Complex craniomaxillofacial gunshot wounds A step-by-step multidisciplinary approach.

BACKGROUND: Gunshot injuries of the viscerocranium are rarely reported. Penetrating wounds to the cranio-maxillofacial region pose a significant challenge for surgeons as they often comprise serious soft tissue, bone and cerebral defects. We present a case report of a 42-year old female with a gunshot wound to the viscerocranium after suicidal attempt. Series of image of the disease course are available. CASE DESCRIPTION: A 42-year-old female presented with gunshot wound to the viscerocranium after a suicidal attempt. At the arrival GCS was 8/15 and general examination showed the inlet wound in the submental region whereas the outlet one in the left temporal skull area. After first rescue procedures, ICP was monitored before proceeding surgically. Due to massive hemorrhage, embolization of ianternal maxillary artery was performed. Afterwards, tracheostomy, surgical reduction of multiple maxillo-facial fractures and ocular avulsion were performed. In a second time, ICP monitoring and CT scan revealed ICH signs due to intraparenchimal injures. The patient underwent to a second surgical procedure, consisting of bifrontal decompressive craniectomy. The patient was discharged on 20th post-op day to a rehabilitation center. She returned to our department after 4 months to perform a craniomaxillofacial recostruction. She presented 15 in GCS, left ptosis, left VII cranial nerve deficit, decannulated, KPS 100%. CONCLUSION: A step-to-step multidisciplinary approach both with Neurosurgeons and Maxillo-facial surgeons is mandatory in Cranial Gunshot Injuries where extensive damage is linked to a higher mortality. KEY WORDS: Cranial gunshot inuuries, Cranial reconstruction, Maxillofacial reconstruction.

Unusual case of traumatic neuroma of the orbit.

Traumatic or amputation neuromas are neoformations developing after damage to a peripheral nerve. They are not proper tumors but rather a reactive process or a frustrated attempt of nerve regeneration. Traumatic neuromas are potentially found in every sensory peripheral nerve and often at the site of past surgical intervention, including orbital surgery. A 29-year-old Northern African migrant presented progressive exophthalmos and progressive loss of acuity in left eye, which had started about 6 months before after a cranio-facial trauma caused by a violent assault. MRI of the orbits showed a massive intra-orbital, intra-conical lesion, clearly compressing and dislocating the optic nerve and extending posteriorly to the orbital apex. Surgery was performed through lateral approach of Kroenlein and led to complete excision of the lesion. Histology revealed fibrotic, adipose and striated muscle tissues, a disordered, non-neoplastic overgrowth of small and large fascicles of nerves, inflammatory infiltrates, and fibrosis with sparse calcifications were diffusely observed in a background of fat, scar and striated muscle tissued. Patient was discharged on the fifth day in good health condition, without deficit of eye motion but without recovery of visual acuity. In conclusion, this case demonstrates that traumatic neuromas may arise in the orbit in patients with minor direct trauma to nerves and without previous surgical treatment.

Pediatric spinal epidural abscess in an immunocompetent host without risk factors: Case report and review of the literature.

Spinal epidural abscesses (SEAs) are unusual bacterial infections, with possible devastating neurologic sequelae. Despite abundance of case series in adults, reports in children are scanty. We describe a spontaneous SEA due to methicillin susceptible Staphylococcus aureus (MSSA) in a previously healthy 15-year old male, and we perform a literature review regarding management of pediatric SEAs without risk factors, from 2001 to 2014. We found a total of 12 cases (8 males, average age 9.6 years). Clinical presentation was mainly fever, back pain and elevation of inflammation markers. All cases were initially misdiagnosed. Lumbar puncture was performed in 36% of patients. Etiological diagnosis was obtained in 8 cases. MSSA was isolated in 4 patients, methicillin-resistant S. aureus in 1 patient, and S. aureus with unknown susceptibility patterns in 2 cases. The average of therapy duration was 6 weeks. Patients' spine was always evaluated by gadolinium-enhanced magnetic resonance imaging; most abscesses were localized at thoracic and lumbar area, without osteomyelitis. In 8 cases, laminectomy and/or abscess drainage were performed in association with medical therapy; 3 cases were successfully treated with antimicrobial therapy only; no data were available in one case. A good outcome was obtained in all patients, except a reported residual headache and paraspinal pain lasting for 3 years. The rarity and the possible differential diagnosis can lead to underestimate SEA occurrence in children without risk factors. It seems therefore essential to maintain a high attention to pediatric SEAs. A prompt diagnosis and adequate therapy are essential prognostic factors for remission.

Expression of Tight Junction and Drug Efflux Transporter Proteins in an in vitro Model of Human Blood-Brain Barrier.

Interendothelial cell tight junctions (TJs) proteins contribute to maintain the structural and functional integrity of the blood-brain barrier (BBB) and several efflux transporters regulate transport of compounds across BBB. A unique double compartment-model of the BBB, consisting of cerebral endothelial cells isolated from cryopreserved human glial tumors, alone and in the presence of human astroglial cells derived from the same tissue preparation was established. Endothelial cell viability and transendothelial electrical resistance (TEER) were measured in this model and three representative TJ proteins - occludin (OCLN), zonula occludens-1 (ZO-1) and claudin-5 (CLN-5) - as well as several drug efflux transporters - P-glycoprotein (P-gp), multidrug resistance protein-1 and 2 (MRP-1 and MRP-2), organic anion-transporting polypeptide-1 and 3 (oatp1 and oatp3) were analyzed at both the protein and gene transcript level. Functional activity of P-gp and MRP-1 was also assessed. Endothelial cell viability as well as TEER significantly increased in the presence of glial cells. A significant increase of expression of OCLN, ZO-1, and CLN-5 proteins as well as of several drug transporter proteins except oatp3 and MRP-1, was also found in the presence of glial cells. All the gene transcripts protein analyzed were found to be significantly increased in the presence of glial cells. A suitable functional activity of P-gp and MRP-1 was also found. These results demonstrate that this brain endothelium culture system mimics a physiologically relevant situation and may therefore provide a new tool for studying the effects of biological fluids such as serum and cerebrospinal fluid from patients with neurological disorders underlying a BBB alteration in disease pathogenesis.

Orbital glomangioma.

Glomangioma is a vascular hamartomatous tumor originating from the glomus body, a specialized thermoregulatory organ localized in the dermis and precoccygeal soft tissue. Glomus tumors are characteristically found in the hands and are very rarely reported in the head region. Here we describe a 29-year-old woman presenting with acute proptosis and pain in the left eye. A computed tomography scan of the orbit revealed a well-defined circumscribed mass, displacing the globe and lateral rectus muscle inferotemporally. The tumour was surgically removed through a lateral Kronlein approach. On histology, the lesion consisted of cavernous vascular spaces, partly filled with blood and thrombotic material, and a mixture of capillary-sized vessels and tumor cells; immunostaining for smooth actin showed a strong positivity in the cytoplasm of tumor cells, consistent with a diagnosis of glomangioma. Our case adds to the very few cases of orbital glomangioma reported in the literature and demonstrates that this tumor can be safely removed.

Identification of cancer stem cells from human glioblastomas: growth and differentiation capabilities and CD133/prominin-1 expression.

CD133 can be a marker of tumorigenic CSCs (cancer stem cells) in human GBM (glioblastoma multiforme), although tumorigenic CD133-negative CSCs have been also isolated. Additional evidence indicates that CSCs from GBM exhibit different phenotypes, with increasing interest in the potential significance of the different CSCs with respect to diagnosis, prognosis and the development of novel targets for treatment. We have analysed the expression of CD133 in freshly isolated cells from 15 human GBM specimens. Only 4 of them contained cells positive for AC133 by FACS analysis, and all of them yielded distinct CSC lines, whereas only 6 CSC lines were obtained from the other 11 GBMs. Of these 10 CSCs lines, we further characterized 6 CSC lines. Three CSCs grew as fast-growing neurospheres with higher clonogenic ability, whereas the remaining 3 grew as slow-growing semi-adherent spheres of lower clonogenicity. In addition, the former CSC lines displayed better differentiation capabilities than the latter ones. PCR and Western blot analysis showed that all 6 GBM CSC lines expressed CD133/prominin-1, suggesting that cells negative by FACS analysis may actually represent cells expressing low levels of CD133 undetected by FACS. Nevertheless, all the 6 CSC lines were tumorigenic in nude mice. In conclusion, CSCs from human primary GBMs show different phenotypes and variable levels of CD133 expression, but these parameters did not directly correlate with the tumorigenic potential.

ß-catenin and Gli1 are prognostic markers in glioblastoma.

Glioblastomas (GBMs), the most common primary malignancies of the central nervous system, are highly aggressive and heterogeneous, and remain a dramatic therapeutic challenge. Markers mirroring the complex molecular profile of GBMs that are predictive of patient outcomes are needed to define novel multi-targeted treatment strategies. Resistance to current GBM therapies is partly due to a subpopulation of stem-like and other self-renewing cells (hereafter called glioma stem-like cancer cells, GSCC), which are therefore of key interest as therapeutic entry points. Wnt and Hedgehog are among the main pathways involved in GSCC renewal. ß-catenin and Gli1 are markers of Wnt and Hedgehog activation respectively and both pathways are known to be altered in gliomas. To date, there are no investigations of Gli1 protein expression in GBM tissue, and recently a high expression of ß-catenin has been found to have a poor prognostic impact in GBM patients in a study. We have therefore quantified the positivity for ß-catenin, Gli1, as well as Ki-67, p53, and EGFR proteins on immunohistochemically-stained GBM sections from 106 patients in an investigation for potential predictive biomarkers. Correlation between these markers and survival was evaluated by pair-wise Pearson correlation coefficient and by bi-dimensional hierarchical clustering, followed by survival estimations using linear regression models and classification trees. We demonstrated that both ß-catenin and, for the first time, Gli1 proteins are highly predictive markers of short survival, being found in 75 and 90% of the highly predictive trees, respectively, whereas Ki-67, p53 and EGFR were under 30% and thus, not considered as predictive. Our results indicate a role of ß-catenin and Gli1 in GBM malignant behaviour, and suggest that inhibiting members of Wnt and Hedgehog pathways could be a valuable therapeutic strategy for GBM patients.

Prevention of post-operative infections in spine surgery by wound irrigation with a solution of povidone-iodine and hydrogen peroxide.

INTRODUCTION: Starting from January 2009, we systematically irrigated the surgical wounds of patients undergoing spine surgery with a solution of povidone-iodine (PVP-I) and hydrogen peroxide (H(2)O(2)). METHOD: We prospectively recorded the clinical data of patients who underwent spine surgery during 2009 and we compared the results with retrospectively reviewed clinical records of patients operated during 2008. Patients were analyzed for preoperative risk factors, type of surgical procedure, onset of the infection, clinical presentation, treatment, and outcome. We performed 460 spine surgeries during 2008 and 490 during 2009. RESULTS: We recorded seven post-operative infections in 2008 compared to none in 2009. CONCLUSION: We consider the solution of PVP-I plus H(2)O(2) effective in further reducing the rate of post-operative infection in spine surgery.

Three-dimensional conformal radiotherapy, temozolomide chemotherapy, and high-dose fractionated stereotactic boost in a protocol-driven, postoperative treatment schedule for high-grade gliomas.

AIMS AND BACKGROUND: No available scientific report deals with high-dose (> or = 70 Gy) radiotherapy plus temozolomide chemotherapy (TMZ CHT) in high-grade gliomas. The survival results of a protocol-driven, postoperative treatment schedule are reported here to contribute to the discussion on this issue. METHODS AND STUDY DESIGN: Uniform criteria were prospectively adopted for case selection during the period 1993-2006 in the management of 123 patients, and we progressively introduced three-dimensional conformal radiotherapy (3D-CRT, 60 Gy), TMZ CHT and a high-dose (70 Gy) stereotactic boost (HDSRT) in the treatment schedule. Palliative radiotherapy was delivered by whole brain irradiation (WBI, 50 Gy) for bulky tumors, whereas radical irradiation was performed with 3D-CRT throughout the study period. Two periods of accrual are considered: 36 patients were treated before 31 December 1999 (29.25%) and 87 (70.75%) after 1 January 2000. This subdivision was due to the implementation of HDSRT hardware and TMZ CHT from January 2000. RESULTS: The median overall survival was 13 months and the 1-, 2- and 3-year survival rates were 53%, 19.5% and 11.6%, respectively. The differences in survival related to the treatment variables were highly significant, both in univariate and multivariate analysis. The median survival and 1-, 2- and 3-year survival rates in the palliative WBI group were 9.75 months and 37%, 2%, and 0%, respectively; in the 3D-CRT group 17.25 months and 64%, 34%, and 15%, respectively; in the TMZ CHT concomitant with radiotherapy group 20 months and 61%, 39%, and 21%, respectively; in the TMZ CHT concomitant with and sequential to radiotherapy group 25.75 months and 84%, 54%, and 26%, respectively, and in the HDSRT group 22 months and 72%, 48%, and 37%, respectively. No symptomatic radiation necrosis occurred in any of the groups. CONCLUSIONS: The results reported here are generally better than those reported in the literature. The selection of patients on the basis of favorable prognostic factors and suitability to the currently available, aggressive postoperative treatment resources can be the mainstay for improving therapeutic results. In particular, the new treatment option reported here (HDSRT in association with TMZ CHT) proved to be safe and effective in obtaining a relatively favorable outcome.

The prognostic role of Beclin 1 protein expression in high-grade gliomas.

High-grade gliomas (HGG) have a poor outcome, however, prognostic subgroups of patients may be individuated by some clinico-biological parameters. It was recently demonstrated that the main response of HGG to therapy is autophagic death. Autophagy is involved in tumor suppression, and is defective in HGG, in which we previously found an underexpression of beclin 1 autophagic gene protein product. Underexpression of Beclin 1 protein has been correlated to poor patient outcome in other tumor types. In this paper, the prognostic role of Beclin 1 expression in HGG patients was investigated. We first evaluated the tumor cell cytoplasmic expression of Beclin 1 protein (BPCE), in a sample of 76 HGG by immunohistochemistry, and compared it with cell proliferation and apoptosis. We found high BPCE score positively correlated with apoptosis, and negatively with cell proliferation (p < 0.05). We then correlated BPCE score with survival and other prognostic parameters (histological grading, MGMT gene methylation status, age, patient performance status according to the Karnofski classification (KPS), extent of surgery, radiation therapy (RT) modality, temozolomide chemotherapy (TMZ CHT), and optimal/suboptimal post-surgical treatment). Forty-seven (61.8%) and twenty-nine (38.2%) patients showed high and low BPCE scores, respectively. BPCE showed statistically significant correlations with survival both at the univariate (p = 0.03) and multivariate analysis (p = 0.037). High BPCE was also positively correlated with high KPS values (p = 0.023), and with the accomplishment of an optimal postoperative therapy (p = 0.037). Furthermore, among patients showing a MGMT methylated gene, survival was significantly higher in cases with a higher BPCE score. BPCE score might be added to pathological evaluation of HGG for prognostic purposes.

Neuroradiological follow-up of the growth of papillary tumor of the pineal region: a case report.

Papillary tumor of the pineal region (PTPR) is a recently described distinct clinicopathological entity. The purpose of this case report is to increase the knowledge of its neuroradiological findings and natural history by describing the long-term clinical and neuroradiological follow-up of a PTPR occurring in a 56-year-old Italian male patient. At magnetic resonance imaging (MRI) obtained at diagnosis, the lesion showed a subtle high signal intensity on T1-weighted imaging. Twenty-nine months later, MRI showed clearcut enlargement of the lesion, which had only a small area of high signal intensity on T1-weighted images, and a minimum apparent diffusion coefficient of 0.854 x 10(-3) mm(2)/s. Treatment included surgery followed by irradiation. Three-month MRI follow-up did not show disease relapse.

Pediatric sinonasal neuroendocrine carcinoma after treatment of retinoblastoma.

Patients who survive retinoblastoma are at risk for developing additional malignant neoplasms, including tumors of the sinonasal tract. We report 2 cases of secondary sinonasal malignancy arising in pediatric patients previously treated for retinoblastoma, with features of neuroendocrine carcinoma. Both lesions were characterized by a proliferation of round to oval cells arranged in solid sheets, trabeculae, and nests, diffusely infiltrating nasal mucosa and bone tissue. Immunohistochemically, they were diffusely positive for epithelial markers, as well as for neuroendocrine markers and for TP53 and retinoblastoma gene products. TP53 gene analysis showed the presence of a missense mutation P72R (CCC/CGC) and a single nucleotide polymorphism P36P (CCG/CCA) in exon 4 in 1 case. Literature review revealed 5 previously reported cases, all showing primitive undifferentiated morphology with variable expression of neural and epithelial markers. These tumors represent a peculiar subset of undifferentiated sinonasal neoplasms with extremely aggressive clinical behavior.

Remote cerebellar haematoma after lumbar disc surgery. Case report.

Remote cerebellar haematoma (RCH) from the operative site is one of the most serious, although extremely rare, complications of spinal surgery. Dural opening is common to every reported case of a spinal procedure complicated by cerebellar hemorrhage, supporting the hypothesis that CSF loss is central to the pathogenesis of this condition. We report our experience with the case of cerebellar haematoma after lumbar disc surgery and the literature is reviewed.

Intracranial epidermoid cyst: case report.

Intracranial epidermoid cysts are estimated to constitute 0.2 to 1.8% of brain tumours (4) and they can be divided into four categories describing their anatomic origin and frequent primary location: retro-sellar-cerebellopontine angle, parasellar-sylvian fissure, suprasellar-chiasmatic and basilar-posterior fossa. We describe an unusual case of pre-pontine epidermoid cyst arising in the temporal lobe and in inter-peduncles cistern: development and surgical treatment are discussed.

Stem cell treatment in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis is a progressive fatal neurodegenerative disease that targets motor neurons. Its origin is unknown but a main role of reactive astrogliosis and microglia activation in the pathogenesis has been recently demonstrated. Surrounding neurons with healthy adjoining cells completely stops motor neuron death in some cases. Hence stem cell transplantation might represent a promising therapeutic strategy. In this study MSCs were isolated from bone marrow of 9 patients with definite ALS. Growth kinetics, immunophenotype, telomere length and karyotype were evaluated during in vitro expansion. No significant differences between donors or patients were observed. The patients received intraspinal injections of autologous MSCs at the thoracic level and monitored for 4 years. No significant acute or late side effects were evidenced. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. Four patients show a significant slowing down of the linear decline of the forced vital capacity and of the ALS-FRS score. Our results seem to demonstrate that MSCs represent a good chance for stem cell cell-based therapy in ALS and that intraspinal injection of MSCs is safe also in the long term. A new phase 1 study is carried out to verify these data in a larger number of patients.

Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours.

Beclin 1 is is an autophagy gene, the role of which as a tumour suppressor has recently been recognized in a few studies. We examined the expression of Beclin 1 protein in 212 primary human brain tumours, including 97 high-grade glial tumours, 29 low-grade glial tumours, 4 grade III meningiomas, 19 grade II meningiomas, 52 grade I meningiomas, and 11 medulloblastomas. In 94 cases, including 56 glial tumours, 35 meningiomas, and 3 medulloblastomas we also assessed Beclin 1 mRNA expression by real-time RT-PCR. In most high-grade astrocytic, ependymal neoplasms and atypical meningiomas we found a decrease of cytoplasmic protein expression that was, instead, high in the majority of low-grade tumours and in medulloblastomas. The expression level of Beclin 1 mRNA was significantly lower in glioblastomas than in grade II (p=0.04) and grade I (p=0.01) astrocytomas; in grade III than in grade I astrocytomas (p=0.01); in grade II than in grade I meningiomas (p=0.03); and in all glial tumours when compared to all meningiomas (p<0.0001). Cytoplasmic expression is thought to be linked to the functional protein. Our observations are in line with studies that demonstrated decreased expression of Beclin 1 in human breast, ovarian, prostate and ovarian cancer and furtherly support its involvement also in brain tumours, which had previously been demonstrated in a few experimental studies, both in spontaneous and in therapy-induced autophagy. Furthermore, our study suggests possible differences of Beclin 1 involvement and its role among the different histotypes of brain neoplasms. Further studies are needed to highlight Beclin 1 function in tumour suppression and/or in tumour survival through autophagy and other related programmed cell death processes in brain tumours.