Neurological symptoms improved by hyperbaric oxygen therapy in a post-cardiac arrest patient due to carbon monoxide poisoning: a case report.

Background: Carbon monoxide (CO) poisoning and cardiac arrest can cause neurological complications such as mental deterioration and movement disorders through ischemic brain injury. We report a case in which neurological sequelae after cardiac arrest caused by CO poisoning improved after hyperbaric oxygen (HBO2) therapy. Case report: A 43-year-old male visited the hospital with cardiac arrest due to CO poisoning. He developed neurological sequelae including mental deterioration and myoclonus after recovering spontaneous circulation. Anticonvulsant therapy was used after target temperature management but did not have a positive effect on neurological symptoms. However, after HBO2 therapy the patient's neurological symptoms improved, and he was discharged a month later. Conclusion: HBO2 therapy may be considered when neurological sequelae persist after cardiac arrest due to CO poisoning.

[Holistic approach of the care of the infant with hypoxic-ischaemic encephalopathy in Spain]. / Atención integral del neonato con encefalopatía hipóxico-isquémica en España.

INTRODUCTION: There is not much information about the care of infants with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) in Spain. This includes whether protocols are routinely used, the type of neuro-monitoring performed, and how information on the neurological prognosis is presented to families. The answers to these would allow to detect and implement areas of improvement. METHOD: A cross-sectional analysis was performed on the responses to structured questionnaires sent to all the Spanish neonatal units that were performing TH in June 2015. Questions were divided into 5sections: 1) the availability of protocols and technological resources, 2) the use of neuro-monitoring tools, 3) the knowledge and training of the professionals; 4) the prognostic information given to the parents; and 5) the discharge report and the follow-up plan. RESULTS: Most centres (95%) use servo controlled whole-body cooling methods and have specific management protocols. Sedation is used in 70% of centres, and in 68% of them the onset of enteral feeding is delayed until the end of the cooling period. Amplitude-integrated electroencephalography monitoring is used in more than 80% of the centres, although only in 50% are nurses able to interpret it. Cerebral oxygen saturation is not often monitored (16%). As regards diagnostic-prognostic studies, neuroimaging is universal, but brain damage biomarkers are hardly used (29%). Prognostic information is offered within the first 72 posnatal hours in 21% of the centres, and is given without the presence of the nurse in 70% of the centres. Follow-up is performed by a neuro-paediatrician (84%), with an uneven duration between centres. CONCLUSIONS: The care of infants with HIE treated with TH in Spain is generally adequate, although there are areas for improvement in neuromonitoring, sedation, prognostic information, teamwork, and duration of follow-up.

Therapeutic Hypothermia to Treat a Newborn With Perinatal Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy is caused by neonatal asphyxia and can lead to mortality or long-term neurodevelopmental morbidity in neonates. Therapeutic hypothermia (TH) is one of the few effective ways to manage mitigating neurologic sequelae. The authors describe the case of a neonate who had a perinatal hypoxic insult and sustained no long-term sequelae after being treated with TH. It is important that osteopathic physicians who provide obstetric and gynecologic, perinatal, and emergency medical care are able to recognize a perinatal hypoxic event, understand the stratification of hypoxic-ischemic encephalopathy risk factors, and implement early TH protocols.

Correlations between maternal and neonatal serum selenium levels in full term neonates with hypoxic ischemic encephalopathy.

UNLABELLED: Perinatal hypoxic-ischemic encephalopathy (HIE) is an important cause of brain injury in the newborn and can result devastating consequences. The principle mechanisms underlying neurological damage in HIE resulting from hypoxemia and/or ischemia is deprivation of glucose and oxygen supply which energy failure. A consequent reperfusion injury often deteriorates the brain metabolism by increasing the oxidative stress damage. Selenium is a constituent of the antioxidant enzyme Glutathione peroxidase and is vital to antioxidant defense. This study aimed to measure the serum selenium levels in full term neonates with HIE and their mothers and to correlate between them and the severity of HIE. METHODS: The study included 60 full term neonates with HIE admitted to NICU of Minia university hospital during the period from January 2014 to February 2015. Twenty apparently healthy full term neonates selected as a control group. After history taking and careful clinical examination; all neonates were subjected to: Complete blood count, renal and liver function tests and serum electrolytes. Serum selenium was measured for all neonates and their mothers within 48 h of life using atomic flame spectrophotometer method. RESULTS: Neonates with HIE had significant lower serum selenium levels than normal healthy neonates (p = 0.001**) with the lowest levels in neonates with severe HIE but there were no significant differences between patients and controls as regards the maternal serum selenium levels. Significant negative correlations between serum selenium levels and the severity of HIE and base excess were present, while positive significant correlations were present with Apgar score and pH. There were no correlations between serum selenium levels and maternal serum selenium levels urea or creatinine levels. CONCLUSIONS: Neonates with HIE had lower serum selenium level than normal healthy neonates which is not dependent on the maternal serum selenium levels and was negatively correlated with the severity of HIE.

Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To examine the ability of magnetic resonance imaging (MRI) patterns of neonatal brain injury defined by the National Institute of Child Health and Human Development Neonatal Research Network to predict death or IQ at 6-7 years of age following hypothermia for neonatal encephalopathy. STUDY DESIGN: Out of 208 participants, 124 had MRI and primary outcome (death or IQ <70) data. The relationship between injury pattern and outcome was assessed. RESULTS: Death or IQ <70 occurred in 4 of 50 (8%) of children with pattern 0 (normal MRI), 1 of 6 (17%) with 1A (minimal cerebral lesions), 1 of 4 (25%) with 1B (extensive cerebral lesions), 3 of 8 (38%) with 2A (basal ganglia thalamic, anterior or posterior limb of internal capsule, or watershed infarction), 32 of 49 (65%) with 2B (2A with cerebral lesions), and 7 of 7 (100%) with pattern 3 (hemispheric devastation), P < .001; this association was also seen within hypothermia and control subgroups. IQ was 90 ± 13 among the 46 children with a normal MRI and 69 ± 25 among the 50 children with an abnormal MRI. In childhood, for a normal outcome, a normal neonatal MRI had a sensitivity of 61%, specificity of 92%, a positive predictive value of 92%, and a negative predictive value of 59%; for death or IQ <70, the 2B and 3 pattern combined had a sensitivity of 81%, specificity of 78%, positive predictive value of 70%, and a negative predictive value of 87%. CONCLUSIONS: The Neonatal Research Network MRI pattern of neonatal brain injury is a biomarker of neurodevelopmental outcome at 6-7 years of age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00005772.

Hypoxic-ischemic encephalopathy: a review for the clinician.

IMPORTANCE: Hypoxic-ischemic encephalopathy (HIE) occurs in 1 to 8 per 1000 live births in developed countries. Historically, the clinician has had little to offer neonates with HIE other than systemic supportive care. Recently, the neuroprotective therapy of hypothermia has emerged as the standard of care, and other complementary therapies are rapidly transitioning from the basic science to clinical care. OBJECTIVE: To examine the pathophysiology of HIE and the state of the art for the clinical care of neonates with HIE. EVIDENCE REVIEW: We performed a literature review using the PubMed database. Results focused on reviews and articles published from January 1, 2004, through December 31, 2014. Articles published earlier than 2004 were included when appropriate for historical perspective. Our review emphasized evidence-based management practices for the clinician. FINDINGS: A total of 102 articles for critical review were selected based on their relevance to the incidence of HIE, pathophysiology, neuroimaging, placental pathology, biomarkers, current systemic supportive care, hypothermia, and emerging therapies for HIE and were reviewed by both of us. Seventy-five publications were selected for inclusion in this article based on their relevance to these topics. The publications highlight the emergence of serum-based biomarkers, placental pathology, and magnetic resonance imaging as useful tools to predict long-term outcomes. Hypothermia and systemic supportive care form the cornerstone of therapy for HIE. CONCLUSIONS AND RELEVANCE: The pathophysiology of HIE is now better understood, and treatment with hypothermia has become the foundation of therapy. Several neuroprotective agents offer promise when combined with hypothermia and are entering clinical trials.

Arterial spin-labelling perfusion MRI and outcome in neonates with hypoxic-ischemic encephalopathy.

PURPOSE: Hyperperfusion may be related to outcome in neonates with hypoxic-ischemic encephalopathy (HIE). The purpose of this study was to evaluate whether arterial spin labelling (ASL) perfusion is associated with outcome in neonates with HIE and to compare the predictive value of ASL MRI to known MRI predictive markers. METHODS: Twenty-eight neonates diagnosed with HIE and assessed with MR imaging (conventional MRI, diffusion-weighted MRI, MR spectroscopy [MRS], and ASL MRI) were included. Perfusion in the basal ganglia and thalami was measured. Outcome at 9 or 18 months of age was scored as either adverse (death or cerebral palsy) or favourable. RESULTS: The median (range) perfusion in the basal ganglia and thalami (BGT) was 63 (28-108) ml/100 g/min in the neonates with adverse outcome and 28 (12-51) ml/100 g/min in the infants with favourable outcome (p < 0.01). The area-under-the-curve was 0.92 for ASL MRI, 0.97 for MRI score, 0.96 for Lac/NAA and 0.92 for ADC in the BGT. The combination of Lac/NAA and ASL MRI results was the best predictor of outcome (r(2) = 0.86, p < 0.001). CONCLUSION: Higher ASL perfusion values in neonates with HIE are associated with a worse neurodevelopmental outcome. A combination of the MRS and ASL MRI information is the best predictor of outcome. KEY POINTS: • Arterial spin labelling MRI can predict outcome in neonates with hypoxic-ischemic encephalopathy • Basal ganglia and thalami perfusion is higher in neonates with adverse outcome • Arterial spin labelling complements known MRI parameters in the prediction of outcome • The combined information of ASL and MRS measurements is the best predictor of outcome.

[Prognostication of immunological reactivity and the choice of the variant of reflexotherapy for a newborn infant].

AIM: The objective of the present study was to determine the classification differences in immunological reactivity and to identify its predictors in the newborn infants. MATERIAL AND METHODS: The study involved 115 full-term newborn infants presenting with grade 3 prenatal hypoxic ischemic encephalopathy in the late neonatal period. The features of immunological reactivity under the influence of acupuncture were examined. Statistical processing was carried out by means of discriminant analysis. RESULTS: The assessment and prediction of the effectiveness of acupuncture in the neonates suffering from cerebral ischemia are based on the index of immunological reactivity and the leukocyte index of intoxication, as well as on the ratio of monocytes to band neutrophils content. For generation of the group classifier of immunological predictors in a newborn infant and development of indications for reflex therapy, nine parameters of interest were measured. The group specificity of the child was determined by three variables, viz. leukocyte index of intoxication, monocyte and band neutrophil counts with values of the Fisher's exact test (F) and reliability (Wilks Lambda 0.90894; approximation F (3.144) = 4.809; p < 0.0032). The partial Wilks Lambda values showed that the greatest contribution was provided by the leukocyte index of intoxication and monocytes. Prediction accuracy of the classification matrix in the standard treatment group reached 30.8% and 91.7% respectively when reflex therapy was included in the combined rehabilitation treatment. Overall, classification accuracy amounted to 70.3%. The presence of distinctive changes in the subgroups preconditioned a personalized approach to the prescription of reflex therapy to the newborn infants and the choice of the treatment modality on an individual basis (parent, child, or both) in the "mother-newborn" system. The variant of treatment was determined by comparing the values of the results of the formulas. The newborns were referred to the subgroup with the highest value of the classification function. The predictors made it possible to reliably distinguished the second (p = 0.032) and the third (p = 0.022) subgroups from the first one, with some degree of overlapping between the edge zones of centroids of the second and third subgroups (p = 0.073). Therefore, the sensitivity of classification in the individual subgroups was lower than in the group model and was estimated at 34.4, 71.9, and 65.6% for the first, second and third groups, respectively. CONCLUSION: The mathematical models can discriminatebetween the immunological characteristics and predict them in individual newborn infants; also, they can be helpful for preventing the disruption of their adaptation process.

Predictive value of neonatal MRI showing no or minor degrees of brain injury after hypothermia.

BACKGROUND: Magnetic resonance imaging is a surrogate biomarker for major neurodevelopmental disabilities in survivors of perinatal hypoxic-ischemic encephalopathy because injury to the basal ganglia/thalami is highly predictive of major neuromotor and cognitive problems. Major disabilities and the appearance of neonatal magnetic resonance imaging are improved with therapeutic hypothermia. We evaluated neurodevelopmental outcomes when conventional magnetic resonance imaging showed minimal or no brain injury. METHODS: Institutional review board-approved series of 62 infants (≥36 weeks; ≥1800 g; 34 boys/28 girls) cooled for hypoxic-ischemic encephalopathy between 2005 and 2011 who underwent neonatal magnetic resonance imaging and Bayley Scales of Infant and Toddler Development-III at 22 ± 7 months of age. Magnetic resonance imaging at 5-14 (mean 8) days was scored as normal (score = 0), showing focal gray or white matter injury only (score = 1), or basal ganglia/thalamic and/or watershed lesions with or without more extensive hemispheric injury (score = 2). Sensitivity, specificity, and positive and negative predictive values for magnetic resonance scores 0 and 1 and statistical interaction between magnetic resonance imaging score and age at magnetic resonance imaging were determined. RESULTS: Magnetic resonance score = 0 was seen in 35/62 patients; 26/35 (74%) were typically developing, seven (20%) had moderate and two (6%) had severe delay. Magnetic resonance score = 1 was seen in 17/62 (27%) patients; 5/17 (29%) were normal, 11/17 (65%) had moderate delay, and 1/17 (6%) had severe neurodevelopmental delay. Of the 52 patients with magnetic resonance scores of 0 and 1, 40% were abnormal. The negative predictive value of a normal magnetic resonance imaging was 74%. For score 1, sensitivity was 95% (confidence interval 63%-83%), specificity 84% (confidence interval 70%-90%), positive predictive value 84% (confidence interval 71%-93%), and negative predictive value 74% (confidence interval 62%-82%). CONCLUSIONS: Caution is warranted when prognosticating about neurodevelopmental status in early childhood after hypoxic ischemic encephalopathy with cooling, and longer follow-up studies are needed to determine the prognostic significance of a neonatal magnetic resonance imaging showing no or minor degrees of brain injury.

Mechanisms of action of hyperbaric oxygenation in stroke: a review.

This article outlines the therapeutic mechanisms of hyperbaric oxygenation in acute stroke, based on information obtained from peer-reviewed medical literature. Hyperbaric oxygen is an approved treatment modality for ischemia-reperfusion injury in several conditions. It maintains the viability of the marginal tissue, reduces the mitochondrial dysfunction, metabolic penumbra, and blocks inflammatory cascades observed in acute stroke. Basic and clinical data suggest that hyperbaric oxygen could be a safe and effective treatment option in the management of acute stroke. Further work is needed to clarify its clinical utility when applied within the treatment window of "gold standard" treatments (<3-5 hours).

Use of hyperbaric oxygenation in neonatal patients: a pilot study of 8 patients.

This article presents a pilot study to determine the value of hyperbaric oxygenation (HBO2) in the acute management of neonatal hypoxia (hypoxic ischemic encephalopathy) and necrotizing enterocolitis. Neonates with hypoxic-ischemic encephalopathy and NE were treated in a Sechrist monoplace chamber. Electroencephalogram, evoked potential, ophthalmic evaluation, ultrasonograph, laboratory exams, and radiographs were obtained before and after HBO2. Treatment protocol was 2.0 atm abs/45 minutes. Preventive myringotomies were conducted in all patients. A follow-up was done at 3 and 6 months. All patients (n = 8) were ventilator-dependent and required bag-valve-mask ventilation by a neonatologist during the treatment. All showed a resolution after HBO2. There was also a dramatic improvement (P < .05) in hemoglobin, hematocrit, total proteins, serum sodium, triglycerides, and pH. There were favorable changes in all other studies although they did not meet statistical significance. There was a marked reduction of the morbidity and mortality. There were no adverse effects on the ophthalmologic or Central Nervous System. When used promptly, HBO2 can modify the local and systemic inflammatory response caused by intestinal inflammation or cerebral or systemic hypoxia. It helps to preserve the marginal tissue and recover the ischemic and metabolic penumbra. This pilot study suggests that HBO2 could be a safe and effective treatment in the acute management of neonatal necrotizing enterocolitis or hypoxic ischemic encephalopathy. There is a need for a prospective, randomized, controlled, and double-blinded study to determine the real use of HBO2 in these cases.

Pyridoxine and pyridoxalphosphate-dependent epilepsies.

To date we know of four inborn errors of autosomal recessive inheritance that lead to vitamin B6-dependent seizures. Among these, pyridoxine-dependent seizures due to antiquitin deficiency is by far the most common, although exact incidence data are lacking. In PNPO deficiency, samples have to be collected prior to treatment, while PDE, hyperprolinemia type II and congenital HPP can be diagnosed while on vitamin B6 supplementation. A vitamin B6 withdrawal for diagnostic purposes is nowadays only indicated in patients with a clear vitamin B6 response but normal biochemical work-up. In the presence of therapy-resistant neonatal seizures, early consideration of a vitamin B6 trial over 3 consecutive days is crucial in order to prevent irreversible brain damage. While PLP would be effective in all four disorders, pyridoxine fails to treat seizures in PNPO deficiency. As PLP is unlicensed within Europe and North America, pyridoxine is widely used as the first line drug, but if it is ineffective it should be followed by a trial with PLP, especially in neonates. As severe apnea has been described in responders, resuscitation equipment should be at hand during a first pyridoxine/PLP administration. Patients and parents have to be informed about the lifelong dependency and recurrence risks in forthcoming pregnancies.

White matter and cortical injury in hypoxic-ischemic encephalopathy: antecedent factors and 2-year outcome.

OBJECTIVE: To examine the spectrum of isolated white matter (WM)/cortical injury and its relation to outcomes in infants with hypoxic-ischemic encephalopathy (HIE) and normal appearing basal ganglia and thalami. STUDY DESIGN: From 1992-2007, 84 term infants with HIE and normal basal ganglia and thalami on neonatal magnetic resonance imaging were studied; WM/cortical lesions were classified by site and severity. Neurodevelopmental outcomes and head growth were documented at a median age of 2 years. RESULTS: The WM was normal or mildly abnormal in 33.5%, moderate in 40.5%, and severely abnormal in 26% of infants. Cortical involvement was not seen or was only mild in 75.5%, moderate in 13%, and severe in 12% of infants. WM and cortical injury severity were highly correlated (Spearman ρ = 0.74; P < .001). Infants with severe WM injury had more severe neonatal courses and a higher incidence of hypoglycemia. No infant died. Five infants (6%) developed cerebral palsy but all could walk independently. Cognitive, visual, language, behavioral, and seizure problems were highly prevalent and correlated significantly with the severity of WM injury and poor postnatal head growth. CONCLUSION: Infants with HIE and selective WM/cortical injury have a low prevalence of cerebral palsy but have a wide range of other problems, which occur more often with severe WM/cortical lesions.

Thalamic infarct presenting as apparent life-threatening event in infants.

UNLABELLED: Thalamic infarction with distinct manifestations is well-described in adults but less well-delineated in children. We report two infants who presented with an apparent life-threatening event (ALTE) with very early magnetic resonance imaging (MRI) demonstrating a unilateral thalamic infarction. Subsequent MRI demonstrated bilateral changes in the brain stem and basal ganglia, which were in keeping with profound hypoxic ischaemic injury. We propose the thalamic infarction to be the primary event precipitating a profound hypoxic ischaemic injury as an alternative explanation to the neuroimaging observation. CONCLUSION: Thalamic infraction may have a causal role in ALTE. Early and appropriate neuroimaging is required to detect these changes.

[Differentiation of hypoxic-ischemic encephalopathy and acute bilirubin encephalopathy with magnetic resonance imaging in neonates].

OBJECTIVE: To investigate the value of conventional magnetic resonance imaging (MRI) and diffusion weighed imaging (DWI) in the differentiation of hypoxic-ischemic encephalopathy (HIE) and acute bilirubin encephalopathy in neonates. METHODS: The MRI findings along with DWI characteristics in 15 neonates with HIE involving basal ganglia and in 18 neonates with acute bilirubin encephalopathy between November 2006 and June 2008 were retrospectively reviewed. RESULTS: On T1WI, only 5 patients presented hyperintensity in the globus pallidus in the HIE group, but 16 in the acute bilirubin encephalopathy group (p<0.01). Nine patients in the HIE group showed hyperintensity in the putamen, but the hyperintensity in the putamen was not found in the acute bilirubin encephalopathy group. The frequency of hyperintensity in the subthalamus in the acute bilirubin encephalopathy group (55.6%) was significantly higher than that in the HIE group (13.3%) (p<0.05). Eight patients in the HIE group showed abnormal signals in the other regions on T1WI, but only two patients in the acute bilirubin encephalopathy group (p<0.05). On DWI, 7 out of 11 patients with HIE presented hyperintensity in the basal ganglia, while all 10 patients of the acute bilirubin encephalopathy group presented normal in the basal ganglia. CONCLUSIONS: Conventional MRI along with DWI is useful in differentiating HIE from acute bilirubin encephalopathy in neonates.

Proton magnetic resonance spectroscopy in neonates with hypoxic-ischemic injury and its prognostic value.

It is difficult to predict the neurologic outcome of neonates with hypoxic-ischemic encephalopathy (HIE). Our goal was to investigate the prognostic values of magnetic resonance spectroscopy (MRS) in neonatal HIE. During this study, 46 neonates with HIE underwent magnetic resonance imaging (MRI) and proton MRS ((1)HMRS). The sample included 25 cases of mild HIE, 11 cases of moderate HIE, and 10 cases of severe HIE. Nine healthy neonates without asphyxia served as controls. (1)HMRS techniques included single-voxel MRS and 2-D-point-resolved spatially localized spectroscopy (PRESS) multivoxel chemical shift spectroscopy imaging. Then, 31 of 46 neonates with HIE were divided into 3 groups according to their prognosis: dead, abnormal, and normal outcome. Abnormal and normal outcome were defined by follow-up MRI. Metabolic changes were analyzed and compared with HIE grading and prognosis. As a result, the GLx-alpha peak was markedly increased in the moderate and severe HIE groups. The GLx-alpha/Cr ratio in the control, mild, moderate, and severe HIE groups was 0.18, 0.21, 0.64, 1.31, respectively. The Lac/Cr ratio was 0.12, 0.14, 0.19, and 0.26, respectively. A Spearman rank correlation test confirmed that the ratio of GLx-alpha/Cr and Lac/Cr had significant positive correlation with clinical grading of HIE (P < 0.01). The GLx-alpha/Cr ratio in the dead, abnormal, and normal outcome groups was 1.28, 0.82, and 0.25, respectively; the Lac/Cr ratio was 0.34, 0.19, and 0.14, respectively. An anaylsis of variance demonstrated that the differences were significant (both P < 0.01). A Spearman rank correlation test confirmed that the ratio of GLx-alpha/Cr and Lac/Cr had significant negative correlation with prognosis of HIE; GLx-alpha/Cr showed a much stronger correlation than the Lac/Cr ratio (P < 0.01). The formula of the relationship between the poor prognosis of HIE and the ratio of GLx-alpha/Cr in basal ganglia was established by the logistic regression model. In conclusion, (1)HMRS is a useful tool for evaluating the severity and prognosis of HIE. The higher ratio of GLx-alpha/Cr in the basal ganglia and thalamus may predict a poor outcome in neonates with HIE.

Phosphorus magnetic resonance spectroscopy 2 h after perinatal cerebral hypoxia-ischemia prognosticates outcome in the newborn piglet.

Phosphorus magnetic resonance spectroscopy ((31)P MRS) often reveals apparently normal brain metabolism in the first hours after intrapartum hypoxia-ischemia (HI) at a time when conventional clinical assessment of injury severity is problematic. We aimed to elucidate very-early, injury-severity biomarkers. Twenty-seven newborn piglets underwent cerebral HI: (31)P-MRS measures approximately 2 h after HI were compared between injury groups defined by secondary-energy-failure severity as quantified by the minimum nucleotide triphosphate (NTP) observed after 6 h. For severe and moderate injury versus baseline, [Pi]/[total exchangeable high-energy phosphate pool (EPP)] was increased (p < 0.001 and < 0.02, respectively), and [NTP]/[EPP] decreased (p < 0.03 and < 0.006, respectively): severe-injury [Pi]/[EPP] was also increased versus mild injury (p < 0.04). Mild-injury [phosphocreatine]/[EPP] was increased (p < 0.004). Severe-injury intracellular pH was alkaline versus baseline (p < 0.002). For severe and moderate injury [total Mg]/[ATP] (p < 0.0002 and < 0.02, respectively) and [free Mg] (p < 0.0001 and < 0.02, respectively) were increased versus baseline. [Pi]/[EPP], [phosphocreatine]/[Pi] and [NTP]/[EPP] correlated linearly with injury severity (p < 0.005, < 0.005 and < 0.02, respectively). Increased [Pi]/[EPP], intracellular pH and intracellular Mg approximately 2 h after intrapartum HI may prognosticate severe injury, whereas increased [phosphocreatine]/[EPP] may suggest mild damage. In vivo(31)P MRS may have potential to provide very-early prognosis in neonatal encephalopathy.

Distortion product otoacoustic emissions at 6 months in term infants after perinatal hypoxia-ischaemia or with a low Apgar score.

Distortion product otoacoustic emissions (DPOAEs) were analyzed at 6 months of age in term infants who had perinatal hypoxia-ischaemia (HI) and those who had a low Agar score alone to detect any abnormalities in cochlear function and any difference between the two groups of infants. The f2 primary tone was presented at ten frequencies (0.5-10 kHz). Both the left and right ears were tested. Compared to normal term controls, both the infants after perinatal HI and those with a low Apgar score alone showed lower DPOAE pass rates, mainly at 1-4 kHz at which the pass rates were decreased significantly (P < 0.05-0.01). The general pattern of DPOAE pass rates at different frequencies was similar in the two groups of infants. The pass rates at 1, 5 and 6 kHz tended to be lower in the infants after perinatal HI than those with a low Apgar score alone, although not statistically significant. Conclusions At 6 months of age, infants after perinatal HI or with a low Apgar score alone had a relatively poor cochlear function, mainly at 1-4 kHz. There are no major differences between the two groups of infants.

Diffusion tensor imaging in infants with basal ganglia-thalamic lesions.

We performed diffusion tensor imaging in two infants with neonatal hypoxic-ischemic encephalopathy. MRI revealed basal ganglia-thalamic lesions in both patients during the neonatal period. Patient 1 had severe neurological sequelae, whereas patient 2 achieved normal development. Conventional MRI at 12 months of age showed abnormal high-intensity areas in bilateral basal ganglia and thalami in patient 1, whereas no abnormal intensities were recognized in patient 2. Diffusion tensor tractography demonstrated poor depiction of white matter tracts above the level of centrum semiovale in patient 1. Region of interest analysis showed that fractional anisotropy of white matter of centrum semiovale and deep white matter was markedly reduced in patient 1 compared with patient 2, although apparent diffusion coefficient was not largely different between them. Our study suggested that abnormalities of diffusion property will be more widely present than those of conventional MRI. Diffusion tensor imaging will be useful to detect white matter abnormalities in normal-appearing white matter on conventional MRI.

Relationship between electroencephalography and magnetic resonance imaging findings after hypoxic-ischemic encephalopathy at term.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Electroencephalography (EEG) and brain magnetic resonance imaging (MRI) are frequently performed in these infants, but the prognostic value of the combined use of EEG and MRI needs additional exploration. The purpose of this study was to investigate, in neonates with HIE, the role of early EEG and conventional MRI in the prediction of infants at risk for persistent encephalopathy at 18 months of age. Thirty-four term infants with HIE were enrolled in this prospective study. EEG was recorded within the first 72 hours after birth and a brain MRI scan was done between 1 and 4 weeks of age. Denver Developmental Screening Test II was performed at 6, 12, and 18 months of age. Three infants (9%) had mild HIE, 21 infants (62%) had moderate HIE, and 10 infants (29%) had severe HIE. The EEG background was normal, moderately, severely, and extremely discontinuous in eight (24%), three (9%), sixteen (47%), and seven (20%) neonates, respectively. EEG background activities correlated significantly with HIE severity (p = 0.0001). MRI findings significantly correlated with EEG background (p = 0.001). Normal MRI scans and minimal basal ganglia lesions were always associated with normal EEG background. Patients with severe basal ganglia and thalamic lesions in MRI (n = 2) had extreme discontinuous EEG background. For the prediction of poor outcomes, abnormal EEG background activity had a sensitivity (Sn) = 100%, a specificity (Sp) = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 100%, whereas values of abnormal MRI scans were Sn of 100%, Sp = 43%, PPV = 82%, and NPV=100%. EEG background activity is the best element to predict abnormal outcomes. Severe basal ganglia and thalamic injuries on MRI scans are associated with poor outcomes. Otherwise, MRI does not contribute to the prediction of outcomes at 18 months of age.