longer rest periods between tests. Tests that typically reveal deficits, such as the trailmaking test [5-8], the digit-symbol test [2, 8], and the grooved-pegboard [8, 9] and maze tests [2, 10], are timed tests that require a triad of skills: (1) sustained motor performance, (2) focused attention, and (3) visuopractic (including eye-hand coordination and manual dexterity). All of these abilities can be adversely, but reversibly, diminished by anesthesia, fatigue, and pain, all of which inevitably accompany thoracic surgical procedures [11]. Therefore, the postoperative testing interval is delayed until postoperative day 4 to 8 to minimize those effects. Postoperative visual acuity should be assessed, as several studies [3, 12-16] suggest that a substantial n u m b e r of patients undergoing CPB sustain retinal infarctions. Finally, the time and place of testing should be standardized to eliminate the variability in performance that occurs in individual patients as a function of the time of day. The testing should take place in the patient's room or a laboratory at the same time of day, preferably in the morning. A more comprehensive assessment of the psychosocial consequences of CPB can be obtained preoperatively and at the 1- to 3-month follow-up. It is essential to define a clinically important level of deterioration in performance. Individuals who do not have operation (controls) demonstrate highly consistent performance between tests, that is, the standard deviation of intrasubject mean performance is small. Unlike the controls, nearly all patients show deterioration in performance from preoperative to postoperative testing. However, m a n y deficits detected by excessively sensitive criteria are clinically trivial. In our laboratory, no normal, older control has ever demonstrated a decline in performance from the initial test interval that exceeded 20% on any test. Consequently, in our laboratory, a clinically important deterioration in performance is considered a deficit when a patient demonstrates a decrease of at least 20% on two or more neuropsychologic tests from preoperative to postoperative performance. This is a rigorous criterion. Most individuals are approximately 10% more coordinated with their dominant hand than their nondominant hand on tests of fine motor coordination. For a person to have a deficit by this criterion, the postoperative coordination with the dominant hand would have to fall considerably below that of the nondominant hand on tests of manual dexterity. The 4- to 8-day postoperative test interval followed by an evaluation at least 1 month and preferably 3 months
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later should be p e r f o r m e d to d o c u m e n t any i m p r o v e m e n t a n d what type of i m p r o v e m e n t s can be expected in neurologic function. The following is a list of the tests used at Bowman Gray, but it is the categories of function that should be emphasized and not the specific tests. The tests n a m e d have been selected to describe the following brain functions: 1. H i g h e r Cortical Functioning a. Vocabulary subtest of the W e c h s l e r a d u l t intelligence s c a l e - - r e v i s e d : This estimate of global intellectual function is not expected to change after a cardiac operation [1, 2]. 2. M e m o r y Functioning a. Rey auditory verbal learning test I9, 17]: This test of i m m e d i a t e m e m o r y s p a n requires 15 m i n u t e s to a d m i n i s t e r a n d has alternative w o r d lists to avoid practice effects. b. N o n v e r b a l m e m o r y [9, 18]: These n o n v e r b a l m e m ory tests are c o m p u t e r - p r e s e n t e d recognition tasks that consist of a c h e c k e r b o a r d design shown to the patient for 10 seconds followed by three simultaneously p r e s e n t e d designs from which the original m u s t be correctly selected. Two tests are p e r f o r m e d at different levels of difficulty, each with ten trials. The n u m b e r of correct r e s p o n s e s a n d the s p e e d of responses are recorded. Four parallel forms are available. This m a t c h i n g - t o - s a m p l e test is sensitive to both short-term a n d long-term deficits. 3. Attention, Concentration, a n d Psychomotor Performance a. Trail-making forms A a n d B [18, 19]: This sensitive test of h a n d - e y e coordination, attention, a n d concentration is a widely u s e d test that is often rep o r t e d to be a b n o r m a l after CPB [1, 3]. Performance on this test is m o n i t o r e d by a c o m p u t e r that plots the p e r f o r m a n c e curve over time to quantify increasing s p e e d (practice effect), decreasing s p e e d (fatigue), a n d t i m e - r e l a t e d changes in accuracy (attention a n d concentration). Errors are r e c o r d e d in relation to physical q u a d r a n t s of the test form to assess the impact of retinal disorders. b. G r o o v e d - p e g b o a r d test: This t i m e d test of m a n u a l dexterity a n d fine m o t o r coordination discriminates differences in right- a n d left-hemispheric performance. It requires less visual scanning a n d cognitive p l a n n i n g than the trail-making test b u t does not provide as convenient a m e a s u r e of fatigability or m o t o r persistence as the finger-tapping test. The data from the g r o o v e d - p e g b o a r d test can be directly c o m p a r e d with the results o b t a i n e d using this test in three studies [1, 8, 20] of neuropsychologic deficits after cardiac procedures. c. F i n g e r - t a p p i n g test [21]: In this test, the subject taps a key as rapidly as possible with the index finger for 10 seconds. Five trials per h a n d are r e p e a t e d with a 20-second rest b e t w e e n each trial. This test assesses i n t e r h e m i s p h e r i c differences a n d d e t e r m i n e s m a n ual dexterity a n d m o t o r fatigability. C o m m o n l y e m p l o y e d to assess d r u g effects, the finger-tapping
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test has g o o d a g e - m a t c h e d a n d s e x - m a t c h e d normative data. In our experience, this test is not r e d u n d a n t with the grooved pegboard, which is m o r e a test of dexterity, a n d deficits are often r e c o r d e d on one test a n d not the other. d. Letter-cancellation task [9, 22]: This test of sust a i n e d concentration has nine different cancellation tasks. It detects both early a n d late deficits after CPB [22]. The test is c o m p o s e d of several rows of letters. The subject m u s t search the rows sequentially a n d cross out the chosen letter. Symbol-digit r e p l a c e m e n t test [8]: This test, which requires r a p i d visual-motor responses as well as s u s t a i n e d attention a n d concentration, is sensitive to deterioration of m o t o r persistence. The test has b e e n a u t o m a t e d for c o m p u t e r presentation. The patient has to select from a key p a d the a p p r o p r i a t e n u m b e r that c o r r e s p o n d s to a particular symbol continuously d i s p l a y e d in a key on the screen. After 20 practice trials, 50 test items are presented. Parallel forms are available for each a s s e s s m e n t [23]. f. Visual reaction time test: This test, which requires m i n i m a l m a n u a l activity, is u s e d to facilitate discrimination b e t w e e n deterioration in p e r f o r m a n c e caused b y central ischemic neurologic deficits versus p r i m a r y visual i m p a i r m e n t . The visual reaction time test is a c o m p u t e r - p r e s e n t e d test in which the patient is a s k e d to focus on a blinking dot. W h e n the patient presses a pad, the blinking frequency increases a n d then at a variable interval of 0.5 to 1.0 second, the dot d i s a p p e a r s a n d a letter a p p e a r s s o m e w h e r e on the screen. W h e n the patient focuses on the target, a b a r press i m m e d i a t e l y removes the stimulus a n d the patient m u s t choose the correct stimulus from a m o n g ten s a m p l e s by p r e s s i n g a keypad. All four q u a d r a n t s are tested, a n d the eye m o v e m e n t r e q u i r e d is the same for all stimuli. Both accuracy a n d s p e e d are graded. After a surgical procedure, pain m a y interfere with the f i n g e r - t a p p i n g a n d trail-making tests, t h e r e b y suggesting the presence of cortical dysfunction. If the patient shows bilateral slowing on the finger-tapping test but performs well on the visual reaction time test, the likely cause is pain rather than cortical injury. I m p a i r e d function on both tests m o r e strongly suggests neurologic injury. If both tests d e m o n s t r a t e consistent unilateral deficits, a focal injury is likely. Performance on several of the tests m a y decline as a result of visual deficits after CPB [12, 13, 15, 24, 25]. Blauth a n d associates [24] r e p o r t e d that transient retinal vessel occlusion c o m m o n l y occurs during CPB. These findings suggest that visual dysfunction rather than neurologic injury could account for the high incidence of abnormalities in neuropsychologic batteries that rely on tests r e q u i r i n g intact visuopractic function. However, the positive correlation b e t w e e n retinal occlusion a n d n e u r o p s y c h o l o g i c d e t e r m i n a t i o n n o t e d b y Blauth a n d his group [24] suggests that frequent retinal arterial occlusion could also reflect diffuse embolic cerebral vascular occlusion.
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W h e n selecting tests for inclusion in a neuropsychologic battery, the initial choices can be focused by the probability that certain anatomic regions are at greater risk. If microemboli are the most probable cause of the neuropsychologic deficits, then tests that evaluate the distal regions supplied by the middle cerebral arteries should be selected with an emphasis on comparing focal right-sided a n d left-sided functions. A heterogeneous pattern of deficits would be consistent with microemboli as the cause. If the damage is secondary to hypoperfusion, then tests evaluating the watershed areas would be most appropriate, with a more h o m o g e n e o u s a n d predictable pattern of deficits expected. Conclusion The premise is that mortality a n d morbidity after CPB can be reduced by changes in surgical techniques, anesthesia m a n a g e m e n t , perfusion methodology, a n d use of n e w neuroprotective drugs. To evaluate the efficacy of these m a n i p u l a t i o n s on reducing cerebral dysfunction, a reliable outcome m e a s u r e is required. Neurobehavioral testing provides a sensitive, objective, reliable, and valid means to evaluate the function of the brain to determine the presence of trauma. The severity of behavioral dysfunction does not necessarily correlate with the amount of structural trauma. The location and etiology of the lesion are generally more important than the volume of tissue disrupted for predicting the social consequences of central nervous system insult. Neuropsychologic testing can be useful in assessing the efficacy of clinical interventions in both comparing groups a n d monitoring individual progress. The most powerful use of these behavioral tools is in combination with other measures of central nervous system functional integrity such as magnetic resonance imaging or positron emission tomography or w h e n correlated with physiologic monitoring such as for cerebral blood flow or embolic load. Finally, it is a testimony to the dedication of the cardiovascular research a n d clinical c o m m u n i t y that death a n d stroke are so u n c o m m o n , tests of subtle higher cortical function are necessary to evaluate n e w interventions. Supported by grants NS 28955 and NS 27500 from the National Institutes of Health. I thank Professor Stanton P. Newman for assisting in the development of the neuropsychologic battery; Rosie Hibawi, MS, for statistical assistance; Susan Haft, MS, Barbara Ruby, MS, and Kristen Morris, BA, for performing the neuropsychologic evaluations; and Julia Phipps, RN and Jo Beth Holliday, RN, for intraoperative monitoring.
References 1. Smith PL, Treasure T, Newman SP, et al. Cerebral consequences of cardiopulmonary bypass. Lancet 1986;1:823-5. 2. Raymond M, Conkiin C, Schaeffer J, Newstadt G, Mafloff JM, Gray RJ. Coping with transient intellectual dysfunction after coronary bypass surgery. Heart Lung 1984;13:531-9.
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3. Shaw PJ, Bates D, Cartlidge NE, et al. Neurologic and neuropsychological morbidity following major surgery: comparison of coronary artery bypass and peripheral vascular surgery. Stroke 1987;18:700-7. 4. Sotaniemi KA, Mononen H, Hokkanen TE. Long-term cerebral outcome after open-heart surgery: a five-year neuropsychological follow-up study. Stroke 1986;17:410-6. 5. Savageau JA, Stanton BA, Jenkins CD, Klein MD. Neuropsychological dysfunction following elective cardiac operation. I. Early assessment. J Thorac Cardiovasc Surg 1982;84: 585-94. 6. Malone M, Prior P, Scholtz CL. Brain damage after cardiopulmonary by-pass: correlations between neurophysiological and neuropathological findings. J Neurol Neurosurg Psychiatry 1981;44:924-31. 7. Ream AK, Reitz BA, Silverberg G. Temperature correction of PCO 2 and pH in estimating acid-base status: an example of the emperor's new clothes? Anesthesiology 1982;56:41-4. 8. Hammeke TA, Hastings JE. Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 1988;96: 326-31. 9. Harrison MJ, Schneidau A, Ho R, Smith PL, Newman S, Treasure T. Cerebrovascular disease and functional outcome after coronary artery bypass surgery. Stroke 1989;20:235-7. 10. Wechsler D. A standardized memory scale for clinical use. J Psychol 1948;19:87-95. 11. Tufo HM, Ostfeld AM, Shekelle R. Central nervous system dysfunction following open-heart surgery, lAMA 1970;212: 1333-40. 12. Shaw PJ, Bates D, Cartlidge NE, Heaviside D, Julian DG, Shaw DA. Early neurologic complications of coronary artery bypass surgery. Br Med J [Clin Res] 1985;291:1384-7. 13. Blauth CL Arnold JV, Kohner EM, Taylor KM. Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiography. Lancet 1986;2:837-9. 14. Hoyt RJ. Extracranial occlusive cerebrovascular disease. In: Wylie El, Ehrenfeld WK, eds. Diagnosis and management. Philadelphia: WB Saunders, 1970:64-95. 15. Russell RW, Bharucha N. The recognition and prevention of border zone cerebral ischaemia during cardiac surgery. Q J Med 1978;47:303-23. 16. Rogers AT, Newman SP, Stump DA, Prough DS. Neurologic effects of cardiopulmonary bypass. In: Gravlee GP, Davis RF, Utley JR, eds. Cardiopulmonary bypass: principles and practice. Baltimore: Williams and Wilkins, 1993:542-76. 17. Taylor EM. Psychological appraisal of children with cerebral deficits. Cambridge: Harvard University Press, 1959. 18. Reitan RM. Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271-6. 19. Reitan RM. Trail making test. Manual for administration, scoring and interpretation. Indianapolis: Department of Neurology, Indiana University Medical Center, 1958. 20. Nevin M, Colchester AC, Adams S, Pepper JR. Evidence for involvement of hypocapnia and hypoperfusion in aetiology of neurological deficit after cardiopulmonary bypass. Lancet 1987;2:1493-5. 21. Reitan RM, Davidson LA. Clinical neuropsychology: current status and applications. New York: Winston/Wiley, 1974. 22. Diller L, Ben-Yishay Y, Gerstman LJ, Goodkin W, Weinberg J. Studies in cognition and rehabilitation in hemiplegia (rehabilitation monograph 50). New York: New York University Medical Center Institute of Rehabilitation Medicine, 1974. 23. Newman SP. The incidence and nature of neuropsychological morbidity following cardiac surgery. Perfusion 1989;4: 93-100. 24. Blauth CI, Arnold JV, Schulenberg WE, McCartney AC, Taylor KM. Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography. J Thorac Cardiovasc Surg 1988;95: 668-76. 25. Taugher PJ. Visual loss after cardiopulmonary bypass. Am J Ophthalmol 1976;81:280-8.
There have been major advancements in cardiac surgery over the past two decades and a concomitant decrease in mortality and major morbidity. The improved safety in cardiac procedures permitted 330,000 operations involving cardiopulmonary bypass in 1992. However, several recent studies have demonstrated that cardiac surgery poses substantial risk of negative neurologic and neuropsychologic outcomes. Although very few patients die as a result of a cardiac operation, more than two thirds of patients demonstrate evidence of neuropsychologic dysfunction postoperatively. The mechanisms contributing to neuropsychologic deficits after cardiopulmonary by-
pass are uncertain. To characterize the incidence and severity of such deficits after cardiac operations, a concise battery of neuropsychologic tests that provides reliable evidence of subtle brain trauma is essential. With an objective, valid measure of brain injury, the etiology of neuropsychologic deficits can be identified and either eliminated or the effects ameliorated. The proper selection and use of neurobehavioral tools provides a basis to evaluate the efficacy of surgical and pharmacologic interventions to further improve neurologic outcome after cardiopulmonary bypass.
t the inception of every research p l a n to evaluate the effect of c a r d i o p u l m o n a r y b y p a s s (CPB) on the brain, one of the major areas of contention is how best to describe evidence of brain trauma. The p u r p o s e of this discussion is to explore the differences in the developm e n t of a traditional neuropsychologic battery of tests as o p p o s e d to a research battery whose variables are defined not only by the clinical question b u t by environmental a n d patient demographics. There are a variety of reasons w h y a patient m a y b e referred for a clinical neuropsychologic evaluation: (1) to d e t e r m i n e if the patient has e x p e r i e n c e d a brain trauma, (2) to d e t e r m i n e if the patient has d e v e l o p e d a psychiatric dysfunction, or (3) to d e t e r m i n e w h e t h e r the patient has both an organic a n d a psychiatric complaint. The historical p u r p o s e of the clinical neuropsychologic evaluation was localization of the lesion site, but given the advances in imaging, localization of lesions has taken a s e c o n d a r y role. Assessment, with an e m p h a s i s on d e t e r m i n i n g the level of social a n d cognitive i m p a i r m e n t , has taken precedence. The traditional a p p r o a c h for a clinical referral is to give the patient an extensive battery of tests that will survey his or her abilities a n d elicit errors that can be evaluated for clinical significance a n d diagnostic importance. The rationale for the use of an exhaustive neuropsychologic battery is to ensure that all modalities are explored for any potential deficits. A n y errors are carefully e x a m i n e d to d e t e r m i n e if they are evidence for labeling the patient
with a specific s y n d r o m e or higher cortical dysfunction. A l t h o u g h it might take only a few m o m e n t s to recognize a patient has a language disorder, it might take several hours of testing to tease out the specifics of a subcortical aphasia, for example. W h e n a s k e d to provide a battery of tests to a n s w e r a research question, experienced neuropsychologists t e n d to fall back on the familiar basic clinical examination, which covers a b r o a d s p e c t r u m of behaviors a n d takes 2 or m o r e hours to administer. However, w h e n asked to study cardiac surgical patients, these neuropsychologists are r u d e l y a w a k e n e d w h e n it b e c o m e s a p p a r e n t that they have only 45 m i n u t e s to evaluate the most complicated system in the body, the organ of behavior, the brain. The task to refine the question in line with the limited access one has to the patient b e c o m e s a series of compromises. The first level on the decision tree to provide an a b b r e v i a t e d 45-minute evaluation is to a n s w e r this question: W h a t is the research question? In other words, w h a t are we ultimately trying to accomplish with the s t u d y of p a t i e n t s u n d e r g o i n g CPB? Essentially, it is a l r e a d y k n o w n that patients experience varying levels of brain insult s e c o n d a r y to CPB. W h a t is n e e d e d is to either eliminate the source of the t r a u m a or ameliorate its effect. The question then b e c o m e s w h a t level of refinement is necessary to describe a n d define the deficit. Is it sufficient to just d e t e r m i n e that a b r a i n t r a u m a has occurred, or is a m o r e complete description of the deficits necessary? To answer the principal question of w h e t h e r or not an intervention has affected outcome, it is not necessary to exquisitely define specific n e u r o b e h a v i o r a l deficits. Reliability a n d sensitivity are m o r e key to a research evaluation than the n a m e s of specific deficits. In other words, it is m o r e i m p o r t a n t to be able to reliably d e t e r m i n e the
A
Presented at the Conference on CNS DysfunctionAfter Cardiac Surgery: Defining the Problem, Fort Lauderdale, FL, Dec 10-11, 1994. Address reprint requests to Dr Stump, Department of Anesthesia, Bowman Gray School of Medicine, Medical Center Bird, Winston-Salem, NC 27157-1009. © 1995 by The Society of Thoracic Surgeons
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patient has a visual deficit than it is to label the i m p a i r m e n t a prosopagnosia. A n o t h e r highly controversial question a t t e n d a n t on the issue of CPB a n d neuropsychologic outcome is the clinical significance of the deficits exhibited b y these patients. This is the quality of life issue, that is, if the patients are not "significantly" impaired, such as after a major stroke, do we n e e d to intervene? There are two possible answers to this concern: (1) yes, the n e u r o p s y chologic deficits are i m p o r t a n t a n d should be avoided, a n d (2) it does not m a t t e r if the deficits are behaviorally i m p o r t a n t as long as they are reliable m a r k e r s of brain injury a n d can be u s e d to i m p r o v e CPB. If the research were limited to eliminating the factors associated with CPB that cause death, an impossibly large n u m b e r of patients w o u l d be n e e d e d to obtain significance. By using as an end point an objective, reliable, and valid m e a s u r e of brain trauma, such as the relative change b e t w e e n preoperative a n d postoperative neuropsychologic performance of the patient, then fewer patients, h u n d r e d s instead of thousands, are a d e q u a t e to assess the efficacy of a treatment. R e m a r k a b l y few patients die or are completely disa b l e d as a b y - p r o d u c t of CPB. However, most individuals w o u l d agree that a d e c r e m e n t in m e m o r y or coordination w o u l d be a major inconvenience. Further, it s e e m s reasonable to p r e s u m e that if it were possible to eliminate the cause of the small problems, the n u m b e r of " m a j o r " events w o u l d p r o b a b l y be r e d u c e d as well. The criteria for defining a deficit is critical. If the definition is too stringent, then few patients meet the criteria. If the definition is too broad, then most patients have some level of t r a u m a a n d the ability to evaluate an intervention is lost. However, there is not a consensus in the literature on w h a t constitutes an i m p a i r m e n t . There is little a g r e e m e n t on how " s e v e r e " a deficit m u s t be before it is considered clinically important.
A Question of Severity, or Not All Lesions Are Created Equal For the p u r p o s e s of r e d u c i n g cognitive i m p a i r m e n t after CPB, severity can be described in two ways, behaviorally a n d structurally. The first describes the h u m a n condition, m e a n i n g that a small left-hemispheric central cortical stroke resulting in an expressive dysphasia, d o m i n a n t h a n d weakness, a n d eye m o v e m e n t incoordination is a socioeconomic disaster for the patient. Conversely, a larger anterior right frontal lobe stroke m a y go u n n o ticed, although causing a greater level of tissue destruction. The second description of severity is the quantity of tissue d a m a g e d , which, we can see from the example given, does not necessarily correlate with the socioeconomic consequences of a focal stroke. W h i c h is the best a p p r o a c h to ranking severity? An analogy might be along the line of a t t e m p t i n g to stop drivers from r u n n i n g a r e d light. It is i m p o r t a n t to the victim a n d society w h e t h e r the vehicle is struck on the driver or p a s s e n g e r side but largely irrelevant to the engineer assigned to s t o p p i n g the violators. If the side on
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which the victim is struck is relatively r a n d o m , then half the time the consequences to the driver of s o m e o n e r u n n i n g the light are severe and the other half, m e r e l y inconvenient. It w o u l d be i n a p p r o p r i a t e to a t t e m p t to control only the driver-side accidents. It w o u l d be best to try to p r e v e n t all accidents, a n d p r e s u m e if you d e c r e a s e d the n u m b e r of f e n d e r - b e n d e r s , you w o u l d also p r o p o r tionally reduce the n u m b e r of socioeconomically important left-sided crashes w h e r e the driver is hospitalized. The goal of the " e n g i n e e r " is to keep the " e m b o l i c d r i v e r " from entering the intersection, t h e r e b y preventing the severe accidents b y p r e v e n t i n g all accidents. This example helps explain w h y the n u m b e r of tests on which a patient performs abnormally might possibly reflect only the socioeconomic consequences of the lesion and not its severity. A left-hemispheric stroke would cause a patient to do poorly in the following categories of function (tests) relative to preoperative performance: (1) vocabulary test; (2) verbal learning test; (3) visual-motor coordination task; (4) visual-motor, frontal lobe function; (5) motor coordination task; (6) motor coordination, visual scanning, and planning; (7) visual learning and reaction time; and (8) visual scanning, attention, and concentration. The same size stroke in the same location in the right hemisphere would cause deficits in these tests: (1) motor coordination (nondominant hand), and (2) motor coordination (nondominant hand), visual scanning, and planning. One interpretation of these results is that the first (left h e m i s p h e r e ) lesion is four times as severe as the second (right hemisphere), even though they are the s a m e size. From the patient's point of view, the first lesion is far m o r e devastating than the r i g h t - h e m i s p h e r i c stroke, certainly worse than a 4 on a severity scale, even though anatomically equal. This p r o b l e m could potentially be a d d r e s s e d using s t a n d a r d i z e d scores (Z-scores) and categories of dysfunction w h e r e a category such as m o t o r function w o u l d be the composite score of four motor and visual-motor tests using the d o m i n a n t a n d n o n d o m i n a n t hands. M e m o r y w o u l d be the composite of two tests (verbal and nonverbal} a n d p e r c e p t u a l m o t o r functioning, five tests. The composite scores w o u l d be i n d e p e n d e n t of the side of the lesion b u t w o u l d still be subject to location versus size of lesion inequalities. This is not a satisfactory solution because it is not possible to equate the a m o u n t of tissue d i s r u p t i o n with the behavioral consequences of a lesion. At best, a relative rating of the level of i m p a i r m e n t for a given behavioral domain, memory, for example, could be used, but it w o u l d be a description of i m p a i r m e n t rather than an indication of severity. Alternatively, a cutoff score could be u s e d such that a given level or change in performance is abnormal. Again, this a p p r o a c h does not actually a d d r e s s a "severity scale." Further, the social consequences of a deficit are d e p e n d e n t on individual factors such as e m p l o y m e n t , education, hobbies, a n d age. A language i m p a i r m e n t w o u l d be m o r e devastating to a lawyer than a mechanic, w h e r e a s a major left-sided weakness would be a 100% disability for the mechanic b u t not a c a r e e r - e n d i n g deficit for a lawyer or politician.
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Perhaps the most objective method of scaling the relative structural severity of a frank stroke is with neuroimaging techniques. This approach avoids the subjective social bias that ranks behavioral attributes as opposed to lesion size and tissue destruction. The problem with this approach is that it is accurate only for relatively large lesions. If the cause of the behavioral deficit is the absolute volume of small ischemic lesions, the behavioral manifestation may far exceed any radiologic evidence of structural abnormality. A similar example is the early stages of Alzheirner's disease where the patient is obviously impaired but the radiologic examination is equivocal. The preceding discussion highlights several of the dilemmas associated with the question of how to assign a level of severity to a neurobehavioral symptom. It is important to stay focused on the central goal of improving outcome after CPB and not be driven by the accountants in the study of the consequences of cardiac surgery. All brain insults should be prevented, not just those that have quantifiable monetary cost to the individual or society. However, most studies are directed toward reducing the "major" deficits. The reason is most behavioral and neurologic tests are designed to assess either the social consequences of a brain injury or its location. These tests do not determine the size or the destructiveness of a lesion, which, if the brain is to be protected, is the important issue. Currently, there is no way to selectively influence where the lesions occur. There is some possibility that the factors related to lesion site are not random. Microemboli may preferentially go to the right hemisphere. The deficits may be an expression of bilateral watershed infarctions if the lesions are ischemic in nature, secondary to hypoperfusion. Anatomic location will determine the "social relevance" of the lesions independent of their size and destructiveness. It is probably more important to determine the relative size and distribution of lesions than their exact anatomic site. Small strokes 2 cm apart can cause radically different symptoms.
Development of Neuropsychologic Assessment Battery Precise characterization of the neuropsychologic deficits occurring after cardiac operations poses a unique challenge. Although the test battery must quantify the incidence of brain dysfunction occurring after CPB, a short battery cannot be sufficiently detailed to exhaustively characterize subtle higher cortical dysfunctions. The test battery must be concise because of the n u m b e r of timeconsuming perioperative activities and because of patient fatigue, which may reduce patient cooperation and data validity. In addition, the battery must offer good interobserver and intraobserver reproducibility, good discriminative capacity, and appropriate controls for practice effects. Because of patient time constraints, the selection and the evaluation of the battery of tests described in Appendix 1 emphasized specificity and test-retest reliability.
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Tests were deleted if previous studies or personal experience proved they were insensitive and unlikely to identify any abnormalities. Such tests, including the complete Wechsler adult intelligence scale and other measures of general intelligence, show only minor changes in scores [1, 2]. Other tests were chosen to facilitate comparison between the event rates reported by other investigators [3, 4], and several tests were chosen because they had proved to be sensitive in other series. The psychometric examination requires approximately 50 to 60 minutes preoperatively and somewhat longer postoperatively because of longer rest periods between tests. Tests that typically reveal deficits, such as the trailmaking test [5-8], the digit-symbol test [2, 8], and the grooved-pegboard [8, 9] and maze tests [2, 10], are timed tests that require a triad of skills: (1) sustained motor performance, (2) focused attention, and (3) visuopractic (including eye-hand coordination and manual dexterity). All of these abilities can be adversely, but reversibly, diminished by anesthesia, fatigue, and pain, all of which inevitably accompany thoracic surgical procedures [11]. Therefore, the postoperative testing interval is delayed until postoperative day 4 to 8 to minimize those effects. Postoperative visual acuity should be assessed, as several studies [3, 12-16] suggest that a substantial n u m b e r of patients undergoing CPB sustain retinal infarctions. Finally, the time and place of testing should be standardized to eliminate the variability in performance that occurs in individual patients as a function of the time of day. The testing should take place in the patient's room or a laboratory at the same time of day, preferably in the morning. A more comprehensive assessment of the psychosocial consequences of CPB can be obtained preoperatively and at the 1- to 3-month follow-up. It is essential to define a clinically important level of deterioration in performance. Individuals who do not have operation (controls) demonstrate highly consistent performance between tests, that is, the standard deviation of intrasubject mean performance is small. Unlike the controls, nearly all patients show deterioration in performance from preoperative to postoperative testing. However, m a n y deficits detected by excessively sensitive criteria are clinically trivial. In our laboratory, no normal, older control has ever demonstrated a decline in performance from the initial test interval that exceeded 20% on any test. Consequently, in our laboratory, a clinically important deterioration in performance is considered a deficit when a patient demonstrates a decrease of at least 20% on two or more neuropsychologic tests from preoperative to postoperative performance. This is a rigorous criterion. Most individuals are approximately 10% more coordinated with their dominant hand than their nondominant hand on tests of fine motor coordination. For a person to have a deficit by this criterion, the postoperative coordination with the dominant hand would have to fall considerably below that of the nondominant hand on tests of manual dexterity. The 4- to 8-day postoperative test interval followed by an evaluation at least 1 month and preferably 3 months
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later should be p e r f o r m e d to d o c u m e n t any i m p r o v e m e n t a n d what type of i m p r o v e m e n t s can be expected in neurologic function. The following is a list of the tests used at Bowman Gray, but it is the categories of function that should be emphasized and not the specific tests. The tests n a m e d have been selected to describe the following brain functions: 1. H i g h e r Cortical Functioning a. Vocabulary subtest of the W e c h s l e r a d u l t intelligence s c a l e - - r e v i s e d : This estimate of global intellectual function is not expected to change after a cardiac operation [1, 2]. 2. M e m o r y Functioning a. Rey auditory verbal learning test I9, 17]: This test of i m m e d i a t e m e m o r y s p a n requires 15 m i n u t e s to a d m i n i s t e r a n d has alternative w o r d lists to avoid practice effects. b. N o n v e r b a l m e m o r y [9, 18]: These n o n v e r b a l m e m ory tests are c o m p u t e r - p r e s e n t e d recognition tasks that consist of a c h e c k e r b o a r d design shown to the patient for 10 seconds followed by three simultaneously p r e s e n t e d designs from which the original m u s t be correctly selected. Two tests are p e r f o r m e d at different levels of difficulty, each with ten trials. The n u m b e r of correct r e s p o n s e s a n d the s p e e d of responses are recorded. Four parallel forms are available. This m a t c h i n g - t o - s a m p l e test is sensitive to both short-term a n d long-term deficits. 3. Attention, Concentration, a n d Psychomotor Performance a. Trail-making forms A a n d B [18, 19]: This sensitive test of h a n d - e y e coordination, attention, a n d concentration is a widely u s e d test that is often rep o r t e d to be a b n o r m a l after CPB [1, 3]. Performance on this test is m o n i t o r e d by a c o m p u t e r that plots the p e r f o r m a n c e curve over time to quantify increasing s p e e d (practice effect), decreasing s p e e d (fatigue), a n d t i m e - r e l a t e d changes in accuracy (attention a n d concentration). Errors are r e c o r d e d in relation to physical q u a d r a n t s of the test form to assess the impact of retinal disorders. b. G r o o v e d - p e g b o a r d test: This t i m e d test of m a n u a l dexterity a n d fine m o t o r coordination discriminates differences in right- a n d left-hemispheric performance. It requires less visual scanning a n d cognitive p l a n n i n g than the trail-making test b u t does not provide as convenient a m e a s u r e of fatigability or m o t o r persistence as the finger-tapping test. The data from the g r o o v e d - p e g b o a r d test can be directly c o m p a r e d with the results o b t a i n e d using this test in three studies [1, 8, 20] of neuropsychologic deficits after cardiac procedures. c. F i n g e r - t a p p i n g test [21]: In this test, the subject taps a key as rapidly as possible with the index finger for 10 seconds. Five trials per h a n d are r e p e a t e d with a 20-second rest b e t w e e n each trial. This test assesses i n t e r h e m i s p h e r i c differences a n d d e t e r m i n e s m a n ual dexterity a n d m o t o r fatigability. C o m m o n l y e m p l o y e d to assess d r u g effects, the finger-tapping
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test has g o o d a g e - m a t c h e d a n d s e x - m a t c h e d normative data. In our experience, this test is not r e d u n d a n t with the grooved pegboard, which is m o r e a test of dexterity, a n d deficits are often r e c o r d e d on one test a n d not the other. d. Letter-cancellation task [9, 22]: This test of sust a i n e d concentration has nine different cancellation tasks. It detects both early a n d late deficits after CPB [22]. The test is c o m p o s e d of several rows of letters. The subject m u s t search the rows sequentially a n d cross out the chosen letter. Symbol-digit r e p l a c e m e n t test [8]: This test, which requires r a p i d visual-motor responses as well as s u s t a i n e d attention a n d concentration, is sensitive to deterioration of m o t o r persistence. The test has b e e n a u t o m a t e d for c o m p u t e r presentation. The patient has to select from a key p a d the a p p r o p r i a t e n u m b e r that c o r r e s p o n d s to a particular symbol continuously d i s p l a y e d in a key on the screen. After 20 practice trials, 50 test items are presented. Parallel forms are available for each a s s e s s m e n t [23]. f. Visual reaction time test: This test, which requires m i n i m a l m a n u a l activity, is u s e d to facilitate discrimination b e t w e e n deterioration in p e r f o r m a n c e caused b y central ischemic neurologic deficits versus p r i m a r y visual i m p a i r m e n t . The visual reaction time test is a c o m p u t e r - p r e s e n t e d test in which the patient is a s k e d to focus on a blinking dot. W h e n the patient presses a pad, the blinking frequency increases a n d then at a variable interval of 0.5 to 1.0 second, the dot d i s a p p e a r s a n d a letter a p p e a r s s o m e w h e r e on the screen. W h e n the patient focuses on the target, a b a r press i m m e d i a t e l y removes the stimulus a n d the patient m u s t choose the correct stimulus from a m o n g ten s a m p l e s by p r e s s i n g a keypad. All four q u a d r a n t s are tested, a n d the eye m o v e m e n t r e q u i r e d is the same for all stimuli. Both accuracy a n d s p e e d are graded. After a surgical procedure, pain m a y interfere with the f i n g e r - t a p p i n g a n d trail-making tests, t h e r e b y suggesting the presence of cortical dysfunction. If the patient shows bilateral slowing on the finger-tapping test but performs well on the visual reaction time test, the likely cause is pain rather than cortical injury. I m p a i r e d function on both tests m o r e strongly suggests neurologic injury. If both tests d e m o n s t r a t e consistent unilateral deficits, a focal injury is likely. Performance on several of the tests m a y decline as a result of visual deficits after CPB [12, 13, 15, 24, 25]. Blauth a n d associates [24] r e p o r t e d that transient retinal vessel occlusion c o m m o n l y occurs during CPB. These findings suggest that visual dysfunction rather than neurologic injury could account for the high incidence of abnormalities in neuropsychologic batteries that rely on tests r e q u i r i n g intact visuopractic function. However, the positive correlation b e t w e e n retinal occlusion a n d n e u r o p s y c h o l o g i c d e t e r m i n a t i o n n o t e d b y Blauth a n d his group [24] suggests that frequent retinal arterial occlusion could also reflect diffuse embolic cerebral vascular occlusion.
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W h e n selecting tests for inclusion in a neuropsychologic battery, the initial choices can be focused by the probability that certain anatomic regions are at greater risk. If microemboli are the most probable cause of the neuropsychologic deficits, then tests that evaluate the distal regions supplied by the middle cerebral arteries should be selected with an emphasis on comparing focal right-sided a n d left-sided functions. A heterogeneous pattern of deficits would be consistent with microemboli as the cause. If the damage is secondary to hypoperfusion, then tests evaluating the watershed areas would be most appropriate, with a more h o m o g e n e o u s a n d predictable pattern of deficits expected. Conclusion The premise is that mortality a n d morbidity after CPB can be reduced by changes in surgical techniques, anesthesia m a n a g e m e n t , perfusion methodology, a n d use of n e w neuroprotective drugs. To evaluate the efficacy of these m a n i p u l a t i o n s on reducing cerebral dysfunction, a reliable outcome m e a s u r e is required. Neurobehavioral testing provides a sensitive, objective, reliable, and valid means to evaluate the function of the brain to determine the presence of trauma. The severity of behavioral dysfunction does not necessarily correlate with the amount of structural trauma. The location and etiology of the lesion are generally more important than the volume of tissue disrupted for predicting the social consequences of central nervous system insult. Neuropsychologic testing can be useful in assessing the efficacy of clinical interventions in both comparing groups a n d monitoring individual progress. The most powerful use of these behavioral tools is in combination with other measures of central nervous system functional integrity such as magnetic resonance imaging or positron emission tomography or w h e n correlated with physiologic monitoring such as for cerebral blood flow or embolic load. Finally, it is a testimony to the dedication of the cardiovascular research a n d clinical c o m m u n i t y that death a n d stroke are so u n c o m m o n , tests of subtle higher cortical function are necessary to evaluate n e w interventions. Supported by grants NS 28955 and NS 27500 from the National Institutes of Health. I thank Professor Stanton P. Newman for assisting in the development of the neuropsychologic battery; Rosie Hibawi, MS, for statistical assistance; Susan Haft, MS, Barbara Ruby, MS, and Kristen Morris, BA, for performing the neuropsychologic evaluations; and Julia Phipps, RN and Jo Beth Holliday, RN, for intraoperative monitoring.
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