The Impact of Diabetes on Hippocampus

Maternal Diabetes is one of the most common metabolic disorders resulting an increased risk of abnormalities in the developing fetus and offspring. It is estimated that the prevalence of diabetes during pregnancy among women in developing countries is approximately 4.5 percent and this range varies between 1 to 14 percent in different societies. According to earlier studies, diabetes during pregnancy is associated with an increased risk of maternal and child mortality and morbidity as well as major congenital anomalies including central nervous system (CNS) in their offspring. Multiple lines of evidence have suggested that infants of diabetic women are at risk of having neurodevelopmental sequelae. Previous studies reveal that the offspring of diabetic mothers exhibit disturbances in behavioral and intellectual functioning. In the examination of cognitive functioning, a poorer performance was observed in the children born to diabetic mothers when compared with the children of non-diabetic mothers. Therefore, it is important to study the possible effects of maternal diabetes on the hippocampus of these infants.

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Management of mental health disorders and central nervous system sequelae in HIV-positive children and adolescents

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v15i3.7 ◽

2014 ◽

Vol 15 (3) ◽

pp. 81-96 ◽

Cited By ~ 4

Author(s):

R Nassen ◽

K Donald ◽

K Walker ◽

S Paruk ◽

M Vujovic ◽

...

Keyword(s):

Mental Health ◽

Central Nervous System ◽

Nervous System ◽

Mental Disorders ◽

Children And Adolescents ◽

Mental Health Disorders ◽

Hiv Positive ◽

Increased Risk ◽

Health Disorders ◽

The Impact

HIV-positive children and adolescents are at increased risk of both central nervous system (CNS) sequelae and mental disorders owing to a number of factors, including the impact of HIV infection on the brain, social determinants of health (e.g. poverty and orphanhood) and psychosocial stressors related to living with HIV. Every effort should be made to identify perinatally HIV-infected children and initiate them on antiretroviral therapy early in life. HIV clinicians should ideally screen for mental health and neurocognitive problems, as part of the routine monitoring of children attending antiretroviral clinics. This guideline is intended as a reference tool for HIV clinicians to support the early identification, screening and management of mental health disorders and/or CNS impairment in children and adolescents. This guideline covers mental disorders (section 1) and HIV-associated neurocognitive disorders (section 2) among children and adolescents.

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Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia

Blood ◽

10.1182/blood-2011-09-381731 ◽

2012 ◽

Vol 119 (7) ◽

pp. 1658-1664 ◽

Cited By ~ 54

Author(s):

Jitesh D. Kawedia ◽

Chengcheng Liu ◽

Deqing Pei ◽

Cheng Cheng ◽

Christian A. Fernandez ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Acute Lymphoblastic Leukemia ◽

Multivariate Analyses ◽

Lymphoblastic Leukemia ◽

Central Nervous System Relapse ◽

Relapse Risk ◽

Increased Risk ◽

The Impact ◽

Risk Of Relapse

Abstract We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10−8) in patients whose sera was positive (17.7 ± 18.6 L/h per m2) versus nega-tive (10.6 ± 5.99 L/h per m2) for anti–asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti–asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti–asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse.

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Advanced echocardiography in neonates of diabetic mothers: a large population study of newborns

European Heart Journal ◽

10.1093/ehjci/ehaa946.3197 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Paerregaard ◽

R.O.B Voegg ◽

C.A Pihl ◽

H Bundgaard ◽

K.K Iversen

Keyword(s):

Gestational Diabetes ◽

Cardiac Function ◽

Large Population ◽

Maternal Diabetes ◽

Doppler Imaging ◽

Funding Source ◽

Private Company ◽

Increased Risk ◽

The Impact ◽

Diabetic Mothers

Abstract Background Maternal diabetes is associated with increased risk of congenital heart defects in the newborn, but the impact on systolic and diastolic function is less well described and findings are conflicting. Purpose To assess subclinical cardiac abnormalities in newborns of diabetic mothers using advanced echocardiography. Methods Transthoracic echocardiography (TTE) was performed within 30 days after birth in unselected neonates consecutively included in a prospective, multicenter, population-based study (2016–2018 (n=25,750)). Cardiac function in newborns of mothers with pre-gestational (pre-GDM) or gestational diabetes (GDM) and a group of matched controls of newborns of non-diabetic mothers was assessed by Tissue Doppler Imaging (TDI) and Speckle Tracking Echocardiography (STE) to detect myocardial abnormalities. Controls were matched 1:1 by the following criteria; multiple pregnancy, sex, gestational age (± five days), age at TTE (± three days) and weight (± 200 g). Results TDI and STE was performed in 317 newborns exposed to maternal diabetes during pregnancy (98 newborns of mothers with pre-GDM (females; 45.7%) and 219 newborns of mothers with GDM (females; 50%)). The mean age at time of TTE in newborns of diabetic mothers was 12 days (± 7 days). Cardiac function assessed with TDI showed significantly lower mitral valve (MV) systolic annular velocity (MV S') (3.15 cm/sec ± 0.67 vs 3.41 cm/sec ± 0.68, p=0.001), MV early diastolic annular velocity (MV E') (−4.71 cm/sec ± 1.26 vs −5.07 cm/sec ± 1.10, p=0.009), MV late diastolic annular velocity (MV A') (−4.24 cm/sec ± 1.25 vs −4.67 cm/sec ± 1.34, p=0.007) and interventricular septum late diastolic velocity (IVS A') (−4.49 cm/sec ± 0.89 vs −4.84 cm/sec ± 1.01, p=0.005) in newborns of mothers with pre-GDM compared to newborns of non-diabetic mothers. Newborns of mothers with GDM showed significantly lower MV A' (−4.35 cm/sec ± 1.35 vs −4.67 cm/sec ± 1.34, p=0.008) compared to newborns of non-diabetic mothers. When comparing subtypes of diabetes, newborns of mothers with pre-GDM had significantly lower MV E' (−4.71 cm/sec ± 1.26 vs −5.02 cm/sec ± 1.22, p=0.046) and IVS A' (−4.49 cm/sec ± 0.89 vs −4.75 cm/sec ± 0.93, p=0.033) compared to newborns of mothers with GDM. STE analysis showed that end-systolic and peak longitudinal strain (LS) were significantly lower in both subtypes of diabetes when compared to newborns of non-diabetic mothers; pre-GDM: end-systolic LS −17.93% and peak LS −19.18%, GDM: end-systolic LS −18.39% and peak LS −19.56% vs −19.56% and −20.29% in children of non-diabetic mothers, p<0.001 for all. Standard echocardiographic parameters were similar when comparing each subtype of diabetes with the newborns of non-diabetic mothers. Conclusion Advanced echocardiography showed impaired systolic and diastolic cardiac function in newborns of diabetic mothers. The most severe impairment was seen in newborns of mothers with pre-gestational diabetes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): PRIVATE COMPANY, Novo Nordisk Foundation: Pre-graduate Scholarhips 2019 - 6 months scholarship. Public Hospital, Herlev-Gentofte Internal Research Foundation 2019 - 6 months scholarship

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LINC-40. VERY YOUNG PATIENTS AND CENTRAL NERVOUS SYSTEM TUMORS: A SINGLE-CENTER EXPERIENCE IN AN UPPER-MIDDLE-INCOME COUNTRY

Neuro-Oncology ◽

10.1093/neuonc/noaa222.473 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii386-iii386

Author(s):

Claudia Madrigal-Avila ◽

Alfonso Perez-Bañuelos ◽

Martin Perez-Garcia ◽

Rafael Ruvalcaba-Sanchez ◽

Lourdes Vega-Vega ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Pediatric Population ◽

Young Patients ◽

Cns Tumors ◽

Central Nervous System Tumors ◽

Mortality And Morbidity ◽

Nervous System Tumors ◽

Tertiary Center ◽

The Impact

Abstract Tumors of the central nervous system comprise nearly a quarter of all childhood cancers and are the most frequent solid tumor in the pediatric population. Primary central nervous system tumors (PCNST) are a rare and heterogeneous group of tumors responsible for high mortality and morbidity. Around 10% of primary CNS tumors occur during the first year of life with almost half of them during the first six months. About 18% of these tumors appear before the age of two years. Very young children differ from older children and adolescents regarding the incidence and location of different histological entities of CNS tumors. We aimed at providing descriptive epidemiological data and report the outcome in a tertiary center from December 2013 to January 2020 for all histological subtypes of primary central nervous system tumors in very young patients, defined as patients younger than three years. We collect data from 19 patients treated in an oncology exclusive tertiary center in Mexico between 2013 and 2020. This study aims to relate factors such as age, radiotherapy, surgery, chemotherapy with Lansky Performance Scale and determine the impact, not only in the overall survival but also in the quality of life.

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Association between Intraoperative Blood Transfusion and Mortality and Morbidity in Patients Undergoing Noncardiac Surgery

Anesthesiology ◽

10.1097/aln.0b013e3182054d06 ◽

2011 ◽

Vol 114 (2) ◽

pp. 283-292 ◽

Cited By ~ 312

Author(s):

Laurent G. Glance ◽

Andrew W. Dick ◽

Dana B. Mukamel ◽

Fergal J. Fleming ◽

Raymond A. Zollo ◽

...

Keyword(s):

Blood Transfusion ◽

Noncardiac Surgery ◽

Pulmonary Complications ◽

Wound Complications ◽

Severe Anemia ◽

Thromboembolic Complications ◽

Mortality And Morbidity ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Background The impact of intraoperative erythrocyte transfusion on outcomes of anemic patients undergoing noncardiac surgery has not been well characterized. The objective of this study was to examine the association between blood transfusion and mortality and morbidity in patients with severe anemia (hematocrit less than 30%) who are exposed to one or two units of erythrocytes intraoperatively. Methods This was a retrospective analysis of the association of blood transfusion and 30-day mortality and 30-day morbidity in 10,100 patients undergoing general, vascular, or orthopedic surgery. We estimated separate multivariate logistic regression models for 30-day mortality and for 30-day complications. Results Intraoperative blood transfusion was associated with an increased risk of death (odds ratio [OR], 1.29; 95% CI, 1.03-1.62). Patients receiving an intraoperative transfusion were more likely to have pulmonary, septic, wound, or thromboembolic complications, compared with patients not receiving an intraoperative transfusion. Compared with patients who were not transfused, patients receiving one or two units of erythrocytes were more likely to have pulmonary complications (OR, 1.76; 95% CI, 1.48-2.09), sepsis (OR, 1.43; 95% CI, 1.21-1.68), thromboembolic complications (OR, 1.77; 95% CI, 1.32-2.38), and wound complications (OR, 1.87; 95% CI, 1.47-2.37). Conclusions Intraoperative blood transfusion is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia. It is unknown whether this association is due to the adverse effects of blood transfusion or is, instead, the result of increased blood loss in the patients receiving blood.

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QOL-36. USE OF CANNABINOIDS IN THE PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR POPULATION

Neuro-Oncology ◽

10.1093/neuonc/noaa222.695 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii438-iii438

Author(s):

Kathleen Dorris ◽

Jessica Channell ◽

Ashley Mettetal ◽

Molly Hemenway ◽

Natalie Briones ◽

...

Keyword(s):

Quality Of Life ◽

Central Nervous System ◽

Nervous System ◽

Cell Activity ◽

Cns Tumors ◽

Low Grade ◽

Tumor Type ◽

Central Nervous System Tumor ◽

The Impact

Abstract BACKGROUND Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are a class of compounds found in marijuana. Numerous studies in adults have examined cannabinoid use in management of cancer-related symptoms such as nausea, anorexia, and pain. Less is known about the use in the pediatric oncology population. METHODS A prospective observational study has been ongoing since 2016 at Children’s Hospital Colorado to evaluate cannabinoids’ impact using PedsQL™ modules on quality of life of pediatric patients with central nervous system (CNS) tumors who are 2–18 years old. Laboratory assessments of T-cell activity and pharmacokinetics of CBD, THC and associated metabolites are in process. Diaries with exploratory information on cannabinoid use patterns are being collected. RESULTS Thirty-three patients (14:19; male:female) have been enrolled with a median age of 6.4 years (range, 2.9–17.7 years). The most common tumor type in enrolled patients is embryonal tumors (13/33; 39%). Nine (27%) patients have low-grade glial/glioneuronal tumors, and eight (24%) had high-grade/diffuse midline gliomas. The remaining patients had ependymoma or craniopharyngioma. The median time on cannabinoids is 9 months. Most (n=20) patients have used oral products with CBD and THC. One patient continues on cannabinoid therapy in follow up. Preliminary immune function analyses identified impaired neutrophil superoxide anion production and chemotaxis in patients taking cannabinoids at early time points on therapy. CONCLUSIONS Families of children with various CNS tumors are pursuing cannabinoid therapy for both antitumor and supportive care purposes. Analysis of the impact of cannabinoids on patients’ quality of life is ongoing.

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Severe haemophilia A in a preterm girl with Turner syndrome: case report – a diagnostic and therapeutic challenge for a paediatrician (Part 2)

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01103-7 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Berendt Agnieszka ◽

Wójtowicz-Marzec Monika ◽

Wysokińska Barbara ◽

Kwaśniewska Anna

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Family History ◽

Factor Viii ◽

Turner Syndrome ◽

Factor Viii Inhibitor ◽

Haemophilia A ◽

Severe Haemophilia ◽

Prolonged Bleeding ◽

Increased Risk

Abstract Background Haemophilia A is an X-linked genetic condition which manifests itself mainly in male children in the first 2 years of life, during gross motor skill development. This disorder is rare in females. The clinical manifestation of severe haemophilia in preterm infants poses a great challenge to the therapeutic team. As extreme prematurity is linked to an increased risk of central nervous system or gastrointestinal bleeding, a well-informed and balanced treatment from the first days of life is crucial to prevent long-term damage. Haemophilia is most commonly caused by inheriting defective genes, and can also be linked to skewed X inactivation and Turner syndrome. The coincidental occurrence of haemophilia A and Turner syndrome is extremely rare, with only isolated cases described to date. Hence, a multidisciplinary approach is needed. Case presentation The authors report on a preterm girl (gestational age 28 weeks) diagnosed with haemophilia and Turner syndrome. The first manifestation of haemophilia was prolonged bleeding from injection sites on the second day of life. Indeterminate aPTT and factor VIII level < 1% confirmed the diagnosis of haemophilia A. Dysmorphic features which did not match the typical clinical picture of haemophilia, the female sex, and a negative paternal family history led to the diagnosis of Turner syndrome. While in hospital, the girl received multiple doses of recombinant factor VIII in response to prolonged bleedings from the injection sites and from a nodule on the girl’s head, and before and after retinal laser photocoagulation. No central nervous system or abdominal cavity bleeding was observed. The substitutive therapy was complicated by the development of factor VIII inhibitor (anti-factor VIII (FVIII) antibodies). Treatment was continued with recombinant factor VIIa. This article aims at demonstrating the complexity of the diagnostics and treatment of a preterm child with two genetic disorders. Conclusions Haemophilia should always be considered in the differential diagnosis of prolonged bleeding, even in patients with a negative family history. In the case of coinciding atypical phenotypic features, further diagnostics for another genetic disease are recommended. Infant care should follow current care standards, while considering certain individual features.

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EPID-18. TRENDS IN INCIDENCE AND SURVIVAL OF MALIGNANT PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS IN THE NETHERLANDS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.204 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii322-iii322

Author(s):

Raoull Hoogendijk ◽

Jasper van der Lugt ◽

Dannis van Vuurden ◽

Eelco Hoving ◽

Leontien Kremer ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

The Netherlands ◽

Malignant Gliomas ◽

Survival Rates ◽

Tumor Patients ◽

Netherlands Cancer Registry ◽

Malignant Astrocytomas ◽

Brainstem Tumors ◽

The Impact

Abstract BACKGROUND Variation in survival of pediatric central nervous system (CNS) tumors is large between countries. Within Europe, the Netherlands had one of the worst reported survival rates of malignant CNS (mCNS) tumors during 2000–2007. METHODS Using the Netherlands Cancer Registry, we evaluated trends in incidence and survival of pediatric mCNS tumors (behavior /3, 5th digit in the morphology code) diagnosed between 1990–2017. RESULTS 839 newly-diagnosed mCNS tumor patients <18 years were registered between 1990–2017. Incidence of mCNS tumors remained stable (average incidence rate, 21.6 per million person-years). However, an increased incidence of malignant gliomas, NOS was found (Estimated Annual Percentage Change (EAPC) 11.6% p<0.001). This appears to be related to a registration shift between 1990–1999 and 2000–2009 as brainstem tumors increased (+25%, n=79) for astrocytomas and other gliomas but decreased (-31%, n=32) for unspecified intracranial and intraspinal neoplasms. Overall, 5-year observed survival (5Y-OS) of mCNS tumors increased from 51% in 1990–1999 to 61% in 2010–2017 (P-for-trend<0.001). This increase was not constant over time, as 5Y-OS for the period 2000–2009 was 47%. The only significant decrease in survival was found for malignant astrocytomas and other gliomas with a 5Y-OS of 56% in 1990–1999 decreasing to 48% in 2010–2017 (P-for-trend<0.001). CONCLUSION Between 1990–2017 incidence of mCNS tumors in the Netherlands remained stable and survival increased. However, a decrease in survival was seen for malignant astrocytomas and other gliomas, which is partially explained by the registration shift of brainstem tumors. The impact of this shift on survival for all mCNS tumors is subject to further research.

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CASE STUDY ON CIRCUMSCRIBED GLIOMAS, THEIR CLINICOPATHOLOGICAL CORRELATION IN A TERTIARY CARE CENTER

10.36106/ijsr/6424584 ◽

2021 ◽

pp. 42-45

Author(s):

Esther Alffi Papang ◽

K. Rama

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tertiary Care ◽

Biological Behavior ◽

Low Grade ◽

Lower Grade ◽

Who Grade ◽

Primary Tumors ◽

Short Period ◽

The Impact

The histogenesis and biological behavior of primary tumors of the central nervous system(CNS) are very diverse. The majority of present gliomas as benign, slow growing lesions classied as by the WHO classicati grade I or II (Low grade gliomas) on of CNS tumors. However, a signicant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classied as WHO grade III or IV(High grade gliomas). Astrocytomas are primary central nervous system tumours that can develop in adults or in children. They arise from the Astrocytes. They can be divided into diffuse that generally have a higher grade and poorer prognosis and those that are localised that tend to be of a lower grade and have a better prognosis. In this study, we outline the basic histological spectrum and features, epidemiological aspects and grade of circumscribed gliomas (localised) or other Astrocytic tumours according to WHO classication . These are the Pilocytic Astrocytoma, Pilomyxoid Astrocytoma, Subependymal giant cell Astrocytoma, Pleomorphic xanthoastrocytoma and Anaplastic astrocytoma . The knowledge of these tumours are important as they are one of the commonest cause of mortality and morbidity in both the young and old, accounting for about 60% of the glial tumours. Therefore neuropathological diagnosis and tumour characteristics will therefore profoundly inuence the impact of treatment strategies.

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Maternal Overnutrition Induces Long-Term Cognitive Deficits across Several Generations

Nutrients ◽

10.3390/nu11010007 ◽

2018 ◽

Vol 11 (1) ◽

pp. 7 ◽

Cited By ~ 8

Author(s):

Gitalee Sarker ◽

Daria Peleg-Raibstein

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cognitive Deficits ◽

Maternal Obesity ◽

Cognitive Impairments ◽

Long Term Effects ◽

Ample Evidence ◽

Increased Risk ◽

Maternal Overnutrition

Ample evidence from epidemiological studies has linked maternal obesity with metabolic disorders such as obesity, cardiovascular disease, and diabetes in the next generation. Recently, it was also shown that maternal obesity has long-term effects on the progeny’s central nervous system. However, very little is known regarding how maternal overnutrition may affect, in particular, the cognitive abilities of the offspring. We reported that first-generation offspring exposed to a maternal high-fat diet (MHFD) displayed age-dependent cognitive deficits. These deficits were associated with attenuations of amino acid levels in the medial prefrontal cortex and the hippocampus regions of MHFD offspring. Here, we tested the hypothesis that MHFD in mice may induce long-term cognitive impairments and neurochemical dysfunctions in the second and third generations. We found that MHFD led to cognitive disabilities and an altered response to a noncompetitive receptor antagonist of the N-Methyl-D-aspartic acid (NMDA) receptor in adult MHFD offspring in both second and third generations in a sex-specific manner. Our results suggest that maternal overnutrition leads to an increased risk of developing obesity in subsequent generations as well as to cognitive impairments, affecting learning and memory processes in adulthood. Furthermore, MHFD exposure may facilitate pathological brain aging which is not a consequence of obesity. Our findings shed light on the long-term effects of maternal overnutrition on the development of the central nervous system and the underlying mechanisms which these traits relate to disease predisposition.

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