Rosario Maugeri

Peripheral frequency of CD4+ CD28- cells in acute ischemic stroke: relationship with stroke subtype and severity markers.

AbstractCD4+ CD28− T cells also called CD28 null cells have been reported as increased in the clinical setting of acute coronary syndrome. Only 2 studies previously analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic stroke but, to our knowledge, peripheral frequency of CD28 null cells in each TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that CD4+ cells and, in particular, the CD28 null cell subset could show a different degree of peripheral percentage in subjects with acute ischemic stroke in relation to clinical subtype and severity of ischemic stroke.The aim of our study was to analyze peripheral frequency of CD28 null cells in subjects with acute ischemic stroke in relation to TOAST diagnostic subtype, and to evaluate their relationship with scores of clinical severity of acute ischemic stroke, and their predictive role in the diagnosis of acute ischemic stroke and diagnostic subtypeWe enrolled 98 consecutive subjects admitted to our recruitment wards with a diagnosis of ischemic stroke. As controls we enrolled 66 hospitalized patients without a diagnosis of acute ischemic stroke. Peripheral frequency of CD4+ and CD28 null cells has been evaluated with a FACS Calibur flow cytometer.Subjects with acute ischemic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to control subjects without acute ischemic stroke. Subjects with cardioembolic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to subjects with other TOAST subtypes. We observed a significant relationship between CD28 null cells peripheral percentage and Scandinavian Stroke Scale and NIHSS scores. ROC curve analysis showed that CD28 null cell percentage may be useful to differentiate between stroke subtypes.These findings seem suggest a possible role for a T-cell component also in acute ischemic stroke clinical setting showing a different peripheral frequency of CD28 null cells in relation of each TOAST subtype of stroke.

Neuroprotective effect of erythropoietin and darbepoetin alfa after experimental intracerebral hemorrhage.

OBJECTIVEIntracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its long-lasting analog, darbepoetin alfa, have been demonstrated to be neuroprotective in several models of neuronal insult. The objectives of this study were to analyze whether the systemic administration of recombinant human EPO (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery and brain damage in a rat model of ICH. METHODSExperimental ICH was induced in rats by injecting autologous blood into the right striatum under stereotactic guidance. Subsequently, animals underwent placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Animals were killed 14 days after injury. RESULTSBoth rHuEPO and darbepoetin alfa were effective in reducing neurological impairment after injury, as assessed by the neurological tasks performed. rHuEPO- and darbepoetin alfa–treated animals exhibited a restricted brain injury with nearly normal parenchymal architecture. In contrast, the saline-treated group exhibited extensive cerebral cytoarchitectural disruption and edema. The number of surviving NeuN-positive neurons was significantly higher in the rats treated with rHuEPO and darbepoetin alfa compared with those that received saline (P < 0.05). CONCLUSIONThese results demonstrate that weekly administered darbepoetin alfa confers behavioral and histological neuroprotection after ICH in rats similar to that of daily EPO administration. Administration of EPO and its long-lasting recombinant forms affords significant neuroprotection in an ICH model and may hold promise for future clinical applications.

Difference in the expression of IL-9 and IL-17 correlates with different histological pattern of vascular wall injury in giant cell arteritis

OBJECTIVE GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA. METHODS Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed were also enrolled to evaluate the effect of glucocorticoids on IL-9 and IL-17 expression. RESULTS IL-17 overexpression was observed mainly in arteries with transmural inflammation and vasa vasorum vasculitis. IL-9 overexpression and Th9 polarization predominated in arteries with transmural inflammation and small-vessel vasculitis. The tissue expression of both IL-9 and IL-17 was correlated with the intensity of the systemic inflammatory response. IL-4, TGF-β and thymic stromal lymphopoietin, which are involved in the differentiation of Th9 cells, were overexpressed in arteries with transmural inflammation and small-vessel vasculitis. IL-9R was also overexpressed in GCA arteries with transmural inflammation and was accompanied by increased expression of IL-8. CONCLUSION Herein we provide the first evidence that distinct populations of potentially autoreactive T cells, expressing different cytokines (Th17 vs Th9), characterize patients with particular histological subsets of GCA and may thus contribute to the heterogeneity of tissue lesions observed in these patients.

Videoassisted anterior surgical approaches to the craniocervical junction: rationale and clinical results

PurposeIn this narrative review, we aim to give an update on the anatomic fundamentals of endoscopic assisted surgery to the craniocervical junction (transnasal, transoral and transcervical), and to report on the available clinical results.MethodsA non-systematic review and reporting on the anatomical and clinical results of endoscopic assisted approaches to the craniocervical junction (CVJ) is performed.ResultsPure endonasal and cervical endoscopic approaches still have some disadvantages, including the learning curve and the lack of 3-dimensional perception of the surgical field. Endoscopically assisted transoral surgery with 30° endoscopes represents an emerging alternative to standard microsurgical techniques for transoral approaches to the anterior CVJ. Used in conjunction with traditional microsurgery and intraoperative fluoroscopy, it provides a safe and improved method for anterior decompression with or without a reduced need for extensive soft palate splitting, hard palate resection, or extended maxillotomy.ConclusionsTransoral (microsurgical or video-assisted) approach with sparing of the soft palate still remains the gold standard compared to the “pure” transnasal and transcervical approaches due to the wider working channel provided by the former technique. Transnasal endoscopic approach alone appears to be superior when the CVJ lesion exceeds the upper limit of the inferior third of the clivus. Combined transnasal and transoral procedures can be tailored according to the specific pathological and radiological findings.

Aquaporins and Brain Tumors

Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs).

Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with artery tertiary lymphoid organs in giant cell arteritis.

Objectives To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Methods Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. Results ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-β, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. Conclusions ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.

Autologous fibrin sealant (Vivostat(®)) in the neurosurgical practice: Part I: Intracranial surgical procedure.

Background: Hemorrhages, cerebrospinal fluid (CSF) fistula and infections are the most challenging postoperative complications in Neurosurgery. In this study, we report our preliminary results using a fully autologous fibrin sealant agent, the Vivostat® system, in achieving hemostasis and CSF leakage repair during cranio-cerebral procedures. Methods: From January 2012 to March 2014, 77 patients were studied prospectively and data were collected and analyzed. Autologous fibrin sealant, taken from patients blood, was prepared with the Vivostat® system and applied on the resection bed or above the dura mater to achieve hemostasis and dural sealing. The surgical technique, time to bleeding control and associated complications were recorded. Results: A total of 79 neurosurgical procedures have been performed on 77 patients. In the majority of cases (98%) the same autologous fibrin glue provided rapid hemostasis and dural sealing. No patient developed allergic reactions or systemic complications in association with its application. There were no cases of cerebral hematoma, swelling, infection, or epileptic seizures after surgery whether in the immediate or in late period follow-up. Conclusions: In this preliminary study, the easy and direct application of autologous fibrin sealant agent helped in controlling cerebral bleeding and in providing prompt and efficient dural sealing with resolution of CSF leaks. Although the use of autologous fibrin glue seems to be safe, easy, and effective, further investigations are strongly recommended to quantify real advantages and potential limitations.

Aulogous fibrin sealant (Vivostat(®)) in the neurosurgical practice: Part II: Vertebro-spinal procedures.

Background: Epidural hematomas, cerebrospinal fluid fistula, and spinal infections are challenging postoperative complications following vertebro-spinal procedures. We report our preliminary results using autologous fibrin sealant as both fibrin glue and a hemostatic during these operations. Methods: Prospectively, between January 2013 and March 2015, 68 patients received an autologous fibrin sealant prepared with the Vivostat® system applied epidurally to provide hemostasis and to seal the dura. The surgical technique, time to bleeding control, and associated complications were recorded. Results: Spinal procedures were performed in 68 patients utilizing autologous fibrin glue/Vivostat® to provide rapid hemostasis and/or to seal the dura. Only 2 patients developed postoperative dural fistulas while none exhibited hemorrhages, allergic reactions, systemic complications, or infections. Conclusions: In this preliminary study, the application of autologous fibrin sealant with Vivostat® resulted in rapid hemostasis and/or acted as an effective dural sealant. Although this product appears to be safe and effective, further investigations are warranted.

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial.

AbstractStatins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators.We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started.At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-&agr;, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups.At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores.Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

Telemedicine versus WhatsApp: from tradition to evolution.

It is with great interest that we have read the clinical article by Backhaus et al. [1]: ‘Intracranial hemorrhage: frequency, location and risk factors identified in a TeleStroke network’, published on Neuroreport in January 2015. Considering the controversies in many aspects of the treatment of intracerebral hemorrhage and the lack of guidelines, the authors evaluated teleconsultations conducted between 2008 and 2010 in a large cohort of patients consecutively enrolled in the Telemedical Project for Integrated Stroke Care (TEMPiS) network. There are many cases where a prompt neurosurgical second opinion may facilitate and resolve challenging situations. As a resource, telemedicine in neurosurgery has been used extensively in emergent conditions such as triage in head injuries, stroke, and other cerebrovascular accidents. Telemedicine has been considered an established tool to allow the individuals living in remote areas access to modern medicine and to provide an expert neurosurgical opinion tightening time and providing a prompt and thorough response. Telemedicine in general provides clinical healthcare at a distance by using videotelephony and teleradiology and is used particularly in acute stroke care medicine (TeleStroke). TeleStroke considerably improves quality of stroke care (for instance, by increasing thrombolysis) and may be valuable for the management of intracranial hemorrhages in rural hospitals and hospitals lacking neurosurgical departments. In the reported study, TeleStroke networks definitely enabled selection of patients who need advanced neurological and/or neurosurgical care. From their data, it is possible to note that telemedicine allowed to effectively organize, select, and timely interhospital transfer patients to specialized institutions, providing the proper treatment for the specific case [1].