Abnormal microstructure of the atrophic thalamus in preterm survivors with periventricular leukomalacia.

BACKGROUND AND PURPOSE: The neuroanatomic substrate of cognitive deficits in long-term survivors of prematurity with PVL is poorly understood. The thalamus is critically involved in cognition via extensive interconnections with the cerebral cortex. We hypothesized that the thalamus is atrophic (reduced in volume) in childhood survivors of prematurity with neuroimaging evidence of PVL and that the atrophy is associated with selective microstructural abnormalities within its subdivisions. MATERIALS AND METHODS: We performed quantitative volumetric and DTI measurements of the thalamus in 17 children with neuroimaging evidence of PVL (mean postconceptional age, 5.6 ± 4.0 years) who were born prematurely and compared these with 74 term control children (5.7 ± 3.4 years). RESULTS: The major findings were the following: 1) a significant reduction in the overall volume of the thalamus in patients with PVL compared with controls (P < .0001), which also correlated with the severity of PVL (P = .001); 2) significantly decreased FA (P = .003) and increased λ(⊥) (P = .02) in the thalamus overall and increased axial, radial, and mean diffusivities in the pulvinar (P < .03), suggesting injury to afferent and efferent myelinated axons; and 3) a positive correlation of pulvinar abnormalities with those of the parieto-occipital white matter in periventricular leukomalacia, suggesting that the pulvinar abnormalities reflect secondary effects of damaged interconnections between the pulvinar and parieto-occipital cortices in the cognitive visual network. CONCLUSIONS: There are volumetric and microstructural abnormalities of the thalamus in preterm children with PVL, very likely reflecting neuronal loss and myelinated axonal injury. The selective microstructural damage in the pulvinar very likely contributes to abnormal cognitive visual processing known to occur in such survivors.

In utero eye development documented by fetal MR imaging.

BACKGROUND AND PURPOSE: To date, very limited attention has been given to ocular abnormalities or growth parameters detected by fetal MR imaging. Our objective was to retrospectively determine the relationship between different parameters of eye development and estimated gestational age in the human fetus by use of fetal MR imaging. MATERIALS AND METHODS: A retrospective study was performed to measure the transverse diameter, interocular distance, and lens diameter of the globes of 127 fetuses who had a morphologically normal central nervous system. Multiple single-shot T2 fast spin-echo images were obtained with a 1.5T magnet by use of contiguous 3-mm intervals in at least 2 orthogonal planes. Loess curves were fitted to explore the relationship between gestational age and each of the 3 measurements of interest. Different models were compared statistically to determine the model of best fit. RESULTS: For each variable of interest, the "best" model of eye growth was a quadratic function. Specifically, lens growth seems to plateau after 36 weeks of gestation, interocular distance plateaus after 36 weeks of gestation, and globe growth plateaus after 42 weeks of gestation. CONCLUSIONS: The lens, orbit, and interocular distance growth of the fetus can be demonstrated on fetal MR imaging. All 3 measurements suggest a quadratic model of growth, which indicates slowing of growth toward the end of gestation.

Definitive classes of childhood supratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Our objective in this study was to identify histologically homogenous classes of childhood supratentorial neuroglial tumors. Previously, we identified five quantitative histologic factors (differing linear combinations of 17 reliably recognized histologic features in neuroglial tumors). They account for much of the histologic variance in the 703 supratentorial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the factors in cluster analyses and identified eight classes of neuroglial tumors. Each of these classes had significant differences in histology, allowing the separation of many of the conventional types of neuroglial tumors into two or more classes. For instance, fibrillary astrocytoma, pilocytic astrocytoma, subependymal giant cell astrocytoma, anaplastic astrocytoma, oligodendroglioma, and ependymoma were represented in two or more classes. Often these classes had statistically significant differences in survival distributions. For instance, the two classes of "anaplastic astrocytomas" have widely discrepant 5-year survival probabilities of 0.7 and 0.2. Use of the classes identified in this study ensures relatively homogeneous histologic subsets of tumors. We suggest that these classes will be useful for the selection of children for therapeutic clinical trials.

Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors. Children Brain Tumor Consortium.

BACKGROUND: In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. METHODS: The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors. RESULTS: Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas. When the specific combinations of the three features were unambiguously designated, three diagnostic categories resulted. These revised diagnostic categories are consistent with WHO guidelines and have significantly different survival distributions. However, neither the original WHO diagnoses nor the revised categories adequately separated these tumors prognostically, because histologic features other than those specified by WHO were significantly associated with improved or worsened survival. CONCLUSIONS: Classifications based on small numbers of specified histologic features may not be feasible because they inadequately separate childhood astrocytic tumors into prognostically homogeneous groups. Preferable classification techniques are those that simultaneously account for all reliably recognized histologic features.

Prognostic limitations of the Daumas-Duport grading scheme in childhood supratentorial astroglial tumors.

The Daumas-Duport grading scheme (DDGS) is a commonly used method for determining the grade of a tumor. It scores 4 histologic features and is used as a prognostic tool in adult astroglial tumors. This system of assigning children to prognostically homogeneous groups has not been evaluated. The Childhood Brain Tumor Consortium (CBTC) database includes 327 children with a CBTC assigned World Health Organization (WHO) diagnosis of supratentorial astroglial tumor and histologic features necessary for Daumas-Duport grading. We compared survival estimates for tumors within and between DDGS grades using a slightly broadened definition of endothelial prominence. The DDGS yielded only 3 histologic groups in children and only 2 prognostically differing groups. Subgroups within DDGS grades had significantly different survival distributions. The summing of 4 disparate histologic features in the DDGS is inadequate for the assessment of childhood supratentorial astroglial tumors. A classification system more fully summarizing the complete histologic content of tumors is most likely to provide diagnoses useful for clinical purposes.

Clusters of histologic characteristics in children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Five quantitative histologic factors, differing linear combinations of 26 reliably recognized histologic features, account for much of the histologic variance in 1068 children with infratentorial neuroglial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the Spongy, Proliferative, Ring, Fibrillary, and Nuclear factors in cluster analyses and identified 11 clusters of children's tumors. Each had statistically significant differences in histology and relative histologic homogeneity. Three clusters had ependymoma-like histologic features; 4 had astrocytoma-like features; and 4 had primitive neuroectodermal-like (PNET or medulloblastoma) features. Each cluster had a unique high/low mean factor score pattern. Multiple operative and other clinical features characterized the three groups of clusters. We used Kaplan-Meier survival models to test for differences in survival among clusters and proportional hazards survival models to adjust for associated covariates. Among the 'ependymoma' clusters the 5 year survival probability ranged from 0.25 to 0.54. Among the 4 'astrocytoma' clusters, 5 year survival probability ranged from 0.59 to 0.94. The 5 year survival probability for the 'medulloblastoma' clusters ranged from 0.20 to 0.44. Within the three groups, clusters had differing covariates associated with survival. The tumor clusters identified in this study ensure relatively homogeneous histologic subsets. The five factor scores of a child's tumor provide the basis for finding the cluster nearest to that tumor. We propose that this tumor clustering strategy be employed for selection of children and for analyses of therapeutic clinical trials.

Prognosis for children with supratentorial neuroglial tumors.

Factor analysis of reliably identified histologic features in supratentorial glial tumors yielded five interpretable "factors": Spongy, Fibrillary, Proliferative, Jumbo, and Oligodendroglial. Quantitative scores can be calculated for each factor in a tumor to summarize its heterogeneity. The objective was to investigate whether factor scores are useful for prognostic purposes. The sample consisted of 703 children with supratentorial neuroglial tumors with factor scores for each of the five factors. Data were based on the presence or absence of 26 reliably identified histologic features, plus clinical and survival information. Multivariate proportional hazards models assessed each factor's contribution to survival for children who survived 1 month after operation (n = 609). Patient-specific clinical data were allowed in the models. Increased likelihood of survival is associated with greater tumor removal, later decade of surgery, and high Spongy and high Oligodendroglial factor scores. Decreased likelihood of survival is associated with high Proliferative factor scores and radiation and/or chemotherapy treatment. Gender, age, location, and Jumbo and Fibrillary factor scores did not provide additional prognostic information. Three reliable histologic features, nondefining for any histologic factor, added prognostic information: Rosenthal fibers and glomeruli are associated with improved prognosis; pleomorphic nuclei are associated with worse prognosis. A high Oligodendroglial factor score is associated with a worse prognosis for some classes of astrocytoma but with a better prognosis for oligodendroglial tumors. A high Proliferative score is associated with a worse prognosis for anaplastic astrocytomas, ependymomas, and unclassifiable tumors. A high Spongy score is associated with a better prognosis for anaplastic astrocytomas but with a worse prognosis for pilocytic astrocytomas. For giant cell astrocytomas, gangliogliomas, and miscellaneous tumors, none of the factors is prognostic. Spongy, Oligodendroglial, and Proliferative factors provide important prognostic information for children with supratentorial neuroglial tumors.

Quantitative histologic factors for grouping childhood supratentorial neuroglial tumors.

The histologic heterogeneity of childhood supratentorial neuroglial tumors, when quantified, identifies relatively homogeneous subgroups for prognostic purposes and for assignment in clinical trials. Our sample consisted of supratentorial tumors in the Childhood Brain Tumor Consortium. The data consist of reliably identified histologic features and demographic, clinical, operative, and survival information. Factor analysis was used to identify uncorrelated "factors," each represented by a different combination of histologic features in 703 tumors. The defining histologic features were used to label each factor. The heterogeneity of each tumor was summarized using the factor scores for each factor. We compared the survival estimates of subgroups of tumors within common diagnostic classes. We identified five uncorrelated quantitative factors that accounted for much of the histologic variation. Our factor labels were Jumbo, Fibrillary, Proliferative, Spongy, an Oligodendroglial. Two thirds of tumors had high scores on two or more factors, indicating a high degree of heterogeneity among these tumors. Eighty-four percent of supratentorial tumors were accounted for by 19 nonoverlapping relatively homogeneous histologic groups. The five quantitative factors complement standard qualitative taxonomies by summarizing more completely the histologic feature aspects of a tumor than by diagnosis alone and quantify the histologic heterogeneity of individual tumors. Histologically homogeneous groups of tumors are essential for clinical trials, biologic research, and prognostic models.

Quantitative histologic factors for grouping childhood infratentorial neuroglial tumors.

We employed factors analysis to quantify the degree of histologic heterogeneity of childhood infratentorial neuroglial tumors. Our data were 26 reliably ascertained histologic features in 1068 children in the Childhood Brain Tumor Consortium database. The factor analysis identified five uncorrelated quantitative "factors," each derived from a different linear combination of the 26 histologic features, that accounted for much of the histologic variation. Histologic features differed in their importance in each factor. The most important features in each factor were used for naming using simple, histologic, familiar descriptive terms: Spongy, Proliferative, Ring, Fibrillary, and Nuclear. Each tumor has a score on each factor. Two-thirds of tumors had high scores for at least two factors, indicating frequent histologic heterogeneity among these tumors. Ninety-five percent of tumors were allocated to 1 of 11 nonoverlapping histologically homogeneous groups. The five quantitative factors complement standard qualitative taxonomies by making explicit the histologic heterogeneity or homogeneity of individual tumors and provide the pathologist with a method that takes advantage of more of the histology of each tumor than conventional nomenclatures. Histologically homogeneous groups of tumors are likely to be of value in clinical trials and biologic research. Prognostic models based on these factors have been published.

Survival of children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

OBJECTIVE: The goal of this study is the improvement of the prognostic information associated with conventional diagnoses. Our previous factor analysis of 26 reliably identified histological features in infratentorial childhood neuroglial tumors yielded five interpretable, uncorrelated, quantitative histological factors that we named spongy, fibrillary, proliferative, nuclear, and ring. Five quantitative scores, one for each of the five factors, provide an objective method for quantifying the histological heterogeneity of a tumor. The scores, alone or in conjunction with conventional diagnoses, identify groups of histologically homogeneous tumors. METHODS: Multivariate Cox proportional hazards models were developed to assess the contribution of each factor to survival prognosis, after allowing patient-specific demographic and clinical data in the models as covariates. Hazard ratios, estimated for each statistically significant factor and covariate in the multivariate model, provide the basis for the determination of the prognosis. The hazard ratio is the ratio of the hazard function for subjects with an attribute, e.g., an age of 10 years, to the hazard function for subjects who have some chosen baseline attribute, e.g., an age of 1 year. The important criterion of this ratio is beta, a statistic estimated from the survival data in the Childhood Brain Tumor Consortium database of infratentorial neuroglial tumors. Kaplan-Meier survival curves were used to investigate differences in the survival of factor-determined subgroups of patients with various diagnoses. RESULTS: An increased likelihood of survival is associated with older age, more tumor removal, more recent decade of surgical intervention, and high spongy and fibrillary factor scores. A decreased likelihood of survival is associated with high nuclear, proliferative, and ring factor scores. Gender, location within the infratentorial compartment, and subsequent treatment did not add prognostic information. For certain subgroups of astrocytoma and for ependymoma and medulloblastoma, factors are important in predicting survival with greater accuracy. CONCLUSION: Factor scores provide clinically useful quantitative estimates of survival probability that are more specific and accurate than the general estimates based on the conventional diagnosis alone.

Age-related changes in diagnoses, histological features, and survival in children with brain tumors: 1930-1979. The Childhood Brain Tumor Consortium.

In the Childhood Brain Tumor Consortium database, the proportions of older children (> or = 11 yr) with pilocytic astrocytomas, fibrillary astrocytomas, and ependymomas significantly increased (P < 0.05) over the 50 years (1930-1979) of the study. The increased proportions of pilocytic astrocytomas occurred whether the tumors were located in the supratentorial or infratentorial compartments. The increases in fibrillary astrocytomas and ependymomas were found only within the supratentorial tumor location. Some histological features found in pilocytic astrocytomas (e.g., Rosenthal fibers, granular bodies, and very low cell density) were more likely to be found in older children. Other histological features were also more likely to be found in older children (e.g., parenchymal calcification, intertwined fascicles, intermediate and large-size nuclei, pleomorphic, elongated, or irregular nuclei, prominent nucleoli, multinucleated cells, thick hyaline blood vessels, hemosiderin, and parenchymal and perivascular lymphocytes). The probability of 5-year survival for young children with supratentorial ependymomas remained at approximately 0.4 in contrast to that for young children with infratentorial ependymomas, for whom it improved, but without significant linear trend. The probability of 5-year survival for both younger and older children with primitive neuroectodermal tumors (medulloblastomas) improved, but without significant linear trend. The changes in the proportions of childhood brain tumors and histological features occurred without similar changes in the proportions of older and younger children in the cities involved between 1930 and 1979. These changes were so distinctive as to raise the possibility of significant shifts in environmental exposures in younger and older children over the 50 years of this study.

Misclassification of a prognostic dichotomous variable: sample size and parameter estimate adjustment.

Under general conditions, Lagakos showed that for an explanatory variable observed with error, the asymptotic relative efficiency (ARE) when using the observed rather than the true values in linear models, logistic models and proportional hazards models for survival is the square of the correlation between the true and observed variables. The result is useful for sample size adjustment when this correlation is estimable. Often, one cannot observe correct values of the explanatory variable under any circumstances. We show, however, that under the models considered by Lagakos for a dichotomous explanatory variable, the ARE equals the kappa statistic in a read-reread protocol. Consequently, one need not know 'truth' in this situation to estimate the ARE and to adjust sample size to maintain desired power; divide the estimated sample size obtained with the assumption of no measurement error by the consistent estimate of the kappa statistic (which is unlikely to be zero or negative). We then develop heuristically an adjusted estimate of the beta parameter in a proportional hazards survival model. The work was motivated by analyses of the Childhood Brain Tumour Consortium database. Examples from this database illustrate the method.

The applicability of Collins' Law to childhood brain tumors and its usefulness as a predictor of survival.

In 1955, Collins made the observation that tumor recurrence in children with Wilms' tumor was correlated with the child's age plus 9 months. This concept of a period of risk for recurrence was later applied to a variety of tumors in children and became known as Collins' Law (CL). The law has been a successful predictor of survival for some children with neural tumors within the central nervous system and a poor predictor for others. We tested Collins' concept of a period of risk for recurrence and extended it to survival for 14 childhood neural tumors described in the Childhood Brain Tumor Consortium (CBTC) database. The CBTC data describe clinical, surgical, and histological details (over a 49-year period in 10 institutions) from 3921 patients under the age of 21 years at the time of their first surgical procedure for a brain tumor. CL was considered to be a good predictor of survival if fewer than 10% of patients who die survive beyond the expiration of the period of risk for that child. We found that CL applied to tumors such as anaplastic astrocytoma, glioblastoma, pineoblastoma, medulloblastoma or "primitive neuroectodermal tumor," teratoma, and germinoma, as well as ependymoma, papilloma, and tumors that could not be classified; it had no predictive value in craniopharyngioma, oligodendroglioma, or plain, fibrillary, pilocytic, or protoplasmic astrocytoma. We had sufficient follow-up data to determine adherence to CL when the child's age at diagnosis was less than 8 years; it is likely that CL applies to older children with these tumors, but we did not have the data to show this unequivocally.

Medulloblastoma and Collins' law: a critical review of the concept of a period of risk for tumor recurrence and patient survival.

Collins' law (CL) states that the period of risk for recurrence for a tumor is the age of the patient plus 9 months. Originally a clinical observation in Wilms' tumor, CL has been applied to other tumors such as medulloblastoma (MB). Although CL does not apply to all childhood tumors, it seems to be a valid observation for childhood MB, despite several reports of violations or exceptions to CL in the literature. We sought to test CL in a large population of children with MB from the Childhood Brain Tumor Consortium (CBTC). We analyzed data from 602 children with MB, of whom 421 died and 181 were censored but alive at the last follow-up. We found 16 additional CL exceptions to supplement the 22 already present in the literature. This is both the greatest number of exceptions and the largest MB study population for CL reported to date. We provide clinical data on our 16 uncensored exceptions to CL and critically review those 22 cases cited previously in the literature. All of the CBTC exceptions were under 6 years of age at the time of initial diagnosis and were followed for an average of 7.5 years. All 16 CBTC exceptions died. Children older than 8 years of age could not be followed for a sufficient period of time to be able to state whether CL applies; as age at initial diagnosis increases, the period of observation required to determine CL validity becomes impractically long. Exceptions to CL are rare and amounted to 3.8% of 405 uncensored CBTC patients who died.(ABSTRACT TRUNCATED AT 250 WORDS)

Histologic feature reliability in childhood neural tumors. Childhood Brain Tumor Consortium.

We studied intraobserver reproducibility in recognizing the presence or absence of 57 histologic feature or patterns in a random subset of tumors (822) from the Childhood Brain Tumor Consortium database. The study protocol maximized consistency of the observer. We found that only six histologic features had high (> or = 0.75) reliability estimates while a large number had intermediate estimates of 0.50-0.74. Supratentorial or infratentorial tumor location sometimes altered reliability. Reliability estimates were unacceptable for certain histologic features often used as diagnostic criteria, descriptors of tumor characteristics, or markers of anaplasia. We hypothesize that low reliability reflects, in part, the need for more specific operational definitions, particularly those with subjective boundaries (e.g. granular bodies) may also contribute to low reliability. We also show that the kappa statistic, a commonly used measure of reliability, is inappropriate for very common or uncommon histologic features (e.g. features at the extremes of prevalence in the study cases) and we offer a simple empiric method for determining when an alternative measure, the Jaccard statistic, is appropriate.

Childhood brain tumors that occupy more than one compartment at presentation. Multiple compartment tumors.

Children whose brain tumor involves two or more compartments at presentation differ clinically and pathologically from children whose brain tumor is confined to one compartment. In this study of 3,291 children with a brain tumor, at least 10% had a tumor that occupied two or three compartments at first hospitalization. Infratentorial tumors occupying multiple compartments were 1.7 times more likely to involve the cervicomedullary junction than the mesodiencephalic junction. Younger children (1-3 years) were more likely to have had multiple compartment tumors than older children. Children whose tumor was limited to the infratentorial compartment had a longer survival than children whose tumor also occupied other compartments. Ependymoma, anaplastic ependymoma, and astrocytoma (nos) were over represented among infratentorial multiple compartment tumors. Pilocytic astrocytoma, primitive neuroectodermal tumor (medulloblastoma), and desmoplastic medulloblastoma were less likely to have occupied multiple compartments at the time of the first surgical exploration. The distributions of histologic features in tumors at the cervicomedullary junction differed from those in tumors limited to the posterior fossa or to the spinal canal. Seizures were more likely if the tumor was confined to the supratentorial compartment, whereas nausea or vomiting and headache were more likely if the tumor was confined to the infratentorial compartment. Children whose tumor was confined to the spinal canal were significantly more likely to have bladder symptoms and back and/or abdominal pain than those whose tumor also involved compartments above the foramen magnum. We conclude that brain tumors apparently confined to one compartment at presentation are biologically and structurally different from tumors evident in two or more compartments.

Temporal trends among childhood brain tumor biopsies. The Childhood Brain Tumor Consortium.

We sought temporal trends in the demographic, clinical, histologic feature, diagnostic class, and quality of life data over the interval 1930-1979 in the Childhood Brain Tumor Consortium database. The proportion of children younger than eight years old declined from 72% to 55% and the proportion of those older than ten more than doubled from 12% to 27%. The relative frequency of tumors in the supratentorial compartment increased significantly, while infratentorial tumors decreased. We found significant declines in supratentorial ependymomas and pilocytic astrocytomas. Similarly, some infratentorial tumors, especially ependymomas, decreased and brain stem tumors increased. Infratentorial medulloblastoma (primitive neuroectodermal tumor) increased significantly. Some individual histologic features which are markers of anaplasia increased in frequency in both supratentorial and infratentorial tumors. There was a significant increase in biopsies that contained nonneoplastic neural tissue in addition to tumor for both compartments and among supratentorial tumors there was a marked increase in the proportion of cases containing an indistinct neural tissue boundary. The probability of postoperative death declined, but the probability of survival five or ten years after surgery did not improve significantly for children who had tumors in either compartment. Among children who survived five years after the initial craniotomy, the proportion who had significant long term deficits increased. Most of this increase occurred in the last decade (1970-79). In this decade, the proportion of children for whom no deficits were reported five years following operation was 4% if they had a supratentorial tumor and 27% if they had an infratentorial tumor. The proportions of children alive five years following first surgery who had arachnoidal metastases increased significantly for infratentorial tumors.

Epidemiology of seizures in children with brain tumors. The Childhood Brain Tumor Consortium.

We examined potential clinical and pathologic correlates of seizures among the 3,291 children in the Childhood Brain Tumor Consortium database. Fourteen percent had seizures prior to their hospitalization for a brain tumor. Among children who had a supratentorial tumor, seizures occurred in 22% of those less than 14 years of age. The prevalence of seizures increased to 68% of older teenagers. Among children with an infratentorial tumor, the prevalence of seizures was relatively constant at 6% over all age groups. The onset of seizures began more than one year prior to surgical tumor removal in over half of the children aged five or more with supratentorial tumors, significantly longer than for those of the same age with infratentorial tumors. Almost all children (98.9%) with an infratentorial tumor and seizures had at least one other symptom and more than three-fourths of them had at least three. Eighty-nine percent of children with a supratentorial tumor and seizures had at least one other symptom and more than one-half had at least three symptoms. Regardless of whether the tumor was above or below the tentorium, confusion or stupor and coma were more common in children with seizures than in children without seizures. Among children with supratentorial tumors, symptoms of a declining academic performance or an abnormality of personality, speech, walking, or sensation were significantly more frequent in children with seizures, while visual symptoms (other than visual loss or diplopia) and nausea or vomiting were less frequent. Among children with supratentorial tumors, those who had seizures were more likely to have paralysis of an arm, hand, or face, confusion or stupor, or coma and less likely to exhibit irritability, papilledema, optic atrophy, decreased visual acuity, pupillary abnormalities, or abducens paresis. Among children with infratentorial tumors, those with seizures were significantly less likely to have truncal ataxia, but more likely to experience confusion, stupor, or coma. In the supratentorial compartment, astrocytoma (nos), protoplasmic astrocytoma, anaplastic astrocytoma, and ependymoma were more frequently associated with seizures than was craniopharyngioma. No infratentorial tumor type was more or less likely to be associated with seizures. All common tumor types that were represented in both the supratentorial and the infratentorial compartment except astrocytoma (nos) were associated with significantly greater rates of seizures when located in the supratentorial compartment. The tumor location with the highest incidence of seizures was, as expected, the superficial cerebrum. More than 40% of the children with such tumors had seizures.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of the Sheffield system for identifying children at risk from unexpected death in infancy. Results from Birmingham and Newcastle upon Tyne.

The "at birth" system which is used in Sheffield to identify children likely to die unexpectedly in infancy, was tested retrospectively in Birmingham (83 cases) and in Newcastle upon Tyne (56 cases). The discrimination between cases and age-matched controls was poor in both cities. Analysis of the 8 factors used in the system showed that only 2 maintained significant case/control differences in Birmingham and Newcastle. Further investigation showed that other factors from maternity records showed significant case/control differences in these cities. Although the system used in Sheffield would not be of use in a prospective prevention programme in either Newcastle or Birmingham, the possibility of evolving an "at risk" system which might apply more widely is discussed.