Neuraxis Research Articles

Dihydrotestosterone in Amyotrophic lateral sclerosis-The missing link?

ObjectiveTestosterone has been postulated to be involved in ALS causation.Materials and methodsCSF levels of free testosterone and dihydrotestosterone were measured in 13 ALS patients [7 males, 6 females] and 22 controls [12 males, 10 females].ResultsCSF free testosterone levels did not show any significant differences but CSF dihydrotestosterone levels were significantly decreased in all male and female ALS patients.ConclusionsDHT is probably integral to survival of motor neurons. In patients predisposed to develop ALS, there is possibly a sort of “testosterone resistance” at level of blood–brain barrier [BBB] existing right from birth and is likely the result of dysfunctional transport protein involved in testosterone transfer across the BBB. In these patients, lesser amount of testosterone is able to breach the BBB and enter the central neural axis. Lesser amount of testosterone is available to 5 α reductase in the anterior pituitary to be converted to DHT and lesser amount of DHT is generated. There is inadequate negative feedback suppression of LH at the level of anterior pituitary by DHT. As a result of higher LH levels, testosterone levels rise in the peripheral testosterone fraction [the fraction outside the BBB] and this explains the various physical attributes of ALS patients like lower Ratio of the index and ring finger lengths (2D:4D ratio), increased incidence of early onset alopecia etc. This deficiency of DHT leads to motor neuron death causing ALS.

Overexpression of Long Noncoding RNA HOTAIR Is a Unique Epigenetic Characteristic of Myxopapillary Ependymoma.

Ependymomas are a heterogeneous group of central nervous system tumors. Despite the recent advances, there are no specific biomarkers for ependymomas. In this study, we explored the role of homeobox (HOX) genes and long noncoding RNA (LncRNA) HOTAIR in ependymomas along the neural axis. Bioinformatics analysis was performed on publicly available gene expression data. Quantitative RT-PCR was used to determine the mRNA expression level among different groups of ependymomas. RNA in situ hybridization (ISH) with probes specific to HOTAIR was performed on tumor tissue microarray (TMA) constructed with 19 ependymomas formalin-fixed paraffin-embedded tissue. Gene expression analysis revealed higher expression of posterior HOX genes and HOTAIR in myxopapillary ependymoma (MPE), in comparison to other spinal and intracranial ependymoma. qRT-PCR confirmed the high HOXD10 expression in spinal MPEs. There was a significant upregulation of HOTAIR expression in spinal MPE and elevated HOTAIR expressions were further confirmed by RNA ISH on the TMA. Intriguingly, HOXD10 and HOTAIR expressions were not elevated in nonependymoma spinal tumors. Our collective results suggest an important role for the lncRNA HOTAIR and posterior HOX genes in the tumorigenesis of spinal MPE. HOTAIR may also serve as a potential diagnostic marker for spinal MPE.

Association Between Magnetic Resonance Imaging-Based Spinal Morphometry and Sensorimotor Behavior in a Hemicontusion Model of Incomplete Cervical Spinal Cord Injury in Rats

Aim: Structural connectivity in the reorganizing spinal cord after injury dictates functional connectivity and hence the neurological outcome. As magnetic resonance imaging (MRI)-based structural parameters are mostly accessible across spinal cord injury (SCI) patients, we studied MRI-based spinal morphological changes and their relationship to neurological outcome in the rat model of cervical SCI. Introduction: Functional connectivity assessments on patients with SCI rely heavily on MRI-based approaches to investigate the complete neural axis (both spinal cord and brain). Hence, underlying MRI-based structural and morphometric changes in the reorganizing spinal cord and their relationship to neurological outcomes is crucial for meaningful interpretation of functional connectivity changes across the neural axis. Methods: Young adult rats, aged 1.5 months, underwent a precise mechanical impact hemicontusion incomplete cervical SCI at the C4/C5 level, after which sensorimotor behavioral assessments were tracked during the reorganization period of 1-6 weeks, followed by MRI of the cervical spinal cord at 8 weeks after SCI. Results: A significant ipsilesional forelimb motor debilitation was observed from 1 to 6 weeks after injury. Heat sensitivity testing (Hargreaves) showed ipsilesional forelimb hypersensitivity at 5 and 6 weeks after SCI. MRI of the cervical spine showed ipsilateral T1- and T2-weighted lesions across all SCI rats compared with no significant lesions in sham rats. Morphometric assessments of the lesional and nonlesional changes showed the diverse nature of their interindividual variability in the SCI receiving rats. While the various T1 and T2 MRI lesional volumes associated weakly or moderately with neurological outcome, the nonlesional spinal morphometric changes associated much more strongly. The results have important implications for interpreting functional MRI-based functional connectivity after SCI by providing vital underlying structural changes and their relative neurological impact. Impact statement Functional connectivity assessments on patients with SCI relies heavily upon MRI based approaches. Hence, underlying MRI based structural and morphometric changes in the reorganizing spinal cord and its relationship to neurological outcomes is vital for meaningful interpretation of functional connectivity changes across the complete neural axis (both spinal cord and the brain).

Magnetic resonance imaging effectiveness in adolescent idiopathic scoliosis.

To assess the effectiveness of preoperative magnetic resonance imaging (MRI) in adolescent idiopathic scoliosis (AIS) patients with unremarkable history and physical examination. The imaging data of consecutive patients with presumed AIS treated with a posterior spinal fusion between 2010 and 2016 were reviewed. The presence of traditional risk factors, atypical curve patterns, and its association with relevant abnormalities on MRI were investigated. The number needed to diagnose (NND) and the number needed to misdiagnose (NNM) were calculated to measure MRI effectiveness. A total of 198 consecutive patients were identified and divided according to the presence of MRI findings. Both groups predominantly consisted of females, with a mean age of 15years and right thoracic curvature. Neural axis abnormalities were detected in 25 patients, and the groups had a similar proportion of atypical findings, as curve magnitude, thoracic kyphosis, curve direction, and sex. The NND was 7.9 patients and NNM was 66 patients, meaning that the management was changed before the spine fusion in 12% of patients with neural axis abnormalities. None of the traditional risk factors could predict a higher incidence of neural axis abnormalities in asymptomatic AIS patients. Traditional risk factors may not be predictive of patients with a higher risk of changes in MRI. Both NND and NNM are representations easily understood by clinicians. Using these indexes to define if a patient should be submitted for additional imaging tests may facilitate the decision of using MRI as a preoperative screening tool in AIS patients. Level II.

The rate of intraspinal problems and clinical evaluation of scoliosis: A cross-sectional, descriptive study.

Objectives This study aims to define the chronological, angular, and topographic classes in presumed idiopathic scoliosis and to investigate the frequency of generalized joint hypermobility, pain, neurological deficit, ankle deformity, Risser grade, and magnetic resonance imaging (MRI) findings in these patients.Patients and methods This cross-sectional, descriptive study included a total of 36 patients (11 males, 25 females; mean age 13.4±4.6 years; range, 6 to 24 years) with idiopathic scoliosis between January 2015 and January 2019. Data including age, sex, complaint of pain, generalized joint hypermobility (based on Beighton score), neurological deficit, ankle deformity, and definition of scoliosis were recorded. Chronological, angular, and topographic classification were carried out. The Risser grade and MRI findings were noted.Results Of all patients, 30 (83.3%) were idiopathic, five (13.9%) were neuromuscular, and one (2.8%) was congenital scoliosis based on MRI findings. Of 13 (36.1%) spine MRI scans, six (46.2%) were intraspinal anomalies, four were syringomyelia (30.8%), one was Chiari type 1 malformation (7.7%), and one was hemivertebrae with diastematomyelia (7.7%). The highest rates of classes according to chronological, angular, and topographical classifications of idiopathic scoliosis were adolescent (17/30, 56.7%), low angular (24/30, 80.0%), and lumbar scoliosis (15/30, 50.0%), respectively. Ten patients (33.3%) complained of pain, while 23 patients (76.7%) had no neurological deficit and seven (23.3%) had hypoesthesia. Seventeen patients (56.7%) had generalized joint hypermobility.ConclusionIdiopathic scoliosis with non-severe spinal deformity may present with intraspinal neural axis abnormalities, even when it is neurologically intact. Based on our study results, it seems to be useful to consider whole spine MRI for the evaluation of thoracic and lumbar scoliosis.

263. Detection of scoliosis curve flexibility by means of MRI

BACKGROUND CONTEXT The majority of scoliosis patients are subject to tremendous amounts of x-ray radiation in order to establish the diagnosis or follow the progression of the curves. There are different remedies to reduce the dose of delivered radiation or protect the body against such exposures. In addition, Bi-dimensional slot scattered technique (EOS) has provided some advantages, however, it is not available at all spine centers. The scoliosis patients are frequently requested to obtain MRI to discover neural axis abnormalities. As an attempt to find other alternatives for x-ray imaging, some authors demonstrated that the measured curve in the standing x-ray is correlated with the magnitude of the curve in the supine MRI. PURPOSE The supine MRI can illustrate the curve flexibility as obviously as the bending x-ray images in patients with idiopathic scoliosis. STUDY DESIGN/SETTING Retrospective analysis of imaging records. PATIENT SAMPLE N/A OUTCOME MEASURES N/A METHODS In this study, the imaging of 103 preoperative patients with idiopathic scoliosis were reviewed. The Cobb angle in the bending position toward the convex side was measured by an orthopedic resident. The curve of scoliosis in supine MRI and between the same levels was obtained by a spine flow, separately. The measured angles were entered into SPSS and the assessment was performed by the other researcher. RESULTS A total of 103 patients (33 male, 70 female) with idiopathic scoliosis from age 5 to 35 (mean 16.5 years) were included in the study. Pearson correlation between the curve angle in MRI and bending x-ray was calculated. (0.915°, P-value CONCLUSIONS To diminish the radiation exposure in patients with scoliosis, we can take the advantages of the correlation between bending curve and supine MRI angle measurements. Consequently, the main goal of bending views to assess curve flexibility might be relatively fulfilled by supine MRI images, consistently. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Establishing embryonic territories in the context of Wnt signaling.

This review highlights the work that my research group has been developing, together with international collaborators, during the last decade. Since we were able to establish the Xenopus laevis experimental model in Brazil, we have been focused on understanding early embryonic patterns regarding neural induction and axes establishment. In this context, the Wnt pathway appears as a major player and has been much explored by us and other research groups. Here, we chose to review three published works which we consider to be landmarks within the course of our research and also within the history of modern findings regarding neural induction and patterning. We intend to show how our series of discoveries, when painted together, tells a story that covers crucial developmental windows of early differentiation paths of anterior neural tissue: 1. establishing the head organizer in contrast to the trunk organizer in the early gastrula; 2. deciding between neural ectoderm and epidermis ectoderm at the blastula/gastrula stages, and 3. the gathering of prechordal unique properties in the late gastrula/early neurula.

Fine configuration of the dural fibrous network and the extradural neural axis compartment in the jugular foramen: an epoxy sheet plastination and confocal microscopy study.

The extradural neural axis compartment (EDNAC) is an adipovenous zone that is located between the meningeal (ML) and endosteal (EL) layers of the dura mater and has been minimally investigated in the jugular foramen (JF) region. In this study, the authors aimed to explore the fine architecture of the EDNAC within the JF and evaluate whether the EDNAC can be used as a component for JF compartmentalization. A total of 46 cadaveric heads (31 male, 15 female; age range 54-96 years) and 30 dry skulls were examined in this study. Twelve of 46 cadaveric heads were plastinated as a series of transverse (7 sets), coronal (3 sets), and sagittal (2 sets) slices and examined using stereomicroscopy and confocal microscopy. The dural entry points of the JF cranial nerves were recorded in 34 cadaveric skulls. The volumes of the JF, intraforaminal EDNAC, and internal jugular vein (IJV) were quantified. Based on constant osseous landmarks, the JF was subdivided into preforaminal, intraforaminal, and subforaminal segments. The ML-derived fascial sheath along the anteromedial wall of the IJV demarcated the "venous portion" and the "EDNAC portion" of the bipartite JF. The EDNAC did not surround the intraforaminal IJV and comprised an ML-derived dural fibrous network and an adipose matrix. A fibrovenous curtain subdivided the intraforaminal EDNAC into a small anterior column containing cranial nerve (CN) IX and the anterior condylar venous plexus and a large posterior adipose column containing CNs X and XI. In the intraforaminal segment, the IJV occupied a slightly larger space in the foramen (57%; p < 0.01), whereas in the subforaminal segment it occupied a space of similar size to that of the EDNAC. Excluding the IJV, the neurovascular structures in the JF traverse the dural fibrous network that is dominant in the foraminal EDNAC. The results of this study will contribute to anatomical knowledge of the obscure yet crucially important JF region, increase understanding of foraminal tumor growth and spread patterns, and facilitate the planning and execution of surgical interventions.

Fetal brain, head, and neck tumors: Prenatal imaging and management.

Fetal tumors represent an infrequent pathology when compared to congenital malformations, although their true incidence may be underestimated. A variety of benign and malignant neoplasms may occur anywhere in the neural axis. Imaging plays an important role in the fetal tumor diagnosis and evaluation of their resultant complications. Discovery of a fetal mass on obstetric ultrasound necessitates further evaluation with prenatal magnetic resonance imaging (MRI). New MR sequences and new applications of existing techniques have been successfully implemented in prenatal imaging. A detailed assessment may be performed using a variety of MR. Fetal tumors may be histologically benign or malignant, but their prognosis generally remains poor, especially for intracranial lesions. Unfavorable tumor location or heightened metabolic demands on a developing fetus may result in severe complications and a fatal outcome, even in cases of benign lesions. Nowadays, prenatal treatment focuses mainly on alleviation of secondary complications caused by the tumors. In this article we review congenital tumors of the brain, face, and neck encountered in prenatal life, and discuss diagnostic clues for appropriate diagnosis.

Optical Coherence Tomography Optic Nerve Head Morphology in Myopia I: Implications of Anterior Scleral Canal Opening Versus Bruch Membrane Opening Offset

To measure the magnitude and direction of anterior scleral canal opening (ASCO) offset relative to the Bruch membrane opening (BMO) (ASCO/BMO offset) to characterize neural canal obliqueness and minimum cross-sectional area (NCMCA) in 69 highly myopic and 138 healthy, age-matched, control eyes. Cross-sectional study. Using optical coherence tomography (OCT) scans of the optic nerve head (ONH), BMO and ASCO were manually segmented and their centroids and size and shape were calculated. ASCO/BMO offset magnitude and direction were measured after projecting the ASCO/BMO centroid vector onto the BMO plane. Neural canal axis obliqueness was defined as the angle between the ASCO/BMO centroid vector and the vector perpendicular to the BMO plane. NCMCA was defined by projecting BMO and ASCO points onto a plane perpendicular to the neural canal axis and measuring their overlapping area. ASCO/BMO offset magnitude was greater (highly myopic eyes 264.3 ± 131.1μm; healthy control subjects 89.0 ± 55.8μm, P < .001, t test) and ASCO centroid was most frequently nasal relative to BMO centroid (94.2% of eyes) in the highly myopic eyes. BMO and ASCO areas were significantly larger (P < .001, t test), NCMCA was significantly smaller (P < .001), and all 3 were significantly more elliptical (P ≤ .001) in myopic eyes. Neural canal obliqueness was greater in myopic (65.17° ± 14.03°) compared with control eyes (40.91° ± 16.22°; P < .001, t test). Our data suggest that increased temporal displacement of BMO relative to the ASCO, increased BMO and ASCO area, decreased NCMCA, and increased neural canal obliqueness are characteristic components of ONH morphology in highly myopic eyes.

Cervical Abnormalities in Severe Spinal Deformity: A 10-year MRI Review.

ObjectiveTo investigate the incidence of cervical anomalies (CA), including cervical intraspinal neural axis abnormalities (CIINAA) and/or cervical osseous abnormalities (COA), and the clinical relevance in severe spinal deformities (SSD) at a single center.MethodsA retrospective study of SSD admitted for spinal surgery from January 2003 to January 2015 was conducted at a single center. Inclusion criteria: patients who present with coronal Cobb over 90° (and/or sagittal cobb ≥90°); and patients with complete imaging and clinical data preoperatively. Exclusion criteria: ankylosing spondylitis, adult onset scoliosis, scoliosis secondary to bone destruction. There were 108 SSD patients who fulfilled the criteria in this research (41 males and 67 females). The mean age of the patients was 18.1 ± 2.7 years (range, 10–45 years). The clinical and radiological data of these patients were reviewed to identify CA and to analyze the relationship between clinical and radiographic characteristics in the population of SSD.ResultsThe major curves of scoliosis and segmental kyphosis were 109.1° ± 24.7° and 91.2° ± 29.1°. Cervical abnormalities were detected in 56 patients (51.85%) with 9 different CA, including 28 patients (25.9%) with 6 different COA, 21 patients (19.4%) with 3 different CIINAA, and 7 patients (6.5%) with a combination of COA and cervical intraspinal neural axis abnormalities (CINAA). Basilar invagination and Klippel–Feil syndrome were the most frequent COA. Syringomyelia was the most frequent CINAA. SSD with COA in upper vertebral levels (UVL) had a higher incidence of CINAA than those in subaxial vertebral levels (SVL) (P = 0.024) and SSD with multiple COA (mCOA) in UVL had a higher incidence of CINAA than those with single COA (sCOA) (P = 0.029). In the present study, 83.9% of the SSD with CA were asymptomatic.ConclusionThe incidence of CA in SSD was 51.85%, with most presenting with intact neurologic status. As the diversity of COA increased, we found a higher incidence of CINAA, especially in UVL.

Failure to extubate and delayed reintubation in elective lumbar fusion: An analysis of 57,677 cases

ObjectivesThere is a scarcity of literature exploring the consequences of Failure To Extubate (FTE) and Delayed Reintubation (DRI) in spine surgery. While it is reasonable to believe that patients who FTE or undergo DRI after Posterior Lumbar Fusion (PLF) and Transforaminal Lumbar Interbody Fusion (TLIF) are at risk for graver outcomes, there is minimal data to explicitly support that. The goal of this study was to investigate the morbidity and mortality associated with FTE and DRI after lumbar spine surgery in a large pool of patients. Patients and MethodsWe conducted a retrospective multicenter study of patients that underwent elective posterior lumbar fusion (PLF) and transforaminal lumbar interbody fusion (TLIF) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2006 to 2016. We excluded patients with disseminated cancer, metastatic disease to the neural axis, patient with spinal epidural abscess, and patients with ventilator dependency prior to the operation. Results57,677 patients from 2006 to 2016 were identified; 55 patients (0.1 %) had FTE and 262 patients (0.46 %) had DRI. The incidence of pneumonia was 27.2-fold greater in the FTE group and septic shock was 63.5-fold greater. All complications listed below are significance to p < 0.001. Deep vein thrombosis, pulmonary embolism, myocardial infarction and cardiac arrest were respectively, 10.4-, 12.2-, 22.8-, and 45.5- fold greater in the FTE group. Overall complication rate differed significantly between the two groups and were 9.8-fold greater in the FTE group.FTE was associated with increased, length of stay and all complications except DVT and pulmonary embolism. FTE was profoundly associated with severe complications (OR 13.0, 95 % CI 7.2–23.5) and mortality (OR = 21.5, CI = 7.5–61.0).The DRI group had a significantly higher morbidity (OR = 71.0, CI = 44.1–114.4), including overall complication (OR = 21.2, CI = 16.0–28.0) and severe complications (OR = 34.4, CI = 26.1–45.3). The DRI group had significantly higher rates of pneumonia (OR = 37.0), DVT (OR = 9.6) and pulmonary embolism (OR = 7.0), septic shock (OR = 60.5), myocardial infarction (OR = 32.1,) and cardiac arrest (OR = 236.4). ConclusionFTE and DRI were highly predictive of morbidity and mortality. Overall, investigations of the effects of FTE and DRI following spine procedures are lacking. This large multi-center national database review is one of the first to provide insight into the consequences of FTE and DRI in lumbar fusion cases. Future investigation into the consequences and predictors of FTE and DRI in spine surgery are required.

Central sensory-motor crosstalk in the neural gut-brain axis.

The neural gut-brain axis consists of viscerosensory and autonomic motor neurons innervating the gastrointestinal (GI) tract. Sensory neurons transmit nutrient-related and non-nutrient-related information to the brain, while motor neurons regulate GI motility and secretion. Previous research provides an incomplete picture of the brain nuclei that are directly connected with the neural gut-brain axis, and no studies have thoroughly assessed sensory-motor overlap in those nuclei. Our goal in this study was to comprehensively characterize the central sensory and motor circuitry associated with the neural gut-brain axis linked to a segment of the small intestine. We injected a retrograde (pseudorabies; PRV) and anterograde (herpes simplex virus 1; HSV) transsynaptic viral tracer into the duodenal wall of adult male rats. Immunohistochemical processing revealed single- and double-labeled cells that were quantified per nucleus. We found that across nearly all brain regions assessed, PRV+HSV immunoreactive neurons comprised the greatest percentage of labeled cells compared with single-labeled PRV or HSV neurons. These results indicate that even though sensory and motor information can be processed by separate neuronal populations, there is neuroanatomical evidence of direct sensory-motor feedback in the neural gut-brain axis throughout the entire caudal-rostral extent of the brain. This is the first study to exhaustively investigate the sensory-motor organization of the neural gut-brain axis, and is a step toward phenotyping the many central neuronal populations involved in GI control.

Development and evolution of the tetrapod skull-neck boundary.

ABSTRACTThe origin and evolution of the vertebrate skull have been topics of intense study for more than two centuries. Whereas early theories of skull origin, such as the influential vertebral theory, have been largely refuted with respect to the anterior (pre‐otic) region of the skull, the posterior (post‐otic) region is known to be derived from the anteriormost paraxial segments, i.e. the somites. Here we review the morphology and development of the occiput in both living and extinct tetrapods, taking into account revised knowledge of skull development by augmenting historical accounts with recent data. When occipital composition is evaluated relative to its position along the neural axis, and specifically to the hypoglossal nerve complex, much of the apparent interspecific variation in the location of the skull–neck boundary stabilizes in a phylogenetically informative way. Based on this criterion, three distinct conditions are identified in (i) frogs, (ii) salamanders and caecilians, and (iii) amniotes. The position of the posteriormost occipital segment relative to the hypoglossal nerve is key to understanding the evolution of the posterior limit of the skull. By using cranial foramina as osteological proxies of the hypoglossal nerve, a survey of fossil taxa reveals the amniote condition to be present at the base of Tetrapoda. This result challenges traditional theories of cranial evolution, which posit translocation of the occiput to a more posterior location in amniotes relative to lissamphibians (frogs, salamanders, caecilians), and instead supports the largely overlooked hypothesis that the reduced occiput in lissamphibians is secondarily derived. Recent advances in our understanding of the genetic basis of axial patterning and its regulation in amniotes support the hypothesis that the lissamphibian occipital form may have arisen as the product of a homeotic shift in segment fate from an amniote‐like condition.

Long-Term Surgical Resection Outcomes of Pediatric Myxopapillary Ependymoma: Experience of Two Centers and Brief Literature Review

Myxopapillary ependymoma (MPE) is a rarely reported lesion of the spinal cord in the pediatric population. Based on their low mitotic index and slow-growth, MPEs are classified as low-grade glial tumors. However, MPEs have malignant characteristics, such as distant neural axis and extraneural axis dissemination. We present the long-term surgical resection outcomes of 5 consecutive pediatric MPE cases and the results of a literature search for reported cases of pediatric spinal MPE. We retrospectively reviewed the medical records of 38 primary spinal MPE cases who underwent surgery at 2 neurosurgical centers over a 16-year period from January 2004 to January 2019. All pediatric cases (age <18 years; n= 5) who were diagnosed with MPE composed the core sample for this study. This series comprised 5 patients (3 females and 2 males), with a mean age at first presentation of 13.6 ± 2.3 years. The mean preoperative course was 8.2 ± 9.3 months. The predominant location was the lumbar spine, for 4 tumors. Gross total resection (GTR) was achieved in 4 patients. All patients were diagnosed histopathologically as MPE, World Health Organization grade I. No adjuvant treatment was provided after the first surgery. Three patients experienced spinal drop metastasis. The mean interval between the first diagnosis and diagnosis of neural dissemination was 44.0 ± 31.5 months. The location of neural dissemination in all patients was the sacral spine; 1 patient experienced distant metastasis in the brain along with her sacral metastasis. The mean duration of follow-up was 75.0 ± 37.6 months. Even with GTR, pediatric MPE has a high propensity for neural axis dissemination. We recommend close clinical and radiologic follow-up for pediatric patients with MPE.

Remote CB1 receptor antagonist administration reveals multiple sites of tonic and phasic endocannabinoid neuroendocrine regulation

Endogenous cannabinoids (endocannabinoids, eCB) are expressed throughout the body and contribute to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and general stress reactivity. This study assessed the contributions of CB1 receptors (CB1R) in the modulation of basal and stress-induced neural and HPA axis activities. Catheterized adult male rats were placed in chambers to acclimate overnight, with their catheters connected and exteriorized from the chambers for relatively stress-free remote injections. The next morning, the CB1R antagonist AM251 (1 or 2 mg/kg) or vehicle was administered, and 30 min later, rats were exposed to loud noise stress (30 min) or no noise (basal condition). Blood, brains, pituitary and adrenal glands were collected immediately after the procedures for analysis of c-fos and CB1R mRNAs, corticosterone (CORT) and adrenocorticotropin hormone (ACTH) plasma levels. Basally, CB1R antagonism induced c-fos mRNA in the basolateral amygdala (BLA) and auditory cortex (AUD) and elevated plasma CORT, indicating disruption of eCB-mediated constitutive inhibition of activity. CB1R blockade also potentiated stress-induced hormone levels and c-fos mRNA in several regions such as the bed nucleus of the stria terminalis (BST), lateral septum (LS), and basolateral amygdala (BLA) and the paraventricular nucleus of the hypothalamus (PVN). CB1R mRNA was detected in all central tissues investigated, and the adrenal cortex, but at very low levels in the anterior pituitary gland. Interestingly, CB1R mRNA was rapidly and bidirectionally regulated in response to stress and/or antagonist treatment in some regions. eCBs therefore modulate the HPA axis by regulating both constitutive and activity-dependent inhibition at multiple levels.

The Role of MRI in Children With Congenital Limb Deficiencies With Associated Scoliosis.

The association of scoliosis and congenital limb deficiency has been well described. However, the incidence of neural axis abnormalities in this population is not known. The ability to assess the neural axis by physical examination may be limited in patients with a limb deficiency. Although mobility of the spine is important for all children, it can be especially so in children with a limb deficiency. As spinal fusion in children with limb deficiency potentially has more functional impact, detecting reversible forms of scoliosis seems particularly important. Retrospective review of children treated at 1 institution between 1990 and 2017 with both a diagnosis of a congenital limb deficiency, upper or lower, and scoliosis. Children were excluded if they had any neurological difference on history or physical examination, if they had sacral agenesis or spina bifida, or if their limb deficiency was related to trauma or early amniotic rupture sequence. Twenty-four children were identified, 11 with lower extremity deficiency, 14 with upper extremity deficiency with 1 having both. Fifteen children demonstrated neural axis abnormalities, 6 (40%) required neurosurgery. Five (45%) of 11 lower extremity deficiency children had MRI findings, 3 of these needing neurosurgery. Of the 14 upper extremity deficiency children, 10 had MRI changes, and 3 required neurosurgery. Eight children with congenital scoliosis, 5 had MRI findings, with 4 children requiring neurosurgery. The other 16 children had scoliosis without vertebral abnormalities, 10 had MRI findings, and 2 required neurosurgery. There is a high incidence of neural axis abnormalities (63%) in children with congenital limb deficiencies and scoliosis. A large portion of these require neurosurgical intervention. MRI should be considered soon after presentation in this population of children. Level IV. Retrospective cohort.

PATH-66. THE GENOMIC LANDSCAPE OF SPINAL CORD EPENDYMOMA

Abstract INTRODUCTION Ependymomas are seen throughout the neural axis but spinal cord is most common in adults. A subset arises in the setting of neurofibromatosis 2, whereas most are sporadic, potentially with somatic NF2 inactivation. The genetic drivers in NF2 wildtype tumors are unknown, as is the spectrum of cooperating genetic alterations. METHODS We performed targeted next-generation sequencing (NGS) to assess mutations, rearrangements, and chromosomal copy number alterations in 46 adult spinal cord ependymomas. RESULTS The 24 females and 22 males ranged from 20–73 (median 46) years of age. Tumors were in the cervical (n=24), thoracic (n=12), and lumbar (n=10) spinal cord. Nine tumors (20%) harbored truncating NF2 mutations with loss of the remaining wildtype allele, with frequent monosomy 13q. Thirteen NF2-wildtype tumors (28%) showed monosomy 22q with frequent monosomy 13q and trisomy 7, 9, and 12. Seventeen tumors (37%) carried a near-tetraploid genome, likely due to genomic reduplication with frequent preservation of diploidy in chromosomes 13q (77%), 14q (88%), 21q (53%) and 22q (65%). Remaining cases did not show a recurrent pattern, but one harbored focal high-level MYCN amplification. Three of the six recurrences were seen in the last subgroup; however, there was no significant difference for progression-free survival between four subgroups. None of the NF2-mutant tumors were in lumbar spinal cord, but there was no difference for tumor location or patient age between four subgroups. DISCUSSION Biallelic NF2 mutational inactivation characterizes only a subset of spinal cord ependymomas, and MYCN amplification is likely a genetic driver in a small subset of NF2 wildtype cases. The high frequency of chromosome 22q loss even in NF2-wildtype tumors raises the possibility of cryptic alterations in the NF2 gene not detected by our panel, or perhaps implicates the presence of another as yet unidentified tumor suppressor gene on chromosome 22q.

Obesity Is Associated With Increased Thoracic Kyphosis in Adolescent Idiopathic Scoliosis Patients and Nonscoliotic Adolescents

Study DesignRetrospective comparative cohort study. ObjectiveTo compare radiographic parameters between adolescents with a greater body mass index (BMI) percentile to underweight individuals. Summary of Background DataIncreased BMI percentile has been associated with increased complications after surgical correction of adolescent idiopathic scoliosis (AIS). However, association between BMI percentile and preoperative sagittal plane alignment has not been evaluated. The purpose of this study was to evaluate the effect of BMI percentile on sagittal alignment in AIS patients compared with nonscoliotic adolescents. MethodsPosterior-anterior and lateral spinal radiographs of 1,551 AIS patients with a thoracic major curve (Lenke 1–4) and 70 nonscoliotic adolescent patients were compared. BMI percentile was determined based on age and sex, and patients were divided into four categories: underweight (<5th percentile), normal-weight (5th–85th percentile), overweight (85th–95th percentile), and obese (≥95th percentile). ResultsCoronal plane deformity magnitude was not significantly different between the 4 categories of AIS patients (p = .51). Increased BMI percentile was associated with increased thoracic kyphosis globally (T2–T12: p < .005) as well as segmentally (T2–T5: p < .001; T5–T12: p < .001) in patients with AIS. This was also true in obese adolescents without spinal deformity (p < .04). Lumbar lordosis, pelvic incidence, and pelvic tilt were not significantly different between AIS patients in the four BMI percentile categories (p > .07). Pelvic incidence was significantly greater in AIS patients compared with nonscoliotic adolescents (54 ± 13 vs. 46 ± 11; p = .01). ConclusionIncreased BMI percentile is associated with increased thoracic kyphosis in AIS patients and nonscoliotic adolescents. Excess weight may reduce anterior vertebral growth. AIS patients have an increased pelvic incidence compared with nonscoliotic adolescents; however, this variable is not influenced by body mass. These relationships should be taken into account when planning sagittal plane deformity correction or considering neuro axis disorders (also associated with increased kyphosis) in patients with scoliosis. Level of EvidenceLevel II.

Мозг и микробиота: нейроэндокринные и гериатрические аспекты

Neuro communication brain ‘the gut-brain’ provides the neural network with the ‘axis of the bowel-brain’ (Gut-Brain Axis, GBA). Promising are the studies of neural networks ‘microbiota-brain’ at the neuroendocrine and neurophysiological level. Microbiota - an organ that plays an important role in ensuring human health and in the development of various diseases, including age-associated. The treatment regimens for age-related pathology include traditional methods of treatment (recovery of melatonin and circadian rhythms, physical exercise, proper, balanced, functional nutrition, principles of a healthy lifestyle, etc.), but taking into account the available scientific data, it is necessary to include in the list of therapeutic and rehabilitation measures methods of managing the composition and/or diversity of intestinal microbiota. Visceral and cognitive brain regulating melatonin levels alter intestinal flora and improve antimicrobial actions. Functional and a balanced diet ensure the functioning of the circadian neuro axis ‘brain-gut’ while eating ‘brain’ and ‘microbiota’...