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Background: There is limited knowledge regarding the impact of perioperative critical care on frequency of neurological imaging findings following esophageal atresia (EA) repair., Methods: This is a retrospective study of infants (n = 70) following EA repair at a single institution (2009-2020). Sex, gestational age at birth, type of surgical repair, underlying disease severity, and frequency of neurologic imaging findings were obtained. We quantified the length of postoperative pain/sedation treatment and anesthesia exposure in the first year of life. Data were presented as numerical sums and percentages, while associations were measured using Spearman's Rho., Results: Vertebral/spinal cord imaging was performed in all infants revealing abnormalities in 44% (31/70). Cranial/brain imaging findings were identified in 67% (22/33) of infants in the context of clinically indicated imaging (47%; 33/70). Long-gap EA patients (n = 16) received 10 times longer postoperative pain/sedation treatment and twice the anesthesia exposure compared with short-gap EA patients (n = 54). The frequency of neurologic imaging findings did not correlate with underlying disease severity scores, length of pain/sedation treatment, or cumulative anesthesia exposure. Lack of associations between clinical measures and imaging findings should be interpreted with caution given possible underestimation of cranial/brain findings., Conclusions: We propose that all infants with EA undergo brain imaging in addition to routine spinal imaging given the high burden of abnormal brain/cranial findings in our cohort. Quantification of pain/sedation and anesthesia exposure in long-gap EA patients could be used as indirect markers in future studies assessing the risk of neurological sequelae as evidenced by early abnormalities on brain imaging., (© 2023 Wiley Periodicals LLC.)

We present a case of a 12-year-old female with a history of infantile spasms who developed a propofol-associated acute dystonic reaction after emergence from general anesthesia for foot surgery. Uniquely, the patient's postoperative symptoms of an acute dystonic reaction were refractory to standard treatment with anticholinergics but were successfully treated with corticosteroids. The absence of any dystonic symptoms following subsequent foot surgery under general anesthesia without propofol supported a propofol-associated etiology. This case may contribute to a better understanding of the underlying mechanisms of propofol-associated acute dystonic reactions and adds a possible new treatment option., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Recent findings implicate brain vulnerability following long-gap esophageal atresia (LGEA) repair. We explored the relationship between easily quantifiable clinical measures and previously reported brain findings in a pilot cohort of infants following LGEA repair. MRI measures (number of qualitative brain findings; normalized brain and corpus callosum volumes) were previously reported in term-born and early-to-late premature infants (n = 13/group) <1 year following LGEA repair with the Foker process. The severity of underlying disease was classified by an (1) American Society of Anesthesiologist (ASA) physical status and (2) Pediatric Risk Assessment (PRAm) scores. Additional clinical end-point measures included: anesthesia exposure (number of events; cumulative m inimal a lveolar c oncentration (MAC) exposure in hours), length (in days) of postoperative intubated sedation, paralysis, antibiotic, steroid, and total parenteral nutrition (TPN) treatment. Associations between clinical end-point measures and brain MRI data were tested using Spearman rho and multivariable linear regression. Premature infants were more critically ill per ASA scores, which showed a positive association with the number of cranial MRI findings. Clinical end-point measures together significantly predicted the number of cranial MRI findings for both term-born and premature infant groups, but none of the individual clinical measures did on their own. Listed easily quantifiable clinical end-point measures could be used together as indirect markers in assessing the risk of brain abnormalities following LGEA repair., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Data were previously published as an abstract at the 2021 American Society of Anesthesiologists (ASA) Conference.

Objective: To determine brain magnetic resonance imaging (MRI) measures of cerebrospinal fluid (CSF) and whole brain volume of full-term and premature infants following surgical treatment for thoracic non-cardiac congenital anomalies requiring critical care. Methods: Full-term ( n = 13) and pre-term ( n = 13) patients with long-gap esophageal atresia, and full-term naïve controls ( n = 19) < 1 year corrected age, underwent non-sedated brain MRI following completion of thoracic non-cardiac surgery and critical care treatment. Qualitative MRI findings were reviewed and reported by a pediatric neuroradiologist and neurologist. Several linear brain metrics were measured using structural T1-weighted images, while T2-weighted images were required for segmentation of total CSF and whole brain tissue using the M orphologically A daptive N eonatal T issue S egmentation ( MANTiS ) tool. Group differences in absolute (mm, cm 3 ) and normalized (%) data were analyzed using a univariate general linear model with age at scan as a covariate. Mean normalized values were assessed using one-way ANOVA. Results: Qualitative brain findings suggest brain atrophy in both full-term and pre-term patients. Both linear and volumetric MRI analyses confirmed significantly greater total CSF and extra-axial space, and decreased whole brain size in both full-term and pre-term patients compared to naïve controls. Although linear analysis suggests greater ventricular volumes in all patients, volumetric analysis showed that normalized ventricular volumes were higher only in premature patients compared to controls. Discussion: Linear brain metrics paralleled volumetric MRI analysis of total CSF and extra-axial space, but not ventricular size. Full-term infants appear to demonstrate similar brain vulnerability in the context of life-saving thoracic non-cardiac surgery requiring critical care as premature infants.

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of disorders characterized by degeneration of the corticospinal and spinocerebellar tracts leading to progressive spasticity. One subtype, spastic paraplegia type 47 (SPG47 or HSP-AP4B1), is due to bi-allelic loss-of-function mutations in the AP4B1 gene. AP4B1 is a subunit of the adapter protein complex 4 (AP-4), a heterotetrameric protein complex that regulates the transport of membrane proteins. Since 2011, 11 individuals from six families with AP4B1 mutations have been reported, nine of whom had homozygous mutations and were from consanguineous families. Here we report eight patients with AP4B1-associated SPG47, the majority born to non-consanguineous parents and carrying compound heterozygous mutations. Core clinical features in this cohort and previously published patients include neonatal hypotonia that progresses to spasticity, early onset developmental delay with prominent motor delay and severely impaired or absent speech development, episodes of stereotypic laughter, seizures including frequent febrile seizures, thinning of the corpus callosum, and delayed myelination/white matter loss. Given that some of the features of AP-4 deficiency overlap with those of cerebral palsy, and the discovery of the disorder in non-consanguineous populations, we believe that AP-4 deficiency may be more common than previously appreciated., (© 2017 Wiley Periodicals, Inc.)

Purpose: Current diagnosis of fetal posterior fossa anomalies by sonography and conventional MRI is limited by fetal position, motion, and by two-dimensional (2D), rather than three-dimensional (3D), representation. In this study, we aimed to validate the use of a novel magnetic resonance imaging (MRI) technique, 3D super-resolution motion-corrected MRI, to image the fetal posterior fossa., Methods: From a database of pregnant women who received fetal MRIs at our institution, images of 49 normal fetal brains were reconstructed. Six measurements of the cerebellum, vermis, and pons were obtained for all cases on 2D conventional and 3D reconstructed MRI, and the agreement between the two methods was determined using concordance correlation coefficients. Concordance of axial and coronal measurements of the transcerebellar diameter was also assessed within each method., Results: Between the two methods, the concordance of measurements was high for all six structures (P < .001), and was highest for larger structures such as the transcerebellar diameter. Within each method, agreement of axial and coronal measurements of the transcerebellar diameter was superior in 3D reconstructed MRI compared to 2D conventional MRI (P < .001)., Conclusions: This comparison study validates the use of 3D super-resolution motion-corrected MRI for imaging the fetal posterior fossa, as this technique results in linear measurements that have high concordance with 2D conventional MRI measurements. Lengths of the transcerebellar diameter measured within a 3D reconstruction are more concordant between imaging planes, as they correct for fetal motion and orthogonal slice acquisition. This technique will facilitate further study of fetal abnormalities of the posterior fossa., (Copyright © 2016 by the American Society of Neuroimaging.)

Background: Functional neurological symptom disorders are frequently the basis for acute neurological consultation. In children, they are often precipitated by high-frequency everyday stressors. The extent to which a severe traumatic experience may also precipitate functional neurological abnormalities is unknown., Methods: For the 2-week period after the Boston Marathon bombings, we prospectively collected data on patients whose presentation suggested a functional neurological symptom disorder. We assessed clinical and demographic variables, duration of symptoms, extent of educational impact, and degree of connection to the Marathon bombing. We contacted all patients at 6 months after presentation to determine the outcome and accuracy of the diagnosis., Results: In a parallel study, we reported a baseline of 2.6 functional neurological presentations per week in our emergency room. In the week after the Marathon bombings, this frequency tripled. Ninety-one percent of presentations were delayed by 1 week, with onset around the first school day after a city-wide lockdown. Seventy-three percent had a history of a prior psychiatric diagnosis. At the 6 months follow-up, no functional neurological symptom disorder diagnoses were overturned and no new organic diagnosis was made., Conclusions: Pediatric functional neurological symptom disorder may be precipitated by both casual and high-intensity stressors. The 3.4-fold increase in incidence after the Boston Marathon bombings and city-wide lockdown demonstrates the marked effect that a community-wide tragedy can have on the mental health of children. Care providers must be aware of functional neurological symptom disorders after stressful community events in vulnerable patient populations, particularly those with prior psychiatric diagnoses., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: The purpose of this study was to correlate 2-dimensional magnetic resonance (MR) measurements of lateral ventricular width and 3-dimensional measurements of lateral ventricular and supratentorial parenchymal volumes to postnatal outcomes in fetuses with ventriculomegaly., Methods: A total of 307 fetuses (mean gestational age, 26.0 weeks; range, 15.7-39.4 weeks) had MR volumetry after referral for ventriculomegaly. Fetuses were grouped into those with (n = 114) and without (n = 193) other central nervous system (CNS) anomalies. Pregnancy and postnatal neurodevelopmental outcomes up to 3 years of age were obtained. A subgroup analysis was performed excluding fetuses with other CNS anomalies. Logistic regression analysis was performed to assess which measurement was most predictive of outcomes., Results: There were 50 terminations, 2 stillbirths, and 255 live births. Seventy-five cases were lost to follow-up. Among 180 live-born neonates with follow-up, 140 had abnormal and 40 had normal outcomes. Atrial diameter (P < .0001), frontal horn diameter (P < .0001), and ventricular volume (P = .04) were predictive of live birth, with 92% specificity at 60% sensitivity. Among fetuses without other CNS anomalies, 180 of 193 pregnancies (93%) resulted in live deliveries, with atrial diameter (P < .0001), frontal horn diameter (P = .003), and ventricular volume (P = .008) associated with live birth and atrial diameter having the highest specificity (>99% at 60% sensitivity). Parenchymal volume was not associated with normal or abnormal outcomes (either live birth versus death or normal versus abnormal neurodevelopmental outcome). Among live-born neonates, no age-adjusted threshold for any of the measurements reliably distinguished between normal and abnormal neurodevelopmental outcomes., Conclusions: Ventricular volume and diameter, but not parenchymal volume, correlate with live birth in fetuses with ventriculomegaly. However, once live born, neither 2- nor 3-dimensional measurements can distinguish a fetus that will have a normal outcome.

Poly-N-acetyl-glucosamine (PNAG) is a staphylococcal surface polysaccharide influencing biofilm formation that is also under investigation for its vaccine potential. Antibodies that bind to PNAG with either low (<15%) or high (>90%) levels of acetate are superior at opsonic and protective activity compared with antibodies that bind to PNAG with only high levels (>70%) of acetate. PNAG is synthesized by four proteins encoded within the intercellular adhesin (ica) locus icaADBC. In Staphylococcus epidermidis, icaB encodes a deacetylase needed for the surface retention of PNAG and optimal biofilm formation. In this study, we confirmed that icaB plays a similar role in Staphylococcus aureus and found that an icaB mutant of S. aureus expressed significantly less surface-associated PNAG, was highly susceptible to antibody-independent opsonic killing that could not be enhanced with antibody raised against deacetylated PNAG (dPNAG), and had reduced survival capacity in a murine model of bacteremia. In contrast, an icaB-overexpressing strain produced primarily surface-associated PNAG, was more susceptible to opsonophagocytosis with antibody to dPNAG, and had increased survival in a murine bacteremia model. The highly acetylated secreted PNAG was more effective at blocking opsonic killing mediated by a human monoclonal antibody (mAb) to native PNAG than it was at blocking killing mediated by a human mAb to dPNAG, which by itself was a more effective opsonin. Retention of dPNAG on the surface of S. aureus is key to increased survival during bacteremia and also provides a molecular mechanism explaining the superior opsonic and protective activity of antibody to dPNAG.

Infections involving Staphylococcus aureus are often more severe and difficult to treat when the organism assumes a biofilm mode of growth. The polysaccharide poly-N-acetylglucosamine (PNAG), also known as polysaccharide intercellular adhesin, is synthesized by the products of the intercellular adhesin (ica) locus and plays a key role in biofilm formation. Numerous conditions and exogenous factors influence ica transcription and PNAG synthesis, but the regulatory factors and pathways through which these environmental stimuli act have been only partially characterized. We developed a DNA affinity chromatography system to purify potential regulatory proteins that bind to the ica promoter region. Using this technique, we isolated four proteins, including the staphylococcal gene regulator SarA, a MarR family transcriptional regulator of the teicoplanin-associated locus TcaR, DNA-binding protein II, and topoisomerase IV, that bound to the ica promoter. Site-directed deletion mutagenesis of tcaR indicated that TcaR was a negative regulator of ica transcription, but deletion of tcaR alone did not induce any changes in PNAG production or in adherence to polystyrene. We also investigated the role of IcaR, encoded within the ica locus but divergently transcribed from the biosynthetic genes. As has been shown previously in Staphylococcus epidermidis, we found that IcaR was also a negative regulator of ica transcription in S. aureus. We also demonstrate that mutation of icaR augmented PNAG production and adherence to polystyrene. Transcription of the ica locus, PNAG production, and adherence to polystyrene were further increased in a tcaR icaR double mutant. In summary, TcaR appeared to be a weak negative regulator of transcription of the ica locus, whereas IcaR was a strong negative regulator, and in their absence PNAG production and biofilm formation were enhanced.