Circulatory immune cells in Cushing syndrome: bystanders or active contributors to atherometabolic injury? A study of adhesion and activation of cell surface markers.

Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim. To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p < 0.05), WC (p < 0.001), WHR (p = 0.003), BMI (p < 0.001), and hs-CRP (p < 0.001). CD14++CD16+ (p = 0.047); CD14+CD16++ (p = 0.053) MN; CD15+ (p = 0.027); CD15+CD16+ (p = 0.008) N; and NK-Lym (p = 0.019) were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5%) versus ACTH-D CS (4.2 ± 1.9%) versus C (4.9 ± 2.3%). NK-Lym correlated with c-LDL (r = 0.433, p = 0.039) and CD15+ N with hs-CRP (r = 0.446, p = 0.037). In multivariate analysis, Leuc, N, and MN depended on BMI (p = 0.021), WC (p = 0.002), and WHR (p = 0.014), while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p = 0.035). Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH

Extended Endoscopic Endonasal Approaches for Cerebral Aneurysms: Anatomical, Virtual Reality and Morphometric Study

Introduction. The purpose of the present contribution is to perform a detailed anatomic and virtual reality three-dimensional stereoscopic study in order to test the effectiveness of the extended endoscopic endonasal approaches for selected anterior and posterior circulation aneurysms. Methods. The study was divided in two main steps: (1) simulation step, using a dedicated Virtual Reality System (Dextroscope, Volume Interactions); (2) dissection step, in which the feasibility to reach specific vascular territory via the nose was verified in the anatomical laboratory. Results. Good visualization and proximal and distal vascular control of the main midline anterior and posterior circulation territory were achieved during the simulation step as well as in the dissection step (anterior communicating complex, internal carotid, ophthalmic, superior hypophyseal, posterior cerebral and posterior communicating, basilar, superior cerebellar, anterior inferior cerebellar, vertebral, and posterior inferior cerebellar arteries). Conclusion. The present contribution is intended as strictly anatomic study in which we highlighted some specific anterior and posterior circulation aneurysms that can be reached via the nose. For clinical applications of these approaches, some relevant complications, mainly related to the endonasal route, such as proximal and distal vascular control, major arterial bleeding, postoperative cerebrospinal fluid leak, and olfactory disturbances must be considered

The Evaluation of Optic Nerves Using 7 Tesla 'Silent' Zero Echo Time Imaging in Patients with Leber's Hereditary Optic Neuropathy with or without Idebenone Treatment

Magnetic Resonance Imaging (MRI) of the Optic Nerve is difficult due to the fine extended nature of the structure, strong local magnetic field distortions induced by anatomy, and large motion artefacts associated with eye movement. To address these problems we used a Zero Echo Time (ZTE) MRI sequence with an Adiabatic SPectral Inversion Recovery (ASPIR) fat suppression pulse which also imbues the images with Magnetisation Transfer contrast. We investigated an application of the sequence for imaging the optic nerve in subjects with Leber's hereditary optic neuropathy (LHON). Of particular note is the sequence's near-silent operation, which can enhance image quality of the optic nerve by reducing the occurrence of involuntary saccades induced during Magnetic Resonance (MR) scanning

Double hemispheric Microdialysis study in poor-grade SAH patients

Delayed cerebral ischemia (DCI) is a dreadful complication present in 30% of subarachnoid hemorrhage (SAH) patients. DCI prediction and prevention are burdensome in poor grade SAH patients (WFNS 4-5). Therefore, defining an optimal neuromonitoring strategy might be cumbersome. Cerebral microdialysis (CMD) offers near-real-time regional metabolic data of the surrounding brain. However, unilateral neuromonitoring strategies obviate the diffuse repercussions of SAH. To assess the utility, indications and therapeutic implications of bilateral CMD in poor grade SAH patients. Poor grade SAH patients eligible for multimodal neuromonitoring were prospectively collected. Aneurysm location and blood volume were assessed on initial Angio-CT scans. CMD probes were bilaterally implanted and maintained, at least, for 48 hours (h). Ischemic events were defined as a Lactate/Pyruvate ratio >40 and Glucose concentration <0.7 mmol/L. 16 patients were monitored for 1725 h, observing ischemic events during 260 h (15.1%). Simultaneous bilateral ischemic events were rare (5 h, 1.9%). The established threshold of ≥7 ischemic events displayed a specificity and sensitivity for DCI of 96.2% and 83.3%, respectively. Bilateral CMD is a safe and useful strategy to evaluate areas at risk of suffering DCI in SAH patients. Metabolic crises occur bilaterally but rarely simultaneously. Hence, unilateral neuromonitoring strategies underestimate the risk of infarction and the possibility to offset its consequences

The feasibility of three port endonasal, transorbital, and sublabial approach to the petroclival region: neurosurgical audit and multiportal anatomic quantitative investigation

Purpose: The petroclival region represents the "Achille's heel" for the neurosurgeons. Many ventral endoscopic routes to this region, mainly performed as isolated, have been described. The aim of the present study is to verify the feasibility of a modular, combined, multiportal approach to the petroclival region to overcome the limits of a single approach, in terms of exposure and working areas, brain retraction and manipulation of neurovascular structures. Methods: Four cadaver heads (8 sides) underwent endoscopic endonasal transclival, transorbital superior eyelid and contralateral sublabial transmaxillary-Caldwell-Luc approaches, to the petroclival region. CT scans were obtained before and after each approach to rigorously separate the contribution of each osteotomy and subsequentially to build a comprehensive 3D model of the progressively enlarged working area after each step. Results: The addition of the contralateral transmaxillary and transorbital corridors to the extended endoscopic endonasal transclival in a combined multiportal approach provides complementary paramedian trajectories to overcome the natural barrier represented by the parasellar and paraclival segments of the internal carotid artery, resulting in significantly greater area of exposure than a pure endonasal midline route (8,77 cm2 and 11,14 cm2 vs 4,68 cm2 and 5,83cm2, extradural and intradural, respectively). Conclusion: The use of different endoscopic "head-on" trajectories can be combined in a wider multiportal extended approach to improve the ventral route to the most inaccessible petroclival regions. Finally, by combining these approaches and reiterating the importance of multiportal strategy, we quantitatively demonstrate the possibility to reach "far away" paramedian petroclival targets while preserving the neurovascular structures

Cost-Effectiveness of Low-Field Intraoperative Magnetic Resonance in Glioma Surgery

Object: Low-field intraoperative magnetic resonance (LF-iMR) has demonstrated a slight increase in the extent of resection of intra-axial tumors while preserving patient`s neurological outcomes. However, whether this improvement is cost-effective or not is still matter of controversy. In this clinical investigation we sought to evaluate the cost-effectiveness of the implementation of a LF-iMR in glioma surgery. Methods: Patients undergoing LF-iMR guided glioma surgery with gross total resection (GTR) intention were prospectively collected and compared to an historical cohort operated without this technology. Socio-demographic and clinical variables (pre and postoperative KPS; histopathological classification; Extent of resection; postoperative complications; need of re-intervention within the first year and 1-year postoperative survival) were collected and analyzed. Effectiveness variables were assessed in both groups: Postoperative Karnofsky performance status scale (pKPS); overall survival (OS); Progression-free survival (PFS); and a variable accounting for the number of patients with a greater than subtotal resection and same or higher postoperative KPS (R-KPS). All preoperative, procedural and postoperative costs linked to the treatment were considered for the cost-effectiveness analysis (diagnostic procedures, prosthesis, operating time, hospitalization, consumables, LF-iMR device, etc). Deterministic and probabilistic simulations were conducted to evaluate the consistency of our analysis. Results: 50 patients were operated with LF-iMR assistance, while 146 belonged to the control group. GTR rate, pKPS, R-KPS, PFS, and 1-year OS were respectively 13,8% (not significative), 7 points (p < 0.05), 17% (p < 0.05), 38 days (p < 0.05), and 3.7% (not significative) higher in the intervention group. Cost-effectiveness analysis showed a mean incremental cost per patient of 789 in the intervention group. Incremental cost-effectiveness ratios were 111 per additional point of pKPS, 21 per additional day free of progression, and 46 per additional percentage point of R-KPS. Conclusion: Glioma patients operated under LF-iMR guidance experience a better functional outcome, higher resection rates, less complications, better PFS rates but similar life expectancy compared to conventional techniques. In terms of efficiency, LF-iMR is very close to be a dominant technology in terms of R-KPS, PFS and pKPS

Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers

Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim. To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p<0.05), WC (p<0.001), WHR (p=0.003), BMI (p<0.001), and hs-CRP (p<0.001). CD14++CD16+ (p=0.047); CD14+CD16++ (p=0.053) MN; CD15+ (p=0.027); CD15+CD16+ (p=0.008) N; and NK-Lym (p=0.019) were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5%) versus ACTH-D CS (4.2 ± 1.9%) versus C (4.9 ± 2.3%). NK-Lym correlated with c-LDL (r = 0.433, p=0.039) and CD15+ N with hs-CRP (r = 0.446, p=0.037). In multivariate analysis, Leuc, N, and MN depended on BMI (p=0.021), WC (p=0.002), and WHR (p=0.014), while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p=0.035). Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH

Endoscopic transorbital resection of the temporal lobe: anatomic qualitative and quantitative study

ObjectiveStarting from an anatomic study describing the possibility of reaching the temporal region through an endoscopic transorbital approach, many clinical reports have now demonstrated the applicability of this strategy when dealing with intra-axial lesions. The study aimed to provide both a qualitative anatomic description of the temporal region, as seen through a transorbital perspective, and a quantitative analysis of the amount of temporal lobe resection achievable via this route.Material and methodsA total of four cadaveric heads (eight sides) were dissected at the Laboratory of Surgical Neuroanatomy (LSNA) of the University of Barcelona, Spain. A stepwise description of the resection of the temporal lobe through a transorbital perspective is provided. Qualitative anatomical descriptions and quantitative analysis of the amount of the resection were evaluated by means of pre- and post-dissection CT and MRI scans, and three-dimensional reconstructions were made by means of BrainLab®Software.ResultsThe transorbital route gives easy access to the temporal region, without the need for extensive bone removal. The resection of the temporal lobe proceeded in a subpial fashion, mimicking what happens in a surgical scenario. According to our quantitative analysis, the mean volume removed was 51.26%, with the most superior and lateral portion of the temporal lobe being the most difficult to reach.ConclusionThis anatomic study provides qualitative and quantitative details about the resection of the temporal lobe via an endoscopic transorbital approach. Our results showed that the resection of more than half of the temporal lobe is possible through this surgical corridor. While the anterior, inferior, and mesial portions of the temporal lobe were easily accessible, the most superior and lateral segment was more difficult to reach and resect. Our study serves as an integration to the current anatomic knowledge and clinical practice knowledge highlighting and also as a starting point for further anatomic studies addressing more selected segments of the temporal lobe, i.e., the mesial temporal region

Abordaje transesfenoidal endoscópico en patología sellar. Descripción y análisis de una nueva técnica en nuestro ámbito hospitalario. Comparación respecto a la vía transesfenoidal clásica.

[spa] -OBJETIVOS: Sistematizar el abordaje endoscópico endonasal transesfenoidal. Valorar el grado de resección tumoral, complicaciones, grado de invasividad tumoral y estancia postoperatoria. Comparar esta nueva técnica con el abordaje sublabial microquirúrgico clásico. -MATERIAL y MÉTODOS: Estudio prospectivo no randomizado de 50 pacientes intervenidos en nuestro centro entre 2002 y 2006 de adenomas hipofisarios con diferentes grados de invasión del seno cavernoso según la clasificación de Knosp. Entre las variables del estudio se incluyeron los grados de invasión, los grados de resección postoperatoria (total, subtotal y parcial) con un seguimiento radiológico medio de 12 meses, lesión del n.óptico, panhipopituitrasimo postoperatorio, fístula de LCR, déficit de pares craneales, epistaxis, meningitis, diabetes insípida y lesión de arteria carótida. Nuestra serie consta de 27 varones y 23 mujeres, con una edad media de 48 años (19 - 80 años). En 23 casos se utilizó una vía transesfenoidal sublabial clásica y en 25 casos se realizó un abordaje transesfenoidal endoscópico. Las relaciones entre el método quirúrgico aplicado y las variables de naturaleza categórica del estudio se realizaron mediante tablas de contingencia y el cálculo del test Chi-cuadrado. Para el caso de tablas de contingencia 2X2 con valores esperados inferiores a 5 en alguna celda, se realizó el cálculo del test exacto de Fisher. En cuanto a la medición de la relación entre el método quirúrgico y las variables de naturaleza cuantitativa, ésta se realizó mediante un test T. La relación entre el método quirúrgico y a la invasión del tumor se realizó mediante una Regresión Logística No-Condicionada. La estimación del número de días de postoperatorio de los pacientes se realizó mediante un Análisis de la Covarianza (ANCOVA). -RESULTADOS: En nuestra experiencia la técnica endoscópica presenta un porcentaje de exéresis completa superior al de la técnica clásica (60% frente a 34,8%) y un mayor porcentaje de resección subtotal (32% frente 26%) existiendo una diferencia estadísticamente significativa (p=0,033). En contraposición no encontramos diferencias en cuanto a complicaciones. También hemos evidenciado que existe una diferencia estadísticamente significativa en cuanto a la estancia postoperatoria (p=0,111), reduciéndose ésta a la mitad (3 días) con la técnica endoscópica. Si bien no hemos encontrado diferencias significativas en cuanto al grado de invasividad tumoral y al grado de resección, un mayor grado de invasividad aumenta en 3,59 veces el riesgo de poco éxito de la operación. - DISCUSIÓN Y CONCLUSIONES: En nuestra experiencia con la técnica endoscópica obtenemos un mayor grado de resección quirúrgica y una estancia postoperatoria menor. No hemos observado diferencias en cuanto a las complicaciones. La técnica endoscópica es relativamente nueva y en vías de desarrollo; nos permite una mejor visión de las estructuras sellares y una menor invasividad, traduciéndose esto en mejores resultados y en una mayor confortabilidad para nuestros pacientes.[eng] "ENDOSCOPIC ENDONASAL TRANSSPHENOIDAL APPROACH IN SELLAR TUMORS: ANALYSIS AND DESCRIPTION OF A NEW TECHNIQUE. COMPARISON WITH THE STANDARD SUBLABIAL TRANSEPTAL APPROACH". OBJECTIVE: In the present study we evaluate our experience regarding the treatment of pituitary adenomas. A comparison of the endoscopic transnasal vs the sublabial transseptal approach is illustrated. MATERIALS, METHODS: We consider 50 patients, 27 males and 23 females, the age range was between 19 to 80, with a mean of 48 years. All patients were operated upon by a single surgeon between 2002 and 2006. 23 cases were treated with a standard sublabial approach and 25 cases were with the endoscopic approach. The study population was evaluated with MRI and staged according to the Knosp classification. Postoperatively, the excision was classified as Complete, Subtotal or Partial. Mean follow up was 12 months. The variables considered for analysis include invasion grades, resection grades and complications. A Prospective no randomised study was performed. The relationship between surgical techniques and categorical variables was carried out using x-square and Fisher Exact tests. The relationship between surgical techniques and quantitative variables was carried out using a Student's T test. RESULTS: Complete resection was achieved in 60% of patients operated by the endoscopic approach vs 34,8% operated using a sublabial approach. Subtotal resection was 32% in the endoscopic group and 26% in sublabial group (p=0,033). Concerning surgical complications there were not statistical differences. On the contrary, patients operated endoscopically were discharged on postoperative day 3 (p=0,11) while patients operated by the sublabial approach were discharged on postoperative day 6. Higher invasive tumor grades were associated with a 3,59 times higher risk of non optimal surgical results. CONCLUSION: The endoscopic endonasal transsphenoidal approach improves the extent of tumor resection and reduce the postoperative stay. This approach is a new minimally invasive technique which provide a straight, multiangled, and close-up view of the midline areas around the sella