Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution.

INTRODUCTION: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution's experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children's National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. CONCLUSION: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

FKBP38 Regulates Self-Renewal and Survival of GBM Neurospheres.

Glioblastoma is the most common malignant primary brain tumor. The outcome is dismal, despite the multimodal therapeutic approach that includes surgical resection, followed by radiation and chemotherapy. The quest for novel therapeutic targets to treat glioblastoma is underway. FKBP38, a member of the immunophilin family of proteins, is a multidomain protein that plays an important role in the regulation of cellular functions, including apoptosis and autophagy. In this study, we tested the role of FKBP38 in glioblastoma tumor biology. Expression of FKBP38 was upregulated in the patient-derived primary glioblastoma neurospheres (GBMNS), compared to normal human astrocytes. Attenuation of FKBP38 expression decreased the viability of GBMNSs and increased the caspase 3/7 activity, indicating that FKBP38 is required for the survival of GBMNSs. Further, the depletion of FKBP38 significantly reduced the number of neurospheres that were formed, implying that FKBP38 regulates the self-renewal of GBMNSs. Additionally, the transient knockdown of FKBP38 increased the LC3-II/I ratio, suggesting the induction of autophagy with the depletion of FKBP38. Further investigation showed that the negative regulation of autophagy by FKBP38 in GBMNSs is mediated through the JNK/C-Jun-PTEN-AKT pathway. In vivo, FKBP38 depletion significantly extended the survival of tumor-bearing mice. Overall, our results suggest that targeting FKBP38 imparts an anti-glioblastoma effect by inducing apoptosis and autophagy and thus can be a potential therapeutic target for glioblastoma therapy.

Healthcare disparities in pediatric neurosurgery: a scoping review.

OBJECTIVE: The aim of this scoping review was to identify relevant articles that have contributed to the body of knowledge describing pediatric neurosurgical healthcare disparities. Identifying healthcare disparities in pediatric neurosurgery is essential to understanding how to best provide care for this unique patient population. Although it is undoubtedly important to increase the knowledge of pediatric neurosurgical healthcare disparities, it is also important to understand the current state of the literature. METHODS: This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. The search terms "pediatric neurosurgical disparities" and "pediatric neurosurgical inequities" were entered into the following databases: PubMed, Scopus, and Embase. RESULTS: The initial database search returned a total of 366 results from the PubMed, Embase, and Scopus databases. One hundred thirty-seven duplicates were removed, and the remaining articles were screened by title and abstract. Articles were excluded on the basis of the inclusion and exclusion criteria. Of the remaining 229 articles, 168 were excluded. Sixty-one full-text articles were then examined for eligibility, and 28 did not reach the specified inclusion and exclusion criteria. The remaining 33 articles were included for final review. The results of the reviewed studies were stratified on the basis of disparity type. CONCLUSIONS: Although there has been an increase in the number of publications discussing pediatric neurosurgical healthcare disparities within the last decade, there still remains a scarcity of information regarding healthcare disparities in neurosurgery. Furthermore, less information exists that specifically addresses healthcare disparities in the pediatric population.

The Use of Carbon Fiber-Reinforced Instrumentation in Patients with Spinal Oncologic Tumors: A Systematic Review of Literature and Future Directions.

INTRODUCTION: Metastatic spine tumors affect over 30% of patients who have been diagnosed with cancer. While techniques in surgical intervention have undoubtedly evolved, there are some pitfalls when spinal instrumentation is required for stabilization following tumor resection. However, the use of carbon fiber-reinforced polyetheretherketone (CFR-PEEK) implants has become increasingly popular due to improved radiolucency and positive osteobiologic properties. Here, we present a systematic review describing the use of CFR-PEEK-coated instrumentation in the oncologic population while identifying advantages and potential shortcomings of these devices. METHODS: In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted in March 2022 to identify articles detailing the use of CFR-PEEK implants for spinal instrumentation in patients with primary and secondary spine tumors. The search was performed using the PubMed, Scopus, and Embase databases. RESULTS: An initial search returned a total of 85 articles among the three databases used. After the exclusion of duplicates and screening of abstracts, 21 full-text articles were examined for eligibility. Eleven articles were excluded due to not fitting our inclusion and exclusion criteria. Ten articles were subsequently eligible for full-text review. CONCLUSIONS: CFR-PEEK possesses a similar safety and efficacy profile to titanium implants but has distinct advantages. It limits artifact, increases early detection of local tumor recurrence, increases radiotherapy dose accuracy, and is associated with low complication rates (9.96%)-making it a promising alternative for the demands unique to the treatment/outcome of spinal oncologic patients.

Targeting protein arginine methyltransferase 5 sensitizes glioblastoma to trametinib.

Background: The prognosis of glioblastoma (GBM) remains dismal because therapeutic approaches have limited effectiveness. A new targeted treatment using MEK inhibitors, including trametinib, has been proposed to improve GBM therapy. Trametinib had a promising preclinical effect against several cancers, but its adaptive treatment resistance precluded its clinical translation in GBM. Previously, we have demonstrated that protein arginine methyltransferase 5 (PRMT5) is upregulated in GBM and its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. We tested whether inhibition of PRMT5 can enhance the efficacy of trametinib against GBM. Methods: Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot were analyzed. In vivo, NSG mice were intracranially implanted with PRMT5-intact and -depleted GBMNS, treated with trametinib by daily oral gavage, and observed for tumor progression and mice survival rate. Results: PRMT5 depletion enhanced trametinib-induced cytotoxicity in GBMNS. PRMT5 knockdown significantly decreased trametinib-induced AKT and ERBB3 escape pathways. However, ERBB3 inhibition alone failed to block trametinib-induced AKT activity suggesting that the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib-treated GBMNS resulted from AKT inhibition and not ERBB3 inhibition. In orthotopic murine xenograft models, PRMT5-depletion extended the survival of tumor-bearing mice, and combination with trametinib further increased survival. Conclusion: Combined PRMT5/MEK inhibition synergistically inhibited GBM in animal models and is a promising strategy for GBM therapy.

Myelomeningocele Including Fetal Prescription.

Myelomeningocele (MMC) is one of the most common birth defects, affecting 0.2 to 0.4 per 1,000 live births in the United States. The most strongly associated risk factor is low folate level in pregnancy. For this reason, 0.4- to 1.0-mg supplementation with folic acid is recommended in all pregnancies, and high-risk pregnancies are recommended to supplement with 4.0 mg of folic acid daily. The mechanism behind the development of MMC is believed to be failure of the caudal end of the neural tube to close during primary neurulation. Screening for MMC is achieved by using α-fetoprotein levels in maternal serum or amniocentesis in the first and second trimesters of pregnancy. Ultrasonography and fetal magnetic resonance imaging are used to confirm the presence of MMC as well as the location and size of the defect. Based on the results of the Management of Myelomeningocele Study, fetal repair is performed between 23 weeks and 25 weeks and 6 days of gestational age for appropriate candidates. Postnatal repair is more common and is performed 24 to 72 hours after birth. In general, patients with lesions at lower anatomical levels have a better prognosis. Most children with MMC will have neurogenic bladder and bowel dysfunction that affect the patient's and the caregiver's quality of life. Patients with higher levels of mobility, better familial support, and higher economic status report improved quality of life compared with other patients with MMC.

Use of an External Ventricular Drain for Treatment of a Thoracolumbar Cerebrospinal Fluid Leak: A Case Report and Review of Literature.

Post-operative cerebrospinal fluid (CSF) leak is a known complication in spine surgery. This mostly iatrogenic issue is typically treated using a variety of modalities (i.e., bed rest, epidural patch), CSF diversion methods, or primary repair. The use of an external ventricular drain to treat this post-operative complication has been infrequently reported. We describe a case of a CSF leak after thoraco-lumbar surgery treated using an external ventricular drain and a review of the literature regarding this treatment modality. A 70-year-old man presented to our clinic with a recent diagnosis of multiple myeloma with progressive thoracic kyphosis and spinal stenosis. He developed progressive neurological deficits over the course of several weeks. Radiological studies showed significant thoracic kyphosis and severe cord compression in the thoraco-lumbar area. The patient underwent a T9-L4 posterior instrumentation and fusion with decompression surgery that developed post-operative wound infection and a CSF leak. An external ventricular drain (EVD) was used successfully as a CSF diversion method where direct thoracolumbar approaches were not feasible. Given the effectiveness of EVD placement in treating this post-operative complication, we concluded that the use of an EVD can be a potentially safe and effective way to treat thoracolumbar CSF leakage when lumbar or cervical drainage is not feasible.

Non-invasive in situ Visualization of the Murine Cranial Vasculature.

Understanding physiologic and pathologic central nervous system function depends on our ability to map the entire in situ cranial vasculature and neurovascular interfaces. To accomplish this, we developed a non-invasive workflow to visualize murine cranial vasculature via polymer casting of vessels, iterative sample processing and micro-computed tomography, and automatic deformable image registration, feature extraction, and visualization. This methodology is applicable to any tissue and allows rapid exploration of normal and altered pathologic states.

Immunotherapeutic treatments for spinal and peripheral nerve tumors: a primer.

OBJECTIVE: Spinal and peripheral nerve tumors are a heterogeneous group of neoplasms that can be associated with significant morbidity and mortality despite the current standard of care. Immunotherapy is an emerging therapeutic option to improve the prognoses of these tumors. Therefore, the authors sought to present an updated and unifying review on the use of immunotherapy in treating tumors of the spinal cord and peripheral nerves, including a discussion on mechanism of action, drug delivery, current treatment techniques, and preclinical and clinical studies. METHODS: Current data in the literature regarding immunotherapy were collated and summarized. Targeted tumors included primary and secondary spinal tumors, as well as peripheral nerve tumors. RESULTS: Four primary modalities of immunotherapy (CAR T cell, monoclonal antibody, viral, and cytokine) have been reported to target spine and peripheral nerve tumors. Of the primary spinal tumors, spinal cord astrocytomas had the most preclinical evidence supporting immunotherapy success with CAR T-cell therapy targeting the H3K27M mutation, whereas spinal schwannomas and ependymomas had the most evidence reported for monoclonal antibody therapy preclinically. Of the secondary spinal tumors, primary CNS lymphomas demonstrated some clinical response to immunotherapy, whereas multiple myeloma and bone tumor experiences with immunotherapy were largely limited to concept only. Within peripheral nerve tumors, the use of immunotherapy to treat neurofibromas in the setting of syndromes has been suggested in theory, and possible immunotherapeutic targets have been identified in malignant peripheral nerve tumors. To date, there have been 2 clinical trials involving spine tumors and 2 clinical trials involving peripheral nerve tumors that have reported results, all of which are promising but require validation. CONCLUSIONS: Immunotherapy to treat spinal and peripheral nerve tumors has become an emerging area of research and interest. A large amount of preclinical data supporting the translation of this therapy into practice, aimed at ameliorating the poor prognoses of specific tumors, have been reported. Future clinical studies for translation will focus on the optimal therapy type and administration route to best target these tumors, which often preclude total surgical resection given their proximity to the neural and vascular elements of the spine.

Cervical intramedullary teratoma: a case report and systematic review of the literature.

Here, we report a case of a 3-year-old female who presented to clinic with an enlarging mass in the posterior cervical midline. The mass was present since birth and demonstrated no cutaneous stigmata. Plain film, CT, and MRI of the cervical spine (C3-C5) revealed enlargement of the spinal canal, soft tissue calcification, spinal dysraphism, and an intramedullary, predominantly fatty, mass. The mass had associated calcifications and a highly proteinaceous cyst. Surgical resection of the spinal lesion was subsequently performed. Histopathological evaluation revealed a mature teratoma. Cervical spinal teratomas in the pediatric population are rare entities with few cases currently reported in the literature. We conducted a systematic review to outline the current evidence detailing cases of intramedullary spinal cord teratomas. Six articles were included for final review. All patients in the included articles underwent maximal surgical resection with one patient also receiving chemotherapy and radiation. With our report, we aim to add to the literature on cervical intramedullary spinal cord teratomas in the pediatric population.

Flexible thecoscopy for extensive spinal arachnoiditis.

OBJECTIVE: Chronic adhesive spinal arachnoiditis (SA) is a complex disease process that results in spinal cord tethering, CSF flow blockage, intradural adhesions, spinal cord edema, and sometimes syringomyelia. When it is focal or restricted to fewer than 3 spinal segments, the disease responds well to open surgical approaches. More extensive arachnoiditis extending beyond 4 spinal segments has a much worse prognosis because of less adequate removal of adhesions and a higher propensity for postoperative scarring and retethering. Flexible neuroendoscopy can extend the longitudinal range of the surgical field with a minimalist approach. The authors present a cohort of patients with severe cervical and thoracic arachnoiditis and myelopathy who underwent flexible endoscopy to address arachnoiditis at spinal segments not exposed by open surgical intervention. These observations will inform subsequent efforts to improve the treatment of extensive arachnoiditis. METHODS: Over a period of 3 years (2017-2020), 10 patients with progressive myelopathy were evaluated and treated for extensive SA. Seven patients had syringomyelia, 1 had spinal cord edema, and 2 had spinal cord distortion. Surgical intervention included 2- to 5-level thoracic laminectomy, microscopic lysis of adhesions, and then lysis of adhesions at adjacent spinal levels performed using a rigid or flexible endoscope. The mean follow-up was 5 months (range 2-15 months). Neurological function was examined using standard measures. MRI was used to assess syrinx resolution. RESULTS: The mean length of syringes was 19.2 ± 10 cm, with a mean maximum diameter of 7.0 ± 2.9 mm. Patients underwent laminectomies averaging 3.7 ± 0.9 (range 2-5) levels in length followed by endoscopy, which expanded exposure by an average of another 2.4 extra segments (6.1 ± 4.0 levels total). Endoscopic dissection of extensive arachnoiditis in the dorsal subarachnoid space proceeded through a complex network of opaque arachnoidal bands and membranes bridging from the dorsal dura mater to the spinal cord. In less severely problematic areas, the arachnoid membrane was transparent and attached to the spinal cord through multifocal arachnoid adhesions bridging the subarachnoid space. The endoscope did not compress or injure the spinal cord. CONCLUSIONS: Intrathecal endoscopy allowed visual assessment and safe removal of intradural adhesions beyond the laminectomy margins. Further development of this technique should improve its effectiveness in opening the subarachnoid space and untethering the spinal cord in cases of extensive chronic adhesive SA.

Spinal anesthesia in awake surgical procedures of the lumbar spine: a systematic review and meta-analysis of 3709 patients.

OBJECTIVE: Awake surgery has previously been found to improve patient outcomes postoperatively in a variety of procedures. Recently, multiple groups have investigated the utility of this modality for use in spine surgery. However, few current meta-analyses exist comparing patient outcomes in awake spinal anesthesia with those in general anesthesia. Therefore, the authors sought to present an updated systematic review and meta-analysis investigating the utility of spinal anesthesia relative to general anesthesia in lumbar procedures. METHODS: Following a comprehensive literature search of the PubMed and Cochrane databases, 14 clinical studies were included in our final qualitative and quantitative analyses. Of these studies, 5 investigated spinal anesthesia in lumbar discectomy, 4 discussed lumbar laminectomy, and 2 examined interbody fusion procedures. One study investigated combined lumbar decompression and fusion or decompression alone. Two studies investigated patients who underwent discectomy and laminectomy, and 1 study investigated a series of patients who underwent transforaminal lumbar interbody fusion, posterolateral fusion, or decompression. Odds ratios, mean differences (MDs), and 95% confidence intervals were calculated where appropriate. RESULTS: A meta-analysis of the total anesthesia time showed that time was significantly less in patients who received spinal anesthesia for both lumbar discectomies (MD -26.53, 95% CI -38.16 to -14.89; p = 0.00001) and lumbar laminectomies (MD -11.21, 95% CI -19.66 to -2.75; p = 0.009). Additionally, the operative time was significantly shorter in patients who underwent spinal anesthesia (MD -14.94, 95% CI -20.43 to -9.45; p < 0.00001). Similarly, when analyzing overall postoperative complication rates, patients who received spinal anesthesia were significantly less likely to experience postoperative complications (OR 0.29, 95% CI 0.16-0.53; p < 0.0001). Furthermore, patients who received spinal anesthesia had significantly lower postoperative pain scores (MD -2.80, 95% CI -4.55 to -1.06; p = 0.002). An identical trend was seen when patients were stratified by lumbar procedures. Patients who received spinal anesthesia were significantly less likely to require postoperative analgesia (OR 0.06, 95% CI 0.02-0.25; p < 0.0001) and had a significantly shorter hospital length of stay (MD -0.16, 95% CI -0.29 to -0.03; p = 0.02) and intraoperative blood loss (MD -52.36, 95% CI -81.55 to -23.17; p = 0.0004). Finally, the analysis showed that spinal anesthesia cost significantly less than general anesthesia (MD -226.14, 95% CI -324.73 to -127.55; p < 0.00001). CONCLUSIONS: This review has demonstrated the varying benefits of spinal anesthesia in awake spine surgery relative to general anesthesia in patients who underwent various lumbar procedures. The analysis has shown that spinal anesthesia may offer some benefits when compared with general anesthesia, including reduction in the duration of anesthesia, operative time, total cost, and postoperative complications. Large prospective trials will elucidate the true role of this modality in spine surgery.

The role of an anterior approach in the treatment of ankylosing spondylitis-associated cervical fractures: a systematic review and meta-analysis.

OBJECTIVE: Cervical fractures in patients with ankylosing spondylitis can have devastating neurological consequences. Currently, several surgical approaches are commonly used to treat these fractures: anterior, posterior, and anterior-posterior. The relative rarity of these fractures has limited the ability of surgeons to objectively determine the merits of each. The authors present an updated systematic review and meta-analysis investigating the utility of anterior surgical approaches relative to posterior and anterior-posterior approaches. METHODS: After a comprehensive literature search of the PubMed, Cochrane, and Embase databases, 7 clinical studies were included in the final qualitative and 6 in the final quantitative analyses. Of these studies, 6 compared anterior approaches with anterior-posterior and posterior approaches, while 1 investigated only an anterior approach. Odds ratios and 95% confidence intervals were calculated where appropriate. RESULTS: A meta-analysis of postoperative neurological improvement revealed no statistically significant differences in gross rates of neurological improvement between anterior and posterior approaches (OR 0.40, 95% CI 0.10-1.59; p = 0.19). However, when analyzing the mean change in neurological function, patients who underwent anterior approaches had a significantly lower mean change in postoperative neurological function relative to patients who underwent posterior approaches (mean difference [MD] -0.60, 95% CI -0.76 to -0.45; p < 0.00001). An identical trend was seen between anterior and anterior-posterior approaches; there were no statistically significant differences in gross rates of neurological improvement (OR 3.05, 95% CI 0.84-11.15; p = 0.09). However, patients who underwent anterior approaches experienced a lower mean change in neurological function relative to anterior-posterior approaches (MD -0.46, 95% CI -0.60 to -0.32; p < 0.00001). There were no significant differences in complication rates between anterior approaches, posterior approaches, or anterior-posterior approaches, although complication rates trended lower in patients who underwent anterior approaches. CONCLUSIONS: The results of this review and meta-analysis demonstrated the varying benefits of anterior approaches relative to posterior and anterior-posterior approaches in treatment of cervical fractures associated with ankylosing spondylitis. While reports demonstrated lower degrees of neurological improvement in anterior approaches, they may benefit patients with less-severe injuries if lower complication rates are desired.

Stereo-electroencephalography (SEEG) in pediatric epilepsy: Utility in children with and without prior epilepsy surgery failure.

BACKGROUND: When noninvasive modalities fail to adequately localize the seizure onset zone (SOZ) in children with medically refractory epilepsy, invasive interrogation with stereo-electroencephalography (SEEG) or subdural electrodes may be required. Our center utilizes SEEG for invasive monitoring in a carefully selected population of children, many of whom have seizures despite a prior surgical resection. We describe the cohort of patients who underwent SEEG in the first 5 years of its employment in our institution, almost half of which had a history of a failed epilepsy surgery. METHODS: We retrospectively reviewed the records of the first 44 consecutive children who underwent SEEG at Nicklaus Children's Hospital (Miami, Florida), a large, level 4 epilepsy referral center. Patient demographic, clinical, radiographic, and electrophysiological information was collected prospectively. Student's t-test was used for sampling of means and analysis of variance (ANOVA) for evaluation of variance beyond 2 means; chi-square test of independence was used to assess the relationship between categorical variables. RESULTS: There were 44 patients in this cohort, of whom 17 (38.6 %) were male. The mean age of seizure onset was 6.2 years. Twenty-one patients (47.7 %) had previously failed an epilepsy surgery. Patients with a history of prior epilepsy surgery failure were older at SEEG implantation (17.6 vs. 13.7 years; p = 0.043), were more likely to have SEEG for identification of resection margins (9 vs. 4; p = 0.034), and had fewer electrodes placed (5.9 vs. 7.5; p = 0.016). No difference was seen in complication rates between groups with only 3/297 electrodes placed associated with complications, all of which were minor. Post-SEEG, 29 (65.9 %) patients underwent focal resection, 7 patients had VNS insertion, 3 underwent RNS placement, and 5 had no further intervention. The majority of patients that underwent resection in both groups experienced an improvement in seizures (Engel class I-III), reported by 13/15 (86.7 %) in those naive to surgery and 10/14 (71.4 %) in those with prior surgical failure. Seizure-freedom was much lower in those with prior epilepsy surgery, seen in only 4/14 (28.6 %) versus 8/15 (53.3 %). CONCLUSION: Our data supports current literature on SEEG as a safe and effective method of electrophysiological evaluation in children naive to surgery and adds that it is a safe technique in children with a history of failed epilepsy surgery. There was no difference in complication rates, which were <1 % in both groups. A favorable outcome was seen in the majority of patients in both groups; the seizure freedom rate, however, was much lower in those with prior epilepsy surgery.

Tentorial venous anatomy of mice and humans.

We recently described a transtentorial venous system (TTVS), which to our knowledge was previously unknown, connecting venous drainage throughout the brain in humans. Prior to this finding, it was believed that the embryologic tentorial plexus regresses, resulting in a largely avascular tentorium. Our finding contradicted this understanding and necessitated further investigation into the development of the TTVS. Herein, we sought to investigate mice as a model to study the development of this system. First, using vascular casting and ex vivo micro-CT, we demonstrated that this TTVS is conserved in adult mice. Next, using high-resolution MRI, we identified the primitive tentorial venous plexus in the murine embryo at day 14.5. We also found that, at this embryologic stage, the tentorial plexus drains the choroid plexus. Finally, using vascular casting and micro-CT, we found that the TTVS is the dominant venous drainage in the early postnatal period (P8). Herein, we demonstrated that the TTVS is conserved between mice and humans, and we present a longitudinal study of its development. In addition, our findings establish mice as a translational model for further study of this system and its relationship to intracranial physiology.

Incidence and Clinical Outcomes of Hypothyroidism in Patients Undergoing Spinal Fusion.

Background Hypothyroidism has been independently associated with the development of several comorbidities and is known to increase complication rates in non-spinal surgeries. However, there are limited data regarding the effects of hypothyroidism in major spine surgery. Therefore, we present the largest retrospective analysis evaluating outcomes in hypothyroid patients undergoing spinal fusion. Methods A retrospective review of the National Inpatient Sample (NIS) from 2004-2014 was performed. Patients with an International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) procedure code indicating spinal fusion (81.04-81.08, 81.34-81.38, 81.0x, 81.3x) were included. Patients with an ICD-9-CM diagnosis code indicating hypothyroidism (244.x) were compared to those without. Cervical and lumbar fusions were evaluated independently. Significant covariates in univariable logistic regression were utilized to construct multivariable models to analyze the effect of hypothyroidism on perioperative morbidity and mortality. Results A total of 4,149,125 patients were identified, of which 9.4% were hypothyroid. Although, hypothyroid patients had a higher risk of hematologic complications (lumbar - odds ratio [OR] 1.176, p < 0.0001; cervical - OR 1.162, p < 0.0001), they exhibited decreased in-hospital mortality (lumbar - OR .643, p < 0.0001; cervical - OR .606, p < 0.0001). Hypothyroid lumbar fusion patients also demonstrated decreased rates of perioperative myocardial infarction (MI) (OR .851, p < 0.0001). All these results were independent of patient gender. Conclusions Hypothyroid patients undergoing spinal fusion demonstrated lower rates of inpatient mortality and, in lumbar fusions, also had lower rates of acute MI when compared to their euthyroid counterparts. This suggests that hypothyroidism may offer protection against all-cause mortality and may be cardioprotective in the postoperative period for lumbar spinal fusions independent of patient gender.

Multimodal Atlas of the Murine Inner Ear: From Embryo to Adult.

The inner ear is a complex organ housed within the petrous bone of the skull. Its intimate relationship with the brain enables the transmission of auditory and vestibular signals via cranial nerves. Development of this structure from neural crest begins in utero and continues into early adulthood. However, the anatomy of the murine inner ear has only been well-characterized from early embryogenesis to post-natal day 6. Inner ear and skull base development continue into the post-natal period in mice and early adulthood in humans. Traditional methods used to evaluate the inner ear in animal models, such as histologic sectioning or paint-fill and corrosion, cannot visualize this complex anatomy in situ. Further, as the petrous bone ossifies in the postnatal period, these traditional techniques become increasingly difficult. Advances in modern imaging, including high resolution Micro-CT and MRI, now allow for 3D visualization of the in situ anatomy of organs such as the inner ear. Here, we present a longitudinal atlas of the murine inner ear using high resolution ex vivo Micro-CT and MRI.

Macrocephaly in the Primary Care Provider's Office.

Macrocephaly is commonly encountered in the primary care provider's office. It is defined as an occipitofrontal circumference that is greater than 2 standard deviations above the mean for the child's given age. Macrocephaly is a nonspecific clinical finding that may be benign or require further evaluation. An algorithmic approach is useful for aiding in the clinical decision-making process to determine if further evaluation with neuroimaging is warranted. Abnormal findings may signify a harmful underlying cause, requiring referral to a genetic specialist or neurosurgeon.