Higher neonatal cerebral blood flow correlates with worse childhood neurologic outcome.

Cerebral blood flow (CBF) in newborn infants is often below levels necessary to sustain brain viability in adults. Controversy exists regarding the effects of such low CBF on subsequent neurologic function. We determined the current childhood neurologic status and IQ in 26 subjects who had measurements of CBF performed with PET in the neonatal period between 1983 and 1989 as part of a study of hypoxic-ischemic encephalopathy. Follow-up information at ages 4 to 12 years was obtained on all 26 subjects. Ten subjects had died. All 16 survivors underwent clinical neurologic evaluation, and 14 also underwent intelligence testing. Eight had abnormal clinical neurologic evaluations; eight were normal. The mean neonatal CBF in those with abnormal childhood neurologic outcome was significantly higher than in those with normal childhood neurologic outcome (35.64 +/- 11.80 versus 18.26 +/- 8.62 mL 100 g(-1) min(-1), t = 3.36, p = 0.005). A significant negative correlation between neonatal CBF and childhood IQ was demonstrated (Spearman rank correlation r = -0.675, p = 0.008). Higher CBF was associated with lower IQ. The higher CBF in subjects with worse neurologic and intellectual outcome may reflect greater loss of cerebrovascular autoregulation or other vascular regulatory mechanisms due to more severe brain damage.

Cerebral oxygen metabolism in newborns.

OBJECTIVE: A better understanding of the developmental changes in brain energy metabolism that occur in human neonates is critically important for designing rational treatment strategies that ensure an adequate supply of nutrients to the brain and minimize deleterious side effects of therapeutic interventions in sick newborns. METHODS: Cerebral metabolic rate for oxygen (CMRO2) was measured with positron emission tomography in 11 sick newborns of different gestational ages. RESULTS: In five preterm infants, mean hemispheric CMRO2 was 0.06 to 0.54 mL 100 g-1 min-1. Two of these preterm infants with virtually absent CMRO2 (0.06 mL 100 g-1 min-1) had minimal or no evidence of parenchymal brain injury detected in the newborn period. In six term infants, mean hemispheric CMRO2 was 0.0 to 1.3 mL 100 g-1 min-1. Two with no neurological disease had mean hemispheric CMRO2 of 0.4 and 0.7 mL 100 g-1 min-1 and were normal at 6 and 7 months, respectively. CONCLUSIONS: CMRO2 in four newborns who had minimal or no detectable brain injury was considerably below the threshold for brain viability in adults of 1.3 mL 100 g-1 min-1. This indicates that energy requirements in fetal and newborn brain are minimal or can be met by nonoxidative metabolism.

Symmetric cerebral blood flow in newborns who have undergone successful extracorporeal membrane oxygenation.

Cerebral blood flow (CBF) was measured with positron emission tomography in 23 newborns following extracorporeal membrane oxygenation. In 9 newborns the common carotid artery was reanastomosed after extracorporeal membrane oxygenation and in 14 newborns the common carotid artery remained ligated. The ratio of right/left hemispheric CBF was not significantly different in the newborns with reanastomosed or occluded common carotid arteries (right/left CBF ratio was 0.98 in both groups). The maximum asymmetry was 8% and was observed in 2 newborns. All 9 newborns with reanastomosis of the carotid artery are normal at follow-up at 1 year or longer. Three newborns with ligation of the common carotid artery were lost to follow-up and 1 newborn died. Eight of 10 remaining newborns are normal at follow-up; the 2 other infants have developmental quotients of 60 and 64, respectively, and no other deficits. The data indicate (1) that hemispheric CBF is symmetric in newborns who have undergone extracorporeal membrane oxygenation and have no evidence of brain injury, and (2) that reanastomosis of the common carotid artery does not alter hemispheric CBF in the newborn period.

Positron emission tomography in newborn infants.

Positron emission tomography (PET) is a technique that permits the noninvasive in vivo measurement of a variety of cerebral physiologic and biochemical processes. Numerous complex methodologic and technical features must be considered when PET is applied to the study of the newborn's cerebral physiology and neurologic disease. Although the application of PET to newborn infants is still in its formative stages, important information regarding perturbations of cerebral blood flow in neurologic diseases has been obtained and striking developmental changes in cerebral metabolism are apparent.

Brief inhalation method to measure cerebral oxygen extraction fraction with PET: accuracy determination under pathologic conditions.

The initial validation of the brief inhalation method to measure cerebral oxygen extraction fraction (OEF) with positron emission tomography (PET) was performed in non-human primates with predominantly normal cerebral oxygen metabolism (CMRO2). Sensitivity analysis by computer simulation, however, indicated that this method may be subject to increasing error as CMRO2 decreases. Accuracy of the method under pathologic conditions of reduced CMRO2 has not been determined. Since reduced CMRO2 values are observed frequently in newborn infants and in regions of ischemia and infarction in adults, we determined the accuracy of the brief inhalation method in non-human primates by comparing OEF measured with PET to OEF measured by arteriovenous oxygen difference (A-VO2) under pathologic conditions of reduced CMRO2 (0.27-2.68 ml 100g-1 min-1). A regression equation of OEF (PET) = 1.07 x OEF (A-VO2) + 0.017 (r = 0.99, n = 12) was obtained. The absolute error in oxygen extraction measured with PET was small (mean 0.03 +/- 0.04, range -0.03 to 0.12) and was independent of cerebral blood flow, cerebral blood volume, CMRO2, or OEF. The percent error was higher (19 +/- 37), particularly when OEF is below 0.15. These data indicate that the brief inhalation method can be used for measurement of cerebral oxygen extraction and cerebral oxygen metabolism under pathologic conditions of reduced cerebral oxygen metabolism, with these limitations borne in mind.

Cerebral blood flow requirement for brain viability in newborn infants is lower than in adults.

Measurements of regional cerebral blood flow (CBF) with positron emission tomography in adult humans with cerebrovascular disease have demonstrated consistently that values below 10 ml/(100 gm.min) occur only in infarcted brain. Although experimental data suggest that the newborn brain may be more resistant to ischemic injury than the adult brain, the minimum CBF necessary to sustain neuronal viability in newborn infants is unknown. We have measured CBF with positron emission tomography in 16 preterm and 14 term newborn infants and have determined the relationship between CBF and subsequent brain function as assessed by neurological examination and developmental assessment. The range of mean CBF in the preterm infants was 4.9 to 23 ml/(100 gm.min) and the range of mean CBF in the term infants was 9.0 to 73 ml/(100 gm.min). Five preterm infants and one term infant with mean CBF less than 10 ml/(100 gm.min) survived. Three of these 5 preterm infants, with mean CBF of 4.9, 5.2, and 9.3 ml/(100 gm.min), respectively, have normal neurological examinations and Bayley Scales of 80 or greater at 6, 6, and 24 months of age, respectively. One (mean CBF 6.9) has normal cognitive development (Bayley 103) and a mild spastic diplegia at age 19 months, and one infant (mean CBF 6.2) has a left hemiparesis and a Binet IQ score of 70 at age 33 months. The term infant, with a mean CBF of 9.0 ml/(100 gm.min), was developing normally when he died of sepsis at age 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Salvage of the severely injured ear.

We present three cases of severe external ear injuries and their management. The first patient's ear, amputated in an automobile accident, was revascularized microsurgically. Replantation, when possible, offers the ultimate result. However, disadvantages include the length of the operation and prolonged hospitalization. The second patient sustained a human bite ear amputation. Salvage consisted of immediate coverage with a vascularized temporoparietal fascial flap and split-thickness skin graft. Revision of the external auditory meatus and postauricular sulcus was required. This technique is relatively simple and reliable when microvascular revascularization is not possible. In the third case the patient's ear suffered a full-thickness burn as part of a larger scalding injury to the patient's body, face and scalp. Acute salvage was accomplished in one stage with a technique similar to that used for the second patient. Secondarily, skin was regrafted to achieve an improved color match and cartilage contour.

An unusually aggressive Mycobacterium marinum hand infection.

An unusually aggressive Mycobacterium marinum infection of the hand that progressed despite surgical and medical treatment is presented. The infection progressed over a 3-week period after the patient had surgical treatment and received isoniazid (INH), rifampin, and ethambutol hydrochloride. The patient had a collar-button abscess, destruction of the metacarpophalangeal (MCP) joint capsule, flexor and extensor tenosynovitis, and metacarpal and proximal phalanx bone destruction at the MCP joint and metacarpal shaft. Although atypical mycobacterial infections of the hand are usually indolent but persistent, this Mycobacterium marinum hand infection progressed rapidly, even with surgical and medical treatment. A judgment was made to perform an index ray amputation. With a more complete excision of the infected tissue, there was a higher probability of controlling this severe infection. The patient was treated with antituberculosis medications for 6 months and is doing well 1 year after the operation.

Asymmetric septal hypertrophy and hypothyroidism in children.

Any echocardiographic study of two children with hypothyroidism demonstrated the presence of asymmetric septal hypertrophy. One child died aged 11 months, and pronounced thickening of the interventricular septum was confirmed at necropsy. There was also hypertrophy of the left ventricular free wall. Histological examination showed only slight muscle fibre disarray, but there was striking vacuolation and hypertrophy of muscle fibres. In the second case, a child aged five years, the asymmetric septal hypertrophy disappeared after 18 months' treatment with L-thyroxine. Furthermore, other indices of myocardial function also returned to normal. The mechanism producing asymmetric septal hypertrophy in hypothyroidism is unknown. These are the youngest cases in which this association has been reported.

Effects of dexamethasone in hypoxic-ischemic brain injury in the neonatal rat.

To clarify the effects of corticosteroids in neonatal hypoxic-ischemic brain injury, 7-day-old rats were subjected to unilateral common carotid artery ligation and hypoxia (Levine procedure) after being injected subcutaneously with saline, low-dose dexamethasone (4 mg/kg) or high-dose dexamethasone (40 mg/kg). Neither low-dose nor high-dose dexamethasone ameliorated the brain edema, lactacidemia, or hypoglycemia associated with hypoxia-ischemia. In addition, dexamethasone did not alter the pattern of neuropathologic damage or reduce the fall in brain high-energy phosphates. Finally, high-dose dexamethasone-treated animals experienced significantly more mortality than did either saline- or low-dose dexamethasone-treated animals. In this model of neonatal hypoxia-ischemia, dexamethasone did not confer any significant cerebral protection.