A Kapetanakis

Xenon augmented hypothermia reduces early lactate/N-acetylaspartate and cell death in perinatal asphyxia

Additional treatments for therapeutic hypothermia are required to maximize neuroprotection for perinatal asphyxial encephalopathy. We assessed neuroprotective effects of combining inhaled xenon with therapeutic hypothermia after transient cerebral hypoxia–ischemia in a piglet model of perinatal asphyxia using magnetic resonance spectroscopy (MRS) biomarkers supported by immunohistochemistry.

Passive cooling for initiation of therapeutic hypothermia in neonatal encephalopathy

Objective To determine the feasibility of passive cooling to initiate therapeutic hypothermia before and during transport. Methods Consensus guidelines were developed for passive cooling at the referring hospital and on transport by the London Neonatal Transfer Service. These were evaluated in a prospective study. Results Between January and October 2009, 39 infants were referred for therapeutic hypothermia; passive cooling was initiated at the referring hospital in all the cases. Despite guidance, no rectal temperature measurements were taken before arrival of the transfer team. Cooling below target temperature (33°C–34°C) occurred in five babies before the arrival of the transfer team. In two of these infants, active cooling was performed, rectal temperature was not recorded and their temperature was lower than 32°C. Of the remaining 37 babies, 33 (89%) demonstrated a reduction in core temperature with passive cooling alone. The percentage of the babies within the temperature range at referral, arrival of the transfer team and arrival at the cooling centre were 0%, 15% and 67%, respectively. On arrival at the cooling centre, four babies had cooled to lower than 33°C by passive cooling alone (32.7°C, 32.6°C, 32.2°C and 32.1°C). Initiation of passive cooling before and during transfer resulted in the therapy starting 4.6 (1.8) h earlier than if initiated on arrival at the cooling centre. Conclusions Passive cooling is a simple and effective technique if portable cooling equipment is unavailable. Rectal temperature monitoring is essential; active cooling methods without core temperature monitoring may lead to overcooling.

T2 at MR Imaging Is an Objective Quantitative Measure of Cerebral White Matter Signal Intensity Abnormality in Preterm Infants at Term-equivalent Age

PURPOSE To compare quantitative T2 relaxometry of cerebral white matter (WM) with qualitative assessment of conventional T2-weighted magnetic resonance (MR) images, to assess the relationship between cerebral WM T2 and region-specific apparent diffusion coefficient (ADC), and to examine WM T2 regional variation in preterm infants at term. MATERIALS AND METHODS The local ethical committee granted ethical permission for this study; informed parental consent was obtained for each infant. Sixty-two preterm infants born at less than 32 weeks gestation and nine control infants were examined at 1.5 T; T2-weighted fast spin-echo MR images, T2 relaxometry data, and diffusion-weighted MR images were acquired. Conventional T2-weighted MR images were assessed by a pediatric neuroradiologist for diffuse excessive high signal intensity (DEHSI) in WM. Regions of interest were positioned in frontal WM, central WM, and posterior WM at the level of the centrum semiovale. RESULTS In preterm infants at term, T2 was longer in all WM regions than in control infants; in infants with DEHSI, T2 was longer than in infants without DEHSI and control infants, with posterior WM T2 being longer than central or frontal WM T2. In control infants, T2 was similar in all WM regions. Frontal and posterior WM ADCs were higher in preterm infants at term than in control infants. CONCLUSION Cerebral WM T2 is an objective quantitative measurement that can easily and rapidly be obtained during clinical MR imaging in preterm infants at term.

Therapeutic hypothermia for neonatal encephalopathy: a UK survey of opinion, practice and neuro‐investigation at the end of 2007

Background: The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited.

Anticonvulsant effect of xenon on neonatal asphyxial seizures

Xenon, a monoatomic gas with very high tissue solubility, is a non-competitive inhibitor of N-methyl-D-aspartate (NMDA) glutamate receptor, has antiapoptotic effects and is neuroprotective following hypoxic ischaemic injury in animals. Xenon may be expected to have anticonvulsant effects through glutamate receptor blockade, but this has not previously been demonstrated clinically. We examined seizure activity on the real time and amplitude integrated EEG records of 14 full-term infants with perinatal asphyxial encephalopathy treated within 12 h of birth with 30% inhaled xenon for 24 h combined with 72 h of moderate systemic hypothermia. Seizures were identified on 5 of 14 infants. Seizures stopped during xenon therapy but recurred within a few minutes of withdrawing xenon and stopped again after xenon was restarted. Our data show that subanaesthetic levels of xenon may have an anticonvulsant effect. Inhaled xenon may be a valuable new therapy in this hard-to-treat population.

Methyl‐isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model

Na+/H+ exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia‐ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post‐insult and 8 hourly thereafter. Serial phosphorus‐31 (31P) and proton (1H) MRS data were acquired before, during and up to 48 h after hypoxia‐ischaemia and metabolite‐ratio time‐series Area under the Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N‐acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d‐UTP nick end‐labelling (TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia‐ischaemia was neuroprotective in this perinatal asphyxia model.

Therapeutic hypothermia can be induced and maintained using either commercial water bottles or a phase changing material mattress in a newborn piglet model

Background: Therapeutic hypothermia, a safe and effective treatment for neonatal encephalopathy in an intensive care setting, is not available in low-resource settings. Aims/Methods: To assess two low-tech, low-cost cooling devices for use in low-resource settings: (i) commercially available water bottles filled with tepid water (25°C); (ii) a mattress made of phase changing material (PCM) with a melting point of 32°C (PCM works as a heat buffer at this temperature). Eleven anaesthetised newborn piglets were studied following transient hypoxia–ischaemia. The cooling device was applied 2–26 h after hypoxia–ischaemia with a target rectal temperature (Trectal) of 33–34°C. Trectal undershoot was adjusted using cotton blankets; the cooling device was renewed when Trectal rose above 35°C. Trectal data during cooling were dichotomised (within or without target) to assess: (a) the total period within the target Trectal range; (b) the stability and fluctuation of Trectal during cooling. Results: Therapeutic hypothermia was achieved with both water bottles (n = 5) and the PCM mattress (n = 6). The mean (SD) time to reach target Trectal was 1.8 (0.5) h with water bottles and 1.9 (0.3) h with PCM. PCM cooling led to a longer period within the target Trectal range (p<0.01) and more stable cooling (p<0.05). Water bottle cooling required device renewal (in four out of five piglets). Conclusion: Simple, low-tech cooling devices can induce and maintain therapeutic hypothermia effectively in a porcine model of neonatal encephalopathy, although frequent fine tuning by adjusting the number of blankets insulating the piglet was required to maintain a stable temperature. PCM may induce more stable cooling compared with water bottles.

Regional neonatal brain absolute thermometry by 1H MRS.

Therapeutic hypothermia is standard care for infants with moderate to severe encephalopathy. 1H MRS thermometry (MRSt) measures regional brain absolute temperature using the temperature‐dependent water chemical shift. This study evaluates the clinical feasibility of MRSt in human neonates, and correlates white matter (WM) and thalamus (Thal) MRSt with conventional rectal temperature (Trectal) measurement. Fifty‐six infants born at term underwent perinatal MRSt for suspected hypoxic–ischaemic brain injury and 33 infants born preterm had MRSt at a term‐equivalent age; 56 of the 89 had Trectal measured after MRSt of either a Thal or posterior WM voxel, or both. MRSt used point‐resolved spectroscopy (no water suppression; TR = 1370 ms; TE = 288 ms; 1.5 × 1.5 × 1.5 cm3 Thal and 1.1 × 1.3 × 1.4 cm3 WM voxels). Time domain data were phase and frequency corrected before summation and motion‐corrupted data were excluded from further analysis using simple criteria [preprocessing + quality assurance (QA)]. Two published water temperature‐dependence calibrations [both using cerebral creatine (Cr), choline (Cho) and N‐acetylaspartate (Naa) as independent reference peaks] were compared. The temperature measurements derived from Cr, Cho and Naa were combined to give a single amplitude‐weighted combination temperature (TAWC). WM and Thal TAWC correlated linearly with Trectal (Thal slope, 0.82 ± 0.04, R2 = 0.85, p < 0.05; WM slope, 0.95 ± 0.04, R2 = 0.78, p < 0.05). Preprocessing + QA improved the correlation between WM TAWC and Trectal (R2 increased from 0.27 to 0.78, p < 0.001). Both calibration datasets showed specific inconsistencies between the temperatures calculated using Cr, Cho and Naa reference peaks when applied to this neonatal dataset. Neonatal MRSt is clinically feasible. Preprocessing + QA improved MRSt reliability in WM. The consideration of MRSt calibration internal biases is necessary before combining MRSt temperatures from multiple reference peaks to obtain TAWC. Copyright