Adverse Neurological Outcomes Research Articles

Clinical value of miR-191-5p in predicting the neurological outcome after out-of-hospital cardiac arrest.

The diagnostic and prognostic value of microRNAs (miRNA) in human disease has been confirmed in a number of clinical studies. The purpose of this study was to investigate the predictive value of miR-191-5p in the neurological outcome of patients recovering from out-of-hospital cardiac arrest (OHCA). A total of 260 patients undergoing the target temperature management trial were analyzed. The expression level of serum miR-191-5p was detected by qRT-PCR at 48h after return of spontaneous circulation (ROSC). ROC curve was established to evaluate the ability of miR-191-5p as a biomarker for predicting adverse neurological outcomes after OHCA. Kaplan-Meier curve and Cox regression analysis were used for survival analysis. One hundred eighteen patients (45%) had poor neurological outcomes at 6months. The expression level of serum miR-191-5p in patients with poor neurological outcomes was significantly lower than that in patients with good neurological prognosis (P < 0.001) and was not associated with TTM trial. The AUC, sensitivity, and specificity of the ROC curve were 0.899, 84.7%, and 82.4%, respectively, suggesting that the level of miR-191-5p had the ability to predict neurological outcome. By the end of the experiment, 88 patients (34%) were dead. Results of survival analysis showed that lower miR-191-5p expression level was significantly associated with lower survival rate (HR: 0.344, 95% CI = 0.208-0.567, P < 0.001). The level of miR-191-5p was down-regulated in patients with poor neurological outcomes, and it could be used as a promising novel biomarker for prediction of neurological outcome and survival after OHCA.

Urban air pollution and emergency department visits related to central nervous system diseases, Toronto, Canada

BACKGROUND AND AIM: Ambient air pollution has been associated with various adverse neurological health outcomes. This work comprehensively examined possible associations between concentration of five major urban air pollutants, two air quality indexes, and emergency department (ED) visits. METHODS: The analysis was done by sex, age group, and season for ED visits for central and peripheral nervous system diseases, in the period April 1, 2004-Decembr 31, 2015 (4,292 days in total). The study was done in Toronto, a Canadian megacity, using a case-crossover design. Conditional Poisson regression was realized to construct statistical models. Our focus was on daily ED visits covering all diseases of the nervous system and identified by ICD-10 codes (G00-G99). RESULTS:In the study period, 140,511 ED visits for diseases of the nervous system among Toronto residents were recorded: 83,602 (59.5%) for women and 56,909 (40.5%) for men. We found that nearly 64% of the considered ED visits were related to the episodic and paroxysmal disorders (G40-G47), with the majority of those visits related to migraines (39%). Based on a number of positive consistent associations, largest effect on ED visits for G40-G47, especially G43 (migraines) was among women exposed to ambient CO, especially with either immediate effect (0 and 1 lag) or a week long effect (6 and 7 lag) were found. Relative risks (RR) with 95% confidence intervals were reported for a one interquartile range (IQR) increase, (IQR=0.1 ppm). Women exposed to CO had RR of 1.036 (1.007-1.065) on the same day (especially older women), and 1.019 (1.004-1.033), 1.024 (1.010-1.039), and 1.022 (1.007-1.036) for lags 1, 6, and 7 days, respectively. CONCLUSIONS:Our findings support the associations between onset of possible diseases of the central nervous system (particularly migraines) and concentration of ambient CO, even at relatively low levels, detected in Toronto. KEYWORDS: acute exposure, ambient carbon monoxide, case-crossover, conditional Poisson, migraine, female

Predictors of Neurological Outcome Following Infant Cardiac Surgery Without Deep Hypothermic Circulatory Arrest

The aim of this study is to describe the clinical characteristics, perioperative course and neuroimaging abnormalities of infants with congenital heart disease (CHD) undergoing heart surgery without deep hypothermic circulatory arrest (DHCA) and identify variables associated with neurological outcome. Infants with CHD undergoing open-heart surgery without DHCA between 2009 and 2017 were identified from a cardiac surgery database. Full-term infants < 10weeks of age at the time of surgery who had both a pre- and postoperative brain magnetic resonance imaging exam (MRI) were included. Clinical characteristics and perioperative variables were collected from the electronic medical record. Brain Injury Scores (BIS) were assigned to pre- and postoperative brain MRIs. Variables were examined for association with neurological outcome at 12months of age or greater. Forty-two infants were enrolled in the study, of whom 69% (n = 29) had a neurological assessment ≥ to 12months of age. Adverse neurological outcome was associated with longer intensive care unit (ICU) stay (P = 0.003), lengthier mechanical ventilation (P = 0.031), modified Blalock-Taussig (MBT) shunt procedure (P = 0.005) and postoperative seizures (P = 0.005). Total BIS scores did not predict outcome but postoperative infarction and/or intraparenchymal hemorrhage (IPH) was associated with worse outcome by multivariable analysis (P = 0.018). Infants with CHD undergoing open-heart surgery without DHCA are at increased risk of worse neurological outcome when their ICU stay is prolonged, mechanical ventilation is extended, MBT shunt is performed or when postoperative seizures are present. Cerebral infarctions and IPH on postoperative MRI are also associated with worse outcome.

Interpretation of vaccine associated neurological adverse events: a methodological and historical review

As a result of significant recent scientific investment, the range of vaccines available for COVID-19 prevention continues to expand and uptake is increasing globally. Although initial trial safety data have been generally reassuring, a number of adverse events, including vaccine induced thrombosis and thrombocytopenia (VITT), have come to light which have the potential to undermine the success of the vaccination program. However, it can be difficult to interpret available data and put these into context and to communicate this effectively. In this review, we discuss contemporary methodologies employed to investigate possible associations between vaccination and adverse neurological outcomes and why determining causality can be challenging. We demonstrate these issues by discussing relevant historical exemplars and explore the relevance for the current pandemic and vaccination program. We also discuss challenges in understanding and communicating such risks to clinicians and the general population within the context of the ‘infodemic’ facilitated by the Internet and other media.

Neuroimaging in Children Born With Congenital Zika Syndrome: A Cohort Study

Neuroimaging findings have been associated with adverse neurologic outcomes in children with congenital Zika virus infection. Our purpose is to describe the brain magnetic resonance imaging (MRI) of children around 3 years of age, born with congenital Zika syndrome. This cohort study followed 62 children born with congenital Zika syndrome who had head computed tomography (CT) performed during the first months of life. All these children had clinical, neuroimaging, and serological confirmation of congenital Zika. Around 3 years of age, these children received a brain MRI. In 35 children, we could perform an MRI. All these children had severe impairment in neuromotor development. In general, the examinations showed the same alterations of the CT examinations: delayed myelination (82.8%), intracranial calcification (71.4%) although with decreased intensity and size as compared with previously CT examinations, ventriculomegaly (91.4%), cerebellar hypoplasia (68.5%), and cortical development abnormalities (85.8%). The serious brain alterations observed through head CT examinations in children born with congenital Zika syndrome continued to be detected through an MRI examination carried out at around 3 years of age. This indicates a poor prognosis for these children who had a severe neuromotor development delay.

Neurocognitive, Quality of Life, and Behavioral Outcomes for Patients With Covert Stroke After Cardiac Surgery: Exploratory Analysis of Data From a Prospectively Randomized Trial.

Asymptomatic brain ischemic injury detected with diffusion-weighted magnetic resonance imaging (DWI) is reported in more than one-half of patients after cardiac surgery. There are conflicting findings on whether DWI-detected covert stroke is associated with neurocognitive dysfunction after surgery, and it is unclear whether such ischemic injury affects quality of life or behavioral outcomes. The purpose of this study was to perform exploratory analysis on whether covert stroke after cardiac surgery is associated with delayed neurocognitive recovery 1 month after surgery, impaired quality of life, anxiety, or depression. Analysis of data collected in a prospectively randomized study in patients undergoing cardiac surgery testing whether basing mean arterial pressure (MAP) targets during cardiopulmonary bypass to be above the lower limit of cerebral autoregulation versus usual practices reduces the frequency of adverse neurological outcomes. A neuropsychological testing battery was administered before surgery and then 1 month later. Patients underwent brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. The primary outcome was DWI-detected ischemic lesion; the primary end point was change from baseline in domain-specific neurocognitive Z scores 1 month after surgery. Secondary outcomes included a composite indicator of delayed neurocognitive recovery, quality of life measures, state and trait anxiety, and Beck Depression Inventory scores. Of the 164 patients with postoperative MRI data, clinical stroke occurred in 10 patients. Of the remaining 154 patients, 85 (55.2%) had a covert stroke. There were no statistically significant differences for patients with or without covert stroke in the change from baseline in Z scores in any of the cognitive domains tested adjusted for sex, baseline cognitive score, and randomization treatment arm. The frequency of delayed neurocognitive recovery (no covert stroke, 15.1%; covert stroke, 17.6%; P = .392), self-reported quality of life measurements, anxiety rating, or depression scores were not different between those with or without DWI ischemic injury. More than one-half of patients undergoing cardiac surgery demonstrated covert stroke. In this exploratory analysis, covert stroke was not found to be significantly associated with neurocognitive dysfunction 1 month after surgery; evidence of impaired quality of life, anxiety, or depression, albeit a type II error, cannot be excluded.

Efficacy of endoscopic sinus surgery alone versus in combination with neurosurgical intervention for the treatment of pediatric subdural empyema

ObjectivesTo compare treatment outcomes for sinogenic subdural empyema (SE) between those managed with initial endoscopic sinus surgery (ESS) alone versus those treated with a combination of ESS and craniotomy over the last decade at our institution. To better characterize subdural empyema with regard to presentation, causative pathogens, and treatment course. MethodsRetrospective single-center chart review to identify and evaluate pediatric SE patients between 2009 and 2019. Patients meeting inclusion criteria were classified in one of two groups: those who initially underwent ESS or frontal trephination without concurrent neurosurgical procedure and those who underwent craniotomy or burr hole in addition to a sinus procedure. Presenting characteristics and treatment outcomes were compared between the two groups. ResultsEighteen patients met inclusion criteria. The ESS alone and the ESS + craniotomy subgroups each had 9 patients with similar baseline characteristics. The ESS + craniotomy group was more likely to present with neurological symptoms (p = 0.039) and have multiple intracranial fluid collections (p = 0.046). 74.1% of patients presented to the Emergency Department (ED) or to their primary medical doctor and were treated with outpatient management prior to hospitalization with definitive surgical management. The most common presenting symptoms were fever, headache and nausea/vomiting. There were no differences between treatment groups in rate of return to the operating room (OR) (p = 1.00), length of stay (LOS) (p = 0.553), or adverse neurological outcomes (p = 0.456). 44.4% of patients in the ESS alone group eventually required neurosurgical intervention. ConclusionsSurgical SE patients often present to medical professionals in the primary care setting or ED and are managed with outpatient treatment before admission with definitive treatment. In this small retrospective cohort patients who underwent sinus intervention alone had similar rates of return to OR, LOS and adverse neurological outcomes use as those who underwent a sinus procedure in coordination with a neurosurgical intervention. There may be a group of patients with SE who may be managed with endoscopic procedures alone and further studies should seek to determine the characteristics of this population.

Call to action: long‐term neurodevelopment in monochorionic twins

Call to action: long‐term neurodevelopment in monochorionic twins

Advocating for lifelong follow-up after preterm birth.

I was born preterm at 26 weeks of gestation in 1992 and I spent three months in the hospital. At discharge, my parents were told that my lungs could be permanently impaired (due to bronchopulmonary dysplasia), but that it should not prevent me from doing my everyday life activities. They were also warned about adverse neurological outcomes and learning difficulties, so they happily welcomed each developmental milestone I reached, never knowing when they could be sure that I would no longer be at risk.

Correction to: Neurologic Complications of Poverty: the Associations between Poverty as a Social Determinant of Health and Adverse Neurologic Outcomes

Correction to: Neurologic Complications of Poverty: the Associations between Poverty as a Social Determinant of Health and Adverse Neurologic Outcomes

Hypothermic circulatory arrest time affects neurological outcomes of frozen elephant trunk for acute type A aortic dissection: A systematic review and meta-analysis.

The treatment of complex thoracic aorta pathologies remains a challenge for cardiovascular surgeons. After introducing Frozen Elephant Trunk (FET), a significant evolution of surgical techniques has been achieved. The present meta-analysis aimed to assess the efficacy of FET in acute type A aortic dissection (ATAAD) and the effect of circulatory arrest time on post-operative neurologic outcomes. A standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses search was conducted for all observational studies of patients diagnosed with ATAAD undergoing total arch replacement with FET reporting in-hospital mortality, bleeding, and neurological outcomes. A random-effect meta-analysis was performed using STATA software (StataCorp, TX, USA). Thirty-five studies were eligible for the present meta-analysis, including 3211 patients with ATAAD who underwent total arch replacement with FET. The pooled estimate for in-hospital mortality, postoperative stroke, and spinal cord injury were 7% (95% CI 5 - 9; I2 = 68.65%), 5% (95% CI 4 - 7; I2 = 63.93%), and 3% (95% CI 2 - 4; I2 = 19.56%), respectively. Univariate meta-regression revealed that with increasing the duration of hypothermic circulatory arrest time, the effect sizes for postoperative stroke and SCI enhances. It seems that employing the FET procedure for acute type A dissection is associated with acceptable neurologic outcomes and a similar mortality rate comparing with other aorta pathologies. Besides, increasing hypothermic circulation arrest time appears to be a significant predictor of adverse neurologic outcomes after FET.

Amplitude integrated EEG: how much it helps in prognostication in neonatal encephalopathy?

Introduction Neonatal encephalopathy (NE) is associated with a high risk of adverse neurological outcomes. Several neurodiagnostic tests have been evaluated to predict the prognosis. Amplitude integrated Electroencephalogram (aEEG) is now being commonly used for bedside evaluation of cerebral function. There is limited data on the role of aEEG for prognostication in NE, from resource-limited settings. Objective To evaluate the predictive ability of aEEG for abnormal neurological outcomes in neonatal encephalopathy or neonates with encephalopathy. Methods Neonates above 35 weeks of gestation admitted to NICU in a tertiary care hospital with a diagnosis of encephalopathy were enrolled. Clinical characteristics severity of encephalopathy and seizures were recorded. Amplitude integrated recording was started at admission and continued till recovery of trace to normal or for 10 days. The primary outcome was death or abnormal neurological status at 3–6 months of age. The study was registered in the Clinical Trial Registry of India (CTRI/2013/05/003612) Results The incidence of NE was 6% of total admission. Moderate and severe encephalopathy occurred in 58 and 39% of babies respectively. Hypoxic-ischemic encephalopathy was the most common cause. Clinical seizures occurred in 91% of cases. An abnormal aEEG trace was observed in 51 (76.1%) infants with NE. For adverse neurological outcomes at an age average of 4.5 months of age, aEEG had a sensitivity, specificity, NPV, and PPV of 100, 54.2, 100, and 77.5, respectively. Conclusions Clinical staging and aEEG has good predictive ability to detect an adverse neurological outcome. aEEG improves the ability to predict abnormal outcome in babies with moderate encephalopathy. Early recovery of aEEG abnormality correlates with better neurodevelopmental outcomes. KEY MESSAGES What’s known: aEEG is a useful modality to assess neurodevelopmental outcomes however data from developing countries is lacking. What’s new: aEEG monitoring in babies in neonatal encephalopathy may improve the prediction of abnormal neurological outcomes in babies with moderate encephalopathy.

New Insights Into Microbiota Modulation-Based Nutritional Interventions for Neurodevelopmental Outcomes in Preterm Infants.

Gut microbiota and the central nervous system have parallel developmental windows during pre and post-natal life. Increasing evidences suggest that intestinal dysbiosis in preterm infants predisposes the neonate to adverse neurological outcomes later in life. Understanding the link between gut microbiota colonization and brain development to tailor therapies aimed at optimizing initial colonization and microbiota development are promising strategies to warrant adequate brain development and enhance neurological outcomes in preterm infants. Breast-feeding has been associated with both adequate cognitive development and healthy microbiota in preterms. Infant formula are industrially produced substitutes for infant nutrition that do not completely recapitulate breast-feeding benefices and could be largely improved by the understanding of the role of breast milk components upon gut microbiota. In this review, we will first discuss the nutritional and bioactive component information on breast milk composition and its contribution to the assembly of the neonatal gut microbiota in preterms. We will then discuss the emerging pathways connecting the gut microbiota and brain development. Finally, we will discuss the promising microbiota modulation-based nutritional interventions (including probiotic and prebiotic supplementation of infant formula and maternal nutrition) for improving neurodevelopmental outcomes.

Prognostic Value of Elevated Cardiac Troponin I After Aneurysmal Subarachnoid Hemorrhage.

Object: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have an increased incidence of cardiac events and short-term unfavorable neurological outcomes during the acute phase of bleeding. We studied whether troponin I elevation after ictus can predict future major adverse cardiac events (MACEs) and long-term neurological outcomes after 2 years.Methods: Consecutive aSAH patients within 3 days of bleeding were eligible for review from a prospective observational cohort (ClinicalTrials.gov Identifier: NCT04785976). Potential predictors of future MACEs and unfavorable long-term neurological outcomes were calculated by Cox and logistic regression analyses. Additional Kaplan–Meier curves were performed.Results: A total of 213 patients were enrolled with an average follow-up duration of 34.3 months. Individuals were divided into two groups: elevated cTnI group and unelevated cTnI group. By the last available follow-up, 20 patients had died, with an overall all-cause mortality rate of 9.4% and an annual all-cause mortality rate of 3.8%. Patients with elevated cTnI had a significantly higher risk of future MACEs (10.6 vs. 2.1%, p = 0.024, and 95% CI: 1.256–23.875) and unfavorable neurological outcomes at discharge, 3-month, 1-, 2-years, and last follow-up (p = 0.001, p < 0.001, p = 0.001, p < 0.001, and p < 0.001, respectively). In the Cox analysis for future MACE, elevated cTnI was the only independent predictor (HR = 5.980; 95% CI: 1.428–25.407, and p = 0.014). In the multivariable logistic analysis for unfavorable neurological outcomes, peak cTnI was significant (OR = 2.951; 95% CI: 1.376–6.323; p = 0.005). Kaplan–Meier analysis indicated that the elevated cTnI was correlated with future MACE (log-rank test, p = 0.007) and subsequent death (log-rank test, p = 0.004).Conclusion: cTnI elevation after aSAH could predict future MACEs and unfavorable neurological outcomes.

Short Report: Using Targeted Urine Metabolomics to Distinguish Between Manganese Exposed and Unexposed Workers in a Small Occupational Cohort.

Objectives: Despite the widespread use of manganese (Mn) in industrial settings and its association with adverse neurological outcomes, a validated and reliable biomarker for Mn exposure is still elusive. Here, we utilize targeted metabolomics to investigate metabolic differences between Mn-exposed and -unexposed workers, which could inform a putative biomarker for Mn and lead to increased understanding of Mn toxicity.Methods: End of shift spot urine samples collected from Mn exposed (n = 17) and unexposed (n = 15) workers underwent a targeted assay of 362 metabolites using LC-MS/MS; 224 were quantified and retained for analysis. Differences in metabolite abundances between exposed and unexposed workers were tested with a Benjamini-Hochberg adjusted Wilcoxon Rank-Sum test. We explored perturbed pathways related to exposure using a pathway analysis.Results: Seven metabolites were significantly differentially abundant between exposed and unexposed workers (FDR ≤ 0.1), including n-isobutyrylglycine, cholic acid, anserine, beta-alanine, methionine, n-isovalerylglycine, and threonine. Three pathways were significantly perturbed in exposed workers and had an impact score >0.5: beta-alanine metabolism, histidine metabolism, and glycine, serine, and threonine metabolism.Conclusion: This is one of few studies utilizing targeted metabolomics to explore differences between Mn-exposed and -unexposed workers. Metabolite and pathway analysis showed amino acid metabolism was perturbed in these Mn-exposed workers. Amino acids have also been shown to be perturbed in other occupational cohorts exposed to Mn. Additional research is needed to characterize the biological importance of amino acids in the Mn exposure-disease continuum, and to determine how to appropriately utilize and interpret metabolomics data collected from occupational cohorts.

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures. We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96h) after birth. Cerebral MRI was performed at 40-42weeks of corrected gestational age. Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI. The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.

Neurologic Complications of Poverty: the Associations Between Poverty as a Social Determinant of Health and Adverse Neurologic Outcomes.

Increasing attention has been paid in recent decades to social determinants of health as a risk factor for disease development and disease severity. While traditionally heart disease, family history, lipid profile, and tobacco use have all been associated with increased risk of neurological disease, numerous studies now show that the influence of poverty may be just as strong a risk factor. This study summarizes the recent literature on poverty as it contributes to neurological disease. Children growing up in poverty have increased risk for cognitive deficits and behavioral disorders as reported by Noble et al. (Dev Sci. 9(6):642-54, 2006) and Farah et al. (Brain Res. 1110(1):166-74, 2006) as well as worse outcomes when it comes to epilepsy management and disease course as discussed by Camfield et al. (Epilepsia. 57(11):1826-33, 2016). In adulthood, as the number of social determinants of health increases, the incidence of stroke and severe stroke increases significantly as reported by Reshetnyak et al. (Stroke. 51:2445-53, 2020) as does exposure to neurologically significant infectious diseases and incidence of dementia as reported by Sumilo et al. (Rev Med Virol. 18(2):81-95, 2008) and Zuelsdorff et al. (Alzheimer's Dement. 6(1):e12039, 2020). Social determinants of health including poverty should be considered a risk factor for disease. More attention is needed from clinicians as well as from a public health perspective to address this disparity.

Betamethasone Induces a Unique Transcriptome in Neural Stem Cells

Twelve percent of pregnant women receive glucocorticoids (sGCs) to reduce the risks to reduce morbidity and mortality associated with preterm birth in infants. The two most commonly administered sGC are Dexamethasone (Dex) and Betamethasone (Beta) and they serve to decrease the severity of respiratory distress, intraventricular hemorrhage and necrotizing enterocolitis. However, repeated administration of sGC has been shown to be associated with adverse neurological outcome and depends on the type of sGCs used, dose, timing of sGCs administration and sex. We have previously shown that prenatal exposure to Dex in a murine model lead to sex specific changes in the transcription response and in the biological function of neural stem cells and to long-term changes in brain architecture and behavior. Beta is the predominant sGC used prenatally in the United States, therefore these studies investigated the cellular and molecular responses to beta exposure on the neural stem cells in-vitro and anatomical organization of the brain in-vivo. Murine NSCs were isolated from the E14.5 cerebral cortex and exposed to 10-7 M Dex, 10-7 M Beta, or Vehicle for 4 or 24 hours and the immediate and long-term impact on transcription, proliferation and neuronal, glial and oligodendrocyte differentiation examined. Affymetrix genome transcriptional analyses reveal sex specific responses to Dex vs Beta in 4 hours. In females 682 genes were differentially regulated by Dex compared to 576 by Beta. In contrast, 875 were altered by Dex and 576 by Beta in males (Fold change > +/- 1.5, P< 0.05). Select target genes were independently validated by QPCR. Ingenuity Pathway Analysis was used to identify unique and overlapping pathways that were altered by Dex vs Beta. In males, Dex uniquely altered 34 pathways including, Thyroid Hormone Metabolism, ERK5 Signaling and Opioid Signaling while Bata altered 33 pathways including, Phagasome formation, IL-7 Signaling and JAK STAT signaling. In Females, Dex altered 45 pathways including Calcium Signaling, Serotonin Receptor Signaling and Xenobiotic Signaling, while Beta altered 46 pathways including, FXR/RXR Activation, Tec Kinase Signaling and D-myo-Inositol-5-Phosphate Metabolism. Another 35 pathways were altered by both Dex and Beta but they showed differences in genes activated or repressed. Dex and Beta, both significantly altered genes involved in proliferation and differentiation therefore the biological response of NSC to sGCs stimulation in vitro and the long term consequences of sGC exposure in-vivo was compared. Distinct differences in cell proliferation, glial and oligodendrocyte differentiation were observed. These results reveal gene targets, cellular pathways and processes that are differentially altered by prenatal Dex vs Beta exposure. Our finds may provide insights into the sex specific neurological outcomes observed in children exposed to sGCs in-utero.

Growth hormone deficiency and hypoglycemia: a case report

Recurrent hypoglycemia in childhood may be caused by various endocrine or metabolic disorders, of which growth hormone deficiency is a rare cause. A 5-year-old girl presented to us with short stature and recurrent episodes of hypoglycemic seizures. On evaluating for the same, critical sample showed normal cortisol and low c-peptide levels. Neuroimaging ruled out pituitary anomalies. Growth hormone deficiency was diagnosed after GH stimulation test (with clonidine and insulin) revealed low basal and post-stimulation values. Following GH supplementation, no further hypoglycemia was noted. This rare case is being reported to highlight the importance of treating the underlying etiology of hypoglycemia to prevent adverse neurological outcome.

Pharmacotherapy for Nonconvulsive Seizures and Nonconvulsive Status Epilepticus

Most seizures in critically ill patients are nonconvulsive. A significant number of neurological and medical conditions can be complicated by nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE), with brain infections, hemorrhages, global hypoxia, sepsis, and recent neurosurgery being the most prominent etiologies. Prolonged NCSs and NCSE can lead to adverse neurological outcomes. Early recognition requires a high degree of suspicion and rapid and appropriate duration of continuous electroencephalogram (cEEG) monitoring. Although high quality research evaluating treatment with antiseizure medications and long-term outcome is still lacking, it is probable that expeditious pharmacological management of NCSs and NCSE may prevent refractoriness and further neurological injury. There is limited evidence on pharmacotherapy for NCSs and NCSE, although a few clinical trials encompassing both convulsive and NCSE have demonstrated similar efficacy of different intravenous (IV) antiseizure medications (ASMs), including levetiracetam, valproate, lacosamide and fosphenytoin. The choice of specific ASMs lies on tolerability and safety since critically ill patients frequently have impaired renal and/or hepatic function as well as hematological/hemodynamic lability. Treatment frequently requires more than one ASM and occasionally escalation to IV anesthetic drugs. When multiple ASMs are required, combining different mechanisms of action should be considered. There are several enteral ASMs that could be used when IV ASM options have been exhausted. Refractory NCSE is not uncommon, and its treatment requires a very judicious selection of ASMs aiming at reducing seizure burden along with management of the underlying condition.