From the Blood-Brain Barrier to Childhood Development: A Case of Acute-Onset Psychosis and Cognitive Impairment Attributed to Systemic Lupus Erythematosus in an Adolescent Female.

LEARNING OBJECTIVES: After participating in this CME activity, the clinician will be better able to:• Interpret classifications of neuropsychiatric systemic lupus erythematosus (NPSLE).• Identify determining factors of neuropsychiatric events.• Analyze current evidence regarding disease pathways for NPSLE.

Relationship of withdrawn, anxious/depressed and attention problems to cognitive performance in preterm children at 18 months and 36 months of age.

OBJECTIVE: A positive significant association has been found between behavior problems and lower cognition in very low birthweight (VLBW) preterm children at school age, but there is relatively little information about whether such an association exists in toddlers and on the continuity of this association. The aim of this study was to assess if there is a relationship between behavior problems and cognitive performance in VLBW preterm children at 18 months post conception and 3 years old, independent of socioeconomic status and sex. METHOD: Parents of 124 preterm children completed a behavior rating questionnaire (Child Behavior Checklist 1.5-5) to measure behavior problems characteristic of preterm children (Withdrawn, Anxious/Depressed, and Attention Problems). Children completed the Cognitive Scale of the Bayley Scales of Infant Development-III at 18 months and the Wechsler Preschool and Primary Scale (III or IV) at 36 months old. Socioeconomic status (SES), sex, and diagnoses of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) at 3 years were recorded for each child. RESULTS: Withdrawn problems at 18 months were associated with lower cognitive scores at 18 months and both Withdrawn problems at 18 months and 36 months were associated with lower cognitive scores at 36 months. Increases in Attention Problems scores from 18 to 36 months were associated with decreases in cognitive scores over that period. Lower SES was associated with lower cognitive scores at 36 months and decreases in cognitive scores between 18 and 36 months. Sex was not related to behavior problems or cognition. Diagnoses of ASD and ADHD were significantly associated with increased Withdrawn behavior and Attention Problems, respectively. CONCLUSIONS: The early association of Withdrawn behaviors with less favorable cognitive performance at 18 months and 36 months and the relationship between increases in Attention Problems with decreases in cognitive scores between the toddler and preschool period indicate the need for early assessment of and intervention for behavior problems, as well as concurrent cognitive delays, in VLBW preterm children.

New distributional records of the Samana least gecko (Sphaerodactylus samanensis, Cochran, 1932) with comments on its morphological variation and conservation status.

We report here five new localities across the distribution of the lizard Sphaerodactylus samanensis, extending its current geographic range to the west, in the Cordillera Central of Hispaniola. We also report phenotypic variation in the color pattern and scutellation on throat and pelvic regions of males from both eastern and western populations, which is described below. Furthermore, based on these new data, we confirm that the species is not fitting in its current IUCN category, and in consequence propose updating its conservation status.

Is there a role for therapeutic hypothermia administration in term infants with mild neonatal encephalopathy?

OBJECTIVE: Identifying term infants presenting with early mild neonatal encephalopathy (NE) as candidates for therapeutic hypothermia (TH) remains unclear. Study objectives were to characterize the neonatal clinical, magnetic resonance imaging (MRI), and longer-term outcome in infants with mild NE treated with TH. STUDY DESIGN: Retrospective cohort study of infants admitted with mild or moderate NE treated with TH. Enrollment criteria included a sentinel event, severe acidosis, DR interventions, and low Apgar scores. RESULTS: Infants with mild (n = 11) and moderate NE (n = 37) received TH. Mild NE findings included hyperalertness (64%), hypotonia (73%), high level sensory response (91%); 64% progressed to moderate NE. Infants with mild vs. moderate NE had less severe MRI changes (0 vs. 16%) and no cerebral palsy (CP) (0 vs. 13%). CONCLUSIONS: Outcomes were favorable with mild NE whereas four infants with moderate NE developed CP. A potential role for TH in this population requires further study.

Relationships of biological and environmental factors to cognition of preterm infants in the toddler and preschool periods.

One hundred and nine preterm infants were studied to examine the relative effects of biologic/neurologic factors (length of hospital stay, 18 month cognitive status) and environment (socioeconomic status) on cognition in the toddler (18 months) and preschool periods (3 years). Length of hospital stay was significantly related to toddler cognitive outcome, and less so to preschool outcome. Socioeconomic status predicted only preschool cognitive outcome and not toddler outcome. Cognitive status at 18 months significantly predicted 3 year outcome, and there was relatively little change between those periods. Together, cognitive status at 18 months and socioeconomic status significantly predicted preschool IQ, accounting for 34% of the variance. Results showed that perinatal biologic risks became less salient while socioeconomic status became increasingly important at the preschool period. Relative lack of change in cognitive status indicated the importance of early cognitive evaluation in preterm infants.

Accuracy of Reported Community Diagnosis of Autism Spectrum Disorder.

To compare community diagnoses of Autism Spectrum Disorder (ASD) reported by parents to consensus diagnoses made using standardized tools plus clinical observation. 87 participants (85% male, average age 7.4 years), with reported community diagnosis of ASD were evaluated using the Autism Diagnostic Observation Schedule) (ADOS-2), Differential Ability Scale (DAS-II), and Vineland Adaptive Behavior Scales (VABS-II). Detailed developmental and medical history was obtained from all participants. Diagnosis was based on clinical consensus of at least two expert clinicians, using test results, clinical observations, and parent report. 23% of participants with a reported community diagnosis of ASD were classified as non-spectrum based on our consensus diagnosis. ASD and non-spectrum participants did not differ on age at evaluation and age of first community diagnosis. Non-verbal IQ scores and Adaptive Behavior Composite scores were significantly higher in the non-spectrum group compared to the ASD group (104.5 ± 21.7 vs. 80.1 ± 21.6, p < .01; 71.1 ± 15 versus 79.5 ± 17.6, p < .05, respectively). Participants enrolled with community diagnosis of PDD-NOS were significantly more likely to be classified as non-spectrum on the study consensus diagnosis than Participants with Autism or Asperger (36% versus 9.5%, Odds Ratio = 5.4, p < .05). This study shows suboptimal agreement between community diagnoses of ASD and consensus diagnosis using standardized instruments. These findings are based on limited data, and should be further studied, taking into consideration the influence of DSM 5 diagnostic criteria on ASD prevalence.

The Relationship Between Motor Delays and Language Development in Very Low Birthweight Premature Children at 18 Months Corrected Age.

Purpose: The aim of this study is to determine if there is a specific association between motor delays and receptive and expressive language function, respectively, in prematurely born children. Method: Retrospective data review: 126 premature children ≤ 1,250-g birthweight from English-speaking families were evaluated on motor development (normal, mild delay, and moderate-severe delay) and the cognitive and language scales of the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley, 2006) at 18 months corrected age. Cognitive scores were categorized as normal, suspect, and abnormal. Gender, demographic, and perinatal variables were recorded and analyzed with respect to motor category. Results: Lower birthweight, chronic need for oxygen, severe intraventricular hemorrhage, and intestinal infection/inflammation were related to poorer motor development. On receptive language, the normal motor group attained significantly higher scores than the moderate-severe motor group but did not differ significantly from the mild delay motor group. On expressive language, the normal motor group had significantly higher scores than both the mild and moderate-severe groups. Girls performed better than boys on receptive and expressive language, but there was no significant interaction between gender and motor category on any of the Bayley scores. Cognitive, but not motor, category significantly contributed to variance of receptive language scores; cognitive and motor category each independently contributed to the variance in expressive language. Conclusion: Findings suggest that motor control areas of the brain may be implicated in expressive language development of premature children. Further research is needed to determine the underlying factors for the association between motor and expressive language function.

Using cluster analysis to provide new insights into development of very low birthweight (VLBW) premature infants.

BACKGROUND: Very low birthweight (VLBW) premature infant follow-up studies report on single developmental outcome variables but do not assess profiles of development. AIMS: To identify developmental profiles of VLBW premature infants based on cognitive and language development and their association with demographic, perinatal, and behavior variables. STUDY DESIGN: Retrospective chart review. SUBJECTS: 117 children<1250 g BW seen at 18 months post-term on the Bayley Scales-III and Child Behavior Checklist 1 ½-5 (CBCL 1 ½-5), a behavior problem questionnaire. Demographic and perinatal variables were obtained from medical records. OUTCOME MEASURES: Bayley Cognitive, Expressive Language, and Receptive Language scores were used to cluster the subjects into developmental profiles. Demographic, perinatal, and CBCL variables were analyzed as they related to clusters. RESULTS: Children were clustered into 4 groups based on their Bayley Cognitive, Expressive Language, and Receptive Language scores: Consistently High, Consistently Average, Average with Delayed Expressive Language, and Consistently Low. Socioeconomic status, bronchopulmonary dysplasia, Grades III-IV intraventricular hemorrhage, and summary Behavior Problems and Attention Deficit/Hyperactivity (ADHD) Problems scores were significantly related to clusters. CONCLUSION: Cluster analysis defined distinct outcome groups in VLBW premature children and provides an informative means of identifying factors related to developmental outcome. This approach may be useful in predicting later outcome and determining which groups of children will require early intervention.

Contextually appropriate emotional word use predicts adaptive health behavior: Emotion context sensitivity and treatment adherence.

Emotion context sensitivity is the ability to respond emotionally in a manner that is functionally appropriate for the context in which the emotion arises. This study examined the relationship between emotion context sensitivity and treatment adherence in adults with the chronic illness Thalassemia. Emotional responses were measured by examining the frequency of positive and negative emotional words used to answer two interview questions that created two different emotional contexts. Consistent with previous research on adaptive and contextually appropriate emotions, negative emotion words were related to adherence in the context of the disease itself, while positive emotion words were related to adherence in the context of coping.

Clobazam and Aggression-Related Adverse Events in Pediatric Patients With Lennox-Gastaut Syndrome.

BACKGROUND: Lennox-Gastaut syndrome is an intractable epileptic encephalopathy marked by frequent drop seizures. Most patients develop moderate intellectual disability and behavioral problems, including hyperactivity, aggressiveness, insecurity, and autistic features. Treatment with benzodiazepines, including clobazam, may increase aggression/behavioral problems in patients with Lennox-Gastaut syndrome. Post hoc analyses of data from the OV-1012 trial assessed the potential for behavioral effects with clobazam treatment in pediatric (2 to 18 years) patients with Lennox-Gastaut syndrome. METHODS: OV-1012 was a phase 3, randomized, double-blind, parallel-group trial comprising a 4-week baseline period, 3-week titration period, and a 12-week maintenance period. Data from 194 patients were analyzed for a history of aggression/behavioral problems, occurrence of aggression-related adverse events, and by assessment of potential drug-related effects on four behavior domains of the Child Behavior Checklist. RESULTS: Twenty-nine aggression-related adverse events were reported for 27 (13.9%) patients. Similar percentages of clobazam-treated patients with and without a history of aggressive behavior experienced an aggression-related adverse event (16.7% versus 15.5%, respectively). In the medium- and high-dosage clobazam groups, onset of aggression-related adverse effects occurred within the 3-week titration period with 63.2% resolving by the end of the study. Aggression-related adverse event onset and resolution were similar for the low-dosage clobazam and placebo groups. Analysis of baseline to postbaseline T scores for the behavior domains of the Child Behavior Checklist indicated no significant differences between clobazam and placebo. CONCLUSIONS: Post hoc analyses indicate that the overall rate of aggression with clobazam treatment was low and dosage dependent. Clobazam treatment was effective in reducing drop seizures regardless of aggression experience.

Forest baseline and deforestation map of the Dominican Republic through the analysis of time series of MODIS data.

Deforestation is one of the major threats to habitats in the Dominican Republic. In this work we present a forest baseline for the year 2000 and a deforestation map for the year 2011. Maps were derived from Moderate Resolution Imaging Radiometer (MODIS) products at 250 m resolution. The vegetation continuous fields product (MOD44B) for the year 2000 was used to produce the forest baseline, while the vegetation indices product (MOD13Q1) was used to detect change between 2000 and 2011. Major findings based on the data presented here are reported in the manuscript "Habitat suitability and protection status of four species of amphibians in the Dominican Republic" (Sangermano et al., Appl. Geogr.,) [7].63, 2015, 55-65.

Negative affect differentiation and adherence during treatment for thalassemia.

BACKGROUND: Although research has demonstrated the detrimental effects of excessive negative affect on treatment adherence and morbidity in chronic illness, rarely have researchers investigated the benefits of awareness of negative emotional experiences during treatment. PURPOSE: In this investigation, we examined the association of negative affect differentiation (the ability to report negative emotional experiences as separate and distinct from each other,) to treatment adherence in adult patients with the congenital blood disorder thalassemia. METHOD: Negative affect differentiation was assessed during a 12-16-week treatment-based diary and adherence was operationalized as attendance at routine screenings over 12 months. Participants were adult patients (n = 32; age M = 31.63, SD = 7.72; 72 % female) with transfusion-dependent thalassemia in treatment in a large metropolitan hospital in the Northeastern USA. RESULTS: The results indicate that negative affect differentiation is significantly associated with greater adherence to treatment, even when controlling for disease burden and level of psychological distress. CONCLUSION: Although preliminary, this investigation suggests that differentiated processing of negative emotional experiences during illness can lead to adaptive treatment-related behavior. As such, it may present a new avenue for research and intervention targeting the improvement of adherence during treatment for chronic illness.

Physical growth and cognitive abilities in concordant versus discordant birth weight twins at three years old.

BACKGROUND: Discordant birth weight twins have been shown to have high rates of adverse perinatal outcomes, but little is known about their growth and development. AIM: To determine whether smaller and larger birth weight premature twins in concordant and discordant birth weight groups differ on measures of physical growth and intelligence at 3 years. STUDY DESIGN: Prospective cohort study. Eight-four children, 52 concordant and 32 discordant birth weight twin pairs, were measured for height, weight, and head circumference and on intelligence at 3 years. Perinatal and demographic variables, including birth weight, head circumference, small for gestational age, zygosity, in vitro fertilization, gender and social class were recorded. RESULTS: Smaller and larger birth weight twins did not differ significantly from each other on any growth parameters in either concordant or discordant birth weight groups at 3 years of age. Smaller birth weight twins in the discordant birth weight group performed significantly less well on Verbal, Performance, and Full Scale IQ scores (Verbal IQ for smaller twins was 8.6 points lower, p<0.005; Performance IQ, 11.9 points lower, p<0.03; Full Scale IQ, 12.4 points lower, p<0.004), but there were no significant intra-twin differences between larger and smaller birth weight concordant twins. CONCLUSIONS: Smaller discordant birth weight twins performed significantly less well on intelligence, although they did not differ significantly from their larger twins on growth parameters at 3 years old. We conclude that smaller discordant birth weight twins had less optimal intra-uterine environments than their larger birth weight twin, which affected both their birth weights and brain development.

Effects of implementing family-centered rounds (FCRs) in a neonatal intensive care unit (NICU).

OBJECTIVES: (1) Evaluate impact of FCR on provider satisfaction and collaboration. (2) Evaluate impact of FCR on parent satisfaction with provider communication. METHODS: Collaboration and Satisfaction about Care Decisions (CSACD) questionnaire was given to staff on 4 patients 2 days a week for 5 weeks prior to and 6 months after implementation of FCR. Parents received a Parents Stress Scale and Neonatal Instrument of Parent Satisfaction before discharge, prior to and 6 months after starting FCR. RESULTS: 278/288 (97%) staff surveys were completed, 142 pre and 136 post. On the CSACD survey NNPs and fellows showed increased (p < 0.05) collaboration and satisfaction post FCR. No group had decreased satisfaction. Twenty-eight of 45 (62%) parent surveys were completed, 12 pre and 16 post. Parents' satisfaction scores increased (p < 0.01) pre vs. post on survey items regarding communication, meeting with physicians, and obtaining information about their infants. CONCLUSIONS: FCR was associated with enhanced collaboration among team members for NNPs and fellows. Parents' satisfaction scores increased post FCR on survey items regarding communication. Since NNPs and fellows are the primary communicators with parents, the increased satisfaction may reflect improved communication due to FCR. This added opportunity for open dialogue may also contribute to the increased parent satisfaction.

Neurocognitive impairment in childhood-onset systemic lupus erythematosus: measurement issues in diagnosis.

OBJECTIVE: To assess the prevalence of neurocognitive impairment (NCI) in childhood-onset systemic lupus erythematosus (cSLE) by comparing published classification criteria, and to examine associations between NCI, disease characteristics, psychosocial well-being, and intelligence. METHODS: cSLE patients and ethnicity- and age-matched healthy controls completed a neuropsychological research battery, and results were categorized by 3 different NCI classification criteria with different cutoff scores (e.g., >2, 1.5, or 1 SD below the mean) and the number of required abnormal tests or domains. RESULTS: Forty-one cSLE subjects and 22 controls were included. Subjects were predominantly female (~70%) and Hispanic (∼70%). Executive functioning, psychomotor speed, and fine motor speed were most commonly affected. Method 1 classified 34.1% of cSLE subjects with NCI compared to method 2 (14.6% with decline and 7.3% with NCI) and method 3 (63.4% with NCI). The prevalence of NCI was not significantly different between the controls and patients using any of the categorization methods. NCI was not associated with SLE disease activity or characteristics or with depression. Using method 3, patients in the cognitive impairment group reported significantly lower quality of life estimates (69.7 versus 79.3; P = 0.03). Below average intellectual functioning (intelligence quotient <90) differentiated the number of test scores >1 and >1.5 SDs, but not >2 SDs below the mean. CONCLUSION: NCI was prevalent in cSLE, but varied according to the chosen categorization method. A similar proportion of cSLE patients and controls had NCI, reinforcing the importance of studying an appropriate control group. Categorical classification (i.e., impaired/nonimpaired) may oversimplify the commonly observed deficits in cSLE.

Delayed onset of sleep-wake cycling with favorable outcome in hypothermic-treated neonates with encephalopathy.

OBJECTIVE: To determine whether hypothermia modulates acquisition of sleep-wake cycling in term neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE) and the relationship to outcome. STUDY DESIGN: Twenty-nine term infants with moderate to severe HIE treated with selective head cooling were evaluated. All were monitored with amplitude-integrated electroencephalography during and video electroencephalography immediately after hypothermia for ≥72 hours. Electroencephalograpic data were analyzed for background and sleep-wake cycling. Abnormal outcome included death or severe global neurodevelopmental disability ≥18 months. RESULTS: Acquisition of sleep-wake cycling was noted in nine infants by 72 hours, in 13 by 96 hours, 19 by 120 hours, and 22 by 144 hours. Presence of sleep-wake cycling was associated with normal outcome, that is, 14 of 22 (64%), versus abnormal outcome, that is, none of seven without sleep-wake cycling (P = .006). The presence of sleep-wake cycling by 120 hours had a positive predictive value of 68% and negative predictive value of 90%. Magnetic resonance imaging abnormalities were related to onset of sleep-wake cycling. CONCLUSIONS: Although onset of sleep-wake cycling is markedly delayed in term neonates with moderate to severe HIE treated with hypothermia, approximately 65% with acquisition of cycling have a normal outcome. Sleep-wake cycling is an important additional tool for assessing recovery in term infants with moderate to severe HIE treated with hypothermia.

Chain of Brain Preservation--a concept to facilitate early identification and initiation of hypothermia to infants at high risk for brain injury.

BACKGROUND: Therapeutic hypothermia has been associated with improved outcomes in term infants particularly in those who present with moderate hypoxic-ischemic encephalopathy (HIE). However, in the three major studies the time to initiate cooling was at approximately 4.5 postnatal hours. OBJECTIVE: To determine in term infants who meet criteria for therapeutic hypothermia whether specific clinical and/or biochemical parameters might identify those high risk infants destined for abnormal neurodevelopmental outcome even sooner than is currently possible. DESIGN/METHODS: Retrospective chart review for the following parameters: gestational age, birth weight, sex, labor complications, mode of delivery, 10 min Apgar≤3, cardio-pulmonary resuscitation in the delivery room, cord arterial pH and base deficit, initial postnatal pH and base deficit obtained within 1h, aEEG, Sarnat staging and seizures at enrollment. Abnormal outcome included death and neurodevelopmental deficits. RESULTS: At a single tertiary care center in a metropolitan area, 45 term infants with moderate to severe HIE were treated with selective head cooling initiated at a mean of 4.69±0.79 h of life; 43/45 (96%) were outborn. Five (11%) infants died and of survivors 26 (58%) are normal and 14 (31%) infants are abnormal at follow-up ranging from 12 to 26 months. Infants with abnormal vs. normal outcome were of comparable gestational age, birth weight with no differences in any parameters between groups except that in infants with abnormal vs. normal outcome the postnatal pH obtained within the first postnatal hour was lower, i.e. 6.87±0.15 vs. 7.00±0.22 (p=0.02) and abnormal infants were more likely to present with severe encephalopathy, i.e. 15/19 (79%) vs. 6/26 (23%) (p=0.0002) and clinical seizures, i.e. 14/19 (74%) vs.10/26 (38%) (p=0.03) on admission. CONCLUSIONS: High risk infants who become candidates for therapeutic hypothermia and ultimately have an abnormal outcome may be identified by an additional early postnatal biochemical marker, i.e. the presence of profound metabolic acidosis. An earlier induction of hypothermia that currently occurs particularly in infants with severe encephalopathy may potentially improve outcome. Given that most infants are outborn, a time sensitive education metaphor termed Chain of Brain Preservation may facilitate early recognition of high risk infants and thus earlier treatment.

A proposed framework to standardize the neurocognitive assessment of patients with pediatric systemic lupus erythematosus.

OBJECTIVE: To develop and propose a standardized battery of neuropsychological tests for the assessment of cognitive functioning of children and adolescents with pediatric systemic lupus erythematosus (SLE). METHODS: A committee of health care professionals involved in the assessment of pediatric SLE patients reviewed the literature to identify cognitive domains most commonly affected in pediatric SLE and in adult SLE. They then reviewed the standardized tests available for children and adolescents that assess the cognitive domains identified. Through a structured consensus formation process, the committee considered the psychometric characteristics and durations of the tests. RESULTS: A test battery was developed that appears suitable to provide a comprehensive assessment of cognitive domains commonly affected by pediatric SLE within a 2.5-hour period. CONCLUSION: It is hoped that the consistent use of this reliable and efficient battery increases the practicality of routine evaluations in pediatric SLE, enabling between-cohort comparisons and facilitating the longitudinal assessment of individual patients over time.

Language delay and behavioral/emotional problems in toddlers: findings from two developmental clinics.

PURPOSE: The association between language delay and behavior problems in toddlers was examined in 2 studies, 1 conducted in a developmental clinic in New Jersey (Study 1; N = 83) and the other conducted in a developmental clinic in New York (Study 2; N = 103). METHOD: In both clinics, parents of 18- to 35-month-olds completed the Language Development Survey (LDS) and the Child Behavior Checklist/1.5-5 (CBCL). In Study 2, the Preschool Language Scale-Fourth Edition (PLS-4) was also administered. Neurodevelopmental delay (ND) and pervasive developmental disorder (PDD) symptoms were also assessed in both studies but were done so using different measures. RESULTS: In Study 1, LDS Vocabulary score and CBCL Total Problems, Internalizing, and Withdrawn scores were significantly correlated. However, when children with ND and/or suspected PDD were excluded, only the correlation between LDS Vocabulary and Withdrawn remained significant. In Study 2, only the correlation between LDS Vocabulary and Withdrawn approached significance. Children delayed in language on the PLS-4 had higher CBCL scores than typically developing toddlers only on the CBCL Withdrawn syndrome. CONCLUSION: Significant associations between language delays and behavior problems were not found in 2 samples of 18- to 35-month-olds when children with ND and PDD were excluded, except that toddlers with language delays appeared to show elevated social withdrawal relative to typically developing toddlers.