The utility of the fronto-temporal horn ratio on cranial ultrasound in premature newborns: a ventriculomegaly marker.

BACKGROUND: The aims of this study were to find the normal value of fronto-temporal horn ratio (FTHR) as a marker of ventriculomegaly on cranial ultrasound (CUS) in premature newborns and the relation to white matter injury (WMI) and cerebral palsy (CP). METHODS: This is a retrospective study of newborns admitted between 2011 and 2014. Inclusion criteria were: (1) gestation <29 weeks, (2) birth weight ≤1500 g, (3) referred within 7 days of life, (4) at least two CUS preformed, (5) brain magnetic resonance imaging (MRI) at term age-equivalent. Intraventricular hemorrhage (IVH) grade was identified and FTHR was measured on all CUS. WMI on MRI was evaluated through (1) injury score (Kidokoro 2013) and (2) fractional anisotropy (FA) on the MRI diffusion tensor imaging. CP was estimated using the gross motor function classification system (GMFCS). RESULTS: One hundred neonates met the inclusion criteria: 37 with no IVH, 36 with IVH grade 1-2, and 27 with IVH grade 3-4. The FTHR cut-point of 0.51 had the highest sensitivity and specificity for moderate-to-severe WMI. In the IVH grade 3-4 group, the elevated FTHR correlated with lower FA and higher GMFCS. CONCLUSIONS: FTHR is a useful quantitative biomarker of ventriculomegaly in preterm newborns. It may help standardize ventricular measurement and direct intervention. IMPACT: The fronto-temporal horn ratio has the potential to become a standardized tool that can provide an actionable measure to direct intervention for post-hemorrhagic ventricular dilation. This current study will provide the basis of a future clinical trial to optimize intervention timing to decrease the risk of white matter injury in this vulnerable population.

Atlanto-occipital ligament calcification: a novel imaging finding in pediatric rotational vertebral artery occlusion.

We describe a 2-year-old girl with bow hunter syndrome complicated by vertebral artery dissection and multiple ischemic infarcts. Pediatric bow hunter syndrome is a rare and likely under-recognized disorder. Interestingly, our patient had atlanto-occipital ligament calcification on CT scan, an imaging finding that has not been reported in association with bow hunter syndrome and one that might help increase recognition of this dynamic disorder of the posterior circulation.

Cerebral Lipid Accumulation Detected by MRS in a Child with Carnitine Palmitoyltransferase 2 Deficiency: A Case Report and Review of the Literature on Genetic Etiologies of Lipid Peaks on MRS.

The majority of lipids in the brain are located in the bilayer membranes. These lipids are not visible by magnetic resonance spectroscopy since they have restricted mobility. Only mobile lipids, such as cholesterol esters or triglycerides in neutral lipid droplets, have enough rotational freedom to generate a signal on spectroscopy. These signals are detected as peaks at 1.3 ppm, originating from the methylene groups in the fatty acid chain, and 0.9 ppm, originating from the distal methyl group. We review the literature on the different genetic conditions that have been found to show lipid peaks on brain spectroscopy and report the first patient with carnitine palmitoyltransferase 2 deficiency shown to have such lipid peaks, thus indicating brain fat accumulation.

Rhabdomyosarcoma of the head and neck in children: review and update.

OBJECTIVE: To review the clinical presentation, histology, staging, treatment modalities, and survival for pediatric head and neck rhabdomyosarcoma (non-orbital). STUDY DESIGN: Retrospective chart review at a tertiary pediatric hospital of children treated over 18 years (1996-2014) for primary head and neck non-orbital rhabdomyosarcoma. METHODS: Medical charts were examined for clinical presentation, staging, histology, genetic abnormalities, treatment modalities, recurrence and complications from treatment. RESULTS: Our cohort was 17 children (7 male, 10 female) with rhabdomyosarcoma with a median age of 6.3 years (range <1-19). The majority of tumors were of parameningeal location (13/17) with embryonal histology (11/17). Twenty-nine percent (5/17) demonstrated advanced metastatic disease at initial referral. Fifty-three percent (9/17) had skull base erosion and/or cranial nerve deficits. PET CT scan was performed in 4 patients. The overall survival was 75% for the duration of the study. Primary surgical excision was performed in all 4 patients with nonparameningeal tumors as compared to only 1 patient with a parameningeal tumor. All received chemotherapy and radiotherapy, as none had completely resectable disease. CONCLUSION: Pediatric non-orbital primary rhabdomyosarcoma of the head and neck usually has a rapid onset and presents with advanced disease. Our analysis found that the majority of patients in our series had a cranial neuropathy at presentation, which highlights how advanced the disease is in these patients at presentation. The first mode of surgical intervention should be directed toward biopsy in junction with a metastatic work-up. Primary excision with negative microscopic margins for nonparameningeal rhabdomyosarcoma is ideal to spare radiotherapy but was not achievable in our cohort. The benefits of second-look biopsy after chemotherapy and radiation are still unproven; however, we believe that it was beneficial in two patients in our review for further resection thus decreasing subsequent radiation. Fluorodeoxy-d-glucose positron emission tomography (PET) to evaluate disease post treatment may further define the role for second look surgery.

Laryngotracheal separation in an infant with severe dysgenesis of the larynx.

OBJECTIVES/HYPOTHESIS: We describe management of an infant with chronic aspiration as a result of severe and rarely described laryngeal dysgenesis. RESULTS: A neonate with severe maldevelopment of the laryngeal structures required tracheostomy for respiratory distress on day-of-life 1, but the patient continued to have aspiration pneumonias. After failing to improve with conservative measures, the infant underwent laryngotracheal separation (LTS), which was successful in preventing aspiration. The patient has had no further pneumonias. CONCLUSIONS: The presented case illustrates that LTS may be considered a safe and effective initial treatment option for chronic aspiration in select infants with severe dysgenesis of the larynx.

Presynaptic regulation of quantal size by the vesicular glutamate transporter VGLUT1.

A fundamental question in synaptic physiology is whether the unitary strength of a synapse can be regulated by presynaptic characteristics and, if so, what those characteristics might be. Here, we characterize a newly proposed mechanism for altering the strength of glutamatergic synapses based on the recently identified vesicular glutamate transporter VGLUT1. We provide direct evidence that filling in isolated synaptic vesicles is subject to a dynamic equilibrium that is determined by both the concentration of available glutamate and the number of vesicular transporters participating in loading. We observe that changing the number of vesicular transporters expressed at hippocampal excitatory synapses results in enhanced evoked and miniature responses and verify biophysically that these changes correspond to an increase in the amount of glutamate released per vesicle into the synaptic cleft. In addition, we find that this modulation of synaptic strength by vesicular transporter expression is endogenously regulated, both across development to coincide with a maturational increase in vesicle cycling and quantal amplitude and by excitatory and inhibitory receptor activation in mature neurons to provide an activity-dependent scaling of quantal size via a presynaptic mechanism. Together, these findings underscore that vesicular transporter expression is used endogenously to directly regulate the extent of glutamate release, providing a concise presynaptic mechanism for controlling the quantal efficacy of excitatory transmission during synaptic refinement and plasticity.

Bayesian estimation of transcript levels using a general model of array measurement noise.

Gene arrays demonstrate a promising ability to characterize expression levels across the entire genome but suffer from significant levels of measurement noise. We present a rigorous new approach to estimate transcript levels and ratios from one or more gene array experiments, given a model of measurement noise and available prior information. The Bayesian estimation of array measurements (BEAM) technique provides a principled method to identify changes in expression level, combine repeated measurements, or deal with negative expression level measurements. BEAM is more flexible than existing techniques, because it does not assume a specific functional form for noise and prior models. Instead, it relies on computational techniques that apply to a broad range of models. We use Affymetrix yeast chip data to illustrate the process of developing accurate noise and prior models from existing experimental data. The resulting noise model includes novel features such as heavy-tailed additive noise and a gene-specific bias term. We also verify that the resulting noise and prior models fit data from an Affymetrix human chip set.

High-resolution iontophoresis for single-synapse stimulation.

We present a technique for stimulating post-synaptic receptors with neurotransmitter locally at a single synapse and with a concentration profile that is comparable to endogenous stimulation. We modify the technique of iontophoresis to use a 0.1 microm electrode tip for local stimulation, and we combine it with fast capacitance compensation to achieve high-speed application from a high-resistance tip. Ejection of fluorescent dye from the electrode shows that transmitter can be limited to the width of a single synapse and to a time scale similar to an endogenous event. The speed and localization of transmitter is confirmed by iontophoretically stimulating single labeled synapses in cultured hippocampal neurons held under voltage clamp. The amount of transmitter ejected is linear and reproducible over a physiologically relevant range, making this technique useful for examining receptor kinetics and receptor insertion/removal. The system should be capable of delivering any charged neurotransmitter, and we show examples using glutamate and GABA. The technique is also combined with computer-controlled manipulation to study the strength and plasticity of multiple synapses in real-time.