Gemma Arca

Early identification of brain injury in infants with hypoxic ischemic encephalopathy at high risk for severe impairments: accuracy of MRI performed in the first days of life

BackgroundDespite therapeutic hypothermia 30-70% of newborns with moderate or severe hypoxic ischemic encephalopathy will die or survive with significant long-term impairments. Magnetic resonance imaging (MRI) in the first days of life is being used for early identification of these infants and end of life decisions are relying more and more on it. The purpose of this study was to evaluate how MRI performed around day 4 of life correlates with the ones obtained in the second week of life in infants with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia.MethodsProspective observational cohort study between April 2009 and July 2011. Consecutive newborns with HIE evaluated for therapeutic hypothermia were included. Two sequential MR studies were performed: an •early’ study around the 4th day of life and a •late’ study during the second week of life. MRI were assessed and scored by two neuroradiologists who were blinded to the clinical condition of the infants.ResultsForty-eight MRI scans were obtained in the 40 newborns. Fifteen infants underwent two sequential MR scans. The localization, extension and severity of hypoxic-ischemic injury in early and late scans were highly correlated. Hypoxic-ischemic injury scores from conventional sequences (T1/T2) in the early MRI correlated with the scores of the late MRI (Spearman ρ = 0.940; p < .001) as did the scores between diffusion-weighted images in early scans and conventional images in late MR studies (Spearman ρ = 0.866; p < .001). There were no significant differences in MR images between the two sequential scans.ConclusionsMRI in the first days of life may be a useful prognostic tool for clinicians and can help parents and neonatologist in medical decisions, as it highly depicts hypoxic-ischemic brain injury seen in scans performed around the second week of life.

Neonatal hypoxic‐ischaemic encephalopathy: most deaths followed end‐of‐life decisions within three days of birth

To investigate the circumstances surrounding end‐of life decisions (EoL) of infants with hypoxic‐ischaemic encephalopathy (HIE) and examine changes over a 10‐year period.

Hipotermia cerebral moderada en la encefalopatía hipóxico-isquémica. Experiencia en el primer año de su puesta en marcha

INTRODUCTION Moderate cerebral hypothermia has been shown to be an effective intervention in decreasing mortality and major disabilities in infants with moderate-severe hypoxic-ischaemic encephalopathy (HIE). OBJECTIVES To describe our experience within the first year of implementation, and to evaluate the feasibility and safety of this intervention. METHODS Retrospective study of 20 patients with moderate-severe HIE treated with whole body hypothermia in the Agrupación Sanitaria Hospital Sant Joan de Déu-Hospital Clínic, between January 2009 and June 2010. RESULTS During this period, 50 patients with perinatal HIE, 26 of them moderate- severe, were admitted to our units. Twenty patients received hypothermia (13 with severe and 7 with moderate HIE). All of them had at least one risk factor for perinatal hypoxia-ischaemia, and clinical signs of HIE. Fifteen had clinical and/or EEG seizures. Core temperature was maintained at 33.5 ± 0.5°C in 76.5% of determinations for infants cooled with a manual control device, and in 93.6% for those cooled with a servo-controlled device (P<.0001). Re-warming took a median time of 10.5 hours. No potentially severe complications related to hypothermia were observed. Seven patients (35%) died, all of them with severe HIE. CONCLUSIONS There were no difficulties in any of the steps of this intervention, and no potentially severe complications related to it were recorded. Both manual and servo-control methods are equally effective on maintaining the target temperature, although temperature shows less variability using the servo-controlled equipment.

The Severity of Hypoxic-Ischemic Encephalopathy Correlates With Multiple Organ Dysfunction in the Hypothermia Era.

Objectives: The objectives are to 1) determine whether there is a positive correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction and 2) evaluate the organ dysfunction pattern in infants with hypoxic-ischemic encephalopathy in the hypothermia era. Design: Retrospective observational study of prospective data collected between April 2009 and December 2012. Setting: The study took place in the neonatal ICU of Hospital Sant Joan de Déu–Hospital Clínic of Barcelona. Patients: Prospective consecutive newborns with greater than or equal to 36 weeks of gestation, greater than or equal to 1,800 g of weight at birth, and a diagnosis of hypoxic-ischemic encephalopathy was included. Interventions: Severity of hypoxic-ischemic encephalopathy was established before starting controlled hypothermia. Six organ systems and 23 clinical and laboratory variables were studied by means of an asymmetrical grading scale. Data were recorded daily during the first 72 hours of life. Measurements and Main Results: Seventy-nine patients were studied. All presented with multiple organ dysfunction on day 1. There were differences in the number of affected organs on day 1 according to hypoxic-ischemic encephalopathy stage (p < 0.001). Scale scores correlated positively with the severity of hypoxic-ischemic encephalopathy (area under the curve ranged from 0.77 to 0.87 on every day studied). There were significant differences in the severity of dysfunction of each organ system among the three hypoxic-ischemic encephalopathy stages (p < 0.05). Although the most frequently involved were hepatic and pH and electrolyte imbalance, the most severely affected were the respiratory and cardiovascular systems. Conclusions: In the hypothermia era, multiple organ dysfunction continues to be almost universal in newborns with hypoxic-ischemic encephalopathy. There is a high correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction during the first 3 days of life. A high index of suspicion of relevant multiple organ dysfunction is required in infants admitted with a diagnosis of severe hypoxic-ischemic encephalopathy. Patients with moderate hypoxic-ischemic encephalopathy present wide variability in the severity of multiple organ dysfunction. In the absence of multiple organ dysfunction, a perinatal hypoxic-ischemic origin of acute severe neonatal encephalopathy should be carefully reconsidered.

Three-Dimensional Map of Neonatal Arterial Ischemic Stroke Distribution From Early Multimodal Brain Imaging

Background and Purpose— Although neonatal arterial ischemic stroke (NAIS) location has considerable impact on long-term outcome, a map showing spatial distribution of NAIS is lacking. Our aim was to generate this distribution map, based on early magnetic resonance imaging data. Methods— Lesions from 34 consecutive neonates with NAIS from a single center were segmented using multimodal magnetic resonance imaging (median age at acquisition =5 days). Lesion masks for all subjects were registered onto a standard neonatal brain and then overlaid to generate a 3D map of NAIS distribution. Results— The region posterior to the central sulcus is the most frequently affected in neonates, with 24 of the 34 neonates (71%) showing lesions in this region in at least one hemisphere. Moreover, NAIS frequency is markedly higher in the left hemisphere. Conclusions— This is the first report of an NAIS distribution map. Regions posterior to the central sulcus present increased vulnerability. Our findings suggest that motor areas are not as frequently affected as has been previously reported. By contrast, we find high NAIS vulnerability in functional areas related to language. The distribution of ischemic strokes in neonates seems to be different from that seen in adults.

Neonatal Arterial Ischemic Stroke: Risk Related to Family History, Maternal Diseases, and Genetic Thrombophilia:

The objective of this study was to evaluate the heritability of neonatal arterial ischemic stroke (NAIS) in relation to family history of thromboembolic event, maternal diseases, and thrombophilia in both parents (F5G1691A, F2G20210A, and MTHFRC677 T mutations). Forty-two consecutive infants ≥36 weeks of gestation <28 days of life with acute symptomatic NAIS and their parents, as well as 129 controls, were prospectively recruited. Information on maternal data (age, body mass index, oral contraception, migraine, epilepsy, hypertension, and immune disease) and a 3-generation pedigree regarding myocardial infarction, pulmonary embolism, cerebrovascular event, and deep vein thrombosis were obtained. Thrombophilia and maternal diseases did not differ between cases and controls, except for the use of oral contraceptives (more frequent in mothers of controls). No differences were found regarding each studied antecedent of thromboembolic event in the families. The NAIS group showed a higher presence of positive family history among second-degree maternal relatives than did the control infants (odds ratio 4.10; 95% confidence interval 1.29-12.99). Our study does not support the hypothesis that common genetic thrombophilia or familial predisposition to thromboembolic events is associated with the occurrence of idiopathic NAIS.

Coagulation factor V G1691A, factor II G20210A and methylenetetrahydrofolate reductase C677T gene mutations do not play a major role in symptomatic neonatal arterial ischaemic stroke.

associated with inferior event free and overall survival in Hodgkin lymphoma. American Journal of Hematology, 86, 998–1000. Urayama, K.Y., Jarrett, R.F., Hjalgrim, H., Diepstra, A., Kamatani, Y., Chabrier, A., Gaborieau, V., Boland, A., Nieters, A., Becker, N., Foretova, L., Benavente, Y., Maynadi e, M., Staines, A., Shield, L., Lake, A., Montgomery, D., Taylor, M., Smedby, K.E., Amini, R.M., Adami, H.O., Glimelius, B., Feenstra, B., Nolte, I.M., Visser, L., van Imhoff, G.W., Lightfoot, T., Cocco, P., Kiemeney, L., Vermeulen, S.H., Holcatova, I., Vatten, L., Macfarlane, G.J., Thomson, P., Conway, D.I., Benhamou, S., Agudo, A., Healy, C.M., Overvad, K., Tjonneland, A., Melin, B., Canzian, F., Khaw, K.T., Travis, R.C., Peeters, P.H., Gonzalez, C.A., Quiros, J.R., Sanchez, M.J., Huerta, J.M., Ardanaz, E., Dorronsoro, M., Clavel-Chapelon, F., Buenode-Mesquita, H.B., Riboli, E., Roman, E., Boffetta, P., de Sanjose, S., Zelenika, D., Melbye, M., van den Berg, A., Lathrop, M., Brennan, P. & McKay, J.D. (2012) Genome-wide association study of classical Hodgkin lymphoma and Epstein–Barr virus status-defined subgroups. Journal of the National Cancer Institute, 104, 240–253. de Yebenes, V.G., Bartolome-Izquierdo, N., Nogales-Cadenas, R., Perez-Duran, P., Mur, S.M., Martinez, N., Di Lisio, L., Robbiani, D.F., Pascual-Montano, A., Canamero, M., Piris, M.A. & Ramiro, A.R. (2014) miR-217 is an oncogene that enhances the germinal center reaction. Blood, 124, 229–239.

Incidencia de la encefalopatía hipóxico-isquémica e implementación de la hipotermia terapéutica por regiones en España

INTRODUCTION There are no data on the incidence of hypoxic-ischaemic encephalopathy (HIE) and the implementation of therapeutic hypothermia (TH) in Spain. METHODS This is a cross-sectional, national study, performed using an on-line questionnaire targeting level III neonatal care units in Spain. Participants were requested to provide data of all newborns ≥ 35 weeks of gestational age diagnosed with moderate-severe HIE over a two year-period (2012-2013), and of the implementation of TH up to June 2015. RESULTS All (90) contacted hospitals participated. HIE incidence rate was 0.77/1000 live newborns (95% CI 0.72 - 0.83). During 2012-2013, 86% of the newborns diagnosed with moderate-severe HIE received TH (active or passive). Active TH was increasingly used, from 78% in 2012 to 85% in 2013 (P=.01). Of the 14% that did not receive TH, it was mainly due to a delay in the diagnosis or inter-hospital transfer, and to the fact that the treatment was not offered. More than half (57%) were born in hospitals where TH was not provided, and passive hypothermia was used for inter-hospital patient transfer, and in 39% of the cases by inappropriately trained personnel. By June 2015, 57 out of 90 centres had implemented TH, of which 54 performed whole-body TH (using servo-controlled devices). The geographical distribution of centres with active TH, and the number of newborn that received TH, was heterogeneous. CONCLUSIONS The incidence of moderate-severe HIE is homogeneous across Spanish territory. Significant progress is being made in the implementation of TH, however it is necessary to increase the availability of active TH between Autonomous Communities, to improve early diagnosis, and to guarantee high quality patient transfer to referral centres.