Daniel J. Lacey

Prognostic factors in brainstem gliomas

Although brainstem gliomas carry the worst prognosis of any brain tumor in children, with median survivals of 9 to 12 months, there may be a subgroup of long-term survivors. We have identified 12 children with brainstem gliomas, 5 of whom have survived > 6 years and 6 ≤ 12 months. Another child, alive and well 3 years following diagnosis, was considered in the long-term survivor group. Favorable prognostic factors included neurofibromatosis, symptoms ≥ 12 months before diagnosis, calcification on CT, exophytic location, and pathology suggesting a low-grade tumor. Recognition that certain patients with brainstem gliomas may have prolonged survivals even in the absence of definitive treatment must be taken into consideration when new treatment regimens are being formulated.

Intraventricular Hemorrhage in Full-term Neonates

The neuropathological and general pathological features of intraventricular hemorrhage are described in 32 neonates who had been born at term. Although the most common site of bleeding was the choroid plexus, a significant minority occurred in the subependymal germinal matrix. Associated neuropathological findings included meningeal venous congestion, periventricular white‐matter necrosis and subarachnoid hemorrhage. Pulmonary hemorrhages, hyaline membranes and congenital heart‐defects were common. Most of the infants had low Apgar scores at birth and lived for less than two days. Significant neurological findings included hypotonia, hyporeflexia, decreased activity level and seizures.

Correlating auditory evoked and brainstem histologic abnormalities in infantile Gaucher's disease

In an infant with Gauchers disease, brainstem auditory evoked responses were abnormal on three separate occasions. Only waves I and II were typically present at standard intensity settings, although a third peak was elicited at 88 dB. Histologic studies demonstrated absence of neurons in the cochlear nuclei and a hypoplastic superior olivary complex. This neurophysiologic-pathologic correlation supports contentions that both brainstem auditory evoked response (BAER) waves I and II arise from the auditory nerve and that it may be capable of generating additional peaks.

Normalization of dendritic spine numbers in rat hippocampus after termination of phenylacetate injections (PKU model)

Increased numbers of apical dendritic spines are present on hippocampal CA1 pyramidal cells in rats injected with phenylacetate from 2 to 21 days of life if animals are sacrificed at 20-30 days. However, if sacrificed at 60-90 days, spine counts are not significantly different from saline injected controls. These results suggest that this increased spine density at 3-4 weeks represents retardation of normal maturational spine loss rather than an actual hyperplasia, and is reversible upon termination of the phenylacetate injections. Implications for human pathologic series of phenylketonuria are discussed.

Cortical dendritic spine loss in rat pups whose mothers were prenatally injected with phenylacetate (‘maternal PKU’ model) ☆

Pregnant rats injected with phenylacetate produced pups who had structurally abnormal cortical pyramidal cell dendrites. Neurons whose perikarya were in layer 5 had apical dendritic arbors with reduced numbers of dendritic spines which were longer and thinner than controls. Pyramidal cells of other cortical layers, as well as hippocampal pyramidal cells, were qualitatively and quantitatively normal. These results may be pertinent to children born to mothers with hyperphenylalaninemia (untreated PKU), many of whom have microcephaly, seizures and mental retardation. Application of findings in this rat model of maternal PKU to affected human children is uncertain until human histologic data become available.

Abnormal Cerebral Cortical Neurons in a Child With Maternal PKU Syndrome

A child born to a phenylketonuric (PKU) woman not on dietary treatment was microcephalic and had congenital heart and other physical anomalies consistent with the maternal PKU syndrome. After a repeat cardiac catherization at 3 months of age, he suffered an embolic left cerebral infarct and seizures. He was found by his mother dead in bed at 4 months of age; general autopsy revealed Klebsiella sepsis and pneumonia. Neuropathologic studies of the right cerebral hemisphere showed neuronal loss of the third cortical layer; Golgi studies revealed persistently immature cortical pyramidal cell somata and dendritic spines. This is the first report of specific neuronal abnormalities in a child with the maternal PKU syndrome and may, in part, account for the clinical features of microcephaly, mental retardation, and seizures seen in affected children. (J Child Neurol 1987;2:201-204).

Unusual biochemical and clinical features in a girl with ornithine transcarbamylase deficiency

A girl, ultimately diagnosed as having profound ornithine transcarbamylase (OTC) deficiency, presented as a neonate with feeding intolerance, irritability, and seizures without concurrent hyperammonemia. Developing normally until ten months of age, the girl subsequently experienced two episodes of hyperammonemia, which were associated with focal seizures and residual hemiparesis. She continued to have profound neurologic impairment and seizures and died at 26 months of age, despite appropriate dietary protein restriction, sodium benzoate, and arginine supplementation. Symptomatic OTC deficiency has not been previously reported unassociated with hyperammonemia. The recurrent cerebrovascular episodes are distinctly uncommon in patients with urea cycle enzymopathies.

Diagnosis of Tourette syndrome in childhood. The need for heightened awareness

Acquired movement disorders in children can present a diagnostic dilemma. Chorea, dystonia, and atypical seizures must be distinguished from simple or complex tics. The combination of chronic motor and vocal tics, Tourette syndrome, may in some children be associated with thought and behavioral disorders, sleep disturbances, headaches, and school difficulties (e.g., attention deficit disorder). The increasing numbers of children recognized as having Tourette syndrome, its broadening clinical spectrum and frequent familial nature are detailed in this review.

Inability to verify parasagittal cerebral injury as a neuropathologic entity in the asphyxiated term neonate

Localization of brain injury to parasagittal arterial border zones in the asphyxiated term neonate has been recently described as a frequent, clinically significant finding. However, pathologic examination of the brains of 79 term infants did not reveal a parasagittal distribution of damage. Coronal CT scans of 13 asphyxiated neonates with clinical findings of proximal hypotonia, and repeat scans 6-12 months later in seven patients, have not demonstrated watershed areas of decreased density. A larger series of prospectively identified, surviving neonates is needed to determine whether clinically relevant parasagittal injury may be present in this population.

Sleep EEG abnormalities in children with near-miss sudden infant death syndrome, in siblings, and in infants with recurrent apnea

Electroencephalograms during light sleep were performed in controls and in infants with near-miss sudden infant death syndrome, in siblings of such infants, and in infants with recurrent apnea, all from 2 to 8 months of age. EEG background and multiple sleep spindle characteristics were compared for individual children in each of these groups. From 2 to 6 months of age, but not later, all at-risk groups differed from controls by the presence of excessive variability of sleep spindle frequency during sleep recordings. However, the three groups at risk for SIDS did not significantly differ from each other. It is concluded that careful analysis of routine sleep EEGs may in some cases help differentiate young infants at risk for apnea or SIDS from normal children.