James F. Schwartz

Cytochrome c oxidase-associated Leigh syndrome: Phenotypic features and pathogenetic speculations ☆

Fourteen new cases of cytochrome oxidase (COX)-associated Leigh syndrome (LS) are combined with 20 reported cases to describe the clinical, laboratory, and radiological features of this devastating metabolic condition. Three clinical stages are identified. Most patients have normal neurological development during the first 8-12 months (stage I). Somatic complaints are common, including chronic diarrhea, recurrent vomiting, anorexia, and decelerating body and head growth. The second stage evolves during late infancy and early childhood when motor regression becomes evident. Eye signs, altered breathing patterns, pyramidal, extrapyramidal, and cerebellar signs emerge and sudden clinical deterioration occurs during intercurrent infectious or metabolic stress. The last stage may extend from 2 to 10 years and is manifested by extreme hypotonia, swallowing difficulties and undernutrition. Feeding assistance is necessary and seizures may occur. The CSF lactate concentration is consistently elevated and MRI abnormalities are seen in the subcortical structures. COX deficiency affects most tissues, but is not always generalized. For example, 3 patients with a cardiomyopathy had normal COX activity in cultured skin fibroblasts. Nearly normal amounts of cross-reacting material are present by ELISA and immunoblot analyses. Parental consanguinity has been found in several families, the hereditary pattern is recessive and males are affected more commonly (2:1). The biomolecular abnormality causing COX deficiency in LS is unknown, but the available evidence implicates a nuclear-encoded protein that affects the structure or the stability of the holoenzyme complex.

Spinal cord infarction due to minor trauma in children

In two children, ages 22 months and 4 years, after slight trauma, flaccid weakness of both arms developed, followed by flaccid quadriplegia with sphincter involvement. No vertebral fracture or dislocation was found, myelograms were negative, and diagnosis was made only after the full clinical syndrome developed. Pathologic studies revealed ischemic infarction involving the cervical cord and low medulla in one patient, and central gray matter of low cervical cord in the other, without hematomyelia or external compressive lesions. The pattern of infarction may be related to spasm of distal branches of the central sulcal arteries in a terminal arterial bed.

Islet cell adenomatosis and adenoma in an infant

A newborn infant developed severe symptomatic hypoglycemia which persisted despite combined treatment with parenteral 15 and 20 per cent glucose solutions, prednisone, adrenocorticotropic hormone, a leucine-free formula, and diazoxide. Adenomatosis of the islet cells and isolated adenomas of the pancreas were found when subtotal pancreatectomy was performed at 38 days of age. The child was subsequently mentally retarded.

Brain death in children: Characteristics common carotid arterial velocity patterns measured with pulsed Doppler ultrasound+

The clinical criteria for brain death in children remain controversial. An accepted confirmatory test for brain death is the documented absence of intracranial blood flow, the most common methods being arteriography and radionuclide cerebral angiography. We correlated the common carotid arterial blood velocity patterns measured by pulsed Doppler ultrasound in 32 brain-dead infants and children with results of their clinical examinations and, whenever possible, with radionuclide cerebral angiography. A distinct, characteristic carotid arterial blood velocity waveform indicating absent cerebral blood flow appeared in 19 of the 23 brain-dead patients 4 months of age or older. The velocity patterns of the other four older children were similar, but not identical, to the characteristic waveform. The remaining nine brain-dead patients were infants 4 months of age or younger. These infants had velocity waveforms different from those of healthy infants, but also were totally different from the characteristic brain death pattern of older children. No patient had the characteristic brain death waveform without being clinically brain dead. Measurement of carotid arterial blood velocity with pulsed Doppler ultrasound is a repeatable, noninvasive, portable test useful for confirmation of brain death in children.

Water intoxication from swimming

SWIMMING INSTRUCTION has become increasingly popular for infants for a variety of reasons, including a possible beneficial effect of reducing the risk of drowning. The Amer ican Academy of Pediatr ics Commit tee on Physical Fitness, Recreat ion, and Sports, recognizing the popular i ty of such programs, issued a s ta tement on swimming instruct ions for infants; one of the recommendat ions was tha t controlled studies clarifying the possible risks to infants f rom swimming programs should be carr ied out. l We would like to draw at tent ion to one potential ly serious complicat ion of infant swimming tha t has received litt le at tent ion, i.e., water intoxication.

Adverse events following immunization: Assessing probability of causation

The Monitoring System for Adverse Events Following Immunization of the Centers for Disease Control collects data on events temporally related to immunization. Occasionally, reports are received of neurologic disturbances temporally related to receipt of vaccine. Most of these disturbances are events that regularly occur in the absence of immunization. It is then difficult to determine whether the relationship between the immunization and illness is causal or coincidental. We developed a method to assess causation of serious neurologic events by probability theory. By combining epidemiologic information on disease incidence with specific elements of the patient history, an estimate of the odds of vaccine causation can be derived, based on rational assumptions rather than observer bias. The result is not a diagnosis but an estimate of probability.

1607 PROSPECTIVE LONG-TERM FOLLOW-UP OF PREMATURES WITH SUBEPENDYMAL/INTRAVENTRICULAR HEMORRHAGE (SEH/IVH)

Since 1977, an ongoing study has assessed neurodevelopmental outcome of CT-documented SEH/IVH in infants <35 weeks gestation requiring intensive care. Scans were graded: normal, SEH, mild, moderate, or marked IVH. Follow-up status, at mean corrected age of 34 months, was assessed by neurologic exams, Bayley and Stanford-Binet tests. Outcome was designated: Good-no neurologic deficit and Developmental Index (D.I.) > 90. Intermediate-no or minor neurologic deficit and D.I. = 70-90: Poor-significant neurologic deficit or D.I.<70. The following groups were compared: a) 33/41 surviving SEH/IVH infants with 30/49 non-IVH; b)22 SEH/IVH infants paired with controls, matched for Apgar, gestation and birth weight c) intragroup, according to degree of hemorrhage. Of the 33 SEH/IVH infants, 21 had good outcomes, 8 intermediate, 4 poor. Of controls, outcome was good in 19, intermediate in 8, poor in 3. Among match-control pairs, there was a balanced distribution in outcome. Intragroup comparison showed: 13 had marked IVH with 8 good outcomes, 3 intermediate, 2 poor; 10 had moderate IVH with 5 good, 3 intermediate, 2 poor, 10 had mild IVH or SEH with 8 good, 2 intermediate, 0 poor. By all methods of comparison, outcome in SEH/IVH infants was not significantly different from controls. Marked IVH did not preclude good outcome (60% good). Other neonatal disease may affect outcome more than hemorrhage.

M aple syrup urine disease. A review with a report of an additional case.

A case of maple syrup urine disease is presented, with a discussion of the characteristic clinical syndrome of neonatal feeding difficulty, lethargy, respiratory irregularity, seizures and opisthotonos The biochemical abnormality in the oxidative decarboxylation of the keto‐acids of valine, leucine and isoleucine is described, and an approach to dietary therapy, by carefully controlling the amino‐acid composition of the diet, is outlined. The pathological findings are widespread, but with especially marked alterations in myelin formation in the cerebral hemispheres. This unusual disorder, which is one of the classic inborn errors of metabolism, is no longer merely of academic importance. With the development of diet therapy and means of controlling the metabolic derangement, thereby preventing mental retardation and widespread neurological deficits, the diagnosis of MSUD and early initiation of therapy becomes an urgent and intensely practical matter, especially in the immediate neonatal period.

1137 INTRACEREBRAL HEMORRHAGE IN HIGH RISK PREMATURES

Subependymal (SEH) and intraventricular hemorrhage (IVH) in infants less than 35 weeks gestation, requiring intensive care for 24 hours or longer, were studied prospectively. Initial computerized tomographicscan (CT scan) was obtained, and, if positive for blood, head circumference, clinical course, and serial scans were followed until ventricular size was normal.29/58 infants were shown to have SEH and/or IVH, 26 by CT scan, I by ventricular tap, 2 on autopsy. 8 infants died. 6 of these had marked IVH, 3 shown by CT scan, I by ventricular tap, 2 by autopsy. Acute hydrocephalus of only mild to moderate degree occurred in the 3 fatalities with positive scans. The 23 survivors with positive scans had follow-up scans. 18/23 did not show progressive hydrocephalus, and of these 4 had only SEH. Of the others, 10 had mild, 3 moderate, and I marked IVH. 5 survivors with IVH developed severe progressive hydrocephalus. 2/5 had only mild IVH, which resolved spontaneously. 3/5 required treatment. IVH was moderate in 1, marked in 2. Serial head circumference was not predictive of need for treatment.The incidence of SEH and IVH was 50% in study infants and was not related to gestational age. The quantity of blood may be prognostically significant. No infant with SEH or mild IVH required treatment. Progressive hydrocephalus developed in 2 and resolved spontaneously. 7/10 infants with moderate to marked IVH survived. 3 required treatment.

Recent advances in treating epileptic children.

Epilepsy remains a tough therapeutic problem. Although no dramatic breakthrough has occurred, therapy has improved significantly, partly because physicians more sharply delineate seizure types. New drugs have helped, too. Ethosuximide has replaced trimethadione in treating petit mal epilepsy, and quinacrine, sulthiame, carbamazepine and diazepam show promise for treating various types of seizures.