Cerebral Dysgenesis

The prevalence of brain dysgenesis in children with congenital heart disease approaches 30 percent in some autopsy studies. The risk of cerebral dysgenesis appears related to the specific underlying cardiac lesion. For example, infants with hypoplastic left heart syndrome may be at particular risk of associated developmental brain lesions, which range in severity from microdysgenesis to gross malformations including agenesis of the corpus callosum, holoprosencephaly, and immature cortical mantle. The relationship between cardiac and brain dysgenesis has been more clearly defined through advances in neuroimaging. These cerebral abnormalities may present with seizures, alterations in level of consciousness, and abnormalities in motor tone in the newborn period, or they may remain clinically occult until later infancy and childhood, when they present with developmental delay, epilepsy, and cerebral palsy.

An unresolved question in this population is whether cerebral dysgenetic lesions are a consequence of primary genetic abnormalities or secondary to cerebral oxygen and substrate restriction, or both. More recent advances in quantitative MRI techniques have demonstrated subtle disturbances in cerebral development and maturation. Several studies have suggested that fetal heart anomalies may result in dysmaturity at the cellular, metabolic, and micro- and macrostructural levels in the absence of gross lesions detected by conventional MRI.

Several studies using Doppler flow patterns in the fetal middle cerebral artery have demonstrated evidence of cerebral vasodilation (the “brain sparing” effect), especially in fetuses with hypoplastic left heart syndrome. This compensatory mechanism may be limited in its ability to maintain adequate oxygen/substrate delivery as evidenced by the increased rate of impaired brain growth in these patients.

Chromosomal Disorders

A number of chromosomal disorders have a phenotype that includes both cardiac and neurologic malformations, including trisomies 11, 18, and 21. The most common neurologic manifestation in children with trisomy 21 (Down syndrome) is cognitive dysfunction. Epilepsy develops in approximately 5 percent of these children, and congenital heart defects, most commonly endocardial cushion defects, are present in 40 percent of children with Down syndrome. Gross structural brain alterations in Down syndrome include a narrow superior temporal gyrus and a disproportionately small cerebellum and brainstem. Trisomy 13 is associated with ventricular septal defects and patent ductus arteriosus; the associated cerebral dysgenesis in this syndrome is often severe, with holoprosencephaly and agenesis of the corpus callosum being the most common lesions. The most common cardiac lesions in infants with trisomy 18 are ventricular septal defects and patent ductus arteriosus, with neuronal migration defects being the most common form of brain dysgenesis.

The phenotypic spectrum of specific chromosome 22 deletions, particularly in the 22q11 region, includes a variety of cardiac malformations and neurologic features. Recent population-based data suggest that at least 700 infants with chromosome 22 deletion syndromes are born annually in the United States. The acronym CATCH 22 ( c ardiac defect, a bnormal facies, t hymic hypoplasia, c left palate, h ypocalcemia, and chromosome 22 q11 deletions) has been used to designate this group of related syndromes. The two most common, DiGeorge and velocardiofacial (or Shprintzen) syndromes, have neurologic and cognitive manifestations in association with structural cardiac defects. The fundamental problem in DiGeorge syndrome is a developmental defect of the third and fourth pharyngeal pouches, manifesting with thymic and parathyroid hypoplasia along with conotruncal cardiac malformations, which include an interrupted aortic arch (type B), truncus arteriosus, and tetralogy of Fallot.

A common neurologic presentation in both the DiGeorge and the velocardiofacial syndromes is hypocalcemic seizures due to hypoparathyroidism. In addition to the usual cardiac lesions (i.e., ventricular septal defect or tetralogy of Fallot), the velocardiofacial syndrome is associated with cleft palate or velopharyngeal insufficiency and a typical facial appearance, including a broad, prominent nose and retrognathia, along with microcephaly in up to 40 percent of cases. Neuroimaging and autopsy studies may demonstrate a small posterior fossa and vermis, small cystic lesions adjacent to the frontal horns of the lateral ventricles, dysgenesis of the corpus callosum, and abnormal cortical gyrification patterns. Delayed opercular development and disproportionately enlarged sylvian fissures with white matter abnormalities might underlie some of the developmental problems in these children. The mean intelligence quotient (IQ) in this syndrome is around 70, with mild to moderate cognitive problems present in up to 50 percent of patients.

In recent years, a high rate of autism spectrum disorders and attention deficit/hyperactivity disorder has been described in this group of patients. Psychiatric disorders occur in up to 22 percent of those with 22q11 deletion syndromes. A peculiar and inappropriately blunt effect may be evident during childhood, often evolving to frank psychosis during adolescence and adulthood. Altered prefrontal cortex-amygdala circuitry, reduced cerebellar and thalamic volumes, and increased basal ganglia and corpus callosal volumes, as shown by quantitative neuroimaging studies, may underlie disrupted emotional processing and form the neurobiologic substrate for the psychiatric disturbances in these children.

Focal or Multifocal Hypoxic-Ischemic Injury

The relatively small intravascular volume of the young infant compared with the large blood volume required to “prime” the cardiopulmonary bypass circuit results in an increased exposure to insults related to the bypass. These include both embolic and inflammatory disturbances, the latter due to the extensive interface between blood and artificial surfaces.

The replacement of bubble oxygenators with membrane devices has decreased, but not eradicated, the embolic “load” of bypass circuits. Both gaseous and particulate emboli may enter the bypass circuit directly from the surgical field. Because the circuit delivers oxygenated blood directly to the aorta, circulating emboli circumvent the normal pulmonary filtration bed and enter the systemic (and cerebral) arterial circulation directly. In addition to emboli, cerebral capillary-bed aneurysmal dilatations have been observed.

Cardiopulmonary bypass activates a host of inflammatory cascades that can cause diffuse vascular injury, resulting in a postperfusion syndrome that in severe cases is associated with multiple organ failure. Pathways triggered include those involving eicosanoids, complement, and kallikrein. These pathways activate free radical generation, cause antioxidant depletion, and upregulate adhesion molecules on neutrophils and endothelial cells. These activated neutrophils appear to be potent mediators of cerebral reperfusion injury. Although hypothermia delays and modifies the effect of these processes, it does not completely prevent them.

Global Hypoxic-Ischemic Injury

Several techniques used during neonatal cardiac surgery may jeopardize global cerebral oxygen by altering cerebral perfusion, arterial oxygen content, and tissue oxygen delivery. Under deep hypothermic conditions, cerebral oxygen availability may be limited by cold-induced increases in cerebral vascular resistance, impairment of cerebral pressure–flow autoregulation, and increased oxygen-hemoglobin affinity. The normal response to periods of decreased perfusion pressure involves cerebral oxygen delivery being maintained by an initial vasodilatory response followed by an increase in oxygen extraction. However, both of these compensatory responses are compromised at deep hypothermia.

To approach these often small cardiac defects, the bypass flow rate must be decreased and even arrested for periods, depending on the complexity of the lesion. Although there are general guidelines for “safe periods” of deep hypothermic circulatory arrest at various temperatures, these remain controversial and unpredictable in the individual patient. In addition, the safety of low-flow bypass compared with hypothermic circulatory arrest is controversial. Low-flow bypass prolongs exposure to bypass-related embolic phenomena, as well as increasing the risk of incomplete ischemia. Conversely, deep hypothermic circulatory arrest allows more rapid completion of the intracardiac phases of the repair and reduces the exposure to bypass perfusion; however, the infant is exposed to periods of complete ischemia. Deleterious effects of deep hypothermic circulatory arrest on neurologic outcome have been reported in several studies. In a major clinical trial randomizing infants to a strategy of predominant hypothermic circulatory arrest or low-flow bypass, infants exposed to the former were at significantly greater risk of perioperative and 1-year neurologic sequelae. At age 4 years, the deep hypothermic circulatory arrest group had significantly worse behavior, speech, and language function, but no difference in mean intelligence score. At 8-year follow-up, those assigned to deep hypothermic circulatory arrest scored worse on motor and speech domains, whereas those assigned to low-flow bypass had worse impulsivity and behavior. The long-term follow-up of this large cohort has provided important insights into the evolution of neurodevelopmental outcomes in this complex population over time. Although it is now generally accepted that prolonged periods of uninterrupted deep hypothermic circulatory arrest may have adverse neurologic effects, shorter durations of deep hypothermic circulatory arrest have not consistently been associated with adverse outcomes. Available data suggest that the relationship between duration of deep hypothermic circulatory arrest and neurodevelopmental sequelae is not linear, with the risk of brain injury increasing significantly after about 40 minutes.

In addition to flow rate, a number of other factors associated with cardiopulmonary bypass may affect cerebral perfusion and predispose to hypoxic-ischemic/reperfusion injury. Most centers in the United States use nonpulsatile bypass devices as well as hemodilution in order to reduce the magnitude of red blood cell trauma. Deep hypothermia is widely used in part to suppress oxygen consumption during surgery. In addition to their intended beneficial effects, these techniques all have potential adverse effects on cerebral oxygen delivery. The nonpulsatile perfusion of cardiopulmonary bypass, particularly at low flow rates, may fail to maintain perfusion in distal capillary beds. Furthermore, nonpulsatile blood flow may disrupt autoregulation. Hemodilution is also used during bypass to reduce rheologic injury to circulating red cells; however, because the concentration of oxygenated hemoglobin is the major determinant of oxygen-carrying capacity, this technique may limit cerebral oxygen delivery. In animal studies, extreme hemodilution (to hematocrit levels less than 10%) is associated with neurologic injury, whereas hematocrit levels above 30 percent improved cerebral recovery after deep hypothermic circulatory arrest. These experimental results were confirmed by a randomized clinical trial in which infants randomized to a hematocrit of 20 percent during cardiac surgery had significantly worse developmental scores at 1 year than those randomized to a hematocrit of around 30 percent.

Another important intraoperative factor is the management of acid-base status during cardiopulmonary bypass. In a randomized, single-center trial, infants undergoing cardiac operations were assigned to an alpha-stat versus pH-stat strategy of managing acid-base status during deep hypothermic cardiopulmonary bypass. The use of pH-stat management was associated with lower overall early postoperative morbidity although treatment assignment had no effect on neurodevelopmental outcomes at 1, 2, and 4 years of age. Despite these equivocal findings, many centers are currently using pH-stat management during core cooling.

After repair of the cardiac defect, bypass flow rates are increased using rewarmed and highly oxygenated blood in order to reactivate cellular enzyme function and oxygen utilization. During this period of reperfusion, a number of factors may predispose to free radical injury. Several studies have suggested a delay in the recovery of mitochondrial function, possibly mediated by nitric oxide, which is generated in abundance during the bypass. The combination of highly oxygenated reperfusion along with persistent mitochondrial dysfunction may serve as a major source of oxygen free radicals. Excessively rapid rewarming after deep hypothermia may be particularly deleterious; hyperthermia is a trigger for glutamate release, predisposing to excitotoxicity as well as further stressing the recovering cerebral metabolism.

Delayed Recovery of Consciousness

Prolonged impairment of mental status after cardiac surgery, anesthesia, and postoperative sedation is a common reason for neurologic consultation. The evaluation should follow the usual approach for assessing impaired consciousness in any patient. Common etiologies which should be excluded include postoperative hepatic or renal impairment, which may directly alter the mental state or do so in the setting of impaired metabolism or excretion of sedating drugs. Prolonged use of neuromuscular blocking agents in the preoperative or postoperative period may delay the recovery of motor function and, if severe, may mimic impaired consciousness; this condition may be excluded at the bedside with a peripheral nerve stimulator or formal nerve conduction studies. Postoperative seizures are a common complication of cardiac surgery, and a prolonged postictal state should be considered in the evaluation of a depressed postoperative mental state. A precise cause of an impaired postoperative mental status is not established quickly in most cases, however, and many of these children ultimately demonstrate features suggestive of hypoxic-ischemic/reperfusion injury.

Postoperative Seizures

Seizures early in the postoperative period are among the most common neurologic complications after open heart surgery, occurring in up to 19 percent of survivors of neonatal cardiac surgery ; in some high-risk subgroups this number may reach up to 50 percent. Clinical seizures are reported less frequently than those without typical motor correlates that are only detected by continuous electroencephalographic (EEG) monitoring. Some seizures have a readily identifiable cause, such as hypoglycemia, hypocalcemia, and cerebral dysgenesis. Postoperative seizures may also result from hypoxic-ischemic/reperfusion injury due to either generalized cerebral hypoperfusion (e.g., cardiac arrest) or focal vasoocclusive insults. More commonly, however, the etiology of the seizures remains unknown.

Although these cryptogenic seizures, commonly referred to as postpump seizures , are often assumed to relate to hypoxic-ischemic/reperfusion injury, their etiology is likely multifactorial with risk factors that include the use and duration of deep hypothermic circulatory arrest, younger age at surgery, the type of heart defect (e.g., aortic arch obstruction), and genetic susceptibility. Postpump seizures differ in several respects from other forms of posthypoxic seizures. They typically develop later than, for instance, those occurring after perinatal asphyxia. The prognosis of postpump seizures is significantly better than that of asphyxial seizures, in which up to 50 percent of survivors are neurologically disabled. Both the delayed onset and more favorable outcome may be due to the partial protective effect of hypothermia at the time of the intraoperative insult.

The clinical course of postpump seizures is fairly typical, with onset between 24 and 48 hours after surgery. This is followed by several days during which serial seizures occur, often evolving to status epilepticus; following this period, the tendency toward further seizures wanes rapidly. The clinical manifestations of these electrographic seizures are often subtle even in the absence of sedating and paralyzing drugs; they may even be confined to paroxysmal autonomic changes. When evident, convulsive activity is usually focal or multifocal.

The therapeutic approach to seizures should first involve excluding reversible etiologies such as hypoglycemia, hypomagnesemia, and hypocalcemia. Repeated seizures and status epilepticus should be treated by rapid achievement of therapeutic anticonvulsant levels by an intravenous route. Most postpump seizures are controlled by lorazepam, followed by phenobarbital or phenytoin. Potential cardiotoxicity due to these agents in children recovering from cardiac surgery should be monitored carefully, particularly during treatment initiation. The short window of susceptibility to postpump seizures often allows early withdrawal of anticonvulsants.

Prospective studies have demonstrated a significant correlation between postoperative seizures and the risk of perioperative and 1-year neurologic sequelae, as well as abnormal MRI studies. The longer-term impact of postpump seizures maybe less than previously suspected. The development of subsequent epilepsy is rare; however, West syndrome (infantile spasms, mental retardation, and epilepsy) has been described following a course of intractable postpump seizures.

When postoperative seizures have an identified cause, the long-term outcome is related to etiology. For instance, cerebral dysgenesis, which is increased in patients with congenital heart disease, carries a poor long-term outcome, commonly featuring the development of epilepsy. Infants with seizures due to postoperative stroke have a 20 to 30 percent risk of subsequent epilepsy.

Periventricular White Matter Injury

Preoperative brain MRI in neonates with congenital cardiac disease identifies white matter injury in around 30 percent, especially in those with single ventricle physiology. Postoperative brain MRI studies have shown a prevalence of white matter injury in excess of 50 percent. The precise onset of these postoperative lesions remains unclear, and these MRI features appear to be transient in many cases. Reported risk factors for development of these MRI lesions include prolonged exposure to cardiopulmonary bypass (with or without deep hypothermic cardiac arrest), inflammatory mechanisms which are activated by cardiopulmonary bypass, and early postoperative hypotension (especially diastolic) and hypoxemia. In a recent study, the development of new white matter injury on postoperative MRI was not confined to those patients undergoing cardiopulmonary bypass; however, among those who did undergo bypass, increased duration led to more severe white mater injury. White matter injury has also been associated with a lower brain maturation score, the presence of preoperative white matter injury, the use of deep hypothermic circulatory arrest, and specific cardiac diagnoses including single ventricle physiology and aortic arch obstruction.

Although significant decreases in brain N -acetylaspartate (a neuronal-axonal marker) were described on magnetic resonance spectroscopy, more recent data have demonstrated improved postoperative cerebral oxidative metabolism as evidenced by lactate-to-choline ratios. The long-term significance of these acute structural and metabolic disturbances in these children remains uncertain.

Stroke

The incidence of stroke in children ranges from 2.5 to 8 per 100,000. ¹²⁸ Congenital heart disease is a leading cause of childhood stroke, being present in 25 to 30 percent of cases. In autopsy studies, almost 20 percent of children with congenital heart disease have evidence of infarct.

Stroke associated with heart disease may be related to a number of mechanisms including: (1) cardioembolic (i.e., a probable intracardiac embolic source); (2) paradoxical (i.e., a cardiac anatomy that permits an embolus of systemic venous origin access to the cerebral circulation); or (3) venous (e.g., cerebral vein thrombosis due to central venous hypertension and venous stasis).

Risk factors for cardiogenic stroke include the elements of Virchow triad—altered vascular surface, stasis, and hypercoagulability—-as well as the presence of paradoxical embolic pathways. In earlier studies, the risk of stroke was related mainly to the effects of long-standing heart defects such as chronic hypoxia and polycythemia as well as uncorrected paradoxical pathways leading to right-to-left shunting. The trend toward earlier corrective surgery has shifted the focus to intraoperative and postoperative mechanisms for stroke.

Cardiopulmonary bypass may predispose to cerebral vascular occlusion since embolic material (particulate or gaseous) generated during bypass avoids filtration by the pulmonary bed and gains direct entry to the systemic arterial circulation. The extensive interface between circulating blood and the artificial surface of the bypass circuit may trigger an inflammatory response, which then activates complex physiologic cascades, including endothelium–leukocyte interactions. This process further enhances the risk of ischemic injury during the intraoperative and postoperative periods. Advances in bypass technique, including refinements in membrane oxygenators, in-line arterial filters, and anticoagulation, have reduced the incidence of macroembolization and large-vessel occlusion compared with earlier autopsy studies. The impact of these advances on the incidence of microembolization and small-vessel disease is unclear.

In the postoperative period, factors predisposing to stroke include stasis (intracardiac and extracardiac), altered vascular surfaces (native or prosthetic), and, in some situations, a procoagulant shift in humoral clotting systems. Intracardiac stasis may result from localized areas of low flow or global ventricular dysfunction. Transient or sustained elevations of right heart and central venous pressure predispose to local thrombosis in the right atrium and central veins. Prosthetic material in such areas of disturbed flow increases the likelihood of thrombus formation, and the presence of a right-to-left shunt (native or iatrogenic) can lead to paradoxical embolization. Elevated right atrial pressure transmitted to the cerebral venous circulation also predisposes to venous thrombosis, particularly in the dural venous sinuses. Elevated systemic venous pressure may lead to a protein-losing enteropathy, liver impairment, and pleural effusions, which all are factors that may disturb the humoral coagulant systems. A number of the aforementioned stroke risk factors may be present after the Fontan operation. In one study, a 2.6 percent incidence of stroke was found in a retrospective review of 645 patients after the Fontan operation; this risk extended over 3 years after the procedure. In another study, a 20 percent incidence of thromboembolic complications was found after the Fontan procedure.

Strokes originating during or immediately following cardiac surgery may escape clinical recognition for several days because of the effects of postoperative sedating and paralyzing agents. In young infants, stroke often presents with focal seizures or changes in mental status, with focal motor deficits being subtle. In older infancy and childhood, stroke usually presents with acute focal motor deficits, language disturbance, or visual dysfunction.

The therapeutic approach to stroke in the child with heart disease includes both “rescue” and preventive strategies. Experience with rescue therapies remains mainly confined to adult and experimental stroke where therapies aim to salvage potentially viable brain by revascularization with thrombolytic therapy or to curtail injurious biochemical cascades. Consistent and universally accepted guidelines for both primary and secondary stroke prophylaxis in children are lacking. Current guidelines are largely empiric, anecdotal, and derived from experience in adults. Established indications for primary stroke prophylaxis in children include prosthetic heart valves, dilated cardiomyopathy, or intracardiac thrombus.

The decision regarding whether and when to initiate secondary stroke prophylaxis with antithrombotic agents should aim to balance the risk of recurrent cerebral embolization and secondary hemorrhage into an area of cerebral infarction. Embolus recurrence risks after cardioembolic stroke are unknown in children. In adults following myocardial infarction, this risk is highest in the early poststroke period.

Cardioembolic strokes are particularly prone to hemorrhagic transformation in the early poststroke period; hemorrhagic transformation occurs (often asymptomatically) in 20 to 40 percent of adult cardioembolic strokes. The risk of significant clinical deterioration following hemorrhagic transformation is greatest in patients taking full-dose anticoagulation. Although it is difficult to predict which infarcts will undergo hemorrhagic transformation, most will do so early, within 48 hours after stroke onset. Large infarcts, particularly those involving greater than 30 percent of a cerebral hemisphere, are at higher risk of hemorrhagic transformation. Uncontrolled systemic hypertension and stroke caused by septic emboli and cerebral venous sinus thrombosis are additional risk factors for hemorrhagic infarction.

The many neurologic manifestations of infective endocarditis include meningitis, brain abscess, and seizures (see Chapter 6 ). However, septic embolism and hemorrhage are the most common complications. Even with appropriate antibiotics, neurologic complications occur in one-third of children with infective endocarditis; in one-half of these cases, the complications are embolic in origin. Cerebrovascular complications carry the highest mortality rate (up to 80 to 90%) of all complications of infective endocarditis, primarily due to intracranial hemorrhage. The high risk of cerebral hemorrhage in this population contraindicates anticoagulant therapy. In cases of cardiogenic stroke, the possibility of septic embolism should be considered prior to initiating anticoagulant therapy.

Movement Disorders

Reports of serious postoperative movement disorders were published in the early 1960s and with the emergence of deep hypothermic cardiac surgery. Choreoathetosis was the most frequent complication of cardiac surgery, reaching 19 percent in early reports, although the incidence seems to be decreasing substantially. Other rarer postoperative movement disorders include oculogyric crises and parkinsonism. These movement disorders are often dramatic in clinical presentation, frequently intractable, and, in severe cases, are associated with substantial mortality.

Postoperative movement disorders have a typical clinical course. Involuntary movements occur on day 2 to 7; during the preceding days of the postoperative period, neurologic recovery appears to be uncomplicated. A subacute delirium featuring marked irritability, insomnia, confusion, and disorientation usually precedes the emergence of involuntary movements, which typically start in the distal extremities and orofacial muscles, progressing proximally to involve the girdle muscles and trunk. In severe cases, violent ballismus may develop. The abnormal movements are present during wakefulness, peak with distress, and resolve during sleep. Oculomotor and oromotor apraxia are common, with loss of voluntary gaze, expressive language, and ability to feed. The movements often intensify over a 1-week period, followed by a 1- to 2-week period during which the abnormal movements are relatively constant. Recovery is highly variable in duration, and the long-term outcome of these postoperative movement disorders depends largely on their initial severity. Mild cases tend to resolve within weeks to months, whereas severe cases have a mortality rate approaching 40 percent and are associated with a high incidence of persistent dyskinesia (47%) and long-term neurodevelopmental deficits including diffuse hypotonia and pervasive deficits in memory, attention, and language.

The diagnosis of postoperative hyperkinetic syndromes is clinical; neuroimaging studies are useful only for excluding other disorders. Changes seen on computed tomography (CT), MRI, and single-photon emission CT are nonspecific, seldom focal, and most commonly consist of diffuse cerebral atrophy in patients with movement disorders. The electroencephalogram is usually normal or diffusely slow, with no ictal changes associated with the involuntary movements. Descriptions of neuropathologic findings at autopsy are limited and inconsistent, ranging from normal to showing extensive neuronal loss and gliosis, particularly in the globus pallidus externa. Typical features of infarction are characteristically absent.

Risk factors for the development of these involuntary movements include cyanotic congenital heart disease, particularly with systemic-to-pulmonary collaterals from the head and neck; age at surgery older than 9 months; excessively short cooling periods prior to attenuation of intraoperative blood flow; an alpha-stat pH management strategy; deep hypothermia and extracorporeal circulation; and preexisting developmental delay. Postoperative dyskinesias have been reported after prolonged use of fentanyl and midazolam, although these are usually mild and transient.

Once manifest, these involuntary movements are very refractory to treatment and generally respond poorly to a wide variety of antidyskinetic medications including dopamine receptor blockers (e.g., phenothiazines, butyrophenones), dopamine-depleting agents (e.g., reserpine, tetrabenazine), dopamine agonists (e.g., levodopa, pramipexole), GABAergic agents (benzodiazepines, barbiturates, baclofen), and a variety of other drugs such as valproic acid, carbamazepine, phenytoin, diphenhydramine, and chloral hydrate. In general, successful movement control is achieved only at the expense of excessive sedation.

The management of postoperative movement disorders should therefore focus on the often severe agitation and insomnia that accompanies them. Decreasing the level of external (e.g., noise, light) and internal (e.g., pain) stimuli is useful in limiting the intensity of the involuntary movements. Judicious use of sedation should aim to restore a fragmented sleep-wakefulness cycle which contributes to delirium. Oromotor dyskinesia is often severe enough to impair feeding and predispose to aspiration; nasogastric or even gastrostomy tube feedings may be necessary to meet the high caloric demands of the constant involuntary movements.

Spinal Cord Injury

Spinal cord injury is a relatively rare complication following pediatric cardiac surgery and usually occurs after aortic coarctation repair (0.4 to 1.5%). Intraoperative spinal cord injury is often mediated by hypoxic-ischemic/reperfusion injury to watershed territories, most commonly in the lower thoracic cord, where transverse infarction results in postoperative paraplegia. An additional watershed zone runs between the territories of the anterior and posterior spinal circulations; ischemia in this region results in predominant anterior spinal cord involvement.

Brachial Plexus and Peripheral Nerve Injury

Prolonged immobility during and following cardiac catheterization and surgery predisposes peripheral nerves to pressure and traction injury. Pressure palsies may occur at any dependent site, but most commonly involve the fibular (peroneal) and ulnar nerves.

Brachial plexus injury is not uncommon following cardiac catheterization. Injury to the lower plexus results from prolonged traction during the extreme and sustained arm abduction required for some procedures. Symptoms usually resolve gradually and completely. The insertion of indwelling central venous catheters during cardiac catheterization through the internal jugular vein may injure the upper brachial plexus through direct physical trauma or extravasation of blood into the plexus.

Phrenic nerve injury can result from hypothermic injury due to ice packed around the heart or, alternatively, from direct intraoperative transection. Postoperative phrenic nerve injury has also been described after malposition of chest tubes. Phrenic nerve injury presents with diaphragmatic palsy and prolonged postoperative ventilator dependence. Nerve conduction studies and electromyography can confirm the diagnosis. Most phrenic nerve injuries resolve spontaneously, but occasionally diaphragmatic plication (more likely in infants than children) or, in rare instances, diaphragmatic pacing is required.

Adequate postoperative ventilation is commonly facilitated by the use of neuromuscular blocking agents. Prolonged use of nondepolarizing agents, especially vecuronium and pancuronium, has been associated with prolonged neuromuscular dysfunction, and concomitant use of corticosteroids may increase the risk. The neuropathologic spectrum of these conditions is highly variable, ranging from necrotizing myopathy to an axonal motor neuropathy with variable sensory involvement (see Chapter 56 , Chapter 59 ).