Neurosurgical Management of Rubinstein-Taybi Syndrome: An Institutional Experience.

INTRODUCTION: Rubinstein-Taybi syndrome (RTS) is a rare genetic condition with a distinctive set of physical features. This case series reports a single institutional experience of RTS cases, highlighting the role of neurosurgery in the comprehensive management of RTS patients. METHODS: A retrospective review of patients with genetically confirmed RTS presenting between 2010 and 2023 at Children's Hospital of Pittsburgh was performed. Patient demographics, genetic profile, clinical symptoms, radiographic characteristics, and neurosurgical management were recorded for all patients. RESULTS: Twenty-one patients (13 females, 8 males) aged 0 to 22 years presented for formal genetic counseling and diagnosis. Twenty patients (95%) had CREBBP pathogenic variants (RTS type 1), and 1 patient (5%) had EP300 pathogenic variants (RTS type 2). Ten patients (48%) had a low-lying conus medullaris, and 3 patients (30%) underwent subsequent spinal cord detethering. Four patients (19%) had a Chiari malformation, and three (75%) underwent Chiari decompression surgeries. One patient (5%) had Chiari-associated syringomyelia. CONCLUSIONS: RTS patients have an increased rate of tethered cord syndrome requiring detethering. The incidence of symptomatic Chiari I malformation requiring decompression has not been previously reported. The RTS series presented here demonstrates a high incidence of symptomatic Chiari I malformation in addition to tethered cord syndrome.

Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Crop wild relatives of the United States require urgent conservation action.

The contributions of crop wild relatives (CWR) to food security depend on their conservation and accessibility for use. The United States contains a diverse native flora of CWR, including those of important cereal, fruit, nut, oil, pulse, root and tuber, and vegetable crops, which may be threatened in their natural habitats and underrepresented in plant conservation repositories. To determine conservation priorities for these plants, we developed a national inventory, compiled occurrence information, modeled potential distributions, and conducted threat assessments and conservation gap analyses for 600 native taxa. We found that 7.1% of the taxa may be critically endangered in their natural habitats, 50% may be endangered, and 28% may be vulnerable. We categorized 58.8% of the taxa as of urgent priority for further action, 37% as high priority, and 4.2% as medium priority. Major ex situ conservation gaps were identified for 93.3% of the wild relatives (categorized as urgent or high priority), with 83 taxa absent from conservation repositories, while 93.1% of the plants were equivalently prioritized for further habitat protection. Various taxonomic richness hotspots across the US represent focal regions for further conservation action. Related needs include facilitating greater access to and characterization of these cultural-genetic-natural resources and raising public awareness of their existence, value, and plight.

Serial Neuroendoscopic Lavage for the Treatment of Elevated Cerebrospinal Fluid Protein Levels in Infants with Gram-Negative Rod Ventriculitis.

INTRODUCTION: Gram-negative rod (GNR) bacterial ventriculitis is a rare complication of shunt-dependent hydrocephalus, often requiring an extended and invasive treatment course. Accumulation of purulent material, as well as empyema and septation formation, limits circulation of antibiotics and infection clearance. Supplementation of standard care with neuroendoscopic-guided intraventricular lavage with lactated Ringer solution and fenestration of septations may facilitate infection clearance and simplify the eventual shunt construct required. Here, the utility of serial lavage for ventriculitis is described in a population of shunt-dependent neonates and infants at high risk for morbidity and mortality. METHODS: Five infants with shunt-dependent hydrocephalus and subsequent GNR ventriculitis were treated with standard care measures with the addition of serial neuroendoscopic lavage. A retrospective chart review was performed to collect patient characteristics, shunt dependency, and shunt revisions within a year of ventriculitis resolution. RESULTS: Patients demonstrated a mean 74% decrease in cerebrospinal fluid (CSF) protein following each neuroendoscopic lavage and trended toward a shorter time to infection clearance in comparison to previously published literature. Patients required 0-2 shunt revisions at 1-year follow-up following hospitalization for shunt-related ventriculitis (mean 0.8 +/- 0.8). CONCLUSIONS: Serial neuroendoscopic lavage is an effective technique, used alone or in combination with fenestration of septations, to reduce the CSF protein and bacterial load in the treatment of ventriculitis, decreasing time until eradication of infection. Serial lavage may reduce the risk of future shunt malfunction, simplify the future shunt construct, and decrease duration of infection.

The Eyebrow Approach for the Management of Pediatric Frontal Epidural Abscesses Secondary to Diffuse Sinusitis.

BACKGROUND: Minimally invasive approaches to the anterior cranial fossa have evolved over the past few decades. The management of frontal epidural abscesses (EDAs) secondary to diffuse sinusitis in the pediatric population using minimally invasive techniques is scarcely reported in the literature. Herein, we report the utilization of a minimally invasive eyebrow approach for multidisciplinary concurrent evacuation of frontal EDA secondary to diffuse sinusitis and trephination of the frontal sinus in three pediatric patients. CASE REPORTS: Three pediatric patients presented to the emergency room with severe headaches, visual changes, somnolence, and significant facial and periorbital swelling. Imaging revealed diffuse sinusitis with focal frontal epidural extension. In all cases, progressive clinical deterioration along with the radiographic findings mandated urgent surgical intervention. The eyebrow approach allowed for concomitant evacuation of the frontal EDA and trephination of the frontal sinus followed by functional endoscopic sinus surgery in the same setting. All patients tolerated the procedure well with complete resolution of their symptoms at the completion of antibiotic therapy and complete resolution of the EDA. CONCLUSION: The eyebrow approach is a minimally invasive technique that should be considered as part of the armamentarium in the management of select EDA in the pediatric population. It allows for multidisciplinary collaboration between neurosurgeons and otolaryngologists for concomitant evacuation of the EDA and trephination of the frontal sinus. This approach is a feasible, safe, and effective minimally invasive technique that can be employed for the management of EDA secondary to diffuse sinusitis in the pediatric population.

Long-Term Nonclinical Pulmonary Safety Assessment of Afrezza, a Novel Insulin Inhalation Powder.

Afrezza delivers inhaled insulin using the Gen2 inhaler for the treatment of patients with type 1 and type 2 Diabetes. Afrezza was evaluated in long-term nonclinical pulmonary safety studies in 2 toxicology species. Chronic inhalation toxicology studies in rat (26 weeks) and dog (39 weeks) and an inhalation carcinogenicity study in rats were conducted with Technosphere insulin (Afrezza) and with Technosphere alone as a vehicle control. Respiratory tract tissues were evaluated by histopathology and cells expressing proliferating cell nuclear antigen (PCNA) were quantified in lungs of rats. Microscopic findings in rats exposed to Afrezza were attributed to the Technosphere particle component, were confined to nasal epithelia, and consisted of eosinophilic globules and nasal epithelial degeneration. There were no Afrezza-related changes in pulmonary PCNA labeling indices in alveoli, large bronchioles, or terminal bronchioles. Microscopic findings in rats exposed to Technosphere particles included eosinophilic globules, mucus cell hyperplasia, and epithelial degeneration in the nasal cavities. PCNA labeling indices were increased in large bronchioles and terminal bronchioles but not in alveoli. There were no Technosphere particle-related findings in the dog study. Afrezza did not exhibit carcinogenic potential in the 2-year study in rats. These nonclinical inhalation studies support the use of Afrezza in humans over extended periods.

Comparison of Follow-Up Length-Matched Single-Center Myelomeningocele Postnatal Closure Cohort to the Management of Myelomeningocele Study (MOMS) Trial Results.

OBJECTIVE: We sought to compare our large single-institution cohort of postnatal myelomeningocele closure to the 2 arms of the Management of Myelomeningocele Study (MOMS) trial at the designated trial time points, as well as assess outcomes at long-term follow-up among our postnatal cohort. METHODS: A single-institutional retrospective review of myelomeningocele cases presenting from 1995 to 2015 at Children's Hospital of Pittsburgh was performed. We compared outcomes at 12 and 30 months to both arms of the MOMS trial and compared our cohort's outcomes at those designated time points to our long-term outcomes. Univariate statistical analysis was performed as appropriate. RESULTS: One-hundred sixty-three patients were included in this study. All patients had at least 2-year follow-up, with a mean follow-up of 10 years (range 2-20 years). There was no difference in the overall distribution of anatomic level of defect. Compared to our cohort, the prenatal cohort had a higher rate of tethering at 12 months of age, 8 versus 1.8%. Conversely, the Chiari II decompression rate was higher in our cohort (10.4 vs. 1.0%). At 30 months, the prenatal cohort had a higher rate of independent ambulation, but our cohort demonstrated the highest rate of ambulation with or without assistive devices among the 3 groups. When comparing our cohort at these early time points to our long-term follow-up data, our cohort's ambulatory function decreased from 84 to 66%, and the rate of detethering surgery increased almost 10-fold. CONCLUSIONS: This study demonstrated that overall ambulation and anatomic-functional level were significantly better among our large postnatal cohort, as well as having significantly fewer complications to both fetus and mother, when compared to the postnatal cohort of the MOMS trial. Our finding that ambulatory ability declined significantly with age in this patient population is worrisome for the long-term outcomes of the MOMS cohorts, especially given the high rates of cord tethering at early ages within the prenatal cohort. These findings suggest that the perceived benefits of prenatal closure over postnatal closure may not be as substantial as presented in the original trial, with the durability of results still remaining a concern.

Fetal aqueductal stenosis: Prenatal diagnosis and intervention.

Fetal severe central nervous system ventriculomegaly is associated with poor neurologic outcomes, usually driven by a primary malformation, deformation, or disruption of brain parenchyma. In utero shunting of excess cerebrospinal fluid (CSF) in hopes of improving neurologic outcomes was attempted in the 1980s but was abandoned due to perceived lack of effect, likely due to technological limitations of the time that precluded proper patient selection. Little progress on the antenatal management of severe ventriculomegaly has been made in the intervening decades. A multidisciplinary, evidence-based reassessment of ventriculoamniotic shunting for isolated fetal aqueductal stenosis (FAS), a unique form of severe ventriculomegaly (supratentorial intracranial hypertension), is currently underway. An accurate diagnosis of FAS must precede in utero intervention. Magnetic resonance imaging (MRI) will be an excellent adjunct to high-resolution prenatal ultrasound and next-generation genetic testing to correctly diagnose FAS in a timely fashion while excluding other intracranial and extracranial anomalies. This manuscript will briefly discuss the history, current management, and future directions of the prenatal diagnosis and potential intervention for FAS.

Histologic Appearance of Iatrogenic Obstructive Hydrocephalus in the Fetal Lamb Model.

INTRODUCTION: Documentation of histologic findings associated with congenital hydrocephalus in the fetal lamb model is a critical step in evaluating the efficacy of ventriculoamniotic shunting in the human fetus. METHODS: Four fetal sheep had hydrocephalus induced at approximately 95 days' gestation. Two co-twins remained as controls. The ewes were euthanized at term. The lamb brains were fixed in formalin, paraffin-embedded, stained, and analyzed for markers of neuropathology. Astrocytosis, microgliosis, and axonal loss were assessed with immunocytochemistry for glial fibrillary acidic protein, ionized calcium-binding adapter, and neurofilament/amyloid precursor protein, respectively. Cortical gray matter extracellular matrix was assessed with staining for the lectin Wisteria Floribunda agglutinin. RESULTS: Hydrocephalic lamb brains demonstrated deep white matter damage with loss of projecting axonal tracts in regions physically distorted by hydrocephalus, similar to that seen in hydrocephalic humans. There was no evidence of abnormal neocortical neuronal migration; however, there was evidence for delayed maturation of the neocortical gray matter, possibly from increased intracerebral pressure and subsequent ischemia. Control lamb brains demonstrated none of the above findings. CONCLUSION: This histological approach can be used to further define the mechanism of brain damage associated with hydrocephalus and interpret the efficacy of ventriculoamniotic shunting on fetal lamb brain neuroanatomy.

Identification and Characterization of Circulating Tumor Cells in Men Who have Undergone Prostatectomy for Clinically Localized, High Risk Prostate Cancer.

PURPOSE: Approximately 15% of men with newly diagnosed prostate cancer have high risk features which increase the risk of recurrence and metastasis. Better predictive biomarkers could allow for earlier detection of biochemical recurrence and change surveillance and adjuvant treatment paradigms. Circulating tumor cells are thought to represent the earliest form of metastases. However, their role as biomarkers in men with high risk, localized prostate cancer is not well defined. MATERIALS AND METHODS: Two to 5 months after prostatectomy we obtained blood samples from 37 patients with high risk, localized prostate cancer, defined as stage T3a or higher, Gleason score 8 or greater, or prostate specific antigen 20 ng/ml or greater. Circulating tumor cells were enumerated using a commercial platform. Matched tumor and single circulating tumor cell sequencing was performed. RESULTS: Circulating tumor cells were detected in 30 of 37 samples (81.1%) with a median of 2.4 circulating tumor cells per ml (range 0 to 22.9). Patients with detectable circulating tumor cells showed a trend toward shorter recurrence time (p=0.12). All patients with biochemical recurrence had detectable circulating tumor cells. Androgen receptor over expression was detected in 7 of 37 patients (18.9%). Patients with biochemical recurrence had more circulating tumor cell copy number aberrations (p=0.027). Matched tumor tissue and single circulating tumor cell sequencing revealed heterogeneity. CONCLUSIONS: We noted a high incidence of circulating tumor cell detection after radical prostatectomy and shorter time to biochemical recurrence in men with a higher circulating tumor cell burden and more circulating tumor cell copy number aberrations. Genomic alterations consistent with established copy number aberrations in prostate cancer were detectable in circulating tumor cells but often discordant with cells analyzed in bulk from primary lesions. With further testing in appropriately powered cohorts early circulating tumor cell detection could be an informative biomarker to assist with adjuvant treatment decisions.

Is Schimmelpenning Syndrome Associated with Intracranial Tumors? A Case Report.

Schimmelpenning syndrome is a rare, well-defined constellation of clinical phenotypes associated with the presence of nevus sebaceous and multisystem abnormalities most commonly manifested as cerebral, ocular, and skeletal defects [1]. A single nucleotide mutation in the HRAS or KRAS genes resulting in genetic mosaicism is responsible for the clinical manifestations of this syndrome in the majority of cases. We report a case of an adolescent boy with Schimmelpenning syndrome with a multifocal pilocytic astrocytoma. No HRAS or KRAS gene mutations were noted in the tumor on genetic sequencing. However, glial tumors have been associated with genetic mutations of RAS upregulation, which may imply a common pathway.

Intracranial Myxoid Mesenchymal Tumor with Rare EWSR1-CREM Translocation.

Translocations between EWSR1 and members of the CREB family of transcription factors (CREB1, ATF1, and CREM) are rare genetic findings occurring in various sarcomas. Of these, the EWSR1-CREM translocation is the most rarely reported. We present the case of a 9-year-old boy who presented with a year of fatigue, weight loss, and abulia. A brain MRI revealed a frontal interhemispheric tumor arising from the falx. After resection, pathology demonstrated a myxoid mesenchymal tumor with an EWSR1-CREM translocation. A series of recent reports of similar tumors has generated ongoing debate in the literature over the classification of these tumors either as intracranial angiomatoid fibrous histiocytomas, which also harbor EWSR1-CREB family translocations, or as a novel diagnostic entity. The present case provides another example of the rare EWSR1-CREM fusion in an intracranial myxoid mesenchymal tumor that recurred in just 6 months despite gross total resection. The findings are discussed in the context of the existing literature and the ongoing effort to appropriately classify this type of tumor.

Phenotypic changes and DNA methylation status in cryopreserved seeds of rye (Secale cereale L.).

Conserving genetic diversity is a major priority of the National Laboratory for Genetic Resources Preservation (NLGRP), operated by the U.S. Department of Agriculture, Agricultural Research Service. There are two long-term preservation methods employed in the NLGRP: storage in a -18 °C freezer (conventional storage) and storage in liquid nitrogen vapor phase at -135 to -180 °C (cryopreservation). To test the phenotypic and epigenetic effects of long-term cryopreservation of orthodox seeds, we evaluated 40 cereal rye accessions (20 spring habit and 20 winter habit) stored for 25 years under both conventional storage and cryogenic conditions. In laboratory evaluations of winter habit rye, seeds from cryopreserved samples had significantly higher normal germination percentage (P < 0.05) and lower abnormal germination percentage (P < 0.05) than those stored under conventional conditions. Cryopreserved spring habit rye also had higher normal germination percentage (P < 0.01) than conventionally stored samples. In addition, winter rye seedlings from cryopreserved seeds had longer roots and smaller root diameter (P < 0.05) than seedlings from conventionally stored seeds. In field evaluations conducted in Fort Collins, Colorado in 2014-15, spikes of plants grown from conventionally stored seeds of the winter accessions were slightly longer than those from cryopreserved seeds (P = 0.045). To detect DNA methylation changes, a methylation-sensitive amplified fragment length polymorphism (metAFLP) technique was applied to two accessions. After false discovery rate adjustment, no differences in methylation were detected between storage treatments on an individual locus basis. Our study indicated that cryopreservation slowed seed deterioration as evidenced by higher germination rates compared to conventional storage, had only minimal effects on other phenotypic traits, and had no significant effects on DNA methylation status.

Case Series: Pediatric Shunt Tunnel Catheter Infection.

Shunt infections are common pediatric neurosurgical cases with high morbidity that almost always requires surgical removal of the shunt, external ventricular drain placement, and delayed shunt replacement. Tunnel infections are well-described clinical entities occurring with indwelling catheters, whereby the indwelling tunnel portion of a line becomes externally infected with a sterile central lumen. These infections are typically treated with line replacement or antibiotics depending on clinical circumstances. We describe 2 cases of shunt tunnel infection. Both cases presented as erythema over the thoracic portion of the shunt without signs of CNS infection, with only a remote history of shunt surgery and no recent systemic illness. One case was treated with a course of antibiotics, and the other with surgical removal and eventual replacement. Both children made full recoveries. Our case series juxtaposes 2 alternative successful strategies for treating the rare entity of shunt tunnel infection.

The Use of External Ventricular Drainage to Reduce the Frequency of Wound Complications in Myelomeningocele Closure.

INTRODUCTION: Myelomeningocele (MMC) is an open neural tube defect routinely surgically closed within 48 h of birth to prevent secondary infection. Up to 18% of patients experience wound complications, and 85% require shunting for hydrocephalus. We hypothesized that wound complications could be reduced by cerebrospinal fluid (CSF) diversion at the time of closure. METHODS: Institutional review board approval was obtained to review records of the 88 patients who underwent MMC closure between January 2005 and June 2016 at the Children's Hospital of Pittsburgh. Twenty-three patients (26%) had an external ventricular drain (EVD) placed at the time of MMC closure and underwent 7-11 days of CSF drainage. Fourteen patients (16%) had a shunt placed at the time of MMC closure, and 51 (58%) had no form of CSF diversion at the time of MMC closure. RESULTS: Patients with an EVD or shunt placed at the time of closure had no wound complications. In contrast, 8 patients (16%) without CSF diversion at closure developed wound complications (p = 0.048). Seven of the 8 wound complications occurred in the 71 patients with evidence of hydrocephalus at birth (p = 0.98). Of patients with evidence of hydrocephalus at the time of MMC closure, wound complications had a higher rate of occurrence among patients who did not receive a shunt or EVD at closure (p = 0.01). When comparing only patients with evidence of hydrocephalus at birth, the EVD group alone had a lower rate of wound complications than patients who did not receive CSF diversion at the time of closure (p = 0.031). CONCLUSIONS: These results suggest that addressing hydrocephalus at the time of MMC closure significantly reduces the likelihood of wound complications and may justify temporary CSF diversion at birth, at least in those patients manifesting hydrocephalus.

Drosophila Lipin interacts with insulin and TOR signaling pathways in the control of growth and lipid metabolism.

Lipin proteins have key functions in lipid metabolism, acting as both phosphatidate phosphatases (PAPs) and nuclear regulators of gene expression. We show that the insulin and TORC1 pathways independently control functions of Drosophila Lipin (dLipin). Reduced signaling through the insulin receptor strongly enhanced defects caused by dLipin deficiency in fat body development, whereas reduced signaling through TORC1 led to translocation of dLipin into the nucleus. Reduced expression of dLipin resulted in decreased signaling through the insulin-receptor-controlled PI3K-Akt pathway and increased hemolymph sugar levels. Consistent with this, downregulation of dLipin in fat body cell clones caused a strong growth defect. The PAP but not the nuclear activity of dLipin was required for normal insulin pathway activity. Reduction of other enzymes of the glycerol-3 phosphate pathway affected insulin pathway activity in a similar manner, suggesting an effect that is mediated by one or more metabolites associated with the pathway. Taken together, our data show that dLipin is subject to intricate control by the insulin and TORC1 pathways, and that the cellular status of dLipin impacts how fat body cells respond to signals relayed through the PI3K-Akt pathway.

Pitx2-microRNA pathway that delimits sinoatrial node development and inhibits predisposition to atrial fibrillation.

The molecular mechanisms underlying atrial fibrillation, the most common sustained cardiac arrhythmia, remain poorly understood. Genome-wide association studies uncovered a major atrial fibrillation susceptibility locus on human chromosome 4q25 in close proximity to the paired-like homeodomain transcription factor 2 (Pitx2) homeobox gene. Pitx2, a target of the left-sided Nodal signaling pathway that initiates early in development, represses the sinoatrial node program and pacemaker activity on the left side. To address the mechanisms underlying this repressive activity, we hypothesized that Pitx2 regulates microRNAs (miRs) to repress the sinoatrial node genetic program. MiRs are small noncoding RNAs that regulate gene expression posttranscriptionally. Using an integrated genomic approach, we discovered that Pitx2 positively regulates miR-17-92 and miR-106b-25. Intracardiac electrical stimulation revealed that both miR-17-92 and miR-106b-25 deficient mice exhibit pacing-induced atrial fibrillation. Furthermore electrocardiogram telemetry revealed that mice with miR-17-92 cardiac-specific inactivation develop prolonged PR intervals whereas mice with miR-17-92 cardiac-specific inactivation and miR-106b-25 heterozygosity develop sinoatrial node dysfunction. Both arrhythmias are risk factors for atrial fibrillation in humans. Importantly, miR-17-92 and miR-106b-25 directly repress genes, such as Shox2 and Tbx3, that are required for sinoatrial node development. Together, to our knowledge, these findings provide the first genetic evidence for an miR loss-of-function that increases atrial fibrillation susceptibility.

Sigma receptors [σRs]: biology in normal and diseased states.

This review compares the biological and physiological function of Sigma receptors [σRs] and their potential therapeutic roles. Sigma receptors are widespread in the central nervous system and across multiple peripheral tissues. σRs consist of sigma receptor one (σ1R) and sigma receptor two (σ2R) and are expressed in numerous regions of the brain. The sigma receptor was originally proposed as a subtype of opioid receptors and was suggested to contribute to the delusions and psychoses induced by benzomorphans such as SKF-10047 and pentazocine. Later studies confirmed that σRs are non-opioid receptors (not an µ opioid receptor) and play a more diverse role in intracellular signaling, apoptosis and metabolic regulation. σ1Rs are intracellular receptors acting as chaperone proteins that modulate Ca2+ signaling through the IP3 receptor. They dynamically translocate inside cells, hence are transmembrane proteins. The σ1R receptor, at the mitochondrial-associated endoplasmic reticulum membrane, is responsible for mitochondrial metabolic regulation and promotes mitochondrial energy depletion and apoptosis. Studies have demonstrated that they play a role as a modulator of ion channels (K+ channels; N-methyl-d-aspartate receptors [NMDAR]; inositol 1,3,5 triphosphate receptors) and regulate lipid transport and metabolism, neuritogenesis, cellular differentiation and myelination in the brain. σ1R modulation of Ca2+ release, modulation of cardiac myocyte contractility and may have links to G-proteins. It has been proposed that σ1Rs are intracellular signal transduction amplifiers. This review of the literature examines the mechanism of action of the σRs, their interaction with neurotransmitters, pharmacology, location and adverse effects mediated through them.

The impact of mode of delivery on infant neurologic outcomes in myelomeningocele.

BACKGROUND: Controversy exists regarding the optimal route of delivery for fetuses who are diagnosed prenatally with myelomeningocele. Current recommendations are based partly on antiquated studies with questionable methods. All studies that have been published to date suffer from nonstandardized outcome measures, selection bias, and small sample size. The larger studies are >15 years old. OBJECTIVE: The purpose of this study was to provide information for evidence-based decision-making regarding the impact of route of delivery on motor outcomes for pediatric patients with prenatally were diagnosed myelomeningocele in a well-defined retrospective cohort. STUDY DESIGN: Medical records were reviewed retrospectively for all neonates who had been diagnosed with a myelomeningocele at birth from 1995-2015 within the University of Pittsburgh Medical Center system, as identified through the Children's Hospital of Pittsburgh Neurosurgery Department operative database. Records were matched with maternal records with the use of the Center for Assistance in Research that used eRecord. Data from 72 maternal-neonatal pairs were analyzed for multiple variables. The primary outcome measure was the difference between the functional and anatomic motor levels in the child at the age of 2 years, stratified by mode of delivery and presence or absence of labor. The sample size necessary to detect a difference between the groups with power of 0.8 and significance of .05 was calculated to be 52 subjects total (26 per group). RESULTS: Functional levels were slightly better than predicted by anatomic levels for all pediatric patient groups, regardless of mode of delivery or presence of labor. Anatomic levels were slightly lower (better), and defects were smaller for those infants who underwent vaginal delivery or a trial of labor, likely attributable to selection bias. Attempts to correct for this selection bias did not change the results. No other outcomes that were analyzed were associated significantly with mode of delivery or presence of labor. CONCLUSION: No benefit to motor function from delivery by cesarean section or avoidance of labor was demonstrated statistically in this mother-infant cohort.