Current treatment of thalamic gliomas in children.

Historically, the outcome of children with thalamic gliomas has been poor. Because of the potential for severe perioperative mortality, conservative approaches toward these lesions have been commonly instituted. However, recent improvements in therapeutic approaches have been numerous. These refinements have most importantly centered on improving the neurosurgical technique of tumor resection by integrating computer-assisted, stereotactic approaches. In so doing, perioperative mortality has dropped from as high as 40% to as low as 0-1%. Gross total resection confirmed with postoperative imaging is becoming an expectation. However, because of anatomical limitations or malignant histology, incomplete resections will undoubtedly occur in an effort to preserve neurological function. At the same time, not all residual disease implies a poor outcome. Indolent, low-grade gliomas of childhood are not limited to the cerebellum or optic/hypothalamic regions, and histologically similar lesions in the region of the thalamus occur with some frequency. In this case scenario, incompletely resected low-grade lesions should be followed sequentially with routine imaging; further therapy, be it surgical or adjuvant, is instituted only if disease progression is documented. Children found to have malignant gliomas of the thalamus should undergo surgical resection in an effort to relieve them of any existing mass effect. Subsequently, adjuvant therapy is utilized depending on the exact histopathology and the child's age. Thus, what evolves from recent data and current surgical techniques is an aggressively directed therapy based upon anatomical considerations and tumor type.

Management and outcome of low-grade astrocytomas of the midline in children: a retrospective review.

Low-grade astrocytomas of the midline of the brain can be difficult to manage because of their location. To evaluate treatment and outcome, we performed a retrospective study of children with midline low-grade astrocytomas admitted to The Hospital for Sick Children between 1976 and 1991. Eighty-eight children with biopsy-proven low-grade astrocytomas were identified. Forty-three tumors occurred in the optic pathways or hypothalamus, 13 in the thalamus, 7 in the pineal region, 14 in the midbrain, and 11 in the medulla. Patient follow-up ranged from 6 months to 15 years, with a mean of 4 years, 9 months. Overall outcome was related to the extent of resection, histological type, and location. Partial resections were often associated with involution of the tumor. Response to radiation was variable, and serious sequelae were observed. Thirty-three patients experienced recurrence, often with a good response to subsequent surgery; however, 12 of these patients died. The probability of survival was calculated to be 96% at 1 year, 91% at 5, and 80% at 10 years. Our study suggests that resection should be considered in all patients, both at presentation and recurrence.

Optic pathway/hypothalamic gliomas: a dilemma in management.

Optic pathway gliomas follow an unpredictable course. Some remain static for years; others increase rapidly in size and often lead to death. This unpredictability, along with the histological similarity of these tumors, has resulted in controversy about their management. We have reviewed the results of management of all 62 patients with a diagnosis of optic pathway/hypothalamic glioma treated at The Hospital for Sick Children during the years 1976-1990. Twelve patients received no direct treatment, and 3 only a biopsy. Six patients were treated with radiotherapy alone. Eight patients received radiotherapy following a biopsy. Seventeen patients were treated by resection alone and 16 had a resection followed by radiotherapy. Eight patients received chemotherapy in addition to other therapy, and in 5 of them the chemotherapy was given as an initial therapy. Forty-eight patients are well with their visual deficits but 7 of them are receiving hormone replacement therapy. Six patients have significant neurologic deficits and 8 have died.

Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome.

To evaluate the relationship between folate and zinc, and its effect on pregnancy outcome, maternal serum folate and zinc concentrations were determined at 18 and 30 wk gestation in a defined population of 285 pregnant women as part of a large-scale study to identify risk factors for fetal growth retardation (FGR). These results were correlated with birth weight and Apgar scores of newborn infants and with maternal infections during the perinatal period. A weak linear relationship was observed between maternal serum folate and zinc concentrations at 30 wk gestation. Folic acid supplementation had favorable effects on birth weight and Apgar scores of newborns, and reduced prevalence of FGR and maternal infections. No significant correlation was found between serum zinc concentration and birth weight of infants. The concept that folic acid supplementation has an adverse effect on maternal zinc nutriture and pregnancy outcome was not supported.

Serum folate and fetal growth retardation: a matter of compliance?

Serum folate levels were measured at 30 weeks' gestational age in 289 pregnant women, each of whom had been provided with folate supplementation at enrollment in prenatal care. There was a significant association between low serum folate levels and fetal growth retardation. High folate levels were most likely explained by recent folic acid intake. Therefore, we were concerned that the decreased fetal growth associated with low folate levels may have been related to a combination of psychological and behavioral characteristics for which low serum folate levels were only a surrogate measure. A profile of maternal psychosocial status was created, which included measures of depression, anxiety, self-esteem, mastery, stress, and social support. Poorer psychological scores were significantly related to lower serum folate levels. However, in women with both good and poor psychosocial scores, high folate levels were significantly associated with increased birth weight, a relationship that persisted even after adjusting for maternal race, body mass index, smoking, history of a low birth weight infant, and infant gender. Our findings suggest that women with good psychosocial scores are more likely to take folate, but that the use of folate itself is related to a lower risk of fetal growth retardation and increased birth weight.

Gelastic seizures treated by resection of a hypothalamic hamartoma.

A 7-year-old girl presented for evaluation of a peculiar kind of epilepsy. Her seizures began before 1 year of age and consisted of episodes of brief, uncontrolled and unprovoked laughter than with time progressed to include cursive, complex partial and generalized tonic-clonic seizures. Progressive impairment of cognitive functions was noted as well as precocious puberty. Neuroimaging examination disclosed a hypothalamic hamartoma. It was excised by a pterional approach, and no further seizures were noted. The authors propose direct surgery for the hypothalamic hamartoma as a treatment for this progressive syndrome.

Vitamins, folic acid and neural tube defects: comments on investigations in the United States.

No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy-makers face difficulties in applying results of recurrence or occurrence studies in high-risk areas to low-risk areas in the U.S.

Intelligence at six years in relation to neonatal bilirubin levels: follow-up of the National Institute of Child Health and Human Development Clinical Trial of Phototherapy.

Results of the National Institute of Child Health and Human Development Randomized Controlled Trial of Phototherapy were examined for the relationship of neonatal bilirubin level to neurological and developmental outcome at 6-year follow-up. This analysis focused on 224 control children with birth weight of less than 2000 g. Bilirubin levels were maintained below previously specified levels by the use of exchange transfusion only (24%). Rates of cerebral palsy were not significantly higher for children with elevated maximum bilirubin level than for those whose level remained low. No association was evident between maximum bilirubin level and IQ (Full Scale, Verbal, or Performance) by simple correlation analysis (r = -.087, P = .2 for Full Scale) or by multiple linear regression adjusting for factors that covary with IQ (beta = -.15, P = .58). IQ was not associated with mean bilirubin level, time and duration of exposure to bilirubin, or measures of bilirubin-albumin binding. Thus, over the range of bilirubin levels permitted in this clinical trial, there was no evidence of bilirubin toxicity to the central nervous system. Measures used to control the level of bilirubin in low birth weight neonates appear to prevent effectively the risk of bilirubin-induced neurotoxicity.

Phototherapy for neonatal hyperbilirubinemia: six-year follow-up of the National Institute of Child Health and Human Development clinical trial.

The National Institute of Child Health and Human Development Randomized, Controlled Trial of Phototherapy for Neonatal Hyperbilirubinemia was conducted to determine whether phototherapy used to control serum bilirubin is safe and is as effective in preventing brain injury as exchange transfusion. The study, conducted at six neonatal care centers, randomly assigned 1339 newborn infants to phototherapy or control groups by the following subgroups: (1) birth weight less than 2000 g; (2) birth weight 2000 to 2499 g and bilirubin level greater than 171 mumol/L (10 mg/dL); or (3) birth weight greater than or equal to 2500 g and bilirubin level greater than 222 mumol/L (13 mg/dL). Phototherapy was administered for 96 hours, and exchange transfusion was used to control hyperbilirubinemia at the same predetermined levels in both groups. Neurological and developmental examinations were conducted at 1 and 6 years of age, with follow-up rates of 83% and 62%, respectively. The two groups did not differ in mortality or diagnosed medical conditions. The phototherapy and control groups had similar rates of cerebral palsy (5.8% vs 5.9%), other motor abnormalities including clumsiness and hypotonia (11.1% vs 11.4%), and sensorineural hearing loss (1.8% vs 1.9%). The Wechsler Intelligence Scale for Children-Revised scores overall were not significantly different for the two groups (Verbal, 96.8 vs 94.8; Performance, 95.8 vs 95.1 for phototherapy and control groups, respectively). Phototherapy effectively controlled neonatal hyperbilirubinemia without evidence of adverse outcome at 6 years of age and was at least as effective as management with exchange transfusion alone.

The absence of a relation between the periconceptional use of vitamins and neural-tube defects. National Institute of Child Health and Human Development Neural Tube Defects Study Group.

Whether taking multivitamins or folate around the time of conception can reduce a woman's risk of having a child with a neural-tube defect is controversial. To investigate this question, we examined the periconceptional use of vitamin supplements by women who had a conceptus with a neural-tube defect (n = 571), women who had had a stillbirth or a conceptus with another malformation (n = 546), and women who had had a normal conceptus (n = 573). Women with conceptuses with neural-tube defects were identified either prenatally or postnatally and were matched to control mothers for gestational age. To minimize recall bias, we interviewed nearly all the women within five months of the diagnosis of a birth defect or the birth of the infant (mean, 84 days); information on vitamin use was obtained by an interviewer who was unaware of the outcome of pregnancy. The rate of periconceptional multivitamin use among the mothers of infants with neural-tube defects (15.8 percent) was not significantly different from the rate among mothers in either the abnormal or the normal control group (14.1 percent and 15.9 percent, respectively). After adjustment for potential confounding factors, the odds ratio for having an infant with a neural-tube defect among women classified as having had full supplementation with multivitamins was 0.95 as compared with the mothers of the abnormal infants (95 percent confidence interval, 0.78 to 1.14) and 1.00 as compared with the mothers of normal infants (95 percent confidence interval, 0.83 to 1.20). There were no differences among the groups in the use of folate supplements. The adjusted odds ratio for having an infant with a neural-tube defect among those receiving the recommended daily allowance of folate was 0.97 as compared with the mothers of abnormal infants (95 percent confidence interval, 0.79 to 1.18) and 0.98 as compared with the mothers of normal infants (95 percent confidence interval, 0.80 to 1.20). We conclude that the periconceptional use of multivitamins or folate-containing supplements by American women does not decrease the risk of having an infant with a neural-tube defect.

Male sexual development in the monkey. II. Cross-sectional analysis of pulsatile hypothalamic-pituitary secretion in castrated males.

Pulsatile secretion of serum gonadotropins was studied in 16 castrated monkeys from 4 weeks of age through adult life. Animals were castrated at various ages from birth through adult life. Although some studies of the gonadotropin-secretory patterns were longitudinal in nature, most comparisons were cross-sectional. On the basis of our observations, we have arbitrarily grouped the animals into 4 developmental ages: postnatal (less than 7 months), prepubertal or juvenile (7-27 months), pubertal (28-59 months), and adult (greater than or equal to 60 months). In carrying out these studies, blood was withdrawn at 15-min intervals over 24 h without anesthesia using a mobile vest and tether assembly to support an indwelling catheter. GnRH challenge tests were done on 1 or more occasions on all animals. Plasma samples were analyzed for concentrations of FSH and LH by established RIAs and an in vitro bioassay for LH. During the frequent sampling period (24 h for all except postnatal animals), the amplitude of gonadotropin pulses was greatest in adult animals followed by postnatal and pubertal monkeys. During pubertal development, there was a marked increase in the magnitude of gonadotropin pulses, and remarkedly, there was a substantial increase in the LH bioassay: RIA (greater than 5:1) by adult life. GnRH challenge tests of gonadotropins correlated with these observations. Time series analysis was applied to the data for objective statistical characterization of cyclic patterns. Our findings can be summarized: 1) during pubertal maturation there is a change in amplitude but not frequency of gonadotropin pulses, 2) pubertal development of the hypothalamic-pituitary axis advances in the absence of gonadal feedback, and 3) there is a significant increase in the LH bioassay: RIA during pubertal development. We conclude that the castrate monkey is a valuable adjunct to direct clinical investigations of the mechanisms controlling human sexual development.

Paraplegia in osteogenesis imperfecta. A case report.

Paraplegia occurred in an adolescent girl with osteogenesis imperfecta after chiropractic manipulation. The child had been able to walk freely out of doors. Complete motor paralysis with sensory sparing resulted due to anterior compression of the cord by spondyloptotic cervical vertebrae. Reconstructed computerised tomography was very helpful in demonstrating the abnormality. Anterior and then posterior decompression relieved the tethered spinal cord and were supplemented with bone grafting. Early diagnosis and surgical treatment will prevent similar neurological accidents.

Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey.

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

Cerebellar stimulation in the management of cerebral palsy: clinical and physiological studies.

Cerebellar stimulators were inserted into seven children who had cerebral palsy and in whom extensive investigation, including computerized tomography, had revealed no structural brain abnormality. A team including physiotherapists, occupational therapists, speech pathologists, and respiratory physiologists assessed the children pre- and postoperatively; their somatosensory evoked potentials were also measured. The mean age at implantation was 8.6 yearsl follow-up has ranged from 8 to 23 months (mean, 17.3 months). No adverse effects of the cerebellar stimulation have been noted. Detailed case histories obtained from the parents, together with formal assessment scores, indicate good improvement in six patients and mild but significant improvement in the seventh. Clinically, there has been gradual improvement in all seven patients. The charge density range associated with clinical improvement was 0.8 to 2.1 muCi/cm2/phase. The stimulation equipment must be monitored very carefully to ensure that any variation from the desired output is acceptably small because it is probable that sizable deviation is a determining factor in lack of response to this therapy.