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PubMed1996

Cure of nocturnal enuresis: why isn't desmopressin very effective?

Prospective controlled studies on the treatment of enuresis with desmopressin (DDAVP) indicate that cure rates (complete dryness) while on therapy are markedly lower than are response rates (decrease in wet nights). In an attempt to explain this discrepancy, we analyzed the etiological mechanisms for enuresis and found evidence that most children are not cured by DDAVP because their nocturnal wetting is not actually caused by the defect which DDAVP therapy aims to cure: low nocturnal vasopressin secretion with high nocturnal urinary output. Our study suggested that an arrest in the normal development of two separate areas of the central nervous system is necessary for enuresis to occur in many patients, yet cure of enuresis occurs if either developmental delay is eliminated. This hypothesis of a dual developmental delay helps to unify many diverse and often seemingly contradictory scientific observations about this condition and to explain why many patients react inconsistently to treatment aimed at a single etiology, yet eventually become dry.

Circadian Rhythm↗

PubMed1987

The peer relations of mildly delayed and nonhandicapped preschool children in mainstreamed playgroups.

Previously unacquainted groups of normally developing and mildly developmentally delayed preschool-age boys (N = 64) were brought together to form a series of 8 mainstreamed playgroups. Each playgroup consisted of 3 normally developing 3-year-olds, 3 normally developing 4-year-olds, and 2 mildly developmentally delayed 4-year-olds. The delayed children were matched with the normally developing older group for chronological age and with the normally developing younger group for developmental level. Each playgroup operated 5 days per week for 2 hours per day for a 4-week period. During that time, the peer-related social and play interactions of each child were videotaped, and peer sociometric ratings were obtained at the completion of each playgroup. Analyses of social participation and individual social behavior measures revealed that the analogue playgroup setting was appropriate for evaluating peer interactions, as expected developmental patterns emerged despite the presence of children heterogeneous with respect to chronological age and developmental status. The existence of a deficit in peer-related social interactions for mildly delayed children was supported in this investigation--a deficit that could not be attributed to reputational factors, the unavailability of responsive peers, inadequate matching procedures, unusual sample characteristics, or similar factors. Selected observational measures, peer preference patterns during free play, and peer sociometric ratings also indicated that the delayed children were perceived to be less competent and of lower social status. However, despite their relative isolation, important developmental opportunities were available for mildly delayed children in the mainstreamed playgroups. Possible processes responsible for these outcomes were discussed.

Child, Preschool↗

PubMed2004

[Clinical analysis of 91 cases with articulation error].

OBJECTIVE: To study classification of the articulation errors, find the related factors which affect the therapy effect, and compare the therapy effect in the different patterns of the phonemic errors and build up a clinical model of the speech therapy on the basis of more than 4 years speech therapy in the clinic. METHOD: After excluding the organic articulation disorders, 91 cases of consonant phonemic errors were classified into different patterns according to the phonemic placement errors. The 91 cases were divided into two groups as effective one and ineffective one depending on whether the symptoms disappeared or not after the speech therapy. Ten factors including sex, age, oral-motor function problem, developmental delay, history of language development delay, history of middle ear affection, lingua frenata, mental retardation, the therapy frequency and times, were analyzed. The statistics software SPSS (SPSS Inc, 1997) was applied to show the factors related to the therapy effect by logistic multiple stepwise regression analysis. The therapy effect was compared between the single pattern (phonemic error < 2 groups) and multiple pattern (phonemic errors > or = 2 groups). RESULTS: The 91 cases with consonant phonemic errors were classified into four groups. The multiple pattern of the articulation errors was the most common (37 cases, 41%) among the 4 groups, followed by velar errors (33 cases, 36%). The third one was the apico-dental errors (12 cases, 13%) and the last one was the linguo-alveolar errors (8 cases, 9%). Only one case had labiodental error (/f/). The logistic multiple stepwise regression analysis showed that the history of the positive developmental delay, language delay and the frequency of the speech therapy were related to the therapy effect. The effective rate of the speech therapy in the single pattern of the phonemic error was as high as 87% while the one in the multiple pattern group was only 2.7%. The difference was significant (P < 0.000 1) when the therapy effect in these two groups was compared. The clinical model of the speech therapy included speech assessment, designing of the goal, choice of the target sound, sound production and oral-motor functional training. CONCLUSION: The consonant phonemic errors in the clinic represent four groups. The developmental delay, the language delay and frequency of the speech therapy influence the therapy effect. The frequency of the speech therapy should be increased every week, for example not less two times a week. The therapy effect of the single pattern of the phonemic errors is much better than that of the multiple pattern. The primary model of the speech therapy has been built in the clinics.

Articulation Disorders↗

PubMed2001

Chronic ethanol exposure delays the 'developmental switch' of the NMDA receptor 2A and 2B subunits in cultured cerebellar granule neurons.

Chronic ethanol treatment of cultured neurons from various brain areas has been found to increase NMDA receptor function and to alter the levels of some NMDA receptor subunit proteins. Because the cultured neurons are exposed to ethanol during a period when the NMDA receptor is undergoing developmental changes in subunit expression, we wished to determine whether ethanol treatment alters this developmental pattern. We found that 3 days of treatment of cerebellar granule neurons with ethanol, which was previously reported to increase NMDA receptor function, resulted in a delay in the 'developmental switch' of the NR2A and NR2B subunits, i.e. the developmental decrease in NR2B and increase in NR2A protein expression. As a result, the level of NR2B was higher, and that of NR2A was lower, in the ethanol-treated cells than in control cells. Cross-linking experiments showed that the changes in total receptor subunit proteins levels were reflected in cell-surface expressed proteins, indicating changes in the amount of functional receptors. These results were confirmed by a higher potency of glycine at the NMDA receptor in the ethanol-treated cells, as determined by NMDA/glycine-induced increases in intracellular Ca(2+). The results suggest that the mechanism by which ethanol alters NMDA receptor expression in cultured neurons, where receptors are undergoing development, differs from the mechanism of ethanol's effect on NMDA receptors in adult brain. Changes in the proportion of NR2A and NR2B subunits may contribute to effects of ethanol on neuronal development.

Animals↗

PubMedDate not supplied

[Corpus callosum agenesis].

BACKGROUND: Corpus callosum agenesis (CCA) is an uncommon entity, which can be diagnosed in utero. Uncertain prognosis makes prenatal counseling difficult. AIM. We have tried to establish a positive correlation between clinical history and imaging findings in patients with CCA. PATIENTS AND METHODS: We retrospectively reviewed clinical data and imaging findings of patients with callosal agenesis diagnosed at our institution between December 1995 and September 2002. RESULTS: Eight patients with CCA were found, five males and three females. Mean age at last clinical follow up was six years and six months, ranging from three months to 20 years. All diagnoses except for one were post natal. All patients underwent, at least, one magnetic resonance (MR) of the brain. Abnormal pregnancy was reported in three patients. Family history was unremarkable in all patients. Three patients were diagnosed with isolated CCA. One of these patients was asymptomatic at three months. Another had a slight language delay at seventeen months. The other patient had a mild developmental delay at five years. All other five patients had non isolated CCA and all were symptomatic, with variable clinical pictures: psicomotor developmental delay (4), epilepsy (4), hemiparesis (1), ocular apraxia (1), macrocephaly (2). CONCLUSION: Non isolated CCA is likely to have a worse prognosis. This may be of significant value in prenatal counseling.

Adolescent↗

PubMed2006

Neuroendoscopic management of interhemispheric cysts in children.

OBJECT: Interhemispheric arachnoid cysts are very rare, and they are often associated with complex brain malformations such as corpus callosum agenesis and hydrocephalus. Debate remains concerning the proper management of these lesions. Placement of shunts and microsurgical marsupialization of the cyst are the traditional options. Using endoscopic methods to create areas of communication between the cyst, the ventricular system, and/or the subarachnoid space is an attractive alternative to the use of shunts and microsurgery. METHODS: Between 2000 and 2005, seven consecutive pediatric patients with interhemispheric arachnoid cysts underwent neuroendoscopic treatment involving cystoventriculostomy in two patients, cystocisternostomy in two, and cystoventriculocisternostomy in three. There were three cases of associated hydrocephalus, six cases of corpus callosum agenesis, and one case of corpus callosum hypogenesis. The follow-up period ranged from 12 to 49 months (mean 31.6 months). Endoscopic procedures were completely successful in all but two patients. In one of the remaining two patients, a repeated endoscopic cystocisternostomy was performed with success because of closure of the previous stoma. In the other, a subcutaneous collection of cerebrospinal fluid (CSF) was managed by insertion of an lumboperitoneal shunt. A subdural collection of CSF developed in three patients; it was treated with insertion of a subduroperitoneal shunt in one patient and managed conservatively in the other two patients, resolving spontaneously without further treatment. Neurodevelopmental evaluation performed in six patients showed normal intelligence (total intelligence quotient [IQ] > 80) in three patients, mild developmental delay (total IQ 50-80) in two, and severe developmental delay (total IQ < 50) in one. CONCLUSIONS: Endoscopic treatment of interhemispheric cysts can be considered a useful alternative to traditional treatments, even if some complications are to be expected, such as subdural or subcutaneous CSF collections and CSF leaks due to thinness of cerebral mantle and to the often-associated multifactorial hydrocephalus.

Arachnoid Cysts↗

PubMed1992

Video EEG analysis of non-ictal events in children.

Over a 3 year period 186 children aged 3 weeks to 17 years were studied by telemetry (prolonged video and EEG monitoring) at the Prince of Wales Children's Hospital: 74 had events considered at referral to possibly represent seizures but which were shown by clinical analysis and telemetry to be non-ictal. Nine such patients were developmentally delayed, one was neurologically impaired and 16 were both developmentally delayed and neurologically impaired. A specific diagnosis of the non-ictal events was reached in 24 subjects-postures of spasticity in children with neurological impairment (6), Münchausen-by-proxy (5), pseudoseizures (3), breathholding (2), masturbation (2), reflux (2), shudder (1), movement disorder (1), motor tic (1) and pertussis (1). Specific descriptive patterns were assigned to the remaining 51 events. These included staring (20) and jerks (16) or unusual behaviour (15). 49 inter-event EEGs were normal; 7 displayed abnormal background rhythms and 19 showed epileptiform activity. We discourage use of the term 'pseudoseizure' for the majority of the events described and prefer that a specific diagnosis be made or a descriptive analysis be provided. The events seen illustrate the wide spectrum of childhood behaviour and on occasions suggest the need for telemetry to determine their true nature.

Adolescent↗

PubMed1999

Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion.

A microscopic deletion of chromosome 22q11.2 has been identified in most patients with the DiGeorge, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies. This study presents the neurodevelopmental outcome, including cognitive development, language development, speech, neuromuscular development, and behavioral characteristics of 40 preschool children (ages 13 to 63 months) who have been diagnosed with the 22q11.2 deletion. The impact of cardiac disease, cardiac surgery, and the palatal anomalies on this population was also studied. In the preschool years, children with a 22q11.2 deletion are most commonly found to be developmentally delayed, have mild hypotonia, and language and speech delays. The more significantly delayed children are at high risk to be subsequently diagnosed with mild or moderate mental retardation. The global delays and the variations in intelligence found are directly associated with the 22q11.2 deletion and are not explained by physical anomalies such as palatal defects or cardiac defects, or therapeutic interventions such as cardiac surgery. Our findings demonstrate that there is a pattern of significant speech disorders within this population. All of the children had late onset of verbal speech. Behavioral outcomes included both inhibition and attention disorders. Early intervention services are strongly recommended beginning in infancy to address the delays in gross motor skills, speech and language, and global developmental delays.

Behavioral Symptoms↗

PubMed2006

Birth characteristics associated with early intervention referral, evaluation for eligibility, and program eligibility in the first year of life.

OBJECTIVES: The Individual with Disabilities Education Act mandates Early Intervention (EI) services for infants and toddlers with developmental delay. We assessed the percentage of infants at risk for developmental delay due to characteristics present at birth who were referred to Massachusetts EI within 1 year of birth, evaluated for eligibility, and eligible for services. In addition, we identified birth characteristics that independently predicted 0-1 year program referral, evaluation, and eligibility. METHODS: The Pregnancy to Early Life Longitudinal (PELL) data system linked birth certificate, hospital discharge, and EI program data of 219,037 infants born in Massachusetts, 1998-2000. Multivariate logistic regressions identified independent infant predictors of referral, evaluation, and eligibility. RESULTS: Of 219,037 births, 14,852 (6.8%) were referred to EI within 1 year. Birthweight<1200 g (OR=9.7, 95% CI 3.3-12.9) and birthweight 1200-1499 g (OR=7.4, 95% CI 5.8-9.5) strongly predicted referral. Referral was high (88%) among infants with two or more birth risks. Among referrals, 88% were evaluated for eligibility. The strongest predictor of evaluation was triplet birth (OR=4.3, 95% CI 1.6-11.8). Among infants evaluated, 85% were determined to be eligible. CONCLUSION: EI referral and evaluation are high among infants born at risk for delay in Massachusetts. Some characteristics not included in the state's high-risk definition (e.g. birthweight 1200-1499 g) were identified that predicted referral. Most referrals were eligible for services. Results demonstrate the value to states of using linked population and program data for program evaluation.

Confidence Intervals↗

PubMed1985

The univariate and multivariate relationships among environmental, sociocultural, biological, and developmental variables and the identification of learning disabled children.

Multivariate techniques were used to study the relationships among environmental, sociocultural, biological, and developmental variables, and their ability to discriminate between learning disabled (LD) and regular education students. Univariate analyses were employed to identify variables that were included in a discriminant analysis. Through this combination of analyses, variables that might be considered as risk factors were isolated. Variables which contributed to the separation of LD children from those not placed in special education were developmental delays, baby's length at birth, and sex of child. Developmental delays and serious illness of the child were variables most contributing to the separation of LD from low achieving children. While not increasing the accuracy of classification, these antecedent variables appear to predict probability of LD placement as accurately as academic performance or clinical decision, thus allowing early intervention rather than procedures used after learning problems have been identified.

Body Height↗

PubMed2026

Phenotypes of Hereditary Diseases Associated With Rauch-Steindl Syndrome.

PURPOSE: Prenatal phenotypic manifestations of genetic disorders associated with NSD2 variants remain poorly characterized. This study presents our institutional experience with the prenatal diagnosis of NSD2-associated genetic disorders, specifically Rauch-Steindl syndrome (RAUST), aiming to improve understanding of both the molecular and clinical features of RAUST. METHODS: We performed a retrospective analysis of six fetuses and one adult diagnosed with RAUST at our institution and thoroughly reviewed the prenatal ultrasound reports of six fetuses. Prenatal and postnatal phenotypes of RAUST cases were summarized alongside findings from previously published literature. Correlations between NSD2 variant locations, variant types, and phenotypes were analyzed. Additionally, protein modeling was used to visualize structural changes in NSD2 protein before and after C-terminal variants. We integrated single-cell transcriptomic and gene expression data from multiple public databases to investigate spatiotemporal expression patterns of NSD2 during human fetal development. RESULTS: Fetal growth restriction (FGR) was the most prevalent prenatal manifestation in RAUST fetuses, followed by microcephaly. Bilateral renal hypoplasia emerged as a novel prenatal ultrasonographic feature. Postnatally, speech and motor developmental delays were the most commonly reported phenotypes, followed by physical developmental delays and intellectual disability. Genotype-phenotype correlation analysis revealed an association between N-terminal truncating variants in NSD2 and impaired fetal growth parameters. Notably, C-terminal truncating variants-predicted not to directly impact NSD2 functional domains-also exerted disease-causing effects. CONCLUSION: This study provides a comprehensive analysis of prenatal phenotypes in RAUST cases, enriching the prenatal phenotypic spectrum of the disease and facilitating early diagnosis and clinical management of RAUST. Furthermore, our genotype-phenotype correlation findings lay a foundational basis for future research into the complex molecular mechanisms underlying NSD2-associated genetic disorders.

Humans↗

PubMed2006

Malformations of cortical development and epilepsy, part 1: diagnosis and classification scheme.

Malformations of cortical development (MCDs) are a common cause of epilepsy, although seizures are not always the most prominent neurologic manifestation of these disorders. In localization-related epilepsy, certain features should create a strong suspicion that an MCD is the underlying cause; these include developmental delay and static focal neurologic deficits, a family history of developmental delay or epilepsy, frequent seizures from onset, and episodes of focal status epilepticus. MCDs can be classified according to a number of different criteria emphasizing clinical phenotype, imaging findings, pathology, or genetic defects. The overall classification of MCDs is based on the 3 fundamental events of cortical formation: 1) proliferation of neurons and glia in the ventricular and subventricular zones; 2) multidirectional migration of immature but postmitotic neurons to the developing cerebral cortex; and 3) cortical organization. Among the most common and distinct syndromes and entities affecting patients with MCDs and epilepsy are focal cortical dysplasia, hemimegalencephaly, tuberous sclerosis, classical lissencephaly, periventricular nodular heterotopia, focal subcortical heterotopia, polymicrogyria, and schizencephaly, all of which are discussed herein.

Cerebral Cortex↗

PubMed2006

Early features of autism: Repetitive behaviours in young children.

This study examined whether repetitive behaviours were a differentiating feature of autism in children aged less than 51 months. The study also examined the relationship between age (chronological and developmental) and repetitive behaviours in young children with autism. Standardised developmental and diagnostic assessments were conducted on 55 children aged between 22 and 51 months, consisting of 40 developmentally delayed children with DSM-IV-TR Autistic Disorder and 15 developmentally delayed children without Autistic Disorder. Results indicated that several measures of repetitive behaviour, particularly more complex high-level ones, were significantly positively associated with the probability of receiving a diagnosis of autism. No significant relationships were found between developmental age and the presence of repetitive behaviours in children with autism, but younger chronological age was associated more with simple or low-level repetitive behaviours.

Age Factors↗

PubMed2005

Emotional and behavioral outcomes among adolescents with mild developmental deficits in early childhood.

PURPOSES: To evaluate emotional and behavioral outcomes in adolescents who in early childhood were treated for mild developmental deficits; and to identify predictive factors in early childhood, for future emotional and social competence abnormalities. METHODS: The records of children referred to Hanna Khoushi Child Development Center in Haifa for mild developmental delay were reviewed. Parents and adolescents were requested to complete the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR) 12 to 16 years after discharge from the Child Development Center. Analysis of the two questionnaires and identification of predictive variables in early childhood for emotional problems and social competence difficulties during adolescence were performed, using ANOVA Student's T-test, Chi-square, and multiple regression. RESULTS: The most frequent developmental diagnoses on admission to the Child Development Center were mild motor (27.3%) or language (23.2%) deficits. Of the treated children, 53.4% were discharged without any developmental deficit. All CBCL and YSR T-scores were within the nonpsychopathology range. No notable differences were found between the study scores and the scores regarding typical Israeli and American youths. Significant differences were, however, observed in self-perception of internalizing emotional problems between male and female adolescents: T-scores of 51.9 +/- 8.0 vs. 47.4 +/- 10.8, respectively (p < .05). Motor and language deficits were associated with lower general competence than general developmental delay and emotional developmental disturbances (T-scores: 47.9 vs. 49.1 and 50.9, p< .05). Admission to the Center after the age of 18 months was associated with higher T-scores for general as well as externalizing problems when compared with scores associated with admission before the age of 18 months (by 5.75 points for both parameters, p < .001). CONCLUSION: The perception of parents and children with minor developmental deficits observed in early childhood regarding their emotional and social competence during adolescence is similar to typical youths.

Adolescent↗

PubMed1995

Children with a schizophrenic disorder: neurobehavioral studies.

This paper summarizes retrospective and cross-sectional neurobehavioral studies of schizophrenic children. Retrospective studies of schizophrenic children reveal that during early childhood, prior to the first onset of schizophrenic symptoms, most schizophrenic children showed delays in language acquisition and/or impairments and delays in visual-motor coordination. These impairments appear to be developmental delays rather than fixed neurobehavioral impairments, because cross-sectional studies conducted when the children are at least 10 years of age, after the first onset of psychosis, fail to detect the same deficits. The results of behavioral, cognitive/neuropsychological studies as well as the study of event-related potentials measured during performance of cognitive tasks suggests that schizophrenic children suffer from limitations in processing resources. It is argued that the developmental delays observed in schizophrenic children represent the greater time it takes them to automate certain skills. The delay in automation may reflect their limited information-processing capacity.

Brain↗

PubMed2003

Concurrent and predictive validity of the cognitive adaptive test/clinical linguistic and auditory milestone scale (CAT/CLAMS) and the Mental Developmental Index of the Bayley Scales of Infant Development.

The Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was designed for use by primary pediatric health care providers to identify children with developmental delays. This study assesses the concurrent and predictive validity of CAT/CLAMS developmental quotient (DQ) scores and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development in healthy children without risk factors for developmental delay. Overall CAT/CLAMS DQ scores correlated significantly with Bayley MDI scores at both 12 (r = 0.393; p = 0.008) and 30 months (r = 0.742; p = 0.0001) of age. Overall CAT/CLAMS DQ scores at 12 months of age also correlated modestly with Bayley MDI scores at 30 months of age (r = 0.181; p = 0.036). Despite its modest predictive validity at 12 months, its satisfactory concurrent validity plus its ease and speed of administration make the CAT/CLAMS a reasonable choice for assessment of early development by primary pediatric health care providers.

Child Development↗

PubMed1998

Abnormalities of the central nervous system in very young children with sickle cell anemia.

OBJECTIVE: To determine whether abnormalities of the CNS are present in very young children with sickle cell anemia. STUDY DESIGN: Thirty-nine children with hemoglobin SS between the ages of 7 and 48 months were examined with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). No child had a history of clinical stroke, although 3 had a history of seizures (2 neonatal). Twenty-one patients underwent developmental testing with the Bayley or McCarthy Scales. RESULTS: The overall prevalence of CNS abnormalities in asymptomatic children was 4 of 36 (11%, confidence interval 3, 26%). One patient had a silent infarct observed on MRI and a stenotic lesion on MRA; 3 other patients had stenotic lesions on MRA. The 3 patients who had a history of seizures all had lesions consistent with infarcts on MRI. Of the asymptomatic patients who had psychometric testing, 1 of 18 was developmentally delayed. One of 3 with a history of seizures had mild developmental delay. CONCLUSIONS: Very young children with sickle cell anemia (and no history of clinical stroke) have infarction in the brain and/or stenosis of major cerebral arteries, similar to those reported in older children. These findings indicate a need for larger studies to define the incidence of CNS lesions in this age group and to determine the need for early therapeutic intervention to prevent CNS sequelae of sickle cell disease.

Anemia, Sickle Cell↗

PubMed1989

Effects of streptozotocin- and alloxan-induced diabetes mellitus on mouse follicular and early embryo development.

Mice were made diabetic by intraperitoneal injection of streptozotocin or alloxan. Germinal vesicle breakdown in the ovarian follicles at 8 h after hCG in control animals (57%) was significantly greater than in streptozotocin-(24%) and alloxan-(42%) diabetic animals (P less than 0.001). This delay in oocyte maturation was reversible by in-vivo insulin administration to diabetic mice. A developmental delay was also found for embryos recovered from diabetic mice. This developmental delay extended into the 72 h in-vitro cultures. Compared to control embryos, those from alloxan- and streptozotocin-treated mice demonstrated marked impairment in development as assessed by (1) distribution of developmental cell stages at each observation period and (2) rates of development which increasingly diverged at each observation period. In diabetic mice treated with insulin in vivo, the percentage of 2-cell embryos recovered increased. Furthermore, in streptozotocin- and alloxan-animals treated with insulin, the rate of in-vitro development of embryos, as well as their developmental stage distribution improved. We therefore suggest that uncontrolled diabetes mellitus, as well as contributing to the development of congenital malformations, may deleteriously affect reproductive performance both before fertilization and at the very earliest gestational stages.

Alloxan↗