Mild Delay Research Articles

PP09.12 – 3028: Broad spectrum of c.2015 G>A mutation in GAA gene manifesting as mild infantile variant of Pompe disease in Jordanian patients

Objective A wide spectrum of Pompe disease exists from the infantile form to a milder juvenile or adult form. The clinical heterogeneity primarily relates to the occurrence of different mutations that lead to a different rate of lysosomal glycogen accumulation and non genetic factors that are thought to modulate the disease phenotypes. Methods We describe two unrelated families from Jordan presenting with the infantile variant form of Pompe disease sharing the same homozygous mutation c.2015 G>A in exon 14. Previously this mutation was described in juvenile onset cases. Results The first family consisted of two female siblings (5.5 and 3.5 years of age) born to first degree cousins of Muslim descent. The elder one presented between 3–6 months of age with marked hypotonia, hypertrophic cardiomyopathy, proximal muscle weakness, motor delay and no DTR's. She was started on enzyme replacement therapy at 24 months of age, walked independently at 27 months. Currently she has a nasal speech, muscle weakness and mild cardiomyopathy. Her younger sister, presented at 3 months with mild hypotonia, motor delay and hepatomegaly. She started ERT at 6 months and currently her neurological examination is normal. The second patient is a 5-year-old boy who presented with hypertrophic cardiomyopathy, hypotonia and an enlarged tongue. His parents are first degree cousins. Two siblings died before the age of one month due to heart failure; He started ERT at 14 months of age, walked independently at 18 months and follow-up echocardiography studies improved markedly. Currently he has a nasal speech, articulation disorder and otherwise no muscle weakness. Conclusion Our cases confirm the phenotypic variability among patients, even carrying the same genotype. Two patients, for whom ERT was commenced later, suffer from nasal speech and severe articulation disorder in spite of improved cardiac and motor function.

Mutations in TTC19: expanding the molecular, clinical and biochemical phenotype.

BackgroundTTC19 deficiency is a progressive neurodegenerative disease associated with isolated mitochondrial respiratory chain (MRC) complex III deficiency and loss-of-function mutations in the TT19 gene in the few patients reported so far.MethodsWe performed exome sequencing and selective mutational analysis of TTC19, respectively, in patients from three unrelated families presenting with initially unspecific clinical signs of muscular hypotonia and global developmental delay followed by regression, ataxia, loss of speech, and rapid neurological deterioration. One patient showed severe lactic acidosis at the neonatal age and during intercurrent illness.ResultsWe identified homozygous mutations in all three index cases, in two families novel missense mutations (c.544 T > C/p.Leu185Pro; c.917 T > C/p.Leu324Pro). The younger sister of the severely affected patient 3 showed only mild delay of motor skills and muscular hypotonia so far but is also homozygous for the same mutation. Notably, one patient revealed normal activities of MRC complex III in two independent muscle biopsies. Neuroimaging of the severely affected patients demonstrated lesions in putamen and caudate nuclei, cerebellar atrophy, and the unusual finding of hypertrophic olivary nuclei degeneration. Reviewing the literature revealed striking similarities regarding neuroimaging and clinical course in pediatric patients with TTC19 deficiency: patterns consistent with Leigh or Leigh-like syndrome were found in almost all, hypertrophic olivary nucleus degeneration in all patients reported so far. The clinical course in pediatric patients is characterized by an initially unspecific developmental delay, followed by regression, progressive signs and symptoms of cerebellar, basal ganglia and brainstem affection, especially loss of speech and ataxia. Subsequently, neurological deterioration leading to a vegetative state occurs.ConclusionsOur findings add to the phenotypic, genetic, and biochemical spectrum of TTC19 deficiency. However, TTC19 deficient patients do show characteristic clinical and neuroimaging features, which may facilitate diagnosis of this yet rare disorder. Normal MRC complex III activity does not exclude the diagnosis.

Su1170 Relationship Between Discharge Feeding Method and Neuro-Developmental Outcomes At 18-24 Months of Age in Former Preterm Infants

BACKGROUND: Preterm neonates commonly encounter oral feeding difficulties. We have previously shown that a personalized feeding management approach yields improved oral feeding outcomes at NICU discharge. The association of feeding outcome at discharge to long term neuro-developmental outcomes is not known. AIMS: In preterm infants, we characterized and compared aerodigestive and neurodevelopmental (cognitive, communicative, and motor) outcomes at 18-24 months corrected age of successful (full oral at discharge) feeders vs unsuccessful (gastrostomy tube at discharge) feeders. METHODS: Retrospective analysis was performed on 105 preterm infants (<37 weeks gestation) who were referred to the Neonatal and Infant Feeding Disorders program between July 2006 and July 2012, and also had a neuro-developmental evaluation at 18-24 months corrected age. Aerodigestive outcomes included: first oral feed attainment, weight velocity at 36 wks postmenstrual age (PMA), gastrostomy frequency, feeding method at discharge (full oral or g-tube fed), oxygen at 36 wks PMA, duration of ventilation, tracheostomy frequency, and oxygen at discharge. Neuro-developmental outcomes included: composite Bayley Scales of Infant Development (BSID)-III that were comprised of cognitive, communication, and motor scores. BSID-III composite scores were corrected for gestational immaturity. Statistical comparisons were made using Chi-Square, Mann-Whitney U, or t-tests comparing the two groups (full oral vs. g-tube). Data presented as mean ± SD, median (IQR), or %. RESULTS: Subjects (N = 105, 52 male) were born at 27 ± 3 weeks gestational age, weighing 968 ± 428 grams. Clinical characteristics, aerodigestive milestones, and neuro-developmental outcomes of the 105 infants are shown (Table 1). CONCLUSIONS: Inability to attain full oral feeding milestones at discharge is associated with mild cognitive neuro-developmental delays at 1824 months of age, sparing communication and motor outcomes. Delays in aerodigestive milestones and complex interplay of neurologic and behavioral areas controlling feeding and cognitive functions can be contributory. Timely initiation of oro-motor stimulation and oral feeding may provide opportunities for enhanced feeding skills and improvement in neuro-developmental outcomes. *Supported in part by R01 DK068158 (Jadcherla) and P01 DK068051 (Jadcherla/Shaker)

Amplitude-integrated electroencephalography shows mild delays in electrocortical activity in preterm infants born small for gestational age.

Being born small for gestational age (SGA) seems to be a relevant risk factor for long-term neurologic deficits. We compared the differences between amplitude-integrated electroencephalography (aEEG) signals in very preterm infants born small for gestational age (SGA) and those in age-matched infants born appropriate size for gestational age (AGA). We performed serial aEEG recording on 305 infants: 255 (83.6%) were AGA, and 50 (16.3%) were SGA. The number of bursts per hour decreased over time in both groups, but was higher in the SGA group at every time point. On day one, it was significantly higher in the SGA group (17.4) than in the AGA group (10.1) (p = 0.016). The total Burdjalov score increased with post-natal age and tended to be lower in SGA infants, but did not reach statistical significance at any time point. The percentage of continuous background patterns increased with post-natal age in both groups, with no significant difference between the groups. Very preterm infants born SGA showed normal maturation of aEEG signals during post-natal life, but they also showed mild delays in electrocortical activity compared to age-matched AGA infants. The predictive value of these findings on neurodevelopmental outcome needs to be further evaluated.

Mild maturational delay of the brainstem at term in late preterm small-for-gestation age babies

AimsTo detect any functional abnormality in the brainstem auditory pathway in late preterm babies born of small-for-gestational age (SGA) using maximum length sequence brainstem evoked response. Study designThe response was recorded and analyzed at term in 38 SGA (birthweight <3rd centile) babies born at 33–36week gestation. The results were compared with 40 age-matched babies born of appropriate-for-gestational age (AGA) (birthweight >10th centile). None of the subjects had major perinatal problems. ResultsAll wave latencies and interpeak intervals in the SGA group were slightly longer than those in the AGA group at most click rates. Wave III latency was significantly longer than that in the AGA group at 227/s (P<0.05), and wave V latency was at 227 and 910/s (P<0.05 and 0.05). Of the interpeak intervals, only the I–V interval in the SGA group was significantly longer than that in the AGA group at the highest rate 910/s (P<0.05). The amplitudes of waves I, III and V in the SGA group all tended to be smaller than those in the AGA group at all click rates 91–910/s. The wave V amplitude was significantly smaller at most click rates (227–910/s, all P<0.05). The slopes of all wave latency–, interval–, and amplitude–rate functions were similar in SGA and AGA groups. ConclusionsThere were marginal abnormalities in MLS BAER of low-risk late preterm SGA babies, suggesting a mild degree of maturational delay in the brainstem. Intrauterine growth retardation occurring in late preterm babies has a minor effect on neural maturation of the immature brainstem.

Behaviour and development in 24-month-old moderately preterm toddlers

ObjectiveModerately preterm children (gestational age 32–36+6 weeks) are at risk of cognitive and behaviour problems at school age. The aim of this study was to investigate if these problems are...

Mesenchymal Hox6 function is required for mouse pancreatic endocrine cell differentiation.

Despite significant advances in our understanding of pancreatic endocrine cell development, the function of the pancreatic mesodermal niche in this process is poorly understood. Here we report a novel role for mouse Hox6 genes in pancreatic organogenesis. Hox6 genes are expressed exclusively in the mesoderm of the developing pancreas. Genetic loss of all three Hox6 paralogs (Hoxa6, Hoxb6 and Hoxc6) leads to a dramatic loss of endoderm-derived endocrine cells, including insulin-secreting β-cells, and to mild delays and disruptions in pancreatic branching and exocrine differentiation. Ngn3-expressing pan-endocrine progenitor cells are specified normally in Hox6 mutant pancreata, but fail to mature into hormone-producing cells. Reduced expression of Wnt5a is observed in mutant pancreatic mesenchyme, leading to subsequent loss of expression of the crucial Wnt inhibitors Sfrp3 and Dkk1 in endocrine progenitor cells. These results reveal a key role for Hox6 genes in establishing Wnt mesenchymal-epithelial crosstalk in pancreatic development.

Concomitant deletion of chromosome 16p13.11 and triplication of chromosome 19p13.3 in a child with developmental disorders, intellectual disability, and epilepsy.

BackgroundRare copy number variations (CNVs) are today recognized as an important cause of various neurodevelopmental disorders, including mental retardation and epilepsy. In some cases, a second CNV may contribute to a more severe clinical presentation.ResultsHere we describe a patient with epilepsy, mental retardation, developmental disorders, and dysmorphic features, who inherited a deletion of 16p13.11 and a triplication of 19p13.3 from his father and mother, respectively. The mother presented mild mental retardation and language delay too.ConclusionsWe discuss the phenotypic consequences of the two CNVs and suggest that their synergistic effect is likely responsible for the complicated clinical features observed in our patient.

Clinical Experience of Infantile Posthemorrhagic Hydrocephalus Treated with Ventriculo-Peritoneal Shunt

ObjectiveInfantile posthemorrhagic hydrocephalus (IPHH) is the most common cause of infantile acquired hydrocephalus. We present and discuss our experience of treatment of six IPHH patients treated by a ventriculo-peritoneal (VP) shunt.MethodsSix preterm infants treated by a VP shunt due to germinal matrix hemorrhage and hydrocephalus were included in our study. External ventricular drainage (EVD) was performed in patients with symptomatic ventricular dilatation, and a VP shunt was placed in the case of no improvement of the ventricular index despite several rounds of EVD. Radiographic findings and surgical outcomes were analyzed retrospectively.ResultsFour patients were male and two were female. Mean gestational age was 25 weeks and mean weight at birth was 868.3 g. One patient had a Papile grade II (16.7%) hemorrhage, three had a grade III (50%) hemorrhage, and two had a grade IV (33.3%) hemorrhage. EVD complications (one case of ventriculitis and one case of a ventricular abscess) occurred in two patients. VP shunt complications occurred in two patients (33.3%). Three cases had an isolated 4th ventricle; two of these cases had a VP shunt placed whereas the other case had a VP shunt placed in addition to aqueductoplasty using a neuroendoscope. At the last follow-up, three of the six patients had severe neurodevelopmental delay, two had mild neurodevelopmental delay, and one had normal development status.ConclusionIn our study, although it is difficult to present the significant result for management of IPHH, we think that varied efforts are required to treat IPHH patients.

CEREBRAL PALSY;

Background: Cerebral Palsy is a disorder of movement and postural balance due to insult to the brain. The injury to the developing brain may be prenatal, natal or postnatal. The diagnosis is clinical mainly. The spastic Cerebral Palsy is classified into monoplegic, hemiplegic, diplegic, and quadriplegic types. There is a difference in the frequency of these types of Cerebral Palsy in different studies. The patterns of various forms of Cerebral Palsy emerge gradually with a delay in developmental milestones. A spectrum of associated developmental disabilities has been found to be common in these children. Management is through a multi-disciplinary approach. Objectives: To find out the frequency of different types of Cerebral Palsy and degree of associated developmental delay. Methodology: A cross sectional study was carried out for a period of six months (October 1, 2006 to March 31, 2007) at The Children’s Hospital &amp; Institute of Child Health Lahore. 100 Cases diagnosed as Cerebral Palsy on clinical basis were assessed for the type of cerebral palsy and the degree of associated developmental delay. Results: Out of the total 100 patients 54% had quadriplegia, 32% had diplegia, 10% had himiplegia and 4% had monoplegia. The total fifty-four cases of quadriplegic cerebral palsy 54 had developmental delay and amongst them 4 (7%) had mild delay, 16 (30%) had moderate delay while 34 (63%) had severe delay. Amongst the total forty-six other three types of cerebral palsy 12 (26%) had mild delay, 6 (13%) had moderate delay and 28 (61%) had severe delay. The P-value was &gt;0.05. Conclusions: Quadriplegic is the commonest type of CP, associated with the factors (peri-natal more than socio-demographic) and had significant effect on the developmental parameters.

Paroxysmal kinesigenic dyskinesia caused by 16p11.2 microdeletion.

BackgroundFour cases of paroxysmal kinesigenic dyskinesia (PKD) have been reported in individuals with proximal 16p11.2 microdeletions that include PRRT2.Case ReportWe describe a fifth patient with PKD, features of Asperger’s syndrome, and mild language delays. Sanger sequencing of the PRRT2 gene did not identify any mutations implicated in PKD. However, microarray-based comparative genomic hybridization (aCGH) detected a 533.9-kb deletion on chromosome 16, encompassing over 20 genes and transcripts.DiscussionThis case underscores the importance of aCGH testing for individuals with PKD who do not have PRRT2 mutations, particularly when developmental delays, speech problems, intellectual disability, and/or autism spectrum disorder are present.

Paroxysmal Kinesigenic Dyskinesia Caused by 16p11.2 Microdeletion

<strong>Background:</strong> Four cases of paroxysmal kinesigenic dyskinesia (PKD) have been reported in individuals with proximal 16p11.2 microdeletions that include <em>PRRT2</em>. <strong>Case Report:</strong> We describe a fifth patient with PKD, features of Asperger’s syndrome, and mild language delays. Sanger sequencing of the <em>PRRT2</em> gene did not identify any mutations implicated in PKD. However, microarray-based comparative genomic hybridization (aCGH) detected a 533.9-kb deletion on chromosome 16, encompassing over 20 genes and transcripts. <strong>Discussion:</strong> This case underscores the importance of aCGH testing for individuals with PKD who do not have <em>PRRT2</em> mutations, particularly when developmental delays, speech problems, intellectual disability, and/or autism spectrum disorder are present.

Discal Cyst in a Malamute Dog

7-year-old, male Alaskan malamute was referred for a routine dental management. On the physical examination, the right hindlimb ataxia with a mild delay in proprioception was noted. On magnetic resonance images, an extradural ventral cystic structure compressing the spinal cord was found at the level between the first and second lumbar vertebra. The cyst showed hypointense on a T1-weighted image with rim enhancement and hyperintense on a T2-weighted image. The cystic lesion was removed through right-side hemilaminectomy. In the histopathological examination, evenly distributed fibroblasts and collagenous stroma with several cartilaginous materials were seen. The neurological signs of the right hindlimb were successfully recovered within a week in follow-up neurological examination and showed normal gait at 6 months after surgery.

Heterozygous deletion of CHL1 gene: Detailed array-CGH and clinical characterization of a new case and review of the literature

CHL1 gene maps at 3p26.3 and encodes a cell adhesion molecule of the immunoglobulin superfamily highly expressed in the brain. CHL1 regulates neuronal migration and neurite overgrowth in the developing brain, while in mature neurons it accumulates in the axonal membrane and regulates synapse function via the clathrin-dependent pathways. To our knowledge, to date only three familial cases presenting heterozygous deletion of chromosome 3 at band p26.3, including only the CHL1 gene, have been reported. All the patients presented cognitive impairment characterized by learning and language difficulties. Here, we describe a six-year-old boy in which array-CGH analysis disclosed a terminal 3p26.3 deletion. The deletion was transmitted from his normal mother and included only the CHL1 gene. Our patient presented microcephaly, short stature, mild mental retardation, learning and language delay, and strabismus.In our study we compare the phenotypic and molecular cytogenetic features of CHL1 gene deletion cases. Verbal function developmental delay seems to be a common key finding. The concomitance of the genetic and phenotypic alterations could be a good evidence of a new emerging syndrome associated with the deletion of CHL1 gene alone, although the identification of new cases is required.

PO-0091 5 Year Old Girl With Disproportionate Short Stature With Failure To Thrive And Dysmorphism: Rare Case Of Scheie Syndrome

Background Hurler-Scheie Syndrome is an autosomal recessive mucopolysaccharidois resulting in reduced activity of α-L-iduronidase with accumulation of heparin and dermatan sulphate. Scheie syndrome represents less severely affected form with varied clinical features. Case Report 5 year female, first born child of 2nd degree consanguineous Egyptian parents, referred for short stature presented with following features. On examination: Length: 88 cm; Upper: Lower segment=1:1.3; weight: 12.3 kg; Head circumference: 51 cm Protuberant abdomen, mild proptosis, enlarged skull, prominent forehead, low set ears, simian crease, clawed hand, mild kyphosis, strabismus, normal IQ, hepatomegaly. Investigation: USG: hepatomegaly, Karyotyping normal Mild delay bone age; Elevated TSH, low T4; tissue transglutaminase normal; sweat chloride test normal; ammonia, lactate normal; growth hormone assay normal; Deficient enzyme in fibroblast confirmed diagnosis of Scheie syndrome Discussion Scheie syndrome is an autosomal recessive, rare lysosomal storage disease, with skeletal deformities and motor delay; described first in 1972; caused by mutations in IDUA gene (4p16.3) leading to partial deficiency in alpha-L-iduronidase enzyme and lysosomal accumulation of dermatan and heparan sulfate. Genetic testing is available. Antenatal diagnosis done by measurement of enzymatic activity in chorionic villus/ amniocytes and by genetic testing (if disease-causing mutation is known). Genetic counselling is recommended. Management is multidisciplinary including physiotherapy (to maintain range of movement); bone marrow or umbilical cord blood transplant (to preserve neurocognition, improve somatic disease and increase survival). Enzyme replacement therapy slows disease progression. Conclusion Scheie syndrome should be considered in differential diagnosis of disproportionate short stature with dysmorphism, failure to thrive with normal IQ.

Developmental outcomes in young children born to mothers with West Nile illness during pregnancy.

West Nile virus (WNV) infection is associated with acute morbidity and mortality in adults and children. Information on the effects of maternal WNV illness during pregnancy on early childhood development is limited. This study was designed to examine the relationship between maternal WNV illness during pregnancy and birth and developmental outcomes at age 3 years. Mother-child participants were identified using a national surveillance registry for women with WNV illness during pregnancy. Maternal and infant health data and relevant family characteristics were obtained through medical record reviews and maternal questionnaires. All infants received ophthalmologic examinations. Child development was evaluated at age 3 years using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). As a group, the children's (N = 11) birth weight, head circumference, and infant ophthalmologic examination results were within age expectations; one child was born preterm (gestational age 36 weeks). Mean (SD) age at the time of Bayley-III testing was 36.7 (3.8) months. The group's mean performance on the Bayley-III was at or above age level in all domains, but one child showed a mild delay in the Adaptive domain. The variability observed in this sample (1/53 [1.9%] Domain scores < -2.0 SDs) was consistent with expectations based upon the distribution of Bayley-III Domain scores in the general population. Maternal WNV infection does not appear to be associated with global developmental delays in young children. These results are preliminary, however, and require confirmation in future research.

Thrombosis of the torcular herophili in the fetus: a series of eight cases.

The objective of this study was to describe the prenatal sonographic and magnetic resonance imaging (MRI) findings, antenatal course, and pregnancy outcome in fetuses diagnosed as having thrombosis of the torcular herophili. Retrospective review of cases collected from five fetal medicine referral centers. Eight cases that were prenatally diagnosed by ultrasound between 22 and 32 weeks of gestation were reviewed. Seven cases were further evaluated with fetal MRI. Associated findings included torcular and superior sagittal sinus dilatation in all cases and ventriculomegaly in two (25%) cases. Serial sonographic follow-up scans demonstrated a favorable antenatal course with complete resolution before delivery in four (50%) cases. Postnatal follow-up from 6 months to 5 years revealed normal outcome in four (50%) infants, speech disabilities in three (38%), and mild neurodevelopmental delay in the remaining case (13%). Prenatal sonography is an effective method for diagnosing and monitoring thrombosis of the torcular herophili. As a complementary technique, fetal MRI can provide additional information to rule out cerebral parenchymal lesions secondary to hypoperfusion and associated brain malformations. According to our experience, the thrombus almost invariably resolves over time, although mild neurologic disabilities are frequent on long-term follow-up.

G.P.313: Intrafamilial heterogeneity in an alpha-dystroglycanopathy due to GDP-Mannose Pyrophosphorylase B (GMPPB) mutations

We describe two brothers who presented with different phenotypes and progression, sharing compound heterozygous mutations in the GMPPB gene. The index case, 34 years old, was referred to the muscle clinic for increased CK (>2.000), proximal weakness and calf hypertrophy. He is on therapy for myoclonic epilepsy following encephalitis in infancy and has mild cognitive and motor delay. Because of his symptoms, a muscle biopsy was performed: the immune-histochemistry showed a reduction in alpha dystroglycan labelling, with a secondary reduction of laminin alpha2 chain on western blot. Genes known to be associated to alpha-dystroglycanopathy have been excluded by direct sequencing (FKRP,POMT1, POMT2, POMGnT1,LARGE, FKTN). Two heterozygous variants in the GMPPB gene, a previously described mutation[c.860G>A (p.Arg287Gln)] and a novel variant [c.656T>C (p.Ile219Thr)]. The older brother, 36 years old, shares the same mutations having been shown to also have increased CK (2.832). He has global developmental delay presenting with speech and language difficulties, motor delay, impaired fine motor coordination and autistic spectrum disorder. He is not affected by weakness or fatigue, nor has weakness at physical examination. GMPPB catalyses the formation of GDP-mannose, required for O-mannosylation of alpha-dystroglycan. Mutations in this gene have been recently described in association to a spectrum of muscular dystrophy variants (Carss et al. AJHG, 2013), ranging from congenital to limb girdle muscular dystrophy, with additional symptoms as intellectual disability, epilepsy or brain structural anomalies. The family we describe highlights the clinical variability of these patients, with different presentation despite sharing the same mutations. Furthermore, it underlines the importance of testing CK in children presenting with global developmental delay: if the younger brother had not presented with a LGMD phenotype, the diagnosis in the older brother would have continued to be missed.

Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy

BackgroundErythropoietin is neuroprotective in animal models of neonatal hypoxic-ischemic encephalopathy. We previously reported a phase I safety and pharmacokinetic study of erythropoietin in neonates. This article presents the neurodevelopmental follow-up of infants who were enrolled in the phase I clinical trial. MethodsWe enrolled 24 newborns with hypoxic-ischemic encephalopathy in a dose-escalation study. Patients received up to six doses of erythropoietin in addition to hypothermia. All infants underwent neonatal brain magnetic resonance imaging (MRI) reviewed by a single neuroradiologist. Moderate-to-severe neurodevelopmental disability was defined as cerebral palsy with Gross Motor Function Classification System levels III-V or cognitive impairment based on Bayley Scales of Infant Development II mental developmental index or Bayley III cognitive composite score. ResultsOutcomes were available for 22 of 24 infants, at mean age 22 months (range, 8-34 months). There were no deaths. Eight (36%) had moderate-to-severe brain injury on neonatal MRI. Moderate-to-severe disability occurred in one child (4.5%), in the setting of moderate-to-severe basal ganglia and/or thalamic injury. Seven infants with moderate-to-severe watershed injury exhibited the following outcomes: normal (three), mild language delay (two), mild hemiplegic cerebral palsy (one), and epilepsy (one). All 11 patients with a normal brain MRI had a normal outcome. ConclusionsThis study is the first to describe neurodevelopmental outcomes in infants who received high doses of erythropoietin and hypothermia during the neonatal period. The findings suggest that future studies are warranted to assess the efficacy of this new potential neuroprotective therapy.

Mild Systemic Zinc Imbalance Delays Recovery in a Mouse Model of Surgically-Induced Ileus: Is it Driven by Disturbances in the Cytokine Network or Pro-Inflammatory Components of the Lipidome?

mice. These findings were confirmed by inhibiting the P2X7 receptor with oxi-ATP (40 mg/kg i.p.). Inhibition of P2X7 receptors led to increased bacterial burden, cytokine and chemokine levels in septic shock. P2X7KO/P2X7WT bone marrow chimeras exhibited higher cytokine and chemokine levels than P2X7WT/P2X7WT mice. Septic P2X7KO mice had excessive apoptosis in the thymus and increased inflammation in the heart and lung.