Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects.

OBJECTIVES: To determine the prevalence of persistent developmental impairments in children with congenital heart defects and to identify factors that enhance risk for an adverse outcome. STUDY DESIGN: Eligible infants (n = 131) <2 years of age requiring open heart surgery were recruited prospectively. Subjects were assessed during surgery and again 12 to 18 months later with standardized developmental assessments and formal neurologic examinations. RESULTS: Mean age at follow-up testing was 19.1 +/- 6.6 months. Assessments indicated that 41% had abnormal neurologic examinations. Gross and/or fine motor delays were documented in 42%, and 23% demonstrated global developmental delay. Univariate and multiple regression models identified the following factors increasing the risk for persistent developmental deficits: preoperative and acute postoperative neurodevelopmental status and microcephaly, type of heart lesion, length of deep hypothermic circulatory arrest, age at surgery, and days in the intensive care unit (P <.05). CONCLUSIONS: Children with congenital heart defects commonly have ongoing neurologic, motor, and developmental deficits well after surgical correction. The cause is multifactorial and includes brain injury before, during, and after heart surgery.

Functional limitations in young children with congenital heart defects after cardiac surgery.

UNLABELLED: With the recent dramatic decline in mortality rates of infants undergoing open-heart surgery (OHS), there is growing concern regarding neurodevelopmental sequelae. Outcome studies have primarily focused on delineating developmental impairments; however, the impact on function and family burden has not been investigated. The objective of this study was to determine the prevalence of functional limitations and burden of care of young children with congenital heart defects (CHD) after OHS. STUDY DESIGN: One hundred thirty-one eligible infants with CHD undergoing their first OHS were recruited prospectively. Patients were assessed pre- and postoperatively, and again 12 to 18 months after surgery. Functional assessments included the WeeFIM (Functional Independence Measure) and the Vineland Adaptive Behavior Scale. RESULTS: For the WeeFIM, mean quotients were 84.3 +/- 23.8 (self-care), 77.2 +/- 30.0 (mobility), and 92.4 +/- 27.8 (cognition), with an overall quotient of 83.8 +/- 23.4. Only 21% of the cohort was functioning within their expected age range. Moderate disability was noted in 37%, while only 6% demonstrated a severe disability. For the Vineland scale, mean score for daily living skills was 84.4 +/- 17.6, and 80.3 +/- 15.9 for socialization. Functional difficulties in daily living skills were documented in 40%, whereas >1/2 had poor socialization skills. Factors enhancing risk for functional disabilities included perioperative neurodevelopmental status, microcephaly, length of deep hypothermic circulatory arrest, length of stay in the intensive care unit, age at surgery, and maternal education. CONCLUSIONS: The high prevalence of functional limitations and dependence in activities of daily living is currently underappreciated in the clinical setting, and deserves additional attention by pediatricians and developmental specialists.

Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives.

We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling.

Ependymal abnormalities in lissencephaly/pachygyria.

The ependyma was examined in eight children with neuroblast migratory disorders of diverse origin: three cases of lissencephaly type 1 with severe to mild degrees of agyria/pachygyria, four cases of lissencephaly type 2 in Fukuyama muscular dystrophy and the Walker-Warburg syndrome, and one case of hemimegalencephalic pachygyria. Morphological and immunohistochemical abnormalities of the ependyma were strikingly similar in all. Discontinuities were disproportionate to the degree of ventriculomegaly. In some regions, the ependyma remained a pseudostratified columnar epithelium, though basal processes were absent. The poles of the horns of the lateral ventricles were replaced by extensive heterotopic ependymal rosettes. Rosettes and rows of ependyma also were in other subventricular sites. Subependymal nodules of large astrocytes and their processes bulged into the ventricular lumen after infancy. Ependymal cells did not express glial fibrillary acidic protein, but showed persistent expression of S-100 protein, cytokeratin CK-904 and sometimes vimentin long after these proteins normally disappear. An abnormal ependyma in lissencephaly/pachygyria may contribute to disturbances in neuronogenesis, guidance of axonal projections and neuroblast migrations; it may be a primary factor in pathogenesis.

Ependymal abnormalities in cerebro-hepato-renal disease of Zellweger.

The ependyma in six infants dying with cerebro-hepato-renal (CHR) disease showed similar but less extensive morphological and immunohistochemical abnormalities to those previously demonstrated in lissencephaly/pachygyria. More than two-thirds of the ependyma lining all ventricles was a pseudostratified columnar epithelium resembling midfetal life. Discontinuities did not correlate with minimal ventriculomegaly. Subventricular rosettes were common and not confined to regions of gaps in the overlying ependyma. Subependymal gliosis and glial nodules were absent. Immunoreactivity of ependymal cells for vimentin and GFAP was normal for age, but abnormally positive for S-100 protein and cytokeratin, as in lissencephaly; unlike lissencephaly, the rosettes in CHR disease also are reactive. Ependymal abnormalities may contribute to the pathogenesis of cerebral dysgenesis in CHR disease as in other genetic disorders of neuroblast migration.

Unusual form of seizures induced by eye closure.

Seizures induced by eye closure are a rare but well-recognized form of reflex epilepsy. Two types have been reported: those induced by movement of the eyelids and those caused by lack of visual input. The EEG pattern is typically that of spike and wave discharges, either isolated to the occipital regions or greatest there. We report the case of a 19-year-old woman with a previously undescribed form of seizures induced by eye closure in whom both the physical act of eye closure and total lack of visual input were required for induction of a seizure. Both the EEG pattern of paroxysmal high-amplitude generalized beta activity and poor response to medication were different from what has been previously noted in patients with seizures induced by eye closure. We believe that a third form of seizures induced by eye closure exists and that its prognosis may be significantly worse than that of previously reported forms.

Early introduction to medical problem-solving.

This is a descriptive report of a course unit designed to introduce concepts of medical problem-solving during the first month of an undergraduate MD curriculum. The unit is also used to provide an introduction to the dynamics of cooperative small group learning. The value of the unit was endorsed by the subjective opinions of faculty tutors and students, who recognized the relevance of the unit to the clinical practice of doctors. An end-of-course examination demonstrated that some novice medical problem-solvers have difficulty with recursive hypothesis testing and tend to use linear strategies. This type of learning experience has the potential to identify students who may have subsequent difficulty in clinical reasoning tasks in the curriculum. Medical problem-solving itself is the primary focus of problem-based learning in the unit. Experience with this unit suggests that concepts of medical problem-solving can be introduced into the curriculum at a very early stage, without a prerequisite for substantial knowledge of medical sciences.

Harrington rod instrumentation: a cause of Brown-Sequard syndrome.

We describe a child with Brown-Sequard syndrome beginning at C8-T1, immediately following Harrington rod instrumentation for idiopathic scoliosis. We believe this is most likely related to either a common variation of the branches of the anterior spinal artery to one side or due to rupture of the ipsilateral spinal vein. This possible complication should be considered in patients undergoing Harrington rod instrumentation.

Visual symbol and manual sign learning by children with phonologic programming deficit syndrome.

A study was done of eight children with phonologic programming deficit syndrome (PPDS) and of eight normally developing children, to evaluate learning and recall of Blissymbols and of Signed English manual signs. The results support the view that children with this syndrome not only have motor speech deficits, but also deficits in symbolic processing. Decisions about intervention for nonverbal children should take account of their probable deficits in symbol learning.

The application of i.v. digital subtraction angiography to cranial disease in children.

All intracranial IV digital subtraction angiographic examinations performed over the past 2 years were reviewed retrospectively to ascertain the uses and limitations of this technique for the evaluation of pediatric intracranial disease. Of the various abnormalities studied, this imaging technique was particularly useful in diagnosing venous and dural sinus abnormalities; in screening for suspected large aneurysms, vascular malformations, and major arterial occlusive disease; and in preoperative vascular mapping. IV digital subtraction angiography has selected usefulness in confirming brain death, in evaluating cerebral ischemia, in identifying vascular abnormalities underlying intracranial hemorrhage, and in evaluating vascularity and sinus extension of masses. The IV route for digital subtraction angiography is not useful in diagnosing segmental arterial occlusive or small-vessel disease, nor is it useful in preoperative localization of specific arterial supply to arterial venous malformations, aneurysms, or neoplasms. IV digital subtraction angiography can be performed successfully in children of all ages with minimal patient morbidity. For most patients, the diagnostic information obtained was adequate without the need for standard cerebral arteriography.

Efficacy of phenobarbital in neonatal seizures.

A retrospective study of neonatal seizures in a tertiary care neonatal intensive care unit determined a 3.2% incidence, and confirmed the relatively poor efficacy of the traditional anticonvulsants phenobarbital and phenytoin. Only 33% responded to an initial adequate loading dose of phenobarbital, while 56% responded to either or both anticonvulsants. Although multifocal clonic seizures were most common (42%), tonic seizures were next in frequency (30%). Tonic seizures which did not respond to phenobarbital responded quite poorly to the addition of phenytoin compared to other seizures types. Tonic seizures may be the result of brainstem release phenomena and require a different strategy for management. Among nonresponders in this study, there was a 56% mortality rate but only 33% of responders died. There is a critical need for studies to find more efficacious agents than phenobarbital and phenytoin to treat seizures in the newborn.

Mitochondrial myopathy of cerebro-hepato-renal (Zellweger) syndrome.

The muscles of four infants with cerebro-hepato-renal (Zellweger) syndrome were studied during life and/or at necropsy. A mitochondrial myopathy was demonstrated, similar to mitochondrial alterations demonstrated in liver and brain in this disease. Muscle fibers with red-staining subsarcolemmal aggregates were identified with Gomori trichrome stain in two cases. Subsarcolemmal and intermyofibrillar zones of increased concentrations of NADH-TR, SDH, and cytochrome-c-oxidase activity were demonstrated histochemically in all four cases. Degenerative and cytoarchitectural changes in muscle fibers were not found. Ultrastructural studies showed large aggregates of mitochondria and increased lipid in the subsarcolemmal and intermyofibrillar spaces. Degenerative changes in mitochondria and lipid also were demonstrated, but paracrystalline inclusions were not seen. The distribution of these changes was not uniform between patients or between different muscles in the same patient. The diaphragm was affected more severely than proximal or distal muscles of the extremities. Direct involvement of muscle mitochondria in this disease may interfere with energy metabolism and contribute to the clinical findings of hypotonia, weakness, and respiratory insufficiency. The muscle biopsy with histochemistry and electron microscopy may be used as a diagnostic adjunct in suspected cases, but the variation encountered dictates dictates caution in the interpretation of negative findings.