Choreoathetosis after cardiac surgery with hypothermia and extracorporeal circulation

Choreoathetosis After Cardiac Surgery With Hypothermia and Extracorporeal Circulation José Luiz D. Gherpelli, MD*, Estela Azeka, MD†, Arlindo Riso, MD‡, Edimar Atik, MD†, Munir Ebaid, MD†, and Miguel Barbero-Marcial, MD‡ Eleven children, 4-48 months old, with congenital cyanotic heart defects developed choreoathetoid movements 2-12 days after cardiac surgery with hypothermia and extracorporeal circulation (ECC). The abnormal movements mainly involved the limbs, facial musculature, and tongue, leading to a severe dysphagia. The symptoms had an acute onset, after a period of apparent neurologic normality, and had a variable outcome. Of the nine children that survive, three had abnormal movements when last seen (41 days to 12 months of follow-up). The other six children had a complete regression of the choreoathetoid movements 1-4 weeks after onset. No specific finding was observed in the CT scans, cerebrospinal fluid examination, or EEG that could be related to the abnormal movements. Symptomatic therapy with haloperidol, with or without benzodiazepines led to symptomatic improvement in six children, although there was no evidence that this treatment modified the evolution of the disease. The authors conclude that the choreoathetoid syndrome after cardiac surgery with deep hypothermia and ECC is an ill-defined entity requiring additional study to better understand its pathogenesis so that preventive measures can be taken to avoid a condition that can lead to permanent and incapacitating neurologic sequelae. © 1998 by Elsevier Science Inc. All rights reserved. Gherpelli JLD, Azeka E, Riso A, Atik E, Ebaid M, Barbero-Marcial M. Choreoathetosis after cardiac surgery with hypothermia and extracorporeal circulation. Pediatr Neurol 1998;19:113-118. Introduction Survival of children with complex congenital heart disease has increased significantly in the past decade From Departments of *Child Neurology; †Cardiology; and ‡Thoracic Surgery; Clinics Hospital of the University of São Paulo Medical School; São Paulo, SP, Brazil. © 1998 by Elsevier Science Inc. All rights reserved. PII S0887-8994(98)00036-8 ● 0887-8994/98/$19.00 because of the introduction of new techniques of surgical repair. These techniques involve the frequent use of cardiorespiratory arrest (CRA) and extracorporeal circulation (ECC). Deep hypothermia is used to decrease cell metabolism to protect the central nervous system and other organs against the deleterious effects of hypoxia and ischemia associated with these procedures. Notwithstanding, the incidence of neurologic complications is high in the postoperative period and in long-term follow-up [1]. Neurologic sequelae observed in these children seem to be, at least in part, caused by hypoxic-ischemic phenomena and cerebral blood flow (CBF) disturbances that occur during reperfusion after the deep hypothermia associated with CRA and ECC. During deep hypothermia, there is an important reduction of CBF related to the decrease in cerebral metabolic rate. Children subjected to deep hypothermia and ECC have a persistent decrease in CBF in the rewarming phase with a loss of pressure-dependent cerebrovascular autoregulation [2]. Ferry [3,4] reported the following acute neurologic complications observed in children subjected to open heart surgery: seizures, alterations of consciousness, localized abnormalities such as hemiparesis or delayed choreoathetoid syndrome, and peripheral neuropathies. The longterm sequelae included epilepsy, cerebral palsy, mental retardation, hydrocephalus, and learning disabilities. In 1960, Björk and Hultquist [5] described the histopathologic findings in the brains of four children who died within 102 days after cardiac surgery with deep hypothermia and CRA. They found a marked decrease in the number of ganglion cells of the globus pallidus, with similar but less pronounced changes in the putamen. These findings are similar to those observed experimentally in primates after cardiac arrest, suggesting that ischemia is one of the important factors in the pathogenesis of these lesions [6]. Communications should be addressed to: Dr. Gherpelli; Serviço de Neurologia Infantil; Divisão de Clı́nica Neurológica do Hospital das Clı́nicas da Faculdade de Medicina da Universidade de São Paulo; Av. Eneas Carvalho Aguiar; 255; São Paulo-05403-000-SP, Brazil. Received November 24, 1997; accepted March 5, 1998. Gherpelli et al: Choreoathetoid Syndrome 113 Table 1. General data of the study group Patient No. Age (mo) Diagnosis Onset (PO days) Time of ECC (min) Time of CRA (min) Minimum Body Temperature (°C) 1 2 3 4 5 6 7 8 9 10 11 24 16 12 4 48 15 19 24 10 24 18 TGV TGV 1 VSD 1 ASD TGV TGV 1 AS TGV 1 PS TGV TGV 1 ASD 1 PDA TGV TGV 1 VSD 1 PS 1 PDA DORV 1 VSD 1 ASD TGV 1 ASD 2 2 12 3 4 3 4 2 10 3 4 105 35 100 80 118 90 153 120 110 300 115 52 4 40 57 33 68 38 54 37 36 35 16 18 16 15 16 17 14 15 16 16 15 Abbreviations: ANL 5 Abnormal AS 5 Aortic stenosis ASD 5 Atrial septal defect CRA 5 Cardiorespiratory arrest DORV 5 Double outlet right ventricle EEC 5 Extracorporeal circulation NL PDA PO PS TGV VSD 5 5 5 5 5 5 Material and Methods Between January 1990 and January 1992, 647 children with cardiac problems were operated upon at the Clinics Hospital Heart’s Institute of the São Paulo School of Medicine. ECC and hypothermia were used. During this period, 11 (1.7%) children with complex congenital heart disease, with ages ranging from 4 months to 4 years (mean 5 19.5 months), underwent open heart surgery with ECC and deep hypothermia and developed choreoathetoid syndrome in the postoperative period. Their charts were reviewed and data collected retrospectively. The electroencephalographic (EEG) examinations were performed during the active phase of the choreoathetosis in those children who later turned out to be asymptomatic. Computed tomography (CT) scans were interpreted as cortical atrophy when there was an enlargement of the periencephalic subarachnoid space of the hemispheric convexity. All children were PEDIATRIC NEUROLOGY Vol. 19 No. 2 60 7 41 42 12 9 26 30 30 42 9 d d d d mo d d d d d mo Outcome EEG CT Scan Dead Dead Symptomatic Symptomatic Symptomatic Asymptomatic Asymptomatic Asymptomatic Asymptomatic Asymptomatic Asymptomatic NL — — NL NL NL — NL — ANL — ANL — ANL ANL NL NL — NL — ANL NL Normal Patent ductus arteriosus Postoperative Pulmonary stenosis Transposition of the great vessels Ventricular septal defect Bergouignan et al. [7] in 1961 were the first to describe the clinical findings and outcome of choreoathetoid syndrome in children after cardiac surgery with deep hypothermia, ECC, and CRA. Choreoathetoid movements mainly involving the limbs and oral-facial musculature appear within the first week postoperatively. Oral feeding is often impaired because of the abnormal movements of the tongue and oral-pharyngeal musculature. Muscle hypotonia, irritability, and abnormal conjugate eye movements or paralysis are common findings. The abnormal movements can fade away in a few weeks or months or be permanent, although a decrease in intensity is often noticed [7-15]. In the literature, there are few descriptions of these patients, although the syndrome is well recognized in the specialized centers for pediatric cardiac surgery [4]. The authors report their experience with 11 children who developed choreoathetoid syndrome after open heart surgery with deep hypothermia in the Heart Institute of the Clinics Hospital of the University of São Paulo Medical School. 114 Follow-Up Duration examined weekly by a pediatric neurologist until hospital discharge, and abnormal movements were recorded daily by the cardiologist team responsible for the child. Results Eight of the children were boys and three were girls. All the children had varying degrees of cyanosis and hemoconcentration in the preoperative period. Their weight range was 6.3-15 kg (mean 9.1 kg) and was below average for their ages, a fact very commonly observed in children with cyanotic cardiac defects because of the undernutrition resulting from chronic hypoxemia. The pertinent data of the study group are presented in Table 1. Only one child (Patient 10) had a definite neurologic abnormality before surgery. She had a left-sided hemiparesis after an embolic stroke that occurred 1 year before the operation. No definite neurologic abnormality was observed in the other children in the preoperative period. Ten children had a diagnosis of transposition of the great vessels, associated with other cardiac defects in some. Minimum values of hypothermia were 14-18°C, time spent in ECC was 35-300 minutes (mean 5 120 minutes), and time of CRA varied from 4 to 68 minutes (mean 5 41.3 minutes). These values did not differ from those often observed in other children subjected to these procedures in our institution. In the immediate postoperative period a low cardiac output syndrome was observed in 10 children with a need for vasoactive drugs to maintain adequate systemic blood pressure levels. Clinical complications were observed in seven children and involved the respiratory system in four (Patients 3, 4, 9, and 10), renal system in one (Patient 9), hematologic system in one (Patient 7), gastrointestinal system in one (Patient 9) and metabolic system in four (Patients 2, 3, 9, and 11). These complications are often observed during the postoperative period of children subjected to open heart surgery, and none were temporally related to the appearance of the choreoathetosis, although we did not use a control group to support this statement. Choreoathetosis was first observed between the second and twelfth postoperative day in all children, with a mean appearance of 4.5 days. In nine patients, its appearance occurred after a symptom-free period during which the child had recovered consciousness, was alert, and had behavior considered normal by the cardiologists in charge. The older children were able to talk adequately to the medical team in the days that preceded the beginning of the abnormal movements. The choreoathetoid movements appeared in an abrupt manner, essentially having a choreic nature mainly affecting the proximal portion of the limbs, face, tongue, and oral-pharyngeal musculature. Children were usually irritable; what was remarkable was the restlessness and the continuous movements of tongue protrusion and facial mimic. The athetoid movements were observed distally in the hands. They disappeared during sleep and were continuous during the waking state. The children had to be fed through nasogastric tubing because of the striking dysphagia secondary to the abnormal movements of the tongue and pharyngeal musculature and were unable to speak. There was a mild global hypotonia and the irritability was intense, occupying a great part of the waking state. The conjugated eye movements were normal; however, in some children, we observed roving eye movements during a short period. The doll’s eye maneuver was present in all infants and the older ones could voluntarily direct their sight to all quadrants of the visual field. Patients 3 and 9, in whom the choreoathetosis appeared later (twelfth and tenth day, respectively), developed a global apathy with marked oligokinesia but without stupor preceding the beginning of the abnormal movements. None of the children had seizures, focal motor neurologic dysfunction (hemiparesis), cranial nerves deficits, or abnormal tendon or nociceptive reflexes. Haloperidol, plus benzodiazepines in two patients, was used in 10 children for symptomatic treatment of the abnormal movements (mean dosage was 0.1 mg/kg daily). Although six children had a complete disappearance of the abnormal movements after the drug was introduced, it was not possible to draw any practical conclusions about its efficacy. As soon as the symptoms improved the drug was withdrawn; if they recurred the drug was reinstituted and maintained after the child’s discharge from the hospital. There were two deaths (Patients 1 and 2) from causes unrelated to the choreoathetoid syndrome. Six of the nine surviving children (Patients 6-11) were asymptomatic and without medication; the other three (Patients 3-5) still had the choreoathetoid movements despite taking medication when last examined. The complete remission of the abnormal movements was observed between the end of the first week and the first month after onset. Only Patients 5 and 11 had a follow-up at 12 and 9 months, respectively. Patient 5 had a severe choreoathetosis involving the trunk, limbs, face, and tongue. The child was able to sit unsupported and walk a few steps unaided; he understood spoken language adequately for his age (5 years old) but had a severe dysarthria that made his spoken language barely intelligible. He received 10 mg/day of haloperidol; without the drug he was not even able to sit with support because of the severity of the abnormal movements. Patient 11 had normal psychomotor development for his age when last examined at 27 months of age. The other children were lost to follow-up because they came from other states of the federation and had to be monitored elsewhere. An EEG was performed in six children during the first week after the beginning of the choreoathetosis and was normal in five and abnormal in one (Patient 10), demonstrating a slowing of the electrical activity on the right hemisphere. This child had a left-sided hemiparesis secondary to an embolic stroke that occurred 1 year earlier. CT scans were performed in eight patients in the first 10 days after the beginning of the abnormal movements. Cerebral atrophy was diagnosed in three children (Patients 1, 3, and 4) on the basis of an enlargement of the periencephalic subarachnoid space, a finding that could be secondary to benign external hydrocephalus and not to a specific cerebral abnormality, although all three had a poor outcome. Patient 10 had a hypoattenuating image in the right cerebral hemisphere in the territory of the medial cerebral artery. None had abnormal images in the basal ganglia. Cerebrospinal fluid examination was normal in four patients in the acute phase. Magnetic resonance imaging of the brain was performed in Patient 5, 9 months after hospital discharge, and was normal, although the child was severely impaired by the choreoathetoid movements. Two patients died, one (Patient 2) on the seventh postoperative day from ill-defined reasons, and the other (Patient 1) on the sixtieth postoperative day from septic shock. Histopathologic examination was performed only in Patient 1 and revealed a diffuse cerebral softening with widespread cerebral necrosis secondary to the severe circulatory problems occurring several days before the child’s death. Discussion Choreoathetoid syndrome after open heart surgery with deep hypothermia is a disease with an unknown incidence and an uncertain pathophysiology. Ferry [4] reported that it was recognized in only three of six major pediatric cardiac surgery units that performed a mean of 450 surgeries per year in North America. Medlock et al. [12] reported an incidence of 1.2%, during a period of 10 years, in a group of 668 children 8-34 months old who underwent Gherpelli et al: Choreoathetoid Syndrome 115 Table 2. Reports of choreoathetoid syndrome in the literature N Onset (days) Bergouignan et al., 1961 [7] 4 3-6 4-10 yr Björk and Hultquist, 1962 [18] 4 2-4 4-11 yr Brunberg et al., 1974 [8] 4 3-6 5-22 mo Chaves and Scaltsas-Persson, 1988 [9] 6 3-8 5-30 mo Normal (2) and abnormal (2) Abnormal (2/5) DeLeon et al., 1990 [10] 8 3-7 1, 2-5 yr Abnormal (3/8) Huntley et al., 1993 [11] 4 1-4 3-16 mo Abnormal (4/4) Medlock et al., 1993 [12] 8 3-12 4-34 mo Robinson et al., 1988 [13] 5 3-7 8 mo-6 yr Normal (5) Wical et al., 1990 [14] 4 1-5 8 mo-4, 5 yr Abnormal (2) and normal (1) Authors Age EEG (n) Normal (3) — — open heart surgery with ECC. DeLeon et al. [10] observed the syndrome in 8 (1.05%) of 758 children after cardiac surgery with ECC and hypothermia. There is a consensus among cardiologists that the syndrome is rare and transitory, with most patients being symptom free in the follow-up period [16]. On the other hand, there are several reports demonstrating that the abnormal movements persist in the long-term follow-up, whether or not associated with other signs of neurologic abnormalities [7,10-12,15,17]. The onset of the abnormal movements occurred between the first and twelfth postoperative day, mainly between the third and seventh day, in the patients reported in the literature (Table 2), which is in agreement with the authors’ data. The choreoathetosis onset was either abrupt or occurred after a period in which the child seemed to be apathetic and oligokynetic. Björk and Hultquist [18] reported four children that developed a Parkinson-like state followed by choreoathetoid movements after cardiac surgery with deep hypothermia. We have not observed conjugated eye movement abnormalities as reported by Robinson et al. [13], who described a supranuclear ophthalmoplegia in all four of their patients with choreoathetoid syndrome. Wical et al. [14] found abnormalities in the voluntary eye movements in two of four patients; one had a supranuclear ophthalmoplegia and the other a tendency for downward gaze deviation. The other reports have not mentioned conjugate eye movement abnormalities with the choreoathetoid movements. Although the authors did not observe seizures in the acute phase, they are occasionally observed in the acute phase [8,10,12]. There was a complete resolution of the abnormal movements in six of nine children in the authors’ study group. This is a better 116 PEDIATRIC NEUROLOGY Vol. 19 No. 2 CT Scan (n) MRI (n) — — — — — — Cortical atrophy (1) 1 multiple infarcts (1) Abnormal (1/6) (old infarct) Abnormal (2/2) — Abnormal (cerebral atrophy) (6/8) Normal (3/3) — Normal (3) Normal (1/1) Abnormal (3/3) cortical atrophy — Abnormal (cortical atrophy) (1) and normal (1) Outcome (n) Follow-Up Duration Symptomatic (4) 12 mo Dead (4/4) — Symptomatic (2/4) 2-9 mo Dead (4/6) — Symptomatic 2 mo-3 yr Symptomatic 3-9 mo Symptomatic Dead (1/7) 6-130 mo Symptomatic 9-19 mo Symptomatic 2-15 mo (5/6) (1/4) (6/7) (3/5) (3/4) outcome than reported by others, who found more than 50% of persistent, albeit sometimes less severe, choreoathetoid movements during follow-up (Table 2). The authors did not draw any conclusions about the long-term neurologic outcome of the children because they could not be systematically monitored after hospital discharge. Others have found a high incidence of neurodevelopmental deficits and epilepsy [1,7,9,11,19,20]. However, a detailed review of the patient reports reveals that in many patients, young age, severity of the choreoathetosis, and associated speech disability hindered an adequate evaluation of the cognitive impairment of the children. Haloperidol was the drug used for symptomatic treatment in most of the authors’ patients. It is a symptomatic approach that can be useful in some patients because it allows them to be orally fed earlier because of improvement of the oral-pharyngeal movements. It should be used in the most severe patients and for as short time as possible because of potential chronic and irreversible adverse effects. Some children became less irritable, possibly because of improvement in the restlessness. Medlock et al. [12] used haloperidol in five children with persistent choreoathetosis, with dosages of 0.25-0.5 mg/kg/day, observing beneficial results in only one. The pathogenesis of the choreoathetoid syndrome after cardiac surgery with deep hypothermia and ECC is presently unknown. Deep hypothermia seems to be a possible factor because the reports began after the institution of this method of brain protection [5]. On the other hand, hypothermia and ECC allowed cardiac surgeons to operate on children with more complex cardiac malformations and with a higher risk of circulatory disturbances, which could play an important role in the pathogenesis of the syndrome. During hypothermia and ECC there is a decrease in CBF that is directly related to the degree of hypothermia, as well as loss of cerebrovascular pressure-flow autoregulation. The reduced CBF likely reflects reduced cerebral metabolism secondary to hypothermia. The loss of vascular autoregulation increases the risk of ischemic episodes because of pressure passive oscillations in CBF. Studies of CBF using 133Xe clearance revealed that there was a delay in normalization of the CBF values in children submitted to hypothermia and CRA [2]. The degree of hypothermia (body temperature less than 25°C, often less than 20°C) and duration of more than 1 hour were other factors associated with the choreoathetoid syndrome [10]. Although most of the case reports are associated with hypothermia, there are patients in whom the syndrome developed after cardiac surgery using only ECC or aortic cross-clamping [9]. A clinically indistinguishable choreoathetoid syndrome developed in a child after respiratory arrest [6], an indication that mechanisms other than deep hypothermia, most likely related to hypoxic-ischemic events, are important in the pathogenesis. Du Plessis et al. [20] used near-infrared spectroscopy to study the relationship between cerebral intravascular (hemoglobin) and mitochondrial (cytochrome aa3) oxygenation in infants undergoing deep hypothermic repair of congenital heart defects throughout the intraoperative period. The results indicated that during the deep hypothermic cardiopulmonary bypass the cerebral concentration of oxidized cytochrome aa3 decreased faster than that of oxyhemoglobin, remained low during the entire procedure, and returned to normal values well after rewarming and reperfusion at a time when the oxyhemoglobin values were already normalized. The delay was more than 1 hour in approximately 50% of the 63 children studied. They conclude that these findings suggest impairment of mitochondrial function or of delivery of oxygen to the mitochondrion, or both. The effects were more marked in infants older than 2 weeks of age, suggesting an agedependent factor. The abnormalities found in imaging and electrophysiologic examinations are of little value for the diagnosis. Nonspecific EEG abnormalities, epileptiform or not, as well as abnormalities on CT scans mainly of diffuse or localized cerebral atrophy, were reported by several authors (Table 2). It is important to realize that 30% of children with congenital heart defects demonstrate either enlargement of the periencephalic subarachnoid space or nonhypertensive ventricular dilation on magnetic resonance imaging in the preoperative period [21]. Data on histopathology are scarce. Robinson et al. [13] could not find any histologic abnormality in a child who died 5 months postoperatively who still had mild choreoathetoid movements at the time of death. Chaves and Scaltsas-Persson [9] described hypoxic neuronal degener- ation and capillary proliferation in the basal ganglia in one patient. Björk and Hultquist [5,18] found a severe decrease in the number of ganglionic cells of the globus cells of the globus pallidum associated with an intense gliosis and a similar but milder picture in the putamen and caudate nucleus in three children who died 26 to 102 days postoperatively and had developed a choreoathetoid syndrome. None of the authors’ patients presented with seizures but their presence was found by others not only in the acute phase [7,10,11] but also in the long-term follow-up [19]. The authors conclude that choreoathetoid syndrome after open heart cardiac surgery, whether or not associated with deep hypothermia, ECC, or CRA, is an uncommon disease that can lead to transitory or permanent neurologic dysfunction that can seriously debilitate the affected children. Its pathogenesis is unknown, although there is a relationship with hypoxic-ischemic events, secondary to one or several of the techniques used in the operating room. The identification of the syndrome and the study of the related variables may help in preventing it in the future. References [1] Bellinger DC, Jonas RA, Rappaport LA, et al. Developmental and neurologic status of children after cardiac surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med 1995;332:549-55. [2] Greeley WJ, Ungerleider RM, Smith R, Reves JG. The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children. J Thorac Cardiovasc Surg 1989;97:737-45. [3] Ferry PC. Neurologic sequelae of cardiac surgery in children. Am J Dis Child 1987;141:309-12. [4] Ferry PC. Neurologic sequelae of open-heart surgery in children. Am J Dis Child 1990;144:369-73. [5] Björk VO, Hultquist G. Brain damage after deep hypothermia for open-heart surgery. Thorax 1960;15:284-91. [6] Gingold M, Bodensteiner J, Hogg J. Hypoxia-induced CHAP syndrome. J Child Neurol 1995;10:70-2. [7] Bergouignan M, Fontan F, Trarieux M, Julien J. Syndromes choréiformes de l’enfant au décours d’interventions cardio-chirurgicales sous hypothermie profonde. Rev Neurol (Paris) 1961;105:48-60. [8] Brunberg JA, Doty DB, Reilly EL. Choreoathetosis in infants following cardiac surgery with deep hypothermia and circulatory arrest. J Pediatr 1974;84:232-5. [9] Chaves E, Scaltsas-Persson I. Severe choreoathetosis following congenital heart disease surgery. Neurology 1988;38(suppl 1):284. [10] DeLeon S, Ilbawi M, Arcilla R, et al. Choreoathetosis after deep hypothermia without circulatory arrest. Ann Thorac Surg 1990;50:714-9. [11] Huntley DT, Al-Mateen M, Menkes JH. Unusual dyskinesia complicating cardiopulmonary bypass surgery. Dev Med Child Neurol 1993;35:631-41. [12] Medlock MD, Cruse RS, Winek SJ, et al. A 10-year experience with post pump chorea. Ann Neurol 1993;34:820-6. [13] Robinson RO, Samuels M, Pohl KRE. Choreic syndrome after cardiac surgery. Arch Dis Child 1988;63:1466-9. [14] Wical BS, Tomasi LG. A distinctive neurologic syndrome after induced profound hypothermia. Pediatr Neurol 1990;6:202-5. [15] Wong PC, Barlow CF, Hickey PR, et al. Factors associated with Gherpelli et al: Choreoathetoid Syndrome 117 choreoathetosis after cardiopulmonary bypass in children with congenital heart disease. Circulation 1992;86(suppl 5):V118-26. [16] Barrat-Boyes BG. Choreoathetosis as a complication of cardiopulmonary bypass. Ann Thorac Surg 1990;50:693-4. [17] Brunberg JA, Reilly EL, Doty DB. Central nervous system consequences in infants of cardiac surgery using deep hypothermia and circulatory arrest. Circulation 1974;49-50(suppl II):60-6. [18] Björk VO, Hultquist G. Contraindications to profound hypothermia in open-heart surgery. J Thorac Cardiovasc Surg 1962;44:1-13. 118 PEDIATRIC NEUROLOGY Vol. 19 No. 2 [19] Ginsberg MD, Myers RE. The topography of impaired microvascular perfusion in the primate brain following total circulatory arrest. Neurology 1972;22:998-1011. [20] du Plessis AJ, Newburger J, Jonas RA, et al. Cerebral oxygen supply and utilization during infant cardiac surgery. Ann Neurol 1995; 37:488-97. [21] McConnell JR, Fleming WH, Chu W-K, et al. Magnetic resonance imaging of the brain in infants and children before and after cardiac surgery. Am J Dis Child 1990;144:374-8.