Altered cortical thickness following prenatal sodium valproate exposure

Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA dose and right IFG thickness, and a close relationship between verbal skills and left IFG thickness. A significant interaction between group and hemispheric IFG thickness showed absence of the normal asymmetry in the IFG region of VPA-exposed children. These data provide preliminary insights into the putative neural basis of difficulties experienced by some VPA-exposed children

Language skills of school-aged children prenatally exposed to antiepileptic drugs

OBJECTIVES: Fetal exposure to some antiepileptic drugs (AEDs) carries increased risk of major birth defects, and may be associated with reduced intellectual abilities. The impact on language remains unclear. This study aimed to investigate the impact of fetal AED exposure on language skills. METHODS: Women with epilepsy and their children were recruited to this observational study through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. Language skills of 102 AED-exposed children were assessed using the Clinical Evaluation of Language Fundamentals, fourth edition (CELF-4). Assessments were conducted blind to drug. Maternal epilepsy, pregnancy, and medical histories were obtained from prospectively collected records. RESULTS: Mean CELF-4 Core Language scores of children exposed to sodium valproate in monotherapy (mean 91.5, SD 17.5) or polytherapy (mean 73.4, SD = 22.3) were significantly below the standardized test mean of 100 (p < 0.05). Mean language scores of children exposed to carbamazepine or lamotrigine monotherapy, or polytherapy without sodium valproate, were not significantly different from normal. First-trimester sodium valproate dose was negatively correlated with language scores, and significantly predicted language scores after controlling for other group differences. CONCLUSIONS: Fetal exposure to sodium valproate increases the risk of language impairment. This should be taken into account when making treatment decisions for women with epilepsy of childbearing age

The impact of diabetic ketoacidosis and age on behavior six months post-diagnosis in children with type 1 diabetes

Objectives: Children with type 1 diabetes mellitus (DM1) may be at increased risk of psychosocial and adjustment difficulties. We examined behavioral outcomes six months post-diagnosis in a group of children with newly diagnosed DM1. Methods: This study formed part of a larger longitudinal project examining pathophysiology and neuropsychological outcomes in diabetic patients with or without diabetic ketoacidosis (DKA). Participants were 61 children (mean age 11.8 years, SD 2.7 years) who presented with a new diagnosis of DM1 at the Royal Children’s Hospital, Melbourne. Twenty-three (11 female) presented in DKA and 38 (14 female) without DKA. Parents completed the behavior assessment system for children, second edition six months post-diagnosis. Results: There was a non-linear relationship between age and behavior. Internalising problems (i.e. anxiety depression, withdrawal) peaked in the transition from childhood to adolescence; children aged 10–13 years had elevated rates relative to the normal population (t = 2.55, P = 0.018). There was a non-significant trend for children under 10 to display internalising problems (P = 0.052), but rates were not elevated in children over 13 (P = 0.538). Externalising problems were not significantly elevated in any age group. Interestingly, children who presented in DKA were at lower risk of internalising problems than children without DKA (t = 3.83, P < 0.001). There was no effect of DKA on externalising behaviors. Conclusions: Children transitioning from childhood to adolescence are at significant risk for developing internalising problems such as anxiety and lowered mood after diagnosis of DM1. Somewhat counter-intuitively, parents of children presenting in DKA reported fewer internalising symptoms than parents of children without DKA. These results highlight the importance of monitoring and supporting psychosocial adjustment in newly diagnosed children even when they seem physically well

Inhibition of histone deacetylase in utero causes sociability deficits in postnatal mice

Exposure to sodium valproate (VPA) in utero increases the risk of language impairment and a diagnosis of autism spectrum disorder (ASD). Mice exposed to VPA while in utero have also shown postnatal social deficits. Inhibition of histone deacetylase (HDAC) is one of VPA's many biological effects. The main objective of this study was to test the hypothesis that HDAC inhibition causes these behavioral outcomes following prenatal VPA exposure in mice. We exposed embryonic mice to VPA, the HDAC inhibitor trichostatin A (TSA), or vehicle controls. TSA (1. mg/kg) inhibited HDAC in embryonic tissue at a level comparable to 600. mg/kg VPA, resulting in significant increases in histone H3 and H4 acetylation, and histone H3 lysine 4 tri-methylation. Postnatally, decreases in ultrasonic vocalization, olfactory motivation and sociability were observed in TSA and VPA-exposed pups. Treated mice exhibited elevated digging and grooming suggestive of mild restrictive and repetitive behaviors. Olfactory social preference, social novelty and habituation were normal. Together, these data indicate that embryonic HDAC inhibition alone can cause abnormal social behaviors in mice. This result serves as a molecular understanding of infant outcomes following mild VPA exposure in utero

Fungal inoculum properties : Extracellular enzyme expression and pentachlorophenol removal by New Zealand Trametes species in contaminated field soils

This study was conducted to improve the ability of indigenous New Zealand white-rot fungi to remove pentachlorophenol (PCP) from contaminated field soil. The effects of different bioaugmentation conditions on PCP removal and extracellular enzyme expression were measured in the laboratory. The conditions were fungal growth substrate and co-substrate composition, culture age, and Tween 80 addition to the contaminated soil. The fungi used were Trametes versicolor isolate HR131 and Trametes sp. isolate HR577. Maximum PCP removal was 70% after 7 wk from a 1043 mg kg⁻¹ PCP-contaminated soil inoculated with an 11-d-old fungal culture of T. versicolor isolate HR131. There was minimal production of undesirable pentachloroanisole by the fungi. Tween 80 addition had no affect on PCP removal. Poplar sawdust was more suitable as a fungal growth substrate and a co-substrate amendment for PCP removal and extracellular enzyme expression than the locally available pine and fir sawdust. Pentachlorophenol removal was not necessarily correlated with extracellular enzyme expression. The research results demonstrate that PCP biodegradation was affected by inoculum culture age, by the presence of a co-substrate amendment, and by growth substrate composition after white-rot fungal bioaugmentation into PCP-contaminated field soils

Clinical utility of mental state screening as a predictor of intellectual outcomes 6 months after diagnosis of type 1 diabetes

Background Screening tests of basic cognitive status or ‘mental state’ have been shown to predict mortality and functional outcomes in adults. This study examined the relationship between mental state and outcomes in children with type 1 diabetes. Objective We aimed to determine whether mental state at diagnosis predicts longer term cognitive function of children with a new diagnosis of type 1 diabetes. Methods Mental state of 87 patients presenting with newly diagnosed type 1 diabetes was assessed using the School-Years Screening Test for the Evaluation of Mental Status. Cognitive abilities were assessed 1 wk and 6 months postdiagnosis using standardized tests of attention, memory, and intelligence. Results Thirty-seven children (42.5%) had reduced mental state at diagnosis. Children with impaired mental state had poorer attention and memory in the week following diagnosis, and, after controlling for possible confounding factors, significantly lower IQ at 6 months compared to those with unimpaired mental state (p < 0.05). Conclusions Cognition is impaired acutely in a significant number of children presenting with newly diagnosed type 1 diabetes. Mental state screening is an effective method of identifying children at risk of ongoing cognitive difficulties in the days and months following diagnosis. Clinicians may consider mental state screening for all newly diagnosed diabetic children to identify those at risk of cognitive sequelae

Diabetic ketoacidosis and electroencephalographic changes in newly diagnosed pediatric patients

Objective: To document electroencephalogram (EEG) changes and their correlation with clinical parameters in a newly diagnosed pediatric cohort of type 1 diabetes mellitus (T1DM) patients with and without diabetic ketoacidosis (DKA) and to define their medium term utility and significance.\ud \ud Research design and methods: Prospective longitudinal study of children presenting with T1DM. EEGs were performed within 24 h of diagnosis, day 5, and at 6 months post-diagnosis and reviewed by a neurologist blinded to clinical status. Severity of encephalopathy was graded from 1 to 5 using the Aoki and Lombroso encephalopathy scale. Cognitive abilities were assessed using standardized tests of attention, memory, and intelligence.\ud \ud Results: Eighty eight children were recruited; 34 presented with DKA. Abnormal background slowing was more often observed in the first 24 h in children with DKA (p = 0.01). Encephalopathy scores on day 1 correlated with initial pH, CO2, HCO3, base excess, respiratory rate, heart rate, diastolic blood pressure, and IV fluid intake (all parameters p < 0.05). EEG scores at day 1 did not correlate with contemporaneous mental state or cognition in the medium term.\ud \ud Conclusions: DKA was associated with significant clinical and neurophysiologic signs of brain dysfunction at presentation. While EEG is sensitive to the detection of encephalopathy in newly diagnosed T1DM, it has limited use in identifying children at risk of later cognitive deficits