Serum Activin A as Brain Injury Biomarker in the First Three Days of Life. A Prospective Case—Control Longitudinal Study in Human Premature Neonates

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI.

Neurodevelopment in normocephalic children with and without prenatal Zika virus exposure

ObjectiveZika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls.DesignCohort study.SettingPublic health centres in Grenada, West Indies.Patients384 mother–child pairs were enrolled during a period of active ZIKV transmission (April 2016–March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum.Main outcome measuresThe INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child’s exposure status.ResultsA total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays.ConclusionsOverall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.

Do standard surgical techniques lead to satisfying aesthetic results in nonsyndromic sagittal suture synostosis?

OBJECTIVE Surgical correction of synostotic cranial sutures is typically performed early in an affected child’s life. Depending on the severity of the cranial synostoses, different aspects of the surgical treatment may have varying degrees of importance. In this sense, the aesthetic appearance in children with normal neurological development in single-suture synostosis plays an important role in self-perception and social acceptance for both the patients themselves and their caregivers. Therefore, in this study, the authors aimed to evaluate the aesthetic outcome after surgical correction in a cohort of patients with nonsyndromic sagittal suture synostosis. METHODS Between December 2002 and December 2019, a total of 99 patients underwent surgical correction of a synostotic sagittal suture at the Medical University of Vienna. Depending on their age, patients underwent either an extended midline strip craniectomy (EMSC) (< 4 months) or a modified pi procedure (MPP) (≥ 4 months). After the surgical procedure, the outcome was evaluated by the treating neurosurgeon at 1- and 12-month follow-up visits, and after approximately 5 years, before the patient entered elementary school. In addition to that, the patients’ caregivers were asked to evaluate the aesthetic outcome of the surgical procedure after 12 months. These results were then compared to evaluate potential differences in the perception of the surgical outcome. RESULTS After 12 months, the majority of the included patients were evaluated as having a good aesthetic outcome by the treating neurosurgeon (97%) and by their caregivers (89%). These differences did not show statistical significance (p = 0.11). Similarly, no differences in the aesthetic outcome depending on the surgical procedure performed could be found (p = 0.55). At the last follow-up visit, before entering elementary school, all available patients had an excellent or good surgical outcome. Moreover, the majority of caregivers (73%) reported that their child had a normal head shape appearance after surgical correction. CONCLUSIONS The results of this study have suggested that surgical correction of sagittal suture synostosis by simple operative techniques leads to a good aesthetic outcome and a normal head shape appearance in the majority of patients. An analysis of the evaluation of the surgical outcome by either the treating neurosurgeon or the patient caregivers showed comparable results and, thus, early intervention with simple surgical techniques can be recommended.

Determine the Frequency of Sensorineural Deafness in Children with Cerebral Palsy

Aim: To determine the frequency of sensorineural deafness in child with cerebral palsy. Study Design: Descriptive/cross-sectional Place and Duration of Study: Department of Neurology, Chandka Medical College Hospital, Larkana from 1st October 2020 to 31st March 2021. Methodology: One hundred and seventy patients of both genders age between 1-14 years were enrolled. Children diagnosed as having cerebral palsy and fulfilling the inclusion criteria was included. Hearing assessment was done with audiometry and degree of hearing loss was recorded in both ears in the form of mild, moderate, severe and profound degree of hearing loss. Results: Most of the patients 90 (52.94%) were between 1-5 years old followed by 51(30%) patients between 5-10 years with mean age of 4.8±7.8 years. 115 (67.65%) cases were males and 55 (32.35%) females. 54 (31.8%) cases had microcephaly and116 (68.2) cases had normal head circumference. Among 170 cases of cerebral palsy 48 (28.23%) cases had hearing loss and 122 (71.77%) of patients of CP had no hearing deficit. Among 48 cases of CP with hearing loss 15 (31.25%) cases had mild, 14 (29.17) cases had moderate, 10 (20.83%) had severe and 11 (22.92%) cases had profound hearing loss. Conclusion: The frequency of sensorineural deficit is high and significantly associated with cerebral palsy patients. Keywords: Degree of hearing loss, Sensorineural hearing loss, Cerebral palsy

Hereditary hypophosphatemic rickets and craniosynostosis

Background Craniosynostosis is an underdiagnosed complication associated with hypophosphatemic rickets. The study aims to describe the clinical and auxological characteristic of children with hypophosphatemic rickets and craniosynostosis, describe the usual treatment, and compare the characteristics with those of children without craniosynostosis. Methods and patients An observational and retrospective cohort study was conducted. Clinical notes and cranial images were reviewed. Out of 96 children, only the 50 patients who had skull images were included. Results Out of 50 patients, 26 (15 males) had craniosynostosis (52%). No differences were observed in birth size, age, height, body proportions, alkaline phosphatase, serum phosphate, or percent tubular reabsorption of phosphate at first appointment among children with or without craniosynostosis. Among patients with craniosynostosis, dolichocephaly was prevalent. The sagittal suture was affected in all patients with craniosynostosis, with 19 of 26 children (73%) affected with isolated scaphocephaly. Pan-sutural craniosynostosis was present in 7 children (27%). None of the children had microcephaly, 7 of them presented macrocephaly and, in the remaining subjects, head circumference was normal. Five patients had undergone at least 1 cranial remodeling surgery. One patient with craniosynostosis was diagnosed with a Chiari I malformation. Molecular characterization of PHEX gene was performed in 14 cases. Conclusions Craniosynostosis is an underdiagnosed complication of hypophosphatemic rickets. Many patients with normal head size and growth may go undiagnosed, thus it is important to consider this association for early diagnosis and possible surgical treatment. A multidisciplinary approach is necessary for a correct long-term follow-up.

Analysis of Factors Related To Head MRI Changes In Neonatal Hyperbilirubinemia And Effect On Neurodevelopmental Outcomes.

Background and ObjectiveThis study aims to detect how hyperbilirubinemia affects cerebral structures by imagery (MRI) to prevent irreversible future brain damage. Research Design and MethodsIn this retrospective study, 50 infants of 35 weeks gestation or more with hyperbilirubinemia were assigned to two groups based on abnormal or normal head imaging (MRI). The primary outcomes included peak bilirubin levels according to socio-demographic factors and how these levels influence MRI.The secondary outcome was neurodevelopment at 1, 3, 6, 9 and 12 months for the imaging changes versus the normal imaging groups assessed by a combined formulaire based on the CDC’s developmental milestones, the Denver II Developmental Screening Test (DDST), the Hammersmith infant neurological exam, and auditory brainstem response (ABR) by investigators. ResultsPeak serum bilirubin levels (TSB) in the group with MRI changes, defined as bilaterally symmetrical signal intensity on T1- weighted imaging in the globus pallidus GP, was significantly higher than those in the group without MRI changes (342.5±47.6μmol/L vs. 284.3±46.3μmol/L), p=0.000. Odds ratios when observing TSB values with 342μmol/L as cut-off, showed that participants with TSB ≥ 342μmol/L were 12.4 times more likely of presenting with abnormal MR imaging (OR=12.4, 95% CI 2.191-70.672). In addition, a cross-tab comparison between MRI and milestones depicts MRI as having a 66.7% ，33.3% sensitivity and specificity while 12.5%，97.1% PPV (positive predictive value) and NPV (negative predictive values) respectively for milestone attainment. No relationship was found between abnormal outcomes and abnormal MRI. ConclusionsA significant relationship between high bilirubin levels and head imaging (MRI) was observed, but these changes in imaging could not significantly predict neurodevelopmental outcomes.

Laron syndrome: a case report

Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. A 13-month-old, male child, born of second-degree consanguineous marriage presented with short stature (57 cm, below- 3 SD) with normal head size, mild motor developmental delay, micropenis and bone age of 9 months. Basal GH was 28.7 ng/ml (normal 1-13.6 ng/ml). IGF-1 was less than 20 ng/ml (normal up to 170 ng/ml). GH stimulation test done using clonidine revealed increased levels. Post stimulation levels at 30 min, 60 min, 90 min (ng/ml) were 29.3, 37.9, 29.3 respectively, which was suggestive of resistance to GH that is laron dwarfism. Treatment is focused on improving growth and generally includes injections of insulin-like growth factor 1 (IGF-1). This case is being reported for its rarity and early detection.

Melanotic Neuroectodermal Tumor of Infancy at Skull: Rare and Rapid-Growing Tumor but Histologically Benign

<b><i>Introduction:</i></b> Melanotic neuroectodermal tumor of infancy (MNTI) is a rare and rapid-growing tumor. However, a neurosurgeon should not overlook this entity when differential diagnosing rapid-growing skull tumor because its histology nature is just benign, and the prognosis is much better than other malignant tumors. <b><i>Case Presentation:</i></b> We reported the case of a 5-month old male presenting with progressive rapid-growing skull tumor which became 10 cm in diameter in only 5 months compared to the normal head circumference at birth. At first, we thought of malignant skull tumor and performed only biopsy to establish diagnosis. But, when the pathology revealed benign MNTI, we performed preoperative tumor embolization and then radical surgery. Good result was observed. <b><i>Discussion:</i></b> Skull MNTI is the second most common location after the maxilla. Even advanced imaging nowadays cannot distinguish MNTI from other malignant tumors definitely. Urgent biopsy is recommended to establish diagnosis of this benign tumor first. Preoperative angiography with tumor embolization is recommended when feasible, followed by craniotomy with radical resection.

Cranial Structure of Varanus komodoensis as Revealed by Computed-Tomographic Imaging

This study aimed to describe the anatomic features of the normal head of the Komodo dragon (Varanus komodoensis) identified by computed tomography. CT images were obtained in two dragons using a helical CT scanner. All sections were displayed with a bone and soft tissue windows setting. Head reconstructed, and maximum intensity projection images were obtained to enhance bony structures. After CT imaging, the images were compared with other studies and reptile anatomy textbooks to facilitate the interpretation of the CT images. Anatomic details of the head of the Komodo dragon were identified according to the CT density characteristics of the different organic tissues. This information is intended to be a useful initial anatomic reference in interpreting clinical CT imaging studies of the head and associated structures in live Komodo dragons.