Effects of sex steroid receptor specificity in the regulation of skeletal metabolism

The interaction between estrogens and androgens, with their protective effects in bone, and parathyroid hormone (PTH), a calcitropic peptide hormone, is complex but may be better understood with murine models. The purpose of this study was to characterize skeletal phenotypes of mice deficient in estrogen receptor alpha (ERalpha), androgen receptor (AR, mutant tfm), or both, and determine if ERalpha and AR alter osteoblast differentiation and/or PTH response in vitro. Loss of ERalpha resulted in increased long bone length in females, but reduced length in males, suggesting loss of ERalpha reversed sex steroid-dependent skeletal dimorphism. The AR deficient tfm mice (genetically male but phenotypically female) had the longest bones and, similar to males, lengths were reduced with loss of ERalpha. Loss of AR and/or ERalpha resulted in a reduction in femoral bone mineral density (BMD) compared to male wildtype (WT) mice, suggesting tfm mice follow the female sex for BMD. In males or tfm mice, but not females, loss of AR and/or ERalpha caused a reduction in cortical width of the tibia compared to male WT mice. Reduced trabecular bone was found in tibiae of female and tfm mice versus male littermates, suggesting that tfm mice follow the female sex for trabecular bone but loss of ERalpha did not alter trabecular bone levels. Primary calvarial osteoblasts of male WT mice were less responsive to PTH stimulation of cAMP than all other genotypes, suggesting the female chromosomal sex and/ or loss of ERalpha or AR results in increased sensitivity to PTH. In conclusion, tfm mice follow the male pattern of long bone development, but imitate females in bone density and trabecular bone. Loss of ERalpha and/or AR results in increased osteoblast sensitivity to PTH and may explain actions of PTH noted in hypogonadal humans

Circumferential dural resection technique and reconstruction for the removal of giant calcified transdural herniated thoracic discs

OBJECTIVE The authors report a novel paradigm for resection of the disc or dural complex to treat giant calcified transdural herniated thoracic discs, and they describe a technique for the repair of dural defects. These herniated thoracic discs are uncommon, complicated lesions that often require a multidisciplinary team for effective treatment. The intradural component must be removed to effectively decompress the spinal cord. The opening of the friable dura mater, which frequently adheres to the extradural component of the disc, can result in large defects and difficult-to-manage CSF leaks. METHODS The authors performed a retrospective study of the technique and outcomes in patients with a transdural herniated disc treated at St. Joseph\u27s Hospital and Medical Center within a 4-year period between 2012 and 2015. RESULTS During the study period, 7 patients (mean age 56.1 years) presented to the department of neurosurgery with clinical symptoms consistent with myeloradiculopathy. In all cases, 2-level corpectomies of the involved levels were combined with circumferential resection of the dura and complete decompression of the spinal cord. The dural defect was repaired with an onlay dural patch, and a large piece of AlloDerm (LifeCell Corp) graft was sewn to close the pleural defect. Every patient had a perioperative lumbar drain placed for CSF diversion. No patient suffered neurological decline related to the surgery, and 3 patients experienced clinically significant improvement in function. Two patients developed an early postoperative CSF leak that required operative revision to oversew the defects. CONCLUSIONS This novel technique for decompression of the spinal cord by dural resection for the removal of giant calcified transdural herniated thoracic discs is safe and results in excellent decompression of the spinal cord. The technique becomes necessary when primary repair of the dura is not possible, and it can be used in cases in which the resection of pathology includes the dura

Pupillary changes after clinically asymptomatic high-acceleration head impacts in high school football athletes

OBJECTIVE: Previous studies have shown that clinically asymptomatic high-acceleration head impacts (HHIs) may be associated with neuronal and axonal injury, as measured by advanced imaging and biomarkers. Unfortunately, these methods of measurement are time-consuming, invasive, and costly. A quick noninvasive measurement tool is needed to aid studies of head injury and its biological impact. Quantitative pupillometry is a potential objective, rapid, noninvasive measurement tool that may be used to assess the neurological effects of HHIs. In this study, the authors investigated the effect of HHIs on pupillary metrics, as measured using a pupillometer, in the absence of a diagnosed concussion. METHODS: A prospective observational cohort study involving 18 high school football athletes was performed. These athletes were monitored for both the frequency and magnitude of head impacts that they sustained throughout a playing season by using the Head Impact Telemetry System. An HHI was defined as an impact exceeding 95g linear acceleration and 3760 rad/sec2 rotational acceleration. Pupillary assessments were performed at baseline, midseason, after occurrence of an HHI, and at the end of the season by using the NeurOptics NPi-200 pupillometer. The Sport Concussion Assessment Tool, 5th Edition (SCAT5), was also used at each time point. Comparisons of data obtained at the various time points were calculated using a repeated-measures analysis of variance and a t-test. RESULTS: Seven athletes sustained HHIs without a related diagnosed concussion. Following these HHIs, the athletes demonstrated decreases in pupil dilation velocity (mean difference 0.139 mm/sec; p = 0.048), percent change in pupil diameter (mean difference 3.643%; p = 0.002), and maximum constriction velocity (mean difference 0.744 mm/sec; p = 0.010), compared to measurements obtained at the athletes\u27 own midseason evaluations. No significant changes occurred between the SCAT5 subtest scores calculated at midseason and those after a high impact, although the effect sizes (Cohen\u27s d) on individual components ranged from 0.41 to 0.65. CONCLUSIONS: Measurable changes in pupil response were demonstrated following an HHI. These results suggest that clinically asymptomatic HHIs may affect brain reflex pathways, reflecting a biological injury previously seen when more invasive methods were applied

Pupillary changes after clinically asymptomatic high-acceleration head impacts in high school football athletes

OBJECTIVE: Previous studies have shown that clinically asymptomatic high-acceleration head impacts (HHIs) may be associated with neuronal and axonal injury, as measured by advanced imaging and biomarkers. Unfortunately, these methods of measurement are time-consuming, invasive, and costly. A quick noninvasive measurement tool is needed to aid studies of head injury and its biological impact. Quantitative pupillometry is a potential objective, rapid, noninvasive measurement tool that may be used to assess the neurological effects of HHIs. In this study, the authors investigated the effect of HHIs on pupillary metrics, as measured using a pupillometer, in the absence of a diagnosed concussion. METHODS: A prospective observational cohort study involving 18 high school football athletes was performed. These athletes were monitored for both the frequency and magnitude of head impacts that they sustained throughout a playing season by using the Head Impact Telemetry System. An HHI was defined as an impact exceeding 95g linear acceleration and 3760 rad/sec2 rotational acceleration. Pupillary assessments were performed at baseline, midseason, after occurrence of an HHI, and at the end of the season by using the NeurOptics NPi-200 pupillometer. The Sport Concussion Assessment Tool, 5th Edition (SCAT5), was also used at each time point. Comparisons of data obtained at the various time points were calculated using a repeated-measures analysis of variance and a t-test. RESULTS: Seven athletes sustained HHIs without a related diagnosed concussion. Following these HHIs, the athletes demonstrated decreases in pupil dilation velocity (mean difference 0.139 mm/sec; p = 0.048), percent change in pupil diameter (mean difference 3.643%; p = 0.002), and maximum constriction velocity (mean difference 0.744 mm/sec; p = 0.010), compared to measurements obtained at the athletes\u27 own midseason evaluations. No significant changes occurred between the SCAT5 subtest scores calculated at midseason and those after a high impact, although the effect sizes (Cohen\u27s d) on individual components ranged from 0.41 to 0.65. CONCLUSIONS: Measurable changes in pupil response were demonstrated following an HHI. These results suggest that clinically asymptomatic HHIs may affect brain reflex pathways, reflecting a biological injury previously seen when more invasive methods were applied

Pulmonary Complications After Spontaneous Aneurysmal Subarachnoid Hemorrhage: Experience from Barrow Neurological Institute

Objective: Because the clinical course of spontaneous aneurysmal subarachnoid hemorrhage (aSAH) can be compromised by pulmonary complications, we sought to review posttreatment outcomes in aSAH patients with and without pulmonary complications. Methods: Patient demographic, clinical, and outcome data (March 2003–January 2007) were analyzed retrospectively. Patients underwent microsurgical or endovascular treatment for aSAH; pulmonary complications were reported. Outcomes were assessed using the Glasgow Outcome Scale (GOS) scores at the 1-year, 3-year, and 6-year follow-up visits. Results: The cohort comprised 471 patients (mean age, 53.7 ± 12.4 years; men, 332/471 [70%]). The mean Glasgow Coma Scale (GCS) score at presentation was 11.9 ± 3.0. Of 471 patients, 47% (n = 223) presented with a Hunt and Hess score of ≥3 and 76% (n = 357) with a Fisher grade of 3. Treatment was clipping for 69% (279/407) and coiling for 31% (128/407) of patients. Pulmonary complications occurred in 210 of 471 (45%) patients. Nearly one-half of patients were discharged to home (215/471, 46%), and more than one-half had a good outcome defined as a GOS score of 5 at their 1-year (226/403, 56%), 3-year (217/397, 55%), and 6-year (203/380, 53%) follow-up visits. Logistic regression showed age and GCS scores as outcome predictors at all time points, whereas pulmonary complications predicted poor outcome only at the 1-year follow-up visit. Conclusions: Pulmonary problems represent the most common nonneurologic medical complications after aSAH. Despite advances in critical care, pulmonary complications represented predictors of short-term poor outcome only at the 1-year follow-up visit, whereas the medical history of the patient became more relevant for prognosis in long-term follow-up