The effect of hydrocortisone on neurodevelopmental outcome in premature infants less than 29 weeks' gestation.

The use of postnatal dexamethasone in premature newborns can be associated with a deleterious neurodevelopmental outcome. The effect of hydrocortisone on developmental outcome in these patients is less clear. We therefore sought to examine the effect of hydrocortisone on early developmental outcome in premature newborns. We retrospectively examined the effect of hydrocortisone on developmental outcome during the first 2 years of life in premature infants <29 weeks' gestation at birth. Even though hydrocortisone was used in infants with a greater risk for poor outcome, its use, unless prolonged >7 days, was generally not associated with a worse developmental outcome or higher rate of referral for early intervention. A short course of hydrocortisone in sick premature newborns does not appear to have a deleterious effect on developmental outcome.

Effects of postnatal dexamethasone exposure on the developmental outcome of premature infants.

Extremely low birth weight premature infants are at risk for poor neurodevelopmental outcome. Postnatal dexamethasone has often been used in premature infants to prevent or treat bronchopulmonary dysplasia, and this drug is thought by some to affect neurodevelopmental outcome. We retrospectively examined the effect of this steroid on early neurodevelopment. Dexamethasone exposure was associated with an adverse outcome and was a stronger predictor of outcome than other accepted risk factors. If used, dexamethasone should be used in these high-risk infants for as short a period as possible.

Clinical correlates of white-matter abnormalities on head magnetic resonance imaging.

We undertook this study to investigate the relationship between white-matter abnormalities (seen on brain magnetic resonance imaging [MRI]) and muscle tone and muscle stretch reflexes on clinical examination. We identified all patients less than 5 years of age who had undergone cranial MRI studies at Riley Hospital for Children between June 30, 1999, and July 1, 2000, whose scans were read as showing white-matter abnormalities. We measured two ratios and the thickness of the corpus callosum as indicators of the quantity of cerebral white matter. The ratios were R1, the ratio of the thickness of the white matter at the level just above the body of the lateral ventricle compared with the width of the hemisphere, and R2, the ratio of the thickness of the white matter to the width of the hemisphere at the level of the trigone of the lateral ventricle. The thickness of the corpus callosum was measured at the junction of the anterior two thirds and the posterior third. We also evaluated the signal intensity of the cerebral white matter by reviewing the fluid-attenuated inversion-recovery images and grading the signal as normal to severely abnormal depending on the degree and extent of high signal intensity seen (0 = normal to 4+). Thirty-eight children less than 5 years of age who underwent MRI scans between June and August 2000 and who were found to have normal tone prospectively and normal MRI scan on review served as a control group. We identified 215 patients who had white-matter abnormalities; of these, only 142 (66%) had documented tone assessments in their medical record. Our study group was divided into three groups: increased (n = 35), decreased (n = 53), and normal tone (n = 54). All three measurements of white matter in each of the three study groups were significantly below values for control children. The children with white-matter abnormalities and decreased tone had significantly less signal intensity abnormality than the other study groups. Children with white-matter abnormalities and increased tone had a greater frequency of increased reflexes and tended to have more signal abnormalities than the other groups. The group of children with white-matter abnormalities and normal tone had the least amount of cerebral white-matter deficiency of the three study groups. In patients with strikingly decreased quantities of cerebral white matter, those with normal signal-intensity white matter are likely to be hypotonic with normal reflexes and those with increased signal intensity in the white matter are likely to be spastic.

Cerebral venous thrombosis in children.

Cerebral venous thrombosis is an important cause of stroke in children. Understanding the natural history of the disease is essential for rational application of new interventions. We retrospectively identified 31 children with cerebral venous thrombosis confirmed by head computed tomography (4 patients) or by magnetic resonance imaging (27 patients). Risk factors, clinical and radiographic features, and neurologic outcomes were analyzed. There were 21 males and 10 females aged 1 day to 13 years (median 14 days). Nineteen (61%) were neonates. The most common risk factors included mastoiditis, persistent pulmonary hypertension, cardiac malformation, and dehydration. The chief clinical features were seizures, fever, respiratory distress, and lethargy. Fifteen patients had infarctions (8 hemorrhagic, 7 ischemic). Protein C and antithrombin III deficiency were the most common coagulopathies among 14 tested patients. On discharge, 11 patients were normal, 17 had residual deficits, and 2 patients died. Twenty-seven patients were followed from 1 month to 12 years (mean 22 months). At follow-up, 11 patients were normal, and 13 patients had development delay. One had residual hemiparesis and cortical visual impairment. Two had other deficits. Neonatal cerebral venous thrombosis is probably more common than previously thought, and outcomes are worse in this group. All children with cerebral venous thrombosis should be tested for coagulation disorders.

Recurrence in pituitary adenomas in childhood and adolescence.

Pediatric pituitary adenomas are thought to behave more aggressively than their adult counterparts, and the ability to predict the degree of such behavior remains elusive. Proliferation marker Ki-67 and tumor suppressor gene p53 mutations have been used in adults to assist in the evaluation of invasiveness and recurrence; however, their use in childhood and adolescence remains anecdotal. Our study evaluates the proliferative potential in pituitary adenomas of five patients and its relationship with recurrence or persistence of endocrinologic or clinical abnormalities. For such assessment, tissues were stained with monoclonal antibodies BP53-12 forp53 tumor suppressor gene mutation and MIB-1, which binds to cell cycle-specific nuclear antigen Ki-67. In our series, one patient with recurrent adenoma demonstrated the highest (50%) p53 immunoreactivity. Ki-67-stained nuclei ranged from 0 to 2%, failing to identify the recurrent tumor. Therefore, p53 immunoreactivity, rather than Ki-67 nuclear stain, may be useful for identification of recurrent pituitary adenomas in childhood and adolescence.

The utility of the determination of CTG trinucleotide repeat length in hypotonic infants.

A 9-month-old male infant was floppy from birth with nonprogressive facial and distal limb weakness and apparently normal mother and father. The facial characteristics and distribution of involvement suggested congenital myotonic dystrophy and the infant, but not the mother, had insertional myotonia in one of four muscles tested. Had the number of CTG trinucleotide repeats been tested when the presence of a congenital myotonic dystrophy-like clinical picture was first appreciated, the proper diagnosis could have been made several months earlier. The application of new molecular genetic techniques is changing the usual sequence of studies performed in the evaluation of the hypotonic infant.

Alexander's disease: unique presentation.

Subacute necrotizing encephalomyelopathy (Leigh syndrome) refers to a nebulous disease entity characterized by lactic acidosis, a wide variety a clinical manifestations, and a consistent conglomeration of pathologic findings. Several abnormalities in metabolism have been delineated in association with Leigh syndrome, but many cases have no identified metabolic abnormality. We report a case that clinically, metabolically, and neuroradiologically appeared to be Leigh syndrome. In addition, our patient exhibited other unusual clinical findings, including ocular motility abnormalities. Neuropathologically, however, the diagnosis of Alexander's disease was confirmed. A review of the literature failed to find other cases of Alexander's disease reported with the metabolic abnormalities and clinical manifestations with which our patient presented.

Does selection bias determine the prevalence of the cavum septi pellucidi?

This study was undertaken to ascertain the prevalence of the persistent cavum septi pellucidi in children and adults by magnetic resonance imaging (MRI) and to compare the clinical indications for neuroimaging in the two age groups as a measure of group selection bias. All scans performed at West Virginia University during 1997 were reviewed for the presence of a persistent cavum septi pellucidi. The clinical indications for the MRI study were determined in 100 consecutive adult (17 years of age or older) and 100 consecutive pediatric (younger than 17 years of age) scans. In the 203 pediatric patients the prevalence of a persistent cavum septi pellucidi was 6.9%, and in the 814 adults the prevalence was 2.1%. Mental retardation/developmental delay was the clinical indication for at least 26% of the pediatric patients but was not an indication for neuroimaging in the adult study group. The known association of persistent cavum septi pellucidi with mental retardation and in several groups of patients with conditions clinically characterized by mental dysfunction suggests that the higher prevalence in the pediatric study group may primarily be the result of the patient selection bias operating through the different clinical indications for neuroimaging in the two populations.

The rise and fall of the plantar response in infancy.

To determine when the plantar response becomes reliably flexor in infants, 169 infants underwent serial evaluation from 2 weeks to 12 months of age during routine well-child visits. The plantar response, elicited in a standardized fashion, was extensor in 95.5%, 64.8%, 10.9%, 0.7%, and 0% of the infants at 2, 4, 6, 9, and 12 months, respectively. The plantar response becomes predominately flexor by 6 months of age in normal infants. This maturation of response correlates closely with that of other infantile reflexes.

Basilar artery occlusion and the dense artery sign in the newborn.

A child with basilar artery occlusion in the neonatal period is reported. The occlusion was documented by unenhanced computed tomography performed in the neonatal period demonstrating a "dense" artery at the tip of the basilar artery. The pattern of cerebral damage on MRI scan at 10 years of age confirmed the site of the vascular occlusion. The evidence suggests that embolization was the operating pathogenic mechanism of cerebral vascular occlusion. Neonatal arterial thrombosis involving the carotid circulation has been well documented and may be due to many pathological factors including direct trauma to the carotid artery and embolization from remote sites. Thrombosis of the vertebral artery in the neonate is only rarely reported and only in association with significant cervical trauma. A second child with a similar pattern of cerebral injury demonstrated on neuroimaging is described suggesting that this event may be more common than recognized. The clinical features of basilar artery occlusion as seen in the adult are not apparent in the neonate. Recognition of the neuroimaging characteristics seen in this condition may help to provide the clinician with a reasonable pathogenetic explanation for unexplained cerebral injury.

Volumetric neuroimaging in Usher syndrome: evidence of global involvement.

Usher syndrome is a group of genetic disorders consisting of congenital sensorineural hearing loss and retinitis pigmentosa of variable onset and severity depending on the genetic type. It was suggested that the psychosis of Usher syndrome might be secondary to a metabolic degeneration involving the brain more diffusely. There have been reports of focal and diffuse atrophic changes in the supratentorial brain as well as atrophy of some of the structures of the posterior fossa. We previously performed quantitative analysis of magnetic resonance imaging studies of 19 Usher syndrome patients (12 with type I and 7 with type II) looking at the cerebellum and various cerebellar components. We found atrophy of the cerebellum in both types and sparing of cerebellar vermis lobules I-V in type II Usher syndrome patients only. We now have studied another group of 19 patients (with some overlap in the patients studied from the previous report) with Usher syndrome (8 with type I, 11 with type II). We performed quantitative volumetric measurements of various brain structures compared to age- and sex-matched controls. We found a significant decrease in intracranial volume and in size of the brain and cerebellum with a trend toward an increase in the size of the subarachnoid spaces. These data suggest that the disease process in Usher syndrome involves the entire brain and is not limited to the posterior fossa or auditory and visual systems.

Radiological findings in developmental delay.

This article reviews the neuroimaging findings in patients with nonsyndromic mental retardation and global developmental delays. The frequency and type of abnormal neuroimaging findings in this patient population are discussed. Specifically addressed are the issues of which patients should have neuroimaging studies in light of (in the vernacular) "cost-benefit" analysis. The extension of these studies to "milder" developmental delays, and other neurodevelopmental disorders are also discussed.

Cavum septi pellucidi and cavum vergae in normal and developmentally delayed populations.

Recent studies have shown that the persistence of the cavum septi pellucidi beyond the neonatal period is a marker of cerebral dysgenesis. It has been suggested that the finding of a persistent cavum vergae is also a marker of disturbed brain development. In order to investigate this hypothesis we reviewed 161 brain magnetic resonance imaging scans from normal individuals for the presence of cavum septi pellucidi or cavum vergae, or both. In the 34 prospectively obtained normal adults, there were no individuals with either a cavum septi pellucidi or cavum vergae. In the "defined" normal subjects 3 of 127 individuals (2.4%) had a cavum septi pellucidi whereas a cavum vergae was noted in 26 of 127 (20.5%). We next reviewed the neuroimaging studies of 249 children and adults evaluated for mental retardation or developmental delay. A cavum septi pellucidi was found in 38 of 249 (15.3%) and a cavum vergae in 48 of 249 (19.3%) of these patients. A cavum septi pellucidi and cavum vergae were found together in 19 of 249 (7.6%). We interpret these data as showing that the cavum septi pellucidi is rarely seen in normal individuals although the cavum vergae is seen with the same frequency in normal and retarded populations. Thus we conclude that the cavum septi pellucidi serves as a significant marker of cerebral dysfunction manifested by neurodevelopmental abnormalities while the cavum vergae alone does not identify individuals at risk for cognitive delays.