Role for opioid peptides in self-injurious behavior: dissociation from autonomic nervous system functioning.

The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opioid receptor antagonist, on self-injurious behavior (SIB), heart rate, and blood pressure in three males (one 10-year-old and two 17-year-olds) were investigated. Subjects were evaluated in a structured test session for SIB. The frequency of the most predominant type of SIB (head and face hitting) was significantly reduced by naltrexone (maximum was 71% at the 1.5 mg/kg dose), while self-biting was not significantly decreased at any dose. In contrast, naltrexone had no significant effect on heart rate or blood pressure. Based upon these and other results it was concluded that naltrexone produced decreases in specific SIBs by blocking opioid receptors in brain, and that such opioid blockade had no effect on two measures of cardiovascular function.

Effects of acute administration of naltrexone on cardiovascular function, body temperature, body weight and serum concentrations of liver enzymes in autistic children.

The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opiate receptor antagonist, on auscultated heart rate, systolic blood pressure and axillary body temperature were investigated before and about 1 h postdrug in 5 autistic children (4-12 years of age). In addition, an electrocardiogram was recorded on each child before and about 3 h after placebo or 2.0 mg/kg of naltrexone. Finally, the serum concentrations of the liver enzymes glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were measured 24 h following placebo or naltrexone administration. Naltrexone had no statistically significant effects on any of these measures in comparison with baseline or placebo levels. Thus, these data provide preliminary evidence for the safety of acute administration of naltrexone in children.

Ontogeny of beta-endorphin and cortisol in the plasma of children and adolescents.

The ontogeny of plasma beta-endorphin (B-E) and cortisol concentrations was studied in normal children (3-11 yr old) and adolescents (12-18 yr old) of several ethnic backgrounds. The morning plasma concentrations did not significantly differ as a function of sex or age for either B-E [males (n = 88), 7.19 +/- 0.39 (+/- SE) pmol/L; females (n = 73), 6.80 +/- 0.50 pmol/L] or cortisol [males (n = 87), 383 +/- 14 nmol/L; females (n = 69), 359 +/- 20 nmol/L]. There was a small but significant positive correlation between plasma B-E and cortisol concentrations. When sampled immediately after venipuncture, there were no significant differences in the plasma B-E or cortisol concentrations of children who cried during venipuncture compared with those who did not. These data suggest that morning plasma B-E and cortisol concentrations are constant throughout childhood, adolescence, and into early adulthood.

Effects of chronic diphenylhydantoin on cerebral metabolism in the adult rat.

Diphenylhydantoin is one of the most widely used anticonvulsant agents in humans. To examine its effects on brain metabolism, we used the quantitative autoradiographic [14C]deoxyglucose method to measure local cerebral glucose utilization in adult rats receiving 50 mg/kg/day diphenylhydantoin for 1 week. Thirty-three brain structures were analyzed to determine whether the drug has global or site-specific effects on cerebral metabolism. Chronic administration produced statistically significant decreases in 23 neocortical and subcortical structures compared with those in vehicle-injected control animals. Therefore, our data support the concept that diphenylhydantoin has widespread depressant effects on brain metabolism.

Naltrexone decreases self-injurious behavior.

The effect of naltrexone (0.5, 1.0, 1.5, and 2.0 mg/kg) on the frequency of self-injurious behavior (SIB) was investigated in three male adolescents. The frequency of total SIB was reduced significantly in all three subjects; dose-dependent decreases (at 0.5, 1.0, and 1.5 mg/kg) in SIB frequency were observed in the two mentally retarded subjects. These data suggest a role for opioid peptides in SIB.

A review of the factors influencing the prognosis of medulloblastoma. The importance of cell differentiation.

The clinical, therapeutic, and histological features of 54 patients with medulloblastoma were analyzed retrospectively by a multivariate approach with regard to prognosis. The overall 5-year survival rate was 60%, with 48% of patients free of recurrence at 5 years. Cell differentiation, when present, was associated with a significantly longer recurrence-free period. Seventy-two percent of patients with the histological finding of cell differentiation were recurrence-free at 5 years. A marginally significant increase in the 5-year survival rate was also seen in association with differentiation. Only 34% of the patients whose tumor exhibited necrosis were alive at 5 years. There was no statistically significant difference in 5-year survival for children under 3 years of age or for the group of children aged 5 years or under. However, a significantly larger fraction (72%) of the group aged 5 years or under had a recurrence-free period of 5 years or more. Other factors including sex, extent of surgical resection. Chang tumor stage, posterior fossa radiation dose, and adjuvant chemotherapy did not influence prognosis.

Trilateral retinoblastoma: ocular and pineal retinoblastomas.

Trilateral retinoblastomas, the syndrome of bilateral retinoblastoma associated with ectopic retinoblastoma in the pineal gland, is rare but well recognized. In contrast to bilateral retinoblastomas alone, the ocular retinoblastomas in trilateral retinoblastoma develop before the age of 6 months, and a family history positive for retinoblastoma is usually obtained. The retinal tumors are often quiescent at the time that the pineal tumor is discovered, and show no evidence of metastatic spread after enucleation of the globes. Pathologically, the pineal tumor is indistinguishable from the ocular retinoblastoma. The pathophysiology of this syndrome is not well understood, but a germinal mutation is thought to target photoreceptor tissue for further postzygotic mutation. Eventual expression depends on the inherited host resistance to the carcinogenic manifestation of these genes. The low host resistance of trilateral retinoblastoma is evident by the early age of presentation, the multicentric occurrence of the tumor, and the high early mortality rate despite aggressive management.

Cranial computed tomography in the evaluation of neurologic disorders in two nonhuman primates.

Cranial computed tomography (CCT) was used to evaluate neurologic disorders in 2 primates. In the 1st case, acute left hemiparesis developed in an adult female proboscis monkey (Nasalis larvatus). A CCT scan revealed a right frontal lobe abscess that was subsequently surgically drained. In the 2nd case, a juvenile black spider monkey (Ateles fusciceps) experienced recurrent seizures following an episode of trauma and anoxia. A CCT scan demonstrated enlarged lateral ventricles and cerebral atrophy. Computed tomography proved to be a valuable technique for localizing and characterizing brain lesions in these 2 primates, after more conventional methods of investigation had failed to establish diagnoses.

Computed tomography in the evaluation and management of patients with spina bifida.

Computed tomography (CT) has fundamentally altered our approach to the initial evaluation and follow-up of patients with spina bifida. This safe and simple, non-invasive diagnostic technique has doubtlessly encouraged earlier diagnosis of clinically significant problems associated with spina bifida and has greatly facilitated the day-to-day management of those patients with documented disorders. CT is now effectively employed as a screening measure for both intraspinal and intracranial problems and can be relied upon to objectively guide and monitor elected modes of therapy.

Mapping of cerebral cortical strokes in Rhesus monkeys by laser Doppler spectroscopy.

We have demonstrated the feasibility of using laser doppler spectroscopy to map regional blood flow distribution on the surface of the cerebral cortex. Rhesus monkeys underwent craniotomy, with replacement of part of the calvarium by a transparent plastic dome. A stroke was produced on one side by ligation of the middle cerebral artery. A flow index was computed from a weighted bandwidth of the doppler spectrum of helium-neon laser light scattered from the surface of the cortex, the doppler shift being due to scattering from moving blood cells in the microcirculation. By measuring the doppler flow index at a grid of points over the surface, the region of the stroke was easily delineated, and its progression with time observed. The method provides a rapid measurement with a spatial resolution of about 1 mm.

Computed tomographic presentation of granulomatous reaction from intraventricular shunt.

A case is presented in which the patient was diagnosed as having a large mass lesion arising in the region of the quadrigeminal plate. The patient had been shunted in the past for hydrocephalus. The computed tomographic picture was that of a primary brain neoplasm. At surgery extensive granulation tissue was found. The similarity between the CT presentation of this inflammatory mass and a neoplasm is emphasized.

Stochastic analysis of 133xe clearance for determining regional cerebral blood flow in a primate model.

A technique for stochastic analysis of 133Xe washout using a computer-assisted Anger camera is described. The technique produces functional maps of both regional cerebral blood flow (rCBF) and error in rCBF. The calculational limitations of the technique are discussed and an experimental estimate made of the physical limitations associated with the low energy photon emitted by 133Xe. The method is demonstrated in a rhesus monkey model before and after surgical occlusion of the middle cerebral artery.

Technique for placement of experimental indwelling carotid artery catheter.

A technique for placement of an indwelling carotid artery catheter in the rhesus monkey is presented. These indwelling catheters have proved useful in the investigation of regional cerebral blood flow using xenon-133, positive contrast angiography, and fluorescein angiography. Although limited thus far to studies in experimental anemic stroke, this technique could be adapted to a variety of experimental situations in which serial evaluations of the cerebral vasculature are indicated.

Normal rate of cerebrospinal fluid formation five years after bilateral choroid plexectomy. Case report.

A ventricular perfusion technique was used to determine the rate of cerebrospinal fluid (CSF) formation in a 5-year-old child who had undergone bilateral choroid plexectomy for communicating hydrocephalus during infancy. At the time of the study, the patient had a failed ventriculoperitoneal shunt and was suffering from progressive ventriculomegaly. The calculated rate of CSF formation, 0.35 ml/min +/- 0.02 standard deviation, was within normal limits.

Normal pressure hydrocephalus in patients with myelomeningocele.

Although the syndrome of normal pressure hydrocephalus (NPH) was described in the adult as early as 1964, it has only recently been recognized in the child. In this preliminary report, eight myelomeningocele patients with presumed NPH were evaluated before and after ventricular shunting procedures. Cranial computed tomography and serial psychological testing have proved to be particularly valuable both in the pre-operative and post-operative assessment of these patients and have the distinct advantage of being simple, non-invasive diagnostic measures. Continuous intra-ventricular pressure monitoring has shown what promises to be characteristic elevated pressure plateaux imposed on normal baseline cerebrospinal fluid (CSF) pressures in so-called NPH but is a more difficult clinical procedure, necessarily associated with potential complications. Although decreasing response to growth-stimulating hormone can be demonstrated in patients with long-standing hydrocephalus, this endocrine malfunction cannot be considered an early indicator of intracranial pathology. Single IQ scores are inadequate measures of intellectural function in children with NPH and serial examinations should be carried out. Detailed neuropsychological testing will document performance IQ scores well below verbal IQ scores and will generally show failure of psychomotor development to keep pace with chronological ageing. Initial studies indicate that improved performance scores can be expected within 1 1/2 to 3 months following successful ventricular shunting operations, and that any downward trend in pre-operative test scoring can at least be reversed. Statistically significant improvements in full-scale IQ scores have not been seen, however, before the end of the first post-operative year. Clinically, improved attentiveness and sociability, and decreased spasticity (if present prior to surgery) can be expected following shunting. Over-all, ventriculomegaly, normal CSF pressure, stable head size, and non-progressive neurological symptoms cannot be regarded as sufficient criteria for the diagnosis of an arrested state of hydrocephalus, and should suggest NPH, especially in those children who demonstrate a discrepancy between performance and verbal IQ scores and who fail to exhibit continuing psychomotor development with advancing age.

Primary choroid plexus papilloma of the cerebellopontine angle presenting as brain stem tumor in child.

A case of a primary choroid plexus papilloma of the cerebellopontine angle in an 8-year-old female is presented. The clinical features of progressive cranial nerve palsies and cerebellar signs in the absence of intracranial hypertension initially suggested an intrinsic brain stem lesion. Whereas a radionuclide brain scan demonstrated abnormal uptake in the region of the pons, vertebral angiography and pneumoencephalography were diagnostic of an angle mass. At surgery, the tumor proved to be a choroid plexus papilloma that was totally confined to the cerebellopontine angle. This patient represents the thirteenth reported case of a primary cerebellopontine angle papilloma and the first such case occurring in a child.

Spinal descent of cerebrospinal fluid in man.

The descent of radiopharmaceuticals injected within the right lateral ventricle toward and into the spinal subarachnoidal spaces has been followed by scintiphotographic techniques and by computerized flow analysis in a group of "normal" patients. A substantial and rapid downward progression of the albumin-tagged tracer has been observed. This progression is faster than the subarachnoidal ascent toward the convexity of the brain.

Choroid plexus papilloma. II. Ultrastructure and ultracytochemical localization of Na-K-ATPase.

An electron-microscopic study of a choroid plexus papilloma from the lateral ventricle of a child revealed fine structural features typical of normal choroid plexus tissue. Utilizing the Ernst technique for demonstrating ouabain-sensitive, potassium-dependent phosphatase activity, Na-K-ATPase was localized along the basal and lateral plasmalemmas of the tumor epithelium but not along the ventricular surface (apical plasmalemma). This localization is similar to that found in normal choroid plexus epithelium of all species studied to date.

The cerebrospinal fluid: current concepts of its formation.

Until recently it has been generally accepted that the choroid plexuses are the major source of the cerebrospinal fluid (CSF). However, data now indicate that significant contributions to the CSF are made at extrachoroidal sites. CSF production studies and 24Na transport studies in normal and plexectomized rhesus monkeys supportive of substantial extrachoroidal CSF formation will be presented. Although the exact mechanisms of CSF formation remain to be defined, ultrafiltration is probably involved to a considerable extent. Data indicative of a lymphatic-like role for the CSF will be considered.

Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction.

Utilizing a ventricular perfusion technique, the rate of CSF formation was determined in a 2-year-old child before and after removal of a 74 g choroid plexus papilloma from the left lateral ventricle. Preoperatively, the CSF formation rate was 1.05 +/- SD 0.01 ml/min (1,656 ml/day). Postoperatively, the CSF formation rate was reduced fivefold to 0.20 +/- SD 0.01 ml/min (288 ml/day). Whereas these data are regarded as conclusive evidence of CSF overproduction by a choroid plexus papilloma, the pathogenesis of generalized ventricular enlargement in this case was due to part to obstruction of the subarachnoid pathways.