GPR56 mutations cause an autosomal recessive polymicrogyria syndrome that has distinctive radiological features combining bilateral frontoparietal polymicrogyria, white matter abnormalities and cerebellar hypoplasia. Recent investigations of a GPR56 knockout mouse model suggest that bilateral bifrontoparietal polymicrogyria shares some features of the cobblestone brain malformation and demonstrate that loss of GPR56 leads to a dysregulation of the maintenance of the pial basement membrane integrity in the forebrain and the rostral cerebellum. In light of these findings and other data in the literature, this study aimed to refine the clinical features with the first description of a foetopathological case and to define the range of cobblestone-like features in GPR56 bilateral bifrontoparietal polymicrogyria in a sample of 14 patients. We identified homozygous GPR56 mutations in 14 patients from eight consanguineous families with typical bilateral bifrontoparietal polymicrogyria and in one foetal case, out of 30 patients with bifrontoparietal polymicrogyria referred for molecular screening. The foetal case, which was terminated at 35 weeks of gestation in view of suspicion of Walker Warburg syndrome, showed a cobblestone-like lissencephaly with a succession of normal, polymicrogyric and ‘cobblestone-like’ cortex with ectopic neuronal overmigration, agenesis of the cerebellar vermis and hypoplastic cerebellar hemispheres with additional neuronal overmigration in the pons and the cerebellar cortex. The 14 patients with GPR56 mutations (median 8.25 years, range 1.5–33 years) were phenotypically homogeneous with a distinctive clinical course characterized by pseudomyopathic behaviour at onset that subsequently evolved into severe mental and motor retardation. Generalized seizures (12/14) occurred later with onset ranging from 2.5 to 10 years with consistent electroencephalogram findings of predominantly anterior bursts of low amplitude α-like activity. Neuroimaging demonstrated a common phenotype with bilateral frontoparietally predominant polymicrogyria (13/13), cerebellar dysplasia with cysts mainly affecting the superior vermis (11/13) and patchy to diffuse myelination abnormalities (13/13). Additionally, the white matter abnormalities showed a peculiar evolution from severe hypomyelination at 4 months to patchy lesions later in childhood. Taken as a whole, these observations collectively demonstrate that GPR56 bilateral bifrontoparietal polymicrogyria combines all the features of a cobblestone-like lissencephaly and also suggest that GRP56-related defects produce a phenotypic continuum ranging from bilateral bifrontoparietal polymicrogyria to cobblestone-like lissencephaly.

We aimed to examine current bedside analgesia/sedation (A/S) and pain assessment (PA) practices in Italian neonatal intensive care units (NICUs) in relation to the findings of an epidemiological European study and recently-introduced national guidelines. We analyzed the Italian data from the EUROPAIN (EUROpean-Pain-Audit-In-Neonates) prospective observational study on A/S practices that involved 6680 newborns admitted to tertiary-level NICUs in 18 European countries. Demographics, type of assisted ventilation, type and mode of A/S administration and PA were analyzed. Multivariate linear regression models were used to identify factors predicting A/S and PA practices. From October 1st, 2012 to June 30th, 2013, thirty Italian NICUs gathered data on 422 newborn: 131 on invasive ventilation (IV); 150 on noninvasive ventilation (NIV); and 141 on spontaneous ventilation (SV). A/S was documented for 35.3% of all infants admitted (86.3% IV; 17.3% NIV; 7.1% SV [p = 0.0001]), and varied considerably between NICUs (as reported in other European countries). Strong analgesics were used in 32.5% of cases, sedatives in 10.2%, mild analgesics in 3.8%. Fentanyl was used in 78.6% of cases, morphine in 8.4%, neuromuscular blockers in 5.3%, midazolam in 22.1%. The performance of PA was documented in 67.5% of all newborn (85.5% IV; 67.3% NIV; 51.1% SV [p = 0.001]). Illness severity, type of ventilation, bedside PA, and number of NICU beds were all factors associated with A/S use on multivariate analysis, while gestational age ≤ 32 weeks, and type of ventilation and presence of a pain team were associated with PA. We documented a generally widespread, but still highly variable use of A/S and PA at Italian NICUs, despite the diffusion of national guidelines. There is an urgent need to improve routine PA to enable customized pain and stress control (and prevention) in all infants. Clinical Trials.gov # NCT01694745 .

Extracorporeal membrane oxygenation support is indicated in severe and refractory respiratory or circulatory failures. Neurological complications are typically represented by acute ischemic or hemorrhagic lesions, which induce higher morbidity and mortality. The primary goal of this study was to assess the prognostic value of cerebral tissue oxygen saturation (StcO₂) on mortality in neonates and young infants treated with ECMO. A secondary objective was to evaluate the association between StcO₂ and the occurrence of cerebral lesions. This was a prospective study in infants < 3 months of age admitted to a pediatric intensive care unit and requiring ECMO support. The assessment of cerebral perfusion was made by continuous StcO₂ monitoring using near-infrared spectroscopy (NIRS) sensors placed on the two temporo-parietal regions. Neurological lesions were identified by MRI or transfontanellar echography. Thirty-four infants <3 months of age were included in the study over a period of 18 months. The ECMO duration was 10±7 days. The survival rate was 50% (17/34 patients), and the proportion of brain injuries was 20% (7/34 patients). The mean StcO₂ during ECMO in the non-survivors was reduced in both hemispheres (p = 0.0008 right, p = 0.03 left) compared to the survivors. StcO₂ was also reduced in deceased or brain-injured patients compared to the survivors without brain injury (p = 0.002). StcO₂ appears to be a strong prognostic factor of survival and of the presence of cerebral lesions in young infants during ECMO.

OBJECTIVES: To systematically review and assimilate literature on children receiving extracorporeal membrane oxygenation (ECMO) support in pediatric acute respiratory distress syndrome (PARDS) with the goal of developing an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research. DATA SOURCES: Electronic searches of MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: The search used a medical subject heading terms and text words to capture studies of ECMO in PARDS or acute respiratory failure. Studies using animal models and case reports were excluded from our review. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. There were 18 studies identified for full-text extraction. When pediatric data was lacking, adult and neonatal data from randomized clinical trials and observational studies were considered. Six clinical recommendations were generated related to ECMO indications, initiation, and management in PARDS. There were three good practice statements generated related to ECMO indications, initiation, and follow-up in PARDS. Two policy statements were generated involving the impact of ECMO team organization and training in PARDS. Last, there was one research statement. CONCLUSIONS: Based on a systematic literature review, we propose clinical management, good practice and policy statements within the domains of ECMO indications, initiation, team organization, team training, management, and follow-up as they relate to PARDS.

Objective: We compared two polymethylpentene oxygenators being used in our unit: the Maquet Quadrox-iD paediatric® and the Medos Hilite 800LT®. Study design: A mono-centric, prospective pilot study was conducted on ten consecutive newborn patients who had been admitted to our hospital service for extracorporeal circulation (EC) treatment. We examined the rate of oxygen transfer, the CO₂ removal capacity and the average sweep gas flow required to produce this result. We also assessed the disturbances of haemostasis, the need for labile blood products and the membrane oxygenator lifetime and cost of use. Conclusions: According to our study, it seems to us that Medos Hilite 800LT® membrane oxygenators demonstrate greater oxygen transfer and CO₂ removal capacity than Maquet Quadrox-iD paediatric® membrane oxygenators, at a similar cost. These results lead us to conclude that it is reasonable to continue using Medos Hilite 800LT® membrane oxygenators. A broader comparison study would be necessary in order to support these initial results.