Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case.

BACKGROUND: Schwannomatosis is a genetic disorder that belongs to NF family. The mutation of SMARCB1 gene has been related to this entity and Coffin-Siris syndrome, as well. We reported a case of a female patient with SMARCB1 mutation who has developed a spontaneuous spleen rupture. CASE DESCRIPTION: A 28 years old female patient with a story of a Sjogren syndrome, celiac disease and a surgically treated schwannoma, presented to our observation in July 2013 for a pain on the left elbow, where a tumefation was present. After neuroradiological evaluations, a surgical resection was performed and a schwannoma was diagnosed. Genetic exams revealed a puntiform SMARCB1 gene mutation. During 2015, she was subdued to the removal of an another schwannoma located into the cervical medullary canal. Few months later, she was operated in an another hospital for a spontaneous spleen rupture in a possible context of wandering spleen. CONCLUSION: We think that the patient could suffer from a partially expressed Coffin-Siris syndrome. No cases of spontaneous rupture in a context of wandering spleen have been ever described as for as schwannomatosis or Coffin-Siris syndrome are concerned. More cases are necessary to establish a direct relationship.

The "Skull Flap" a new conceived device for decompressive craniectomy/cranioplasty: Feasibility study on cadaver specimen.

BACKGROUND: Decompressive craniectomy (DC) is a procedure that is currently performed with increasing frequency. The reason is that its indications have become much broader. This procedure may be associated with the relevant morbidity in the postoperative stage due to the creation of a large bone defect. On the other hand, cranioplasty is associated too with some of the common complications related to any reconstructive head surgery. The authors present a newly developed device: The "Skull Flap" (SF). This new device allows the surgeon to complete a DC, yet providing at the same time a cranial reconstruction that will not require the patient to undergo a second reconstructive procedure. MATERIALS AND METHODS: Different size and location craniectomies were carried out on four human cadaveric heads; the bone flaps were then repositioned in a more elevated position with respect to the skull edges. The flaps were placed at a distance of 12 and 15 mm from the skull edges using the SF system. Crash tests were conducted on each flap while in open and closed positions to assess its reliability and efficacy. RESULTS: SF was shown to be a strong fixation device that allows satisfactory brain decompression by keeping the original bone flap away from the swollen brain; at the same time, in a later stage, it allows cranial reconstruction in a simple way. CONCLUSION: The SF device was shown to be very easy to use, adaptable, and practical to apply; thus, allowing both satisfactory brain decompression as well as bone flap repositioning at a later time after the brain swelling has subsided.

Cognitive deficits in patients with low and high grade gliomas.

AIM: Studies in the literature with specific information concerning the neuropsychological alterations in patients with high and low grade gliomas are poor. The aim of the present study was to investigate and compare the cognitive functioning in patients with high and low-grade glioma pre- and postoperatively. METHODS: Between January 2009 and January 2011 27 patients with high-grade glioma (HG group) and 15 patients with low-grade glioma (LG group) were neuropsychologically assessed in the preoperative time, as well as 6 months and 1 year after surgery. During the examination, memory, visuo-constructive abilities, language and executive functions were tested. In addition in the preoperative time, the effect on cognition of lateralization, size and edema was analyzed for each group. RESULTS: Both in the HG and LG group statistical comparisons of the pre- and postoperative assessments of cognitive abilities showed a postoperative improvement in memory functions and in processing speed (P<0.05). In particular the analysis of the significance of clinical factors in the postoperative outcome of patients with glioma showed that lesion size, edema and lateralization affect cognitive functioning in varying degree. CONCLUSION: These findings demonstrated different levels of impairments in executive and memory domains and in processing speed in patients with low and high grade gliomas. These deficits may have a strong impact on quality of life. Psychiatric interventions may be useful for patients and their families; in particular for helping the patient to become aware of the illness, in bolstering coping strategies, and for facilitating their support at home.

IL-36 receptor antagonist with special emphasis on IL-38.

IL-36 is another family member of IL-1 and induces the production of proinflammatory cytokines and activates MAPK and NFkB pathways. IL-36 is a common mediator of innate and adaptive immune response and is inhibited by IL-36 receptor antagonist (RA). IL-36RA acts on IL-36 receptor ligand which exerts proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor as does IL-36RA and has similar biological effects on immune cells. IL-38 is also a member of IL-1 cytokine and shares some characteristics of IL-1RA, binding the same IL-1 receptor type I. IL-38 plays a role in the pathogenesis of inflammatory diseases, exerting protective effect in some autoimmune diseases. Both IL-38 and IL-36RA have an anti-inflammatory biological effect, however in some cases have contrary effects.

Comparison of beneficial actions of non-steroidal anti-inflammatory drugs to flavonoids.

Inflammation is involved in increasing number of diseases necessitating the development of new, effective and safe treatments. Non steroidal anti-inflammatory drugs (NSAIDs) have been helpful in many instances, but they only inhibit cyclooxygenase (COX), but not the generation or actions of cytokines. Instead, some natural flavonoids have multiple anti-inflammatory effects, including COX inhibition, and a much safer profile. Increasing evidence indicates that inflammation plays a critical role in the pathogenesis of many diseases that also involve mast cells. Consequently, the need for new, effective and safe anti-inflammatory drugs is all the more urgent. Corticosteroids are quite potent, but have many adverse effects such as increased risk of infections, osteoporosis, glaucoma and depression. Biological agents such anti-TNF are useful in certain conditions, such as rheumatoid arthritis and psoriasis, but has been associated with increased risk of infection and leukemia.

Impact of IL -9 and IL-33 in mast cells.

Cytokines serve as chemical communicators from one cell to another and most of them have pro-inflammatory activity. Mast cells have been recognised as important mediators of the pathogenesis of allergy and inflammation, suggesting a role for IL-33-mediated mast cell activation. IL-33 was recently identified as a ligand for the orphan IL-1 family receptor T1/ST2 and is mainly expressed by mast cells, fibroblasts, epithelial cells, and endothelial cells, particularly in high endothelial venules. IL-33 is a potent inducer of pro-inflammatory cytokines such as IL-1, IL-6, IL-13 and TNF, and chemokines (MCP-1), by mast cells. Substance P is capable to induce VEGF from mast cells, and IL-33, the newest pro-inflammatory member of the IL-1 cytokine family, augments the effect of SP in VEGF transcription and translation protein. IL-9 is a pleiotropic and is expressed by multiple T helper (TH) cell subsets. IL-9 promotes the expression of mast cell pro-inflammatory cytokines in vitro and is involved in Th2 responses. This article focuses on recent developments of mast cells, IL-9 and IL-33, and recent literature and investigations were reviewed.

Survival prognostic factors in patients with glioblastoma: our experience.

AIM: Approximate survival for glioblastoma is less than 1 year. Age, histological features and performance status at presentation represent the three statistically independent factors affecting longevity. The purpose of the study was to assess the role of surgery and to analyze prognostic factors in our patients operated for glioblastoma. METHODS: We evaluated in 56 patients operated for glioblastoma their depressive and performance status in the preoperative and postoperative time. Moreover we analyzed the extent of surgery, the site and the size of lesions. RESULTS: Median overall survival was 17 months. An age of ≥60 years (P<0.03), a preoperative Karnofsky Performance Status KPS≤70 (P=0.04), a subtotal tumor resection (P<0.001), a tumor size >5 cm (P=0.01), and no postoperative adjuvant treatment (P=0.01) were associated with the worst prognosis. Before surgery we found the presence of depression in 10 patients with a significative reduction of mean Back Depression Inventory scores after tumor resection (P=0.03). Finally, a KPS≤70 was significantly associated with an increased incidence of depression in the postoperative time. CONCLUSION: Tumor size, total resection and affective disorders were identified as predictors of survival in our series of patients with glioblastoma in addition to age and KPS score. In our opinion an early diagnosis and the use of specific safeguards in the operating room contribute to have an extension of the tumor progression time and median survival.

Reorganization of functional connectivity of the language network in patients with brain gliomas.

BACKGROUND AND PURPOSE: fcMRI measures spontaneous and synchronous fluctuations of BOLD signal between spatially remote brain regions. The present study investigated potential LN fcMRI modifications induced by left hemisphere brain gliomas. MATERIALS AND METHODS: We retrospectively evaluated fcMRI in 39 right-handed patients with a left hemisphere brain glioma and 13 healthy controls. Patients and controls performed a verb-generation task to identify individual BOLD activity in the left IFG (Broca area); the active region was used as seed to create whole-brain background connectivity maps and to identify the LN (including bilateral regions of the IFG, STS, and TPJ) following regression of task-evoked activity. We assessed differences between patients and controls in the pattern of functional connectivity of the LN, as well as potential effects of tumor position, histopathology, and volume. RESULTS: Global fcMRI of the LN was significantly reduced in patients with tumor compared with controls. Specifically, fcMRI was significantly reduced within seed regions of the affected hemisphere (left intrahemispheric fcMRI) and between the TPJ of the 2 hemispheres. In patients, the left TPJ node showed the greatest decrease of functional connectivity within the LN. CONCLUSIONS: The presence of a brain tumor in the left hemisphere significantly reduced the degree of fcMRI between language-related brain regions. The pattern of fcMRI was influenced by tumor position but was not restricted to the area immediately surrounding the tumor because the connectivity between remote and contralateral areas was also affected.

Glycosilated nucleolin as marker for human gliomas.

Nucleolin is a multifunctional DNA and RNA binding protein involved in regulation of gene transcription, chromatin remodeling, RNA metabolism, and ribosomal RNA synthesis. Nucleolin seems to be over-expressed in highly proliferative cells and is involved in many aspect of gene expression: DNA recombination and replication, RNA transcription by RNA polymerase I and II, rRNA processing, mRNA stabilization, cytokinesis, and apoptosis. Although nucleolin is localized predominantly in the nucleolus, it has also been shown to be localized in a phosphorylated/glycolsilated form on the cell surface of different cells. Numerous articles dealing with surface nucleolin targeting for tumor therapy have been recently published. However, at present, no extensive informations are so far available for the presence of nucleolin in human gliomas. In the present work we investigated on the presence and localization of nucleolin in glioma on glioma specimens at different grade of malignancy and on primary glioma cell cultures derived by surgical resection, trying to correlate the presence of glycosilated membrane nucleolin with the malignancy grade. To this purpose an antibody produced by us against gp273 protein, demonstrated to recognized the glycosilated surface nucleolin, has been used. The results obtained demonstrate that surface nucleolin increase with the malignancy grade thus suggesting that it may constitute a histopathological marker for glioma grading and a possible tool for targeted therapy.

Less invasive approaches for the treatment of cervical schwannomas: our experience.

PURPOSE: The purpose of our paper is to illustrate our experience with minimally invasive approaches for the treatment of cervical schwannomas. Moreover, a brief review of the literature was conducted. METHODS: All data regarding patients treated for cervical schwannomas were retrospectively revised. Site, size and extension of the lesions and preoperative neurological status were obtained through re-examination of neuroimaging and clinical records. Postoperative clinical examinations and radiological images were available for all patients. The clinical course was documented using the visual analog scale (VAS), Karnofsky score (KPS) and the Klekamp-Samii score system. RESULTS: Sixteen patients harboring cervical schwannomas were treated from 2003 to 2009. Hemilaminectomy was performed in eight cases, subtotal hemilaminectomy in four cases, interlaminar fenestration in two cases, osteoplastic hemilaminotomy and laminoplasty in one case each. Postoperative neuroimaging revealed complete removal of the lesion and no signs of spinal instability. At discharge, neurological improvement was observed in 14 patients and all patients demonstrated reduction of VAS score and improvement of KPS and Klekamp-Samii's score. CONCLUSIONS: Minimal access procedures are increasingly gaining popularity but their use is poorly described in the treatment of cervical tumors. Less invasive approaches may effectively be used instead of traditional laminectomy in the treatment of cervical tumors, especially schwannomas, providing less iatrogenic traumatism and preventing postsurgical spinal instability. Modern neuroimaging allows adequate preoperative planning and microsurgical techniques provide adequate execution of the surgical act. The procedure has to be tailored case by case considering the specific lesional features and the individual anatomical situation.

Distinct cellular responses induced by saporin and a transferrin-saporin conjugate in two different human glioblastoma cell lines.

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults, with a median survival of ~12-18 months post-diagnosis. GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are urgently needed. The marked difference of tumour cells with respect to normal brain cells renders glioblastoma a good candidate for selective targeted therapies. Recent experimental strategies focus on over expressed cell surface receptors. Targeted toxins represent a new class of selective molecules composed by a potent protein toxin and a carrier ligand. Targeted toxins approaches against glioblastoma were under investigation in phase I and II clinical trials with several immunotoxins (IT)/ligand toxins such as IL4-Pseudomonas aeruginosa exotoxin A (IL4-PE, NBI-3001), tumour growth factor fused to PE38, a shorter PE variant, (TGF)alpha-TP-38, IL13-PE38, and a transferrin-C diphtheriae toxin mutant (Tf-CRM107). In this work, we studied the effects of the plant ribosome-inactivating saporin and of its chimera transferrin-saporin against two different GBM cell lines. The data obtained here indicate that cell proliferation is affected by the toxin treatments but that different mechanisms are used, directly linked to the presence of an active or inactive p53. A model is proposed for these alternative intracellular pathways.

Impact of neuropeptide substance P an inflammatory compound on arachidonic acid compound generation.

There is much evidence that neuropeptide substance P is involved in neurogenic inflammation and is an important neurotransmitter and neurmodulator compound. In addition, substance P plays an important role in inflammation and immunity. Macrophages can be activated by substance P which provokes the release of inflammatory compounds such as interleukins, chemokines and growth factors. Substance P is involved in the mechanism of pain through the trigeminal nerve which runs through the head, temporal and sinus cavity. Substance P also activates mast cells to release inflammatory mediators such as arachindonic acid compound, cytokines/chemokines and histamine. The release of these chemical mediators is crucial for inflammatory response. Among these mediators there are prostoglandins and leukotrines. Here we review the impact of substance P on inflammatory compounds.

A rare case of intracranial rosai-dorfman disease mimicking multiple meningiomas. A case report and review of the literature.

Rosai-Dorfman disease (RDD) was firstly described in 1969 as a benign proliferative disorder of histiocytes with systemic symptoms and lymphadenopathy. This disease is of uncertain pathogenesis and mostly occurs in children and young adults. The typical clinical features of RDD include bilateral painless cervical lymphadenopathy, but extranodal involvement may also be present. The most common extranodal sites include organs such as the respiratory tract, skin, nasal cavity, orbit and bone. Isolated central nervous system (CNS) manifestations are extremely rare. In case of CNS involvement, the commonest imaging findings are dural-based extra-axial enhancing masses. We describe a case of intracranial RDD mimicking multiple meningiomas both clinically and radiologically in a 57-year-old man presenting with a six-year history of progressive right visual and hearing loss and tinnitus. In cases of multiple extra-axial lesions it is worth bearing in mind the possible differential diagnosis for intracranial RDD and eventually propose to the patient further investigations.

Cholesterol, cytokines and diseases.

A high level of cholesterol is associated with obesity, cardiovascular diseases and atherosclerosis. Immune response in atherosclerosis is mediated by chemokines which attract monocytes, leading to the innate immune response characterised by the production of cytokines. The immunoregulatory cytokines are an important bridge between innate and adductive immunity. TH1 cytokines are involved as effector T cells in inflammatory response, while TH2 cytokines can be anti-inflammatory such as IL-10 and IL-4. It is well known that statins enhance the production of TH2 cytokines whereas the secretion of TH1 cytokines is suppressed. For this purpose, we studied the significance of anti-inflammatory effect and suppression of inflammation by statins. In this paper we revisited the role of cholesterol and cytokines IL-18, IL-10, IL-12, TNF-α, interferon-γ, and chemokines in inflammatory diseases.

Psychological stress and vitamins.

Conditions of stress and anxiety have complex interactions with insufficient vitamin intake and malnutrition. This study, based on literature research in Medline, analyzes the inter-relationship between vitamins and stress. This report concerns a number of vitamins that have been receiving much attention in earlier reviews of the literature, for their potential to protect against stress-related events, and focus is placed upon recent findings.

Hypoxia induces peroxisome proliferator-activated receptor α (PPARα) and lipid metabolism peroxisomal enzymes in human glioblastoma cells.

Glioblastoma multiforme (GBM) represents the most severe type of glioma, the most common brain tumor. Their malignancy shows a relationship with an increased proliferation and a poorly organized tumor vascularization, an event that leads to inadequate blood supply, hypoxic areas and at last to the formation of necrotic areas, a feature of glioblastoma. Hypoxic/necrotic tumors are more resistant to chemotherapy and radiation therapies, thus it is crucial to formulate new therapeutic approaches that can render these tumors more sensitive to the action of conventional therapies. It has been demonstrated that under hypoxia, gliomas accumulate lipid droplets and that this event is positively correlated with the degree of malignancy, glioblastoma being the most endowed with lipid droplets. We have previously demonstrated in ex vivo glioma specimens a grade-dependent lipid metabolism perturbation. Here we studied the lipid pathways and the presence of stemness markers in glioma primary cultures, obtained from surgical specimens of patients affected by glioma at different grade of malignancy, GBM primary cultures cultured under both hypoxic and normoxic conditions, as well as normal human astrocytes. The results obtained demonstrate that hypoxia plays a crucial role in regulating the expression of lipid metabolism peroxisomal enzymes, the lipid droplets accumulation as well as the transcription factor PPARα.

Allergic inflammation: role of cytokines with special emphasis on IL-4.

This review examines recent articles on the relationship of cytokines to allergy and inflammation with particular emphasis on interleukin (IL)-4. The objective of this article is therefore to review published studies to identify cytokines consistently involved in allergic inflammation. Proinflammatory cytokines, including IL-4, IL-5, IL-13 and GM-CSF along with TNF-alpha play a role in allergen-induced airway leukocyte recruitment and these cytokines can be generated by T mast cells and other cells. In addition, IL-9, IL-25, IL-33, IL-17, IL-27 and IFN-gamma are deeply involved in the regulation of asthma. Blocking the effect of these proinflammatory cytokines might provide new therapeutic approaches for the control of allergy and inflammation.

Impact of IL-18 on inflammation.

IL-18 is produced by many cell types, such as Kupffer cells, keratinocytes, macrophages, dendritic cells, and activated T cells stimulated by LPS. It is an important regulator of both innate and acquired immune responses. IL-18 plays a central role in rheumatoid arthritis since the T cells and macrophages that invade the synovial. These finding support a role for IL-18 in inflammation, allergy and immune diseases.

Skull bone flap fixation - reliability and efficacy of a new grip-like titanium device (Skull Grip) versus traditional sutures: a clinical randomized trial.

BACKGROUND: After completing a craniotomy, it is important to replace the removed bone flap in its natural position in order to guarantee brain protection as well as improve cosmesis. A skull defect can expose the brain to accidental damage, and in cases of larger defects it may also cause the patients psychosocial problems. The ideal fixation device should provide reliable attachment of the flap to the skull and promote fast bony healing to avoid possible pseudo-arthrosis and/or osteolytic changes. MATERIALS AND METHODS: This is a pilot randomized clinical trial on a series of 16 patients undergoing different craniotomies for benign brain lesions in which the bone flaps were replaced using traditional sutures (Prolene 0.0) in 8 cases and with a new skull fixation device (Skull Grip) in the other 8 (randomly allocated). All patients underwent CT scans of the head with 3D reconstruction at day 1 and day 90 postoperatively to evaluate bone flap position and fusion. These scans were independently reviewed by a neuroradiologist. Cosmesis was also evaluated clinically by the surgeon and radiologically by the neuroradiologist in the 2 patient groups. RESULTS: The new "Skull Grip" device has shown stronger fixation qualities with optimal bone flap fusion and increased cosmetic healing features vs. traditional sutures. CONCLUSION: The "Skull Grip" has shown to be a reliable, effective and stronger bone flap fixation device when compared to traditional sutures.

Interrelationship between vitamins and cytokines in immunity.

Cytokines are important proteins that modulate immunity and inflammation. Vitamins are also involved in immunity and inflammation. They are found to restore the ability of some cells to produce certain cytokines. Vitamin deficiency appears to affect the mechanism of immune cells, though the impact of reduced cytokine response in vitamin malnutrition is not clear. Vitamin D is involved in many medical conditions, such as infections and inflammation, and mediates innate immunity. Deficiency of vitamin D increases the risk of infectious and inflammatory diseases. In addition, this vitamin modulates Treg function and IL-10 production which is important for therapeutic treatment. Vitamin A increases inflammatory response and is involved in tissue damage; moreover, vitamin A is a key modulator of TGFbeta which can suppress several cytokines. Vitamin E, an anti-ageing compound, is associated with a defect of naive T cells and may inhibit some inflammatory compounds such as prostaglandin generation.