Nonfunctioning Adrenocortical Carcinoma in Pediatric Acute Lymphoblastic Leukemia: A Case Report of a Rare Multiple Primaries Combination.

Childhood adrenocortical carcinoma (ACC) is a rare tumor and its association with acute lymphoblastic leukemia (ALL) is even rarer. One such case is discussed in this case report. A 3-year-old patient was concomitantly diagnosed with ALL and an initially nonmetastatic ACC. Management started by following the Total XV protocol without a window phase. Left adrenalectomy was conducted after the consolidation phase. Recurrence of a mass at the tumor bed was discovered at week 33 of the continuation phase. Reexcision was conducted, followed by the administration of an ACC protocol including cisplatin, etoposide, and doxirubicin. Mitotane was added when a pulmonary metastasis was discovered and then stopped after the patient suffered from an arachnoid cyst and speech difficulties. The ALL protocol was resumed from week 34 of the continuation phase. Progression of pulmonary nodules was noted after week 45. A pulmonary metastectomy was performed. The ALL protocol was resumed up to week 51 with a good response as proven by assessment of minimal residual disease. A further recurrence was diagnosed at the abdominal tumor bed with a paravertebral mass and a pulmonary nodule. The patient was assigned to palliative treatment and died after a 32-month survival. Such rare associations need more extensive discussions of the best possible management in scientific literature.

Latent Class Analysis of Neurodevelopmental Deficit After Exposure to Anesthesia in Early Childhood.

INTRODUCTION: Although some studies have reported an association between early exposure to anesthesia and surgery and long-term neurodevelopmental deficit, the clinical phenotype of children exposed to anesthesia is still unknown. METHODS: Data were obtained from the Western Australian Pregnancy Cohort Study (Raine) with neuropsychological tests at age 10 years measuring language, cognition, motor function, and behavior. Latent class analysis of the tests was used to divide the cohort into mutually exclusive subclasses of neurodevelopmental deficit. Multivariable polytomous logistic regression was used to evaluate the association between exposure to surgery and anesthesia and each latent class, adjusting for demographic and medical covariates. RESULTS: In our cohort of 1444 children, latent class analysis identified 4 subclasses: (1) Normal: few deficits (n=1135, 78.6%); (2) Language and Cognitive deficits: primarily language, cognitive, and motor deficits (n=96, 6.6%); (3) Behavioral deficits: primarily behavioral deficits, (n=151, 10.5%); and (4) Severe deficits: deficits in all neuropsychological domains (n=62, 4.3%). Language and cognitive deficit group children were more likely to have exposure before age 3 (adjusted odds ratio [aOR], 2.11; 95% confidence interval [CI], 1.17-3.81), whereas a difference in exposure was not found between Behavioral or Severe deficit children (aOR, 1.00; 95% CI, 0.58-1.73, and aOR, 0.85; 95% CI, 0.34-2.15, respectively) and Normal children. CONCLUSIONS: Our results suggest that in evaluating children exposed to surgery and anesthesia at an early age, the phenotype of interest may be children with deficits primarily in language and cognition, and not children with broad neurodevelopmental delay or primarily behavioral deficits.

The association between brain injury, perioperative anesthetic exposure, and 12-month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study.

BACKGROUND: Adverse neurodevelopmental outcomes are observed in up to 50% of infants after complex cardiac surgery. We sought to determine the association of perioperative anesthetic exposure with neurodevelopmental outcomes at age 12 months in neonates undergoing complex cardiac surgery and to determine the effect of brain injury determined by magnetic resonance imaging (MRI). METHODS: Retrospective cohort study of neonates undergoing complex cardiac surgery who had preoperative and 7-day postoperative brain MRI and 12-month neurodevelopmental testing with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the first 12 months of life. RESULTS: From a database of 97 infants, 59 met inclusion criteria. Mean ± sd composite standard scores were as follows: cognitive = 102.1 ± 13.3, language = 87.8 ± 12.5, and motor = 89.6 ± 14.1. After forward stepwise multivariable analysis, new postoperative MRI injury (P = 0.039) and higher VAA exposure (P = 0.028) were associated with lower cognitive scores. ICU length of stay (independent of brain injury) was associated with lower performance on all categories of the Bayley-III (P < 0.02). CONCLUSIONS: After adjustment for multiple relevant covariates, we demonstrated an association between VAA exposure, brain injury, ICU length of stay, and lower neurodevelopmental outcome scores at 12 months of age. These findings support the need for further studies to identify potential modifiable factors in the perioperative care of neonates with CHD to improve neurodevelopmental outcomes.

Estimated effects of in utero cocaine exposure on language development through early adolescence.

The potential longitudinal effects of prenatal cocaine exposure (PCE) on language functioning were estimated from early childhood through early adolescence in a large, well-retained urban sample of 451 full-term children (242 cocaine-exposed, 209 non-cocaine-exposed) participating in the Miami Prenatal Cocaine Study (MPCS). The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview, and toxicology assays of maternal and infant urine, and infant meconium. Age-appropriate versions of the Clinical Evaluation of Language Fundamentals (CELF) were used to measure total, expressive, and receptive language at ages 3, 5, and 12years. Longitudinal latent growth curve (LLGC) modeling of the data revealed an association between PCE (measured dichotomously as yes/no) and lower functioning in expressive and total language scores, after considering other sources of variation including child's age at testing, sex, prenatal exposure to alcohol, marijuana, and tobacco, and additional medical and social-demographic covariates. Analyses of level of PCE showed a gradient, i.e. dose-dependent, relationship between PCE level and expressive, receptive, and total language scores in the models controlling for age, child's sex, and other prenatal drug exposures. With additional covariate control these findings were most stable for the total language score. The evidence supports an inference about an enduring stable cocaine-specific effect on children's language abilities, with no effect on language growth over time in the longitudinal trajectory of language development.

The impact of maternal smoking on fast auditory brainstem responses.

Deficits in auditory processing have been posited as one of the underlying neurodevelopmental consequences of maternal smoking during pregnancy that leads to later language and reading deficits. Fast auditory brainstem responses were used to assess differences in the sensory processing of auditory stimuli among infants with varying degrees of prenatal cigarette exposure. Maternal report of consumption of cigarettes and blood samples were collected in the hospital to assess exposure levels and participants were then seen at 6-months. To participate in the study, all infants had to pass the newborn hearing exam or a clinically administered ABR and have no known health problems. After controlling for participant age, maternal smoking during pregnancy was negatively related to latency of auditory brainstem responses. Of several potential covariates, only perinatal complications and maternal alcohol use were also related to latency of the ABR responses and maternal smoking level accounted for significant unique variance after controlling for these factors. These results suggest that the relationship between maternal smoking may lead to disruption in the sensory encoding of auditory stimuli.

[Characterization of language disorders in children with lead poisoning]. / Caracterização das alterações de linguagem em crianças com histórico de intoxicação por chumbo.

BACKGROUND: lead poisoning can have a negative impact on the neuropsychological functions, including language, due to the damage it causes to the development of the Central Nervous System. AIM: to verify the occurrence of language disorders in children who suffered from led poisoning and to verify the correlation between the lead concentration level in the blood and the language disorders presented by the children. METHOD: language evaluation of 20 preschoolers, with lead concentration level in the blood above 10 microg/dl. RESULTS: 13 children presented language impairment involving only phonology or more than one language subsystem. The statistical analysis indicated that no correlation exists between the severity of the language impairment and the concentration levels of lead. CONCLUSION: the number of children with language impairment indicates lead poisoning as a risk factor for the present alterations, even though other risk factors for language disorders were found and the absence of correlation between the investigated variables.

Caracterização das alterações de linguagem em crianças com histórico de intoxicação por chumbo / Characterization of language disorders in children with lead poisoning

TEMA: a intoxicação por chumbo pode causar deficiências neuropsicológicas, que incluem a linguagem, devido aos danos provocados no desenvolvimento do SNC. OBJETIVO: verificar a ocorrência de alterações de linguagem em crianças com histórico de intoxicação por chumbo e a correlação entre o índice de chumbo sangüíneo e as alterações de linguagem apresentadas pelas crianças. MÉTODO: avaliação da linguagem de 20 crianças em idade pré-escolar, com índice de chumbo sangüíneo acima de 10 µg/dl. RESULTADOS: 13 crianças apresentaram distúrbio de linguagem envolvendo somente a Fonologia ou mais de um subsistema lingüístico. A análise estatistica revelou não existir correlação entre a gravidade das alterações e os índices de chumbo apresentado. CONCLUSÃO: a ocorrência de crianças com distúrbio de linguagem aponta a contaminação por chumbo como um fator de risco para as alterações apresentadas, mesmo tendo sido encontrados outros fatores que levem à defasagem no desenvolvimento da linguagem e ausência de correlação entre as referidas variavéis.

BACKGROUND: lead poisoning can have a negative impact on the neuropsychological functions, including language, due to the damage it causes to the development of the Central Nervous System. AIM: to verify the occurrence of language disorders in children who suffered from led poisoning and to verify the correlation between the lead concentration level in the blood and the language disorders presented by the children. METHOD: language evaluation of 20 preschoolers, with lead concentration level in the blood above 10µg/dl. RESULTS: 13 children presented language impairment involving only phonology or more than one language subsystem. The statistical analysis indicated that no correlation exists between the severity of the language impairment and the concentration levels of lead. CONCLUSION: the number of children with language impairment indicates lead poisoning as a risk factor for the present alterations, even though other risk factors for language disorders were found and the absence of correlation between the investigated variables.

Neonatal nicotine exposure impairs nicotinic enhancement of central auditory processing and auditory learning in adult rats.

Children of women who smoke cigarettes during pregnancy display cognitive deficits in the auditory-verbal domain. Clinical studies have implicated developmental exposure to nicotine, the main psychoactive ingredient of tobacco, as a probable cause of subsequent auditory deficits. To test for a causal link, we have developed an animal model to determine how neonatal nicotine exposure affects adult auditory function. In adult control rats, nicotine administered systemically (0.7 mg/kg, s.c.) enhanced the sensitivity to sound of neural responses recorded in primary auditory cortex. The effect was strongest in cortical layers 3 and 4, where there is a dense concentration of nicotinic acetylcholine receptors (nAChRs) that has been hypothesized to regulate thalamocortical inputs. In support of the hypothesis, microinjection into layer 4 of the nonspecific nAChR antagonist mecamylamine (10 microM) strongly reduced sound-evoked responses. In contrast to the effects of acute nicotine and mecamylamine in adult control animals, neither drug was as effective in adult animals that had been treated with 5 days of chronic nicotine exposure (CNE) shortly after birth. Neonatal CNE also impaired performance on an auditory-cued active avoidance task, while having little effect on basic auditory or motor functions. Thus, neonatal CNE impairs nicotinic regulation of cortical function, and auditory learning, in the adult. Our results provide evidence that developmental nicotine exposure is responsible for auditory-cognitive deficits in the offspring of women who smoke during pregnancy, and suggest a potential underlying mechanism, namely diminished function of cortical nAChRs.

Longitudinal influence of prenatal cocaine exposure on child language functioning.

The present study estimates the longitudinal effects of in utero cocaine exposure on language functioning at 3, 5 and 7 years of age in an urban sample of 443 full-term children (236 cocaine-exposed and 207 noncocaine-exposed) participating in the Miami Prenatal Cocaine Study. The sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and urine and meconium toxicology assays. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal Generalized Linear Model and Generalized Estimating Equations (GLM/GEE) analyses revealed an association between prenatal cocaine exposure and deficits in total language functioning after statistically controlling for child sex, visit age, prenatal exposure to alcohol, marijuana and tobacco and over 20 additional medical and sociodemographic covariates drawn from potentially confounding influences assessed at birth and follow-up visits (D=-0.17; 95% CI=-0.32, -0.03; P=.019). The link from prenatal cocaine exposure to later language deficits does not appear to be mediated by cocaine-associated deficits in birth weight, length or head circumference. Overall, the evidence tends to support an inference of a stable cocaine-specific effect on indicators of language functioning during early childhood through age 7 years.

Expressive language development of children exposed to cocaine prenatally: literature review and report of a prospective cohort study.

It was hypothesized that prenatal exposure to cocaine and other substances would be related to delayed expressive language development. Speech and language data were available for 458 6-year olds (204 were exposed to cocaine). No significant univariate or multivariate differences by cocaine exposure group were observed. Classification and regression tree modeling was then used to identify language variable composites predictive of cocaine exposure status. Meaningful cut points for two language measures were identified and validated. Children with a type token ratio of less than 0.42 and with fewer than 97 word types were classified into a low language group. Low language children (n = 57) were more likely to be cocaine exposed (63.1%), with cocaine-exposed children 2.4 times more likely to be in the low language group compared with control children after adjustment for covariates. Prenatal cigarette, but not alcohol exposure, was also significantly related to expressive language delays.

History of in utero cocaine exposure in language-delayed children.

To determine whether children with language delays are more likely to have been exposed to cocaine in utero than children with normal language development, a case-control study was undertaken. Based on routine office screening in our primary-care clinic over a 1-year period, we identified 29 consecutive children, aged 24 to 48 months, as language-delayed. They were compared with an approximate 2:1 match of children without language delay who had been seen in the clinic on the same days and who were of similar age. There was more reported cocaine use during pregnancy (six of 29, 21%) among the language-delayed children than among the controls (five of 71, 7%). This difference is statistically significant (P < 0.05, chi 2 = 3.92; odds ratio = 3.4 +/- 2.2). Discriminant analysis revealed that both cocaine and nicotine exposure were associated with delayed language development--with an unexpected negative, i.e., an antagonistic, protective, interactive effect (F[3,96] = 4.66, R2 = 12.7%, P < .005); neither gender nor caretaker contributed to language development in this sample. These results suggest that children with language delay detected in a clinical setting are more likely to have been exposed in utero to cocaine than children with normal language development. Prenatal cocaine exposure should be a risk factor in monitoring development in children.