The diagnosis and management of delirium in infancy.

OBJECTIVE: Atypical antipsychotics have been documented to be effective in the management of delirium in adults and older children, but despite considerable need, their use has been less studied in the very young. A retrospective chart review was undertaken to describe the use of atypical antipsychotics in controlling symptoms of delirium in infants and toddlers. METHODS: All psychiatric inpatient consultations performed during a 3 year period were reviewed to identify children <36 months old diagnosed with delirium. Delirium Rating Scale (DRS) scores were retrospectively calculated when the antipsychotic was initiated and discontinued, to confirm the diagnosis of delirium and evaluate symptom severity, and then to assess symptom response to pharmacologic intervention. RESULTS: There were 10 boys and 9 girls in the study population (ages 7-30 months, mean 20.5 months). Olanzapine (n=16) and risperidone (n=3) were used, and length of treatment and response were comparable for both medications. Mean DRS scores decreased significantly (p<0.001) with antipsychotic administration, without significant adverse side effects. CONCLUSIONS: Although randomized placebo controlled studies are needed to better characterize the indications, risks, and benefits, these atypical antipsychotic medications appeared to be effective and safe for managing delirium symptoms in very young pediatric patients.

Symptoms before and after posterior fossa surgery in pediatric patients.

UNLABELLED: The posterior fossa syndrome (PFS) is common after cerebellar tumor resection in pediatric patients. It is characterized by postoperative mutism and ataxia and associated with persistent abnormalities in mood and cognition. METHOD: A 2-year prospective study of children and adolescents with cerebellar tumors identified by neuroimaging was performed at the Children's Hospital Los Angeles. RESULTS: There were 8 girls and 14 boys in the study, aged 14 months to 17 years. The tumor sizes ranged from 2 to 6.5 cm in diameter. The patients presented with ataxia, headache, vomiting, depressed or irritable mood and inattention. Symptoms of PFS were present postoperatively in all except for the 2 patients with lateral tumors. The symptoms began before resection, were most prominent immediately after surgery, and improved over time. Neuropsychological assessment of 10 patients documented a persistent cognitive decrement. CONCLUSION: This small, descriptive study provides information on the natural history of pediatric posterior fossa tumors from before surgery through the postoperative period.

Atypical antipsychotic medications to control symptoms of delirium in children and adolescents.

BACKGROUND: Atypical antipsychotics have been documented to be effective in the management of delirium in adults, but despite considerable need, their use has been less studied in pediatric patients. OBJECTIVE: A retrospective chart review was done to describe the use of atypical antipsychotics in controlling symptoms of delirium in children and adolescents. METHODS: Pharmacy records at Children's Hospital Los Angeles were reviewed to identify patients to whom antipsychotic agents were dispensed over a 24-month period. Psychiatric inpatient consultations during the same 24-month period were reviewed. Patients 1-18 years old diagnosed with delirium given antipsychotics constituted the study population. Delirium Rating Scale-Revised-98 (DRS-R98) scores were retrospectively calculated, when possible, at time antipsychotic was started to confirm the initial diagnosis of delirium and evaluate symptom severity, and again when antipsychotic was stopped, to assess symptom response. RESULTS: Olanzapine (n=78), risperidone (n=13), and quetiapine (n=19) were used during the 2 years of the study. Mean patient age, length of treatment, and response were comparable for the three medications. For patients with two DRS-R98 scores available (n=75/110), mean DRS-R98 scores decreased significantly (p<0.001) with antipsychotic without significant adverse side effects. CONCLUSION: Although randomized placebo-controlled studies are needed, atypical antipsychotic medications appeared to be effective and safe for managing delirium symptoms in pediatric patients while underlying etiology was addressed.

Hydrographic magnetic resonance imaging of the fetal eye.

Previous work has shown that fetal hydrographic magnetic resonance imaging (MRI) provided additional information complementary to T2-weighted single-shot fast spin echo (ssFSE) images. The objective of this study was to determine if hydrographic MRI provides better conspicuity of fetal eye structures compared with ssFSE MRI. ssFSE and hydrographic images were retrospectively examined in 82 consecutive fetal studies with normal central nervous system without sensitivity encoding. Relative signal intensity values on ssFSE and hydrographic MRI were obtained for vitreous and sclera. Ratios of the signal intensity of vitreous to the signal intensity of sclera were calculated to determine conspicuity. Similar measurements were obtained in a smaller separate data set (n = 41) using hydrographic imaging with sensitivity encoding techniques. The hydrographic images significantly demonstrated greater conspicuity (ratio of vitreous to sclera) than ssFSE images. This was consistent for both sensitivity encoding and no-sensitivity encoding groups. The difference in conspicuity was on average approximately two times greater in the hydrographic images compared with ssFSE images. Hydrographic MRI of the fetal eye provides on average two times greater conspicuity of fetal eye structures than ssFSE imaging. This enhancement is not affected by gestational age or the use of sensitivity encoding parallel imaging techniques.

Histologic features and prognosis in pediatric medulloblastoma.

Because individual histologic features in childhood medulloblastoma alter survival likelihood, the recent 4th edition of the World Health Organization (WHO) Classification of Brain Tumors recognizes desmoplastic/nodular medulloblastoma, medulloblastoma with extensive nodularity, large cell medulloblastoma, and anaplastic medulloblastoma, in addition to medulloblastoma with no other distinguishing features. To identify features affecting survival likelihood, we investigated 33 histologic features in 556 childhood tumors diagnosed as medulloblastoma in the Childhood Brain Tumor Consortium (CBTC) database; all features have CBTC verified read-reread reliability and those features important in the classification of medulloblastoma and its WHO variants regardless of their measured reliability. Nineteen features had no effect on survival likelihood, and 8 features were too prevalent or too rare to measure their effect on survival. Nodules, balls, high cell density, and fine fibrillary stroma improved survival likelihood; necrosis and prominent nucleoli worsened survival likelihood. Of note, the presence of desmoplasia, currently a defining feature (along with nodules) for desmoplastic/nodular medulloblastoma, had no effect on survival likelihood. We conclude that the presence of nodularity in medulloblastoma is important to improved survival likelihood, particularly when combined with balls and fine fibrillary stroma. Given the "overlap" of desmoplastic/nodular medulloblastoma and nodular medulloblastoma, we suggest they be combined into a diagnosis of nodular medulloblastoma, with nodules, balls, and fine fibrillary stroma as defining criteria. We also suggest that because of the considerable overlap of anaplastic medulloblastoma and large cell medulloblastoma they be combined into 1 diagnosis of anaplastic/large cell medulloblastoma, with necrosis and prominent nucleoli among the defining criteria.

Pathologist interobserver variability of histologic features in childhood brain tumors: results from the CCG-945 study.

In the Children's Cancer Group-945 trial, study design allowed estimation of overall interpathologist observational agreement for 6 histologic features frequently used in brain tumor diagnoses. We evaluated agreement between pairs of 5 experienced neuropathologists, who had knowledge of the general diagnoses prior to slide readings. We performed this study in an attempt to further improve pathologist interinstitutional agreement. The features mitosis, necrosis, and giant cells had "fair" overall kappa estimates of reproducibility of around 0.5, while endothelial proliferation had only a "poor" overall kappa of 0.35. The Rogot reproducibility index averaged 0.5 for pleomorphism and hyperchromia. The upper bounds for the 10 pair summary agreement estimates were at best 0.65 ("good") for all 6 features. These relatively low-reproducibility estimates for the very small number of histologic features being assessed in tumors institutionally diagnosed as high-grade gliomas indicate that neuropathologists either used different operational definitions or interpreted them differently. We found that we could rank the histologic features from best to worst agreement among study pathologists as necrosis, giant cells, mitosis, endothelial proliferation, hyperchromic nuclei, and pleomorphic cells. We suggest that neuropathologists involved in multi-institutional studies of putative therapies not discard these traditional histologic features, but rather develop standardized operational definitions and measure their variability before beginning the studies. Only after such histologic feature variability studies are conducted will we have the data to identify specific histologic features of value to clinicians and researchers. Agreement and strict adherence to improved nonsubjective diagnostic criteria would improve histologic feature reliability and, consequently, their usefulness in studies.

Late onset psychosis in survivors of pediatric central nervous system malignancies.

Survivors of pediatric intracranial malignancies are at recognized high risk for neurocognitive and psychosocial dysfunction, endocrinopathies, growth abnormalities, and second neoplasms. The late onset of persistent psychosis may represent an additional serious psychiatric consequence of childhood intracranial malignancies. The authors report eight survivors of pediatric intracranial malignancies whose course was complicated by the delayed onset of hallucinations, delusions, and bizarre behavior 2 to 12 years after diagnosis and treatment of brain tumors. The purpose of this report is to alert others to the generally unrecognized risk of psychosis following the treatment of brain tumors in children and adolescents.

Comparing symptoms of delirium in adults and children.

Delirium is presumed to be the same syndrome in all ages. Comparing pediatric and adult studies, the authors found many of the same symptoms reported, but often at significantly different rates. Sleep-wake disturbance, fluctuating symptoms, impaired attention, irritability, agitation, affective lability, and confusion were more often noted in children; impaired memory, depressed mood, speech disturbance, delusions, and paranoia, more often in adults; impaired alertness, apathy, anxiety, disorientation, and hallucination occurrence were similar. These may represent true differences in the presentation of delirium across the life-cycle, or may be attributable to inconsistent methodologies. Prospective studies are needed to resolve this question.

Mood and behavioral dysfunction with opsoclonus-myoclonus ataxia.

Opsoclonus-myoclonus ataxia syndrome is a paraneoplastic syndrome of cerebellar damage associated with neuroblastoma. The authors assessed psychiatric symptoms of opsoclonus-myoclonus ataxia syndrome in 17 children, who were 16 months to 12(1/2) years of age. Psychiatric symptoms examined included disruptive behavior, affective dysregulation, irritability, impulsivity, cognitive impairment, and poor attention.

Disordered respiratory control in children with partial cerebellar resections.

While the cerebellum is not traditionally thought of as having an important role in respiratory control, breathing involves cyclic motor acts that require cerebellar coordination. We postulate that children with partial cerebellar resections have disordered respiratory control due to altered synchronization of ventilatory muscles. We reviewed the records of 36 children following partial cerebellar resections due to neoplasms confined to the cerebellum. P aCO2 values were elevated in 19% of patients. Six patients had apneic or bradypneic events documented within the first month after resection. Two patients required intubation with assisted ventilation, and one needed assisted ventilation for 7.3 weeks. Those with apnea had lower oxygen saturations, and a longer need for supplemental oxygen. Patients with apnea were older than those without apnea. Swallowing, which uses many of the same muscles as those needed to maintain upper airway patency, was dysfunctional in 50% of those with apneas. We conclude that children with cerebellar resections have an increased incidence of apnea, hypoventilation, and hypoxemia not otherwise explained by pulmonary disease, and some require prolonged assisted ventilation. We speculate that these abnormalities are manifestations of altered respiratory control caused by dysfunctional cerebellar coordination of ventilatory muscles.

Case series: acute mood symptoms associated with posterior fossa lesions in children.

Nineteen children were acutely dysphoric, inattentive, irritable, and sometimes mute following midline posterior fossa neoplasm resection and arteriovenous malformation hemorrhage. These symptoms represent an acute manifestation of the cerebellar cognitive affective syndrome. The authors aimed to describe the acute psychiatric changes in mood and behavior in children with posterior fossa lesions and to evaluate the relationship of posterior fossa syndrome to cerebellar cognitive affective syndrome.

Prognostic limitations of the Daumas-Duport grading scheme in infratentorial neuroglial tumors in children.

The Daumas-Duport grading scheme (DDGS) utilizes four histologic features in an additive method (grade 1 if none present, grade 2 if only one is present, etc.). Its efficacy in achieving prognostically homogeneous groups of childhood infratentorial neuroglial tumors and its concordance with World Health Organization (WHO) diagnoses has not been evaluated. We investigated these questions using the Childhood Brain Tumor Consortium (CBTC) database of 1241 neuroglial tumors limited to the infratentorial compartment. We calculated survival function estimates for various DDGS grades as well as the histologic features within each grade. The feature of endothelial prominence improved survival expectation, whereas the remaining three features of nuclear atypia, mitoses, and necrosis were associated with worsened survival. Survival estimates for tumors with DDGS grades 2 and 3 did not differ. Some grades contained feature subsets with significantly different survival distributions. The survival distributions of DDGS grade 1, DDGS grade 2 with only endothelial prominence, and DDGS grade 3 with nuclear atypia and endothelial prominence were not significantly different. DDGS grade within WHO diagnoses had no significant effect on survival expectation. We conclude that grading by summation of only four histologic features, as in the DDGS, is inappropriate for assessment of childhood neuroglial tumors. A classification scheme considering the complete histologic content is more likely to provide clinically useful diagnoses. Such a scheme, based on the CBTC database is available. This scheme uses 26 histologic features identified as reliable in read-reread studies.

Delirium in children and adolescents.

Rarely reported in pediatric patients, the characteristic symptoms and course of delirium are well known in adults. This retrospective study was undertaken to describe the clinical presentation, symptoms, and outcome of delirium in children and adolescents. Eighty-four patients age 6 months to 18 years were identified with delirium, from 1,027 consecutive psychiatric consultations during a 4-year period. Mortality was high (20%), and length of stay was prolonged. Symptoms of psychosis and disorientation were less characteristic, but overall the presentation and course of delirium were similar to adults, and the current Diagnostic and Standard Manual of Mental Disorders (DSM) criteria were found applicable in the pediatric population.

Changes in the size of the lateral ventricles in the normal-term newborn following vaginal delivery.

BACKGROUND: This is a study of the size of the lateral ventricles in a population of normal-term newborns following vaginal delivery. OBJECTIVE: To assess the time course for the lateral ventricles to change from closed to open following vaginal delivery. MATERIALS AND METHODS: A total of 143 normal-term newborns had a videotaped cranial ultrasound examination during the period from 1 to 156 h after birth. Many had from one to three additional examinations when returning for well-baby checks. Three methods [overlapping intervals (smoothed percentages), life table, and geometric distribution] were used to construct the approximate distributions of completely closed, partially open, and open ventricles. RESULTS: Using smoothed percentages it was estimated that within 12 h of birth, 80% of newborns had closed lateral ventricles, 19% had partially open ventricles, and only 1% were completely open. The estimated median time from birth to partially open ventricles was in the period 36 to 60 h. The life table gave the estimated median time to partially open ventricles as 74 h. Fitting the data to a geometric distribution gave an estimated mean of 63 h. CONCLUSION: The majority of normal newborns have closed lateral ventricles following vaginal delivery and these are partially opened by day 3 after birth.

The delirium rating scale in children and adolescents.

The study of delirium has been neglected in pediatric patients, and there are no diagnostic criteria or rating scales adapted for use in this age group. The Delirium Rating Scale is widely used to diagnose and rate the severity of delirium in adults. It was retrospectively administered to 84 children and adolescents diagnosed with delirium to evaluate its applicability in pediatric patients. Delirium Rating Scale scores were comparable to those reported for delirium in adults, although single cross-sectional Delirium Rating Scale scores did not predict length of hospital stay or mortality outcome. Therefore, the Delirium Rating Scale can be used to evaluate delirium in the pediatric population.

Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors.

BACKGROUND: In the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial neuroglial tumors in the Childhood Brain Tumor Consortium database. METHODS: The Cox proportional models were used to identify class survival covariates. RESULTS: Age was found to be a survival covariate only in Class 1, in which older age increased the 5-year survival rate 73% from the first year (0.49) to the tenth year (0.85). A greater amount of tumor removed improved survival in Classes 2 and 4 only. Rosenthal fibers improved survival in Class 2 and overrode the negative effects of high Proliferative factor scores and pleomorphic nuclei. Survival for Class 3 children with high Proliferative factor scores improved from 0.60 to 0.95 as the Spongy factor scores increased. Survival in Class 4 increased from 0.17 to 0.39 with total tumor removal. Irregular nuclei and glomeruloid capillaries improved survival in Class 5 patients. Class 6 survival improved with low cell density. Macrocysts in tumors in Classes 1 and 5 were found to improve survival. CONCLUSIONS: As a result of the current study, the authors conclude that survival covariates differ with tumor class and may modify prognosis considerably.

Bone, muscle, and fat: sex-related differences in prepubertal children.

PURPOSE: To determine whether there are sex-related differences in vertebral cross-sectional dimensions, in paraspinous muscle area, and in the amount of fat in the subcutaneous and visceral compartments of prepubertal boys and girls. MATERIALS AND METHODS: Subcutaneous fat, visceral fat, paraspinous musculature, and vertebral cross-sectional dimensions were studied in 31 pairs of prepubertal healthy white girls and boys 5-10 years of age, rigorously matched for age, height, and weight. Data were analyzed with the Student t test and multiple regression analysis. RESULTS: Sex had a differential effect on fat accumulation and musculoskeletal development. Compared with boys, girls had, on average, 28% greater total fat and 30% higher subcutaneous fat (P <.001 for both), but 10% less paraspinous musculature (P =.002) and 15% smaller vertebral cross-sectional dimensions (P <.001). In contrast, the sexes were monomorphic for visceral fat (P =.24). Stepwise regression analysis indicated that only 22% of the difference in vertebral cross-sectional area could be explained by sex-related differences in paraspinous musculature. CONCLUSION: Together, these data indicate that sex is an important determinant of the morphology in humans well before the beginning of puberty.

Globus pallidus glial pigment and its changes with age and chronic illness in childhood.

Glial lipopigment appears in the globus pallidus without accumulating in neurons (except for late adolescence) in multiple chronic childhood diseases. In this observational study, we compared the age-related development of glial pigmentation in children with the chronic illness (cystic fibrosis) and children dying acutely. A secondary goal was to search for pallidal neuronal lipopigment in childhood. We recorded pigmentation in the brains of 37 consecutive cystic fibrosis children ranging in age from 0-23 yr and in 17 controls ranging in age from 0-18 yr. We characterized the lipofuscin histochemically and used several regression models to describe the mode of deposition. We observed that in the controls, intraglial pallidal pigment accumulated in 2 forms (relatively large globules and, separately, as clusters of fine granules) at a slow rate during childhood. In cystic fibrosis, both forms of pallidal glial pigment started accumulating at a younger age and were deposited far more rapidly. There was a further increase in the rate of accumulation between 8 and 10 yr of age. We did not encounter pallidal neuronal lipofuscin at any age. These observations are consistent with 2 propositions: 1) that globus pallidus glial cells are unique in their ability to accumulate lipofuscin before it accumulates in nearby neurons; and 2) that they are particularly susceptible to some systemic effect of this chronic illness.