Corpus callosum long-term biometry in very preterm children related to cognitive and motor outcomes.

BACKGROUND: The corpus callosum (CC) is suggested as an indirect biomarker of white matter volume, which is often affected in preterm birth. However, diagnosing mild white matter injury is challenging. METHODS: We studied 124 children born preterm (mean age: 8.4 ± 1.1 years), using MRI to assess CC measurements and cognitive/motor outcomes based on the Wechsler Intelligence Scale for Children-V (WPPSI-V) and Movement Assessment Battery for Children-2 (MABC-2). RESULTS: Children with normal outcomes exhibited greater height (10.2 ± 2.1 mm vs. 9.4 ± 2.3 mm; p = 0.01) and fractional anisotropy at splenium (895[680-1000] vs 860.5[342-1000]) and total CC length (69.1 ± 4.8 mm vs. 67.3 ± 5.1 mm; p = 0.02) compared to those with adverse outcomes. All measured CC areas were smaller in the adverse outcome group. Models incorporating posterior CC measurements demonstrated the highest specificity (83.3% Sp, AUC: 0.65) for predicting neurological outcomes. CC length and splenium height were the only linear measurements associated with manual dexterity and total MABC-2 score while both the latter and genu were related with Full-Scale Intelligence Quotient. CONCLUSIONS: CC biometry in children born very preterm at school-age is associated with outcomes and exhibits a specific subregion alteration pattern. The posterior CC may serve as an important neurodevelopmental biomarker in very preterm infants. IMPACT: The corpus callosum has the potential to serve as a reliable and easily measurable biomarker of white matter integrity in very preterm children. Estimating diffuse white matter injury in preterm infants using conventional MRI sequences is not always conclusive. The biometry of the posterior part of the corpus callosum is associated with cognitive and certain motor outcomes at school age in children born very preterm. Length and splenium measurements seem to serve as reliable biomarkers for assessing neurological outcomes in this population.

Relationship of early brain growth pattern measured by ultrasound with neurological outcome at two years of age in very low birth weight infants.

The purpose of this study is to define the impact of early brain growth trajectory in very low birth weight infants (VLBWI) on neurological prognosis at 2 years, assessed using sequential ultrasound (US) scans. This is a prospective cohort study with consecutive inclusion of VLBWI ≤ 32 weeks gestational age and ≤ 1500 g at birth. Total brain volume (TBV) was assessed using sequential 3D-US from birth to discharge. Prognosis at 2 years (corrected age) was assessed using the Bayley Scales of Infant and Toddler Development Third Edition. TBV showed slower growth with postmenstrual age (PMA) in those VLBWI who had an adverse cognitive prognosis compared to those with good cognitive prognosis (mean difference in TBV between prognostic groups from 4.56 cm3 at 28 weeks to 42.58 cm3 at 43 weeks) as well as in those with adverse language prognosis (mean difference in TBV from 2.21 cm3 at 28 weeks to 26.98 cm3 at 43 weeks) although other variables showed more impact than TBV on language prognosis (gestational age at birth, brain injury at term, and socioeconomic status). No association was found between TBV and motor prognosis. Brain growth rate was also significantly higher in those VLBWI who presented good cognitive scores (18.78 + (0.33 × (PMA-33)) cm3/week) compared to those with adverse cognitive outcome (13.73 + (0.64 × (PMA-33)) cm3/week).  Conclusion: Early altered brain growth is associated with poor cognitive prognosis at 2 years of age. Using sequential US monitoring, we can detect early brain growth deviation in patients who will have adverse cognitive outcomes. What is known: • The prediction of neurodevelopmental outcome of VLBWI is mostly based on the presence of brain injury in US and structural magnetic resonance imaging (MRI) at term. • Some studies have related brain volume measured on MRI at term with neurodevelopment outcome. What is new: • VLBWI with adverse cognitive prognosis at two years of age present smaller brain volumes detectable by sequential US during NICU admission. • Brain volume can be estimated from 2D and 3D US and has prognostic value in VLBWI.

Assessment of the perception of vertical subjectivity in children born preterm.

Children born preterm have increased rates of paediatric mortality and morbidity. Prematurity has been associated with impaired visual perception and visuo-motor integration. The alteration of the perception of verticality translates into alterations of the vestibular system at central and/or peripheral level, which may manifest itself in symptoms such as imbalance, dizziness or even vertigo. The aim of this study was to compare subjective visual vertical (SVV) test scores in children born preterm with those of children born at term at ages between 7 and 10. One hundred ten children with no neurodevelopmental disorder of 7 to 10 years of age were studied using a mobile application on a smartphone attached to a wall by means of a rotating plate. The SVV test was compared between two groups: a group of 55 preterm children (53 very preterm children born under 32 weeks of gestational age and 2 preterm with very low birth weight) and another group of 55 children born at term (after 37 weeks of gestational age). The SVV results were analysed for comparison with respect to prematurity, sex and age. We found no significant differences in the SVV study in the comparison between preterm and term children. In addition, no significant differences were observed regarding sex or age between 7 and 10 years.  Conclusion: We found no alterations in the perception of vertical subjectivity in children between 7 and 10 years of age, with antecedents of very preterm birth and/or very low birth weight. What is Known: • The different studies published so far suggest the existence of balance disorders in premature children, although in most of these studies the children are examined at an age when the vestibular system is not mature and with non-specific tests for the study of the vestibular system. What is New: • We compared the results of the subjective visual vertical (SVV) test in a group of 55 preterm children (53 very preterm children born under 32 weeks of gestational age and 2 preterm with very low weight at birth) and in a group of 55 children born at term (after 37 weeks of gestational age), at the ages of 7 to 10 years and observed no differences. • We conclude that, if there had been any vestibular alterations due to very premature birth, these must have been compensated by the age of 7.

Ultrasonographic evaluation of the early brain growth pattern in very low birth weight infants.

BACKGROUND: Preterm infants develop smaller brain volumes compared to term newborns. Our aim is to study early brain growth related to perinatal factors in very low birth weight infants (VLBWI). METHODS: Manual segmentation of total brain volume (TBV) was performed in weekly 3D-ultrasonographies in our cohort of VLBWI. We studied the brain growth pattern related to term magnetic resonance image (term-MRI). RESULTS: We found different brain growth trajectories, with smaller brain volumes and a decrease in brain growth rate in those VLBWI who would later have an abnormal term-MRI (mean TBV 190.68 vs. 213.9 cm3; P = 0.0001 and mean TBV growth rate 14.35 (±1.27) vs. 16.94 (±2.29) cm3/week; P = 0.0001). TBV in those with normal term-MRI was related to gestational age (GA), being small for gestational age (SGA), sex, and duration of parenteral nutrition (TPN) while in those with abnormal term-MRI findings it was related to GA, SGA, TPN, and comorbidities. We found a deceleration in brain growth rate in those with ≥3 comorbidities. CONCLUSIONS: An altered brain growth pattern in VLBWI who subsequently present worst scores on term-MRI is related to GA, being SGA and comorbidities. Early ultrasonographic monitoring of TBV could be useful to detect deviated patterns of brain growth. IMPACT STATEMENT: We describe the brain growth pattern in very low birth weight infants during their first postnatal weeks. Brain growth may be affected in the presence of certain perinatal factors and comorbidities, conditioning a deviation of the normal growth pattern. The serial ultrasound follow-up of these at-risk patients allows identifying these brain growth patterns early, which offers a window of opportunity for implementing earlier interventions.

Alteraciones en resonancia magnética asociadas a tratamiento con vigabatrina / Magnetic resonance imaging abnormalities associated with vigabatrin therapy

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Ultrasonographic Estimation of Total Brain Volume: 3D Reliability and 2D Estimation. Enabling Routine Estimation During NICU Admission in the Preterm Infant.

Objectives: The aim of this study is to explore if manually segmented total brain volume (TBV) from 3D ultrasonography (US) is comparable to TBV estimated by magnetic resonance imaging (MRI). We then wanted to test 2D based TBV estimation obtained through three linear axes which would enable monitoring brain growth in the preterm infant during admission. Methods: We included very low birth weight preterm infants admitted to our neonatal intensive care unit (NICU) with normal neuroimaging findings. We measured biparietal diameter, anteroposterior axis, vertical axis from US and MRI and TBV from both MRI and 3D US. We calculated intra- and interobserver agreement within and between techniques using the intraclass correlation coefficient and Bland-Altman methodology. We then developed a multilevel prediction model of TBV based on linear measurements from both US and MRI, compared them and explored how they changed with increasing age. The multilevel prediction model for TBV from linear measures was tested for internal and external validity and we developed a reference table for ease of prediction of TBV. Results: We used measurements obtained from 426 US and 93 MRI scans from 118 patients. We found good intra- and interobserver agreement for all the measurements. US measurements were reliable when compared to MRI, including TBV which achieved excellent agreement with that of MRI [ICC of 0.98 (95% CI 0.96-0.99)]. TBV estimated through 2D measurements of biparietal diameter, anteroposterior axis, and vertical axis was comparable among both techniques. We estimated the population 95% confidence interval for the mean values of biparietal diameter, anteroposterior axis, vertical axis, and total brain volume by post-menstrual age. A TBV prediction table based on the three axes is proposed to enable easy implementation of TBV estimation in routine 2D US during admission in the NICU. Conclusions: US measurements of biparietal diameter, vertical axis, and anteroposterior axis are reliable. TBV segmented through 3D US is comparable to MRI estimated TBV. 2D US accurate estimation of TBV is possible through biparietal diameter, vertical, and anteroposterior axes.

Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy.

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Additionally, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration.

Infección asociada a catéter por Leclercia adecarboxylata y Raoultella ornithinolytica en un paciente con enfermedad mitocondrial / Leclercia adecarboxylata and Raoultella ornithinolytica catheter-related infection in a child with mitocondrial disease

Leclercia adecarboxylata y Raoultella ornithinolytica constituyen bacterias Gram-negativas emergentes. Los casos descritos son excepcionales. En los últimos años, las mejoras en las técnicas de diagnóstico microbiológico han permitido su detección y conocimiento. Se presenta el caso de un niño de 11 años con enfermedad mitocondrial, portador de catéter venoso central de larga duración, que desarrolló dos episodios de sepsis por L. adecarboxylata y R. ornithinolytica, respectivamente. En los casos de infección asociada al uso de catéter, es posible, en ocasiones, el tratamiento sin su retirada con evolución favorable. Es importante reconocer L. adecarboxylata y R. ornithinolytica como patógenos de diagnóstico cada vez más frecuentes, sobre todo, en pacientes inmunodeprimidos o con patologías crónicas asociadas.

Leclercia adecarboxylata and Raoultella ornithinolytica are emergent Gram-negative bacteria. Infections caused by these microorganisms are exceptional. Improvement of microbiologist techniques in the last years has enabled their detection and more accurate knowledge. We present the case of an 11-year-old boy with mitochondrial disease with a longterm central catheter who suffered from two sepsis caused by L. adecarboxylata and R. ornithinolytica, respectively. In catheter-related infections, sometimes it is possible to provide antimicrobial treatment without removal of catheter with good results, as in our patient. It is important to recognize L. adecarboxylata and R. ornithinolytica like increasingly frequent pathogenic bacteria, mostly in immunocompromised or chronic patients.

[Leclercia adecarboxylata and Raoultella ornithinolytica catheter-related infection in a child with mitocondrial disease]. / Infección asociada a catéter porLeclercia adecarboxylata yRaoultella ornithinolytica en un paciente con enfermedad mitocondrial.

Leclercia adecarboxylata and Raoultella ornithinolytica are emergent Gram-negative bacteria. Infections caused by these microorganisms are exceptional. Improvement of microbiologist techniques in the last years has enabled their detection and more accurate knowledge. We present the case of an 11-year-old boy with mitochondrial disease with a longterm central catheter who suffered from two sepsis caused by L. adecarboxylata and R. ornithinolytica, respectively. In catheter-related infections, sometimes it is possible to provide antimicrobial treatment without removal of catheter with good results, as in our patient. It is important to recognize L. adecarboxylata and R. ornithinolytica like increasingly frequent pathogenic bacteria, mostly in immunocompromised or chronic patients.

Leclercia adecarboxylata y Raoultella ornithinolytica constituyen bacterias Gram-negativas emergentes. Los casos descritos son excepcionales. En los últimos años, las mejoras en las técnicas de diagnóstico microbiológico han permitido su detección y conocimiento. Se presenta el caso de un niño de 11 años con enfermedad mitocondrial, portador de catéter venoso central de larga duración, que desarrolló dos episodios de sepsis por L. adecarboxylata y R. ornithinolytica, respectivamente. En los casos de infección asociada al uso de catéter, es posible, en ocasiones, el tratamiento sin su retirada con evolución favorable. Es importante reconocer L. adecarboxylata y R. ornithinolytica como patógenos de diagnóstico cada vez más frecuentes, sobre todo, en pacientes inmunodeprimidos o con patologías crónicas asociadas.

Clinical presentation and early predictors for poor outcomes in pediatric myocarditis: A retrospective study.

BACKGROUND: Myocarditis is an important cause of morbidity and mortality in children, leading to long-term sequelae including chronic congestive heart failure, dilated cardiomyopathy, heart transplantation, and death. The initial diagnosis of myocarditis is usually based on clinical presentation, but this widely ranges from the severe sudden onset of a cardiogenic shock to asymptomatic patients. Early recognition is essential in order to monitor and start supportive treatment prior to the development of severe adverse events. Of note, many cases of fulminant myocarditis are usually misdiagnosed as otherwise minor conditions during the weeks before the unexpected deterioration. AIM: To provide diagnostic clues to make an early recognition of pediatric myocarditis. To investigate early predictors for poor outcomes. METHODS: We conducted a retrospective cross-sectional single-center study from January 2008 to November 2017 at the Pediatric Department of our institution, including children < 18-years-old diagnosed with myocarditis. Poor outcome was defined as the occurrence of any of the following facts: death, heart transplant, persistent left ventricular systolic dysfunction or dilation at hospital discharge (early poor outcome), or after 1 year of follow-up (late poor outcome). We analyzed different clinical features and diagnostic test findings in order to provide diagnostic clues for myocarditis in children. Multivariable stepwise logistic regression analysis was performed using all variables that had been selected by univariate analysis to determine independent factors that predicted a poor early or late outcome in our study population. RESULTS: A total of 42 patients [69% male; median age of 8 (1.5-12) years] met study inclusion criteria. Chest pain (40%) was the most common specific cardiac symptom. Respiratory tract symptoms (cough, apnea, rhinorrhea) (38%), shortness of breath (35%), gastrointestinal tract symptoms (vomiting, abdominal pain, diarrhea) (33%), and fever (31%) were the most common non-cardiac initial complaints. Tachycardia (57%) and tachypnea (52%) were the most common signs on the initial physical exam followed by nonspecific signs of respiratory tract infection (44%) and respiratory distress (35%). Specific abnormal signs of heart failure such as heart murmur (26%), systolic hypotension (24%), gallop rhythm (20%), or hepatomegaly (20%) were less prevalent. Up to 43% of patients presented an early poor outcome, and 16% presented a late poor outcome. In multivariate analysis, an initial left ventricular ejection fraction (LVEF) < 30% remained the only significant predictor for early [odds ratio (OR) (95%CI) = 21 (2-456), P = 0.027) and late [OR (95%CI) = 8 (0.56-135), P = 0.047) poor outcome in children with myocarditis. LVEF correlated well with age (r = 0.51, P = 0.005), days from the initiation of symptoms (r = -0.31, P = 0.045), and N-terminal pro-brain natriuretic peptide levels (r = 0.66, P < 0.001), but not with troponin T (r = -0.05, P = 0.730) or C-reactive protein levels (r = -0.13, P = 0.391). N-terminal pro-brain natriuretic peptide presented a high diagnostic accuracy for LVEF < 30% on echocardiography with an area under curve of 0.931 (95%CI: 0.858-0.995, P < 0.001). The best cut-off point was 2000 pg/mL with a sensitivity of 90%, specificity of 81%, positive predictive value of 60%, and negative predictive value of 96%. CONCLUSION: The diagnosis of myocarditis in children is challenging due to the heterogeneous and unspecific clinical presentation. The presence of LVEF < 30% on echocardiography on admission was the major predictor for poor outcomes. Younger ages, a prolonged course of the disease, and N-terminal pro-brain natriuretic peptide levels could help to identify these high-risk patients.

Ultrasound lineal measurements predict ventricular volume in posthaemorrhagic ventricular dilatation in preterm infants.

AIM: Posthaemorrhagic ventricular dilatation (PHVD) is monitored by conventional two-dimensional ultrasound (2DUS). The aims of this study were to determine the volume of the lateral ventricles using three-dimensional ultrasound (3DUS) in preterm infants with PHVD and to evaluate the relationship between volume and linear measurements. METHODS: Serial 2DUSs and 3DUSs were performed on preterm infants with PHVD admitted to the neonatal intensive care unit at Puerta del Mar Hospital, Cádiz, Spain, from January 2013 to December 2014. The ventricular index, anterior horn width and thalamo-occipital distance were used as ventricular lineal measurements. Ventricular volume was calculated offline. RESULTS: Serial ultrasounds from seven preterm infants were measured. Each linear measurement was significantly associated with volume, and an equation was obtained through a significant multilevel mixed-effects lineal regression model: ventricular volume (cm3 ) = -11.02 + 0.668*VI + 0.817*AHW + 0.256*TOD. Intra-observer and interobserver agreement was excellent with an intraclass correlation coefficient of 0.99. CONCLUSION: Lateral ventricular volumes of preterm infants with PHVD could be reliably determined using 3DUS. Ventricular volume could be accurately estimated using three lineal measurements. More studies are needed to address the importance of volume determination in PHVD.