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Background: Rhinocerebral mucormycosis (ROCM) is an opportunistic fungal infection originating from the paranasal sinuses with extension to the brain. A delayed diagnosis can rapidly result in a poor prognosis. ROCM commonly affects patients with diabetes or immunocompromised states with a variable progression. Case Description: We report the case of a 59-year old patient with an untreated diabetes who developed a ROCM with rapidly progressive neurological symptoms. From the onset of sinus pain, nasal congestion, he rapidly developed facial swelling and masticatory dysfunction. The patient underwent sinus surgery which allowed Rhizopus oryzae to be isolated. Accordingly, a systemic therapy by intensive intravenous amphotericin B was started. Nevertheless, the infection rapidly resulted in bilateral cavernous sinuses thrombosis and occlusion of the left internal carotid artery providing the subsequent patient death. Conclusion: Mucormycosis is a life-threatening fungal infection in diabetic and/or immunosuppressed patients. Our case demonstrates the three main mechanisms for infection spreading that are direct, perineural, and perivascular diffusion. Clear identification of the main risk factors, proper assessment of clinical features, and radiological findings may improve the chance for an early diagnosis and patient survival.

Background We present an unusual but possible complication after ETV for the treatment of acute hydrocephalus due to malfunction of a previously implanted V-P shunt. Case Description A 12-year-old male patient was urgently operated upon by means of an endoscopic third-ventriculostomy and the positioning of a temporary external ventricular catheter because of the malfunction of a previously implanted V-P shunt; immediately after the operation, the tip of the external catheter caused an obstruction of the ostomy, which was resolved with the withdrawn of catheter for circa 1 cm, left closed and ultimately removed after 4 days. The patient did not present any further symptom and remained shunt-free at the last 2-year follow-up visit. Conclusions One should consider such occurrence in cases of early ETV failure when a ventricular catheter is left in situ, even though temporarily.

Background The differential diagnosis between radiation necrosis, tumor recurrence and tumor progression is crucial for the evaluation of treatment response and treatment planning. The appearance of treatment-induced tissue necrosis on conventional Magnetic Resonance Imaging (MRI) is similar to brain tumor recurrence and it could be difficult to differentiate the two entities on follow-up MRI examinations. Dynamic Susceptibility Contrast-enhanced (DSC) and Dynamic Contrast-Enhanced (DCE) are MRI perfusion techniques that use an exogenous, intravascular, non-diffusible gadolinium-based contrast agent. The aim of this study was to compare the diagnostic accuracy of DSC and DCE perfusion MRI in the differential diagnosis between radiation necrosis and tumor recurrence, in the follow-up of primary and metastatic intra-axial brain tumors after Stereotactic RadioSurgery (SRS) performed with CyberKnife. Methods A total of 72 enhancing lesions (57 brain metastases and 15 primary brain tumors) were analyzed with DCE and DSC, by means of MRI acquisition performed by 1,5 Tesla MR scanner. The statistical relationship between the diagnosis of tumor recurrence or radiation necrosis, decided according to clinicoradiologically criteria, rCBV and Ktrans was evaluated by the point-biserial correlation coefficient respectively. Results The statistical analysis showed a correlation between the diagnosis of radiation necrosis or recurrent tumor with Ktrans (rpb = 0.54, p

Cerebrovascular malformations include a wide range of blood vessel disorders affecting brain vasculature. Neuroimaging differential diagnosis can result unspecific due to similar phenotypes of lesions and their deep localization. Next-generation sequencing (NGS) platforms simultaneously analyze several hundreds of genes and can be applied for molecular distinction of different phenotypes within the same disorder's macro-area. We discuss about the main criticisms regarding molecular bases of cerebral cavernous malformations (CCM) and brain arteriovenous malformations (AVM), highlighting both common pathogenic aspects and genetic differences leading to lesion development. Many recent studies performed on human CCM and AVM tissues aim to detect genetic markers to better understand molecular bases and pathogenic mechanism, particularly for sporadic cases. Several genes involved in angiogenesis show different expression patterns between CCM and AVM, and these could represent a valid starting point to project a NGS panel to apply for differential cerebrovascular malformation diagnosis.

Background: Osteomyelitis is a progressive infection of bone and bone marrow by microorganisms, resulting in inflammatory destruction of bone, bone necrosis, and new bone formation. Skull involvement is a rare occurrence which mainly affects children with chronic inflammatory diseases of paranasal sinusitis, or malignant otitis. In adults, cranial vault osteomyelitis can occur after cranial surgery or head trauma. Case Description: We describe an unusual case of chronic cranial osteomyelitis occurred 3 months following a mild traumatic brain injury. The causative mechanisms along with the diagnostic modalities are discussed. Conclusion: Focal cranial vault osteomyelitis, in the absence of severe trauma, can be challenging to diagnose. Imaging findings and patient history should be carefully investigated to make a correct diagnosis.

A 42-year-old woman presented with progressive blurred vision, vertigo, and headache. MRI showed bilateral intraocular protrusion of the optic nerve head and right transverse sinus thrombosis . Low-molecular-weight heparin was administered without symptom relief. Additional MRI showed left frontoparietal arachnoid space obliteration by pathological tissue, and infiltration of the sagittal and right transverse sinuses. After Gd administration, we observed diffuse enhancement of the dura in the left cerebral hemisphere and subdural and epicranial soft-tissue infiltration . A biopsy of the extra-axial tissue was performed. Histological examination showed a neoplasm composed of large cells with ovoid nuclei associated with non-neoplastic lymphocytes. Frequent mitotic figures were observed in the large cells. The large neoplastic cells were positive for CD20, bcl-2, bcl-6, and MUM1 and negative for CD10 and CD30. Accordingly, a diffuse infiltrative form of Bing-Neel syndrome was diagnosed. The patient was treated with 3 cycles of rituximab, dexamethasone, methotrexate HD, and cytarabine. Osmotic and steroid therapies were undertaken.

Background: Intramedullary spinal ependymoma is a tumor, hardly characterizable with conventional magnetic resonance (MR) imaging only. MR diffusion tensor imaging (DTI) with three dimensional fiber tracking reconstructions allows the evaluation of the relationship between neoplasm and white matter fiber tracts, being a powerful tool in presurgical planning. We present DTI findings in a case of a young female with an extensive cervicothoracic spinal ependymoma. Case Description: The patient complained of a 2 month history of acute urinary retention, weakness and numbness on the lower limbs and the upper left limb. She underwent MR imaging that showed an extensive cervicothoracic spinal mass, difficult to characterize with conventional MR sequences. DTI showed peripherally displacement of fibers, without involvement of the spinal cord, findings consistent with an ependymoma. The patient underwent surgery with a complete resection "en bloc" of the lesion, which showed clear cleavage planes, as detected by DTI. Histopathological findings confirmed the diagnosis of ependymoma. Conclusions: DTI is a useful tool in presurgical planning, helping in differentiating not infiltrating neoplasms, such as spinal ependymomas, from other infiltrative and more aggressive neoplasms, which are considered not resectable. © 2017 Surgical Neurology International | Published by Wolters Kluwer - Medknow.

Following aneurysmal subarachnoid hemorrhage, the primary goal of treatment is to exclude the vascular malformation from the intracranial circulation, while preserving the parent artery. In unruptured aneurysms, the decision whether to treat or observe the malformation is made on a case-by-case basis. In this regard, the ISUIA (International Study of Unruptured Intracranial Aneurysms) investigators suggested that aneurysm size and location were independent predictors for aneurysm rupture.1 ISUIA examined 1692 patients with cerebral aneurysms with a mean follow-up time of 4.1 years. Rupture rates differed depending on size and location, ranging from 0% in aneurysms 25 mm located in the posterior circulation. More recently, UCAS (Unruptured Cerebral Aneurysm Study) reported results similar to ISUIA. However, other evidence has contradicted these studies, with a higher percentage of small aneurysms reported among case series of ruptured intracranial aneurysms. This indicates a discrepancy between the ISUIA and UCAS data and the size of ruptured aneurysms seen in routine clinical practice.

Cerebral cavernous malformations (CCMs) are clusters of capillaries in the brain that may cause focal deficits or seizures in affected patients. They occur in both sporadic and inherited autosomal dominant form. Germline mutations in CCM1, CCM2 and CCM3 were identified in familial cases. Over the past 13 years we performed sequencing and MLPA of the CCM genes in all sporadic and familial CCM cases coming from some hospital clinics of Neurology and Neurosurgery of Messina and other Italian cities. Our results showed that CCM sporadic patients, negative for previously reported CCM gene causative mutations, always carried known CCM polymorphisms. Previously, we reported polymorphisms in CCM2 gene associated with an increase in risk for CCM. Here, we undertook a case-control study to investigate the possible association of others polymorphisms (c.485 + 65 C/G, c.989 + 63 C/G, c.1980 A/G in CCM1 gene, c.472 + 127 C/T in CCM2 and c.150 G/A in CCM3) with CCMs. The five polymorphisms were characterized in 64 sporadic patients and in 90 healthy controls by ASO-PCR. Statistically significant differences in frequencies between patients and controls were found for c.485 + 65C/G, c.1980 A/G and c.472 + 127C/T polymorphisms. For c.485 + 65C/G polymorphism, a higher frequency of mutated allele (G) was found in patients group (9%) than in controls (2%) (p = 0.0041); for c.1980 A/G polymorphism, we found a frequency of mutated allele (G) higher in the control group (25%) compared to that of patients (8%) (p = 0.0396). Same trend was observed for c.472 + 127C/T polymorphism (T allele frequency = 34% and 6% in control group and patients, respectively; p = 0.0001). Polymorphisms c.485 + 65C/G, c.1980 A/G and c.472 + 127C/T were associated with an increased risk of CCM as indicated by odds ratio values. Furthermore, c.1980 A/G and c.472 + 127C/T polymorphisms were associated with less severe CCM symptomatology. Identification of these polymorphisms in CCM sporadic patient may represent a useful tool for clinicians to determine prognosis, scheduled periodic checks and appropriate treatment strategy.

Background: The most common etiology of classic trigeminal neuralgia (TN) is vascular compression. However, other causes must be considered. Among these, spontaneous hematoma of the Meckel′s cave (MC) causing symptomatic TN is very rare. Case Description: We present the case of a 60-year-old woman with a 2-month history of left TN and diplopia. Neuroradiological examinations revealed a well-defined hematoma in the left MC. The patient underwent surgical decompression with a progressive neurological improvement. Conclusion: Despite the number of lesions potentially affecting the MC, spontaneous hemorrhage is rare but should be taken into account in the differential diagnosis.

Brain metastases (BM) are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. Metastasis development involves the migration of a cancer cell from the bulk tumor into the surrounding tissue, extravasation from the blood into tissue elsewhere in the body, and formation of a secondary tumor. In the recent past, important results have been obtained in the management of patients affected by BM, using surgery, radiation therapy, or both. Conventional chemotherapies have generally produced disappointing results, possibly due to their limited ability to penetrate the blood–brain barrier. The advent of new technologies has led to the discovery of novel molecules and pathways that have better depicted the metastatic process. Targeted therapies such as bevacizumab, erlotinib, gefitinib, sunitinib and sorafenib, are all licensed and have demonstrated improved survival in patients with metastatic disease. In this review, we will report current data on targeted therapies. A brief review about brain metastatic process will be also presented.

Object Meningiomas constitute 25% of primary spinal tumors and predominantly involve the thoracic spinal cord. Although calcifications are commonly seen in intracranial meningiomas, gross calcifications are observed in only 1–5% of all spinal meningiomas. We report the clinical findings, surgical strategy and histological features of 9 patients with ossified spinal meningiomas (OSMs). Patients and methods Clinical and surgical features of 9 patients with ossified spinal meningiomas were retrospectively reviewed. Results There were 8 women and 1 man with a mean age of 59 years. In 7 patients, the lesions were localized in the thoracic segment of the spine while in 2 patients in the lower cervical segment. All patients presented with weakness of the lower limbs and hypoesthesia below the site level of the lesion. Only 2 patients presented with urinary incontinence. Gross-total resection of the tumor was achieved in 6 patients while in 3 a subtotal removal of the meningioma was obtained. In all patients the postoperative course was uneventful. Six patients presented with a significant neurological improvement while in 3 patients a mild improvement was observed. Microscopically, all tumors showed typical histological pattern of ossified meningioma. Conclusions OSMs are amenable to surgery if the complete removal can be achieved. Because of their hard-rock consistency complete resection can be challenging. In difficult cases, subtotal removal can be advised and follow-up imaging is mandatory. Overall, the risk of long-term recurrence of the lesions is low, and a good clinical outcome after total or subtotal removal can be expected.

The transformation of normal cells into neoplastic cells is based on a series of gradual and progressive processes . One of the most important aspects underlying the tumorigenesis ist hat neoplastic proliferation needs mechanisms to ensure cancer development, bypass the body's protective strategies, and survive the apoptotic mechanisms. Subsequently, measures to promote replicative immortality and vascular support will be required. If cancer develops in an area offering excellent vascularization, pre-existing vascular circuits can supporti ts growth .Otherwise,tumor angiogenetic mechanisms will trigger new vascular networks, which will be necessary for tumor survival and expansion. The latter occurrence is what takes place in most of the neoplasms characterized by high growth pattern: proangiogenic factors secreted by the tumor, the most important being the vascular endothelial growth factor (VEGF), create a chemotactic gradient able to recruit endothelial cells and pericytes from the existing vascular system .

We read with great interest the article by Gazzeri et al1 focusing on tissue-glue–coated collagen sponge (TachoSil) application to repair minor cerebral dural sinus lacerations. In their series, 57 consecutive patients were prospectively enrolled, and tears of the cerebral venous sinus were treated by TachoSil application directly to the site of the bleeding. In all patients, venous bleeding was managed initially by standard techniques for hemostasis such as compression, application of oxidized cellulose, or gelatin sponge. TachoSil application was used when standard measures failed to be effective, were excessively time- consuming or inadequate, or were considered risky. No complications related to the use of the hemostatic device were observed, and the authors concluded that the use of such an agent may shorten the surgical procedure and achieve hemostasis in potentially hazardous bleeding from minor tears of the cerebral venous sinus.

Background A noninvasive method to predict the grade of a meningioma would be desirable since it would anticipate information about tumour nature, recurrence and improve tumour management and outcomes. The aim of the present study was to assess the ability of perfusion computed tomography (PCT) technique in predicting the meningioma grade before surgery. Data from PCT, such as cerebral blood volume (CBV) and permeability surface (PS), were correlated with immunohistolopathological information. Methods Twenty-three patients with a diagnosis of intracranial meningioma underwent PCT for pre-surgical evaluation of CBV and PS. During surgery, samples from the centre and periphery of the tumour were obtained. Two correspondent regions of interest (ROIs) were drawn on CBV and PS maps. Central and peripheral CBV and PS mean values were calculated. PCT parameters were correlated to CD-34 and endoglin. Results There was a positive correlation between PS and CD-34. No correlation was found between PS values and endoglin, CBV values and CD-34 and endoglin values. Conclusion Our findings suggest that PCT may support conventional morphological imaging in predicting meningioma grading before surgery.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. It is estimated that each year TBIs are associated with 1.1 million emergency department visits, 235,000 hospitalizations, and 50,000 deaths (1). Despite improvements in medical interventions, there are still no neuroprotective agents available to counteract secondary or delayed damage to the traumatically injured human brain or to promote its repair. TBI encompasses heterogeneous etiologic, anatomical, and molecular patterns of injury that exhibit different propensities to cause cerebral damage. Without careful consideration of individual injuries, the results of therapeutic trials remain difficult to interpret.

BACKGROUND: Glossopharyngeal neuralgia (GN) is a rare condition characterized by severe, paroxysmal episodes of pain mainly localized to the external ear canal, pharynx, and tongue, usually caused by a neurovascular conflict between postero-inferior cerebellar artery (PICA) and IX cranial nerve. Sometimes there is also a compression of X c.n. CASE DESCRIPTION: We present a case of a 71-year-old female with a 3-year history of intense pain localized in the pharynx and posterior portion of the tongue. Preoperative magnetic resonance imaging (MRI) documented a neurovascular conflict between a loop of PICA and IX left c.n. Surgery was performed through a retrosigmoid craniectomy. The intraoperative findings documented a loop of PICA compressing IX, X, and XI c.n. Microvascular decompression (MVD) of IX c.n. was performed using the interposing technique. No rhizotomy and MVD of the X c.n. was performed. Postoperative course showed the regression of all symptoms. CONCLUSIONS: The surgical treatment of patients with GN caused by complex neurovascular conflicts can be safely performed with the classical MVD of IX c.n. A double MVD of both IX and X c.n. has a role only in patients presenting symptoms from both nerves. Rhizotomy, in our opinion, has to be avoided in all cases. The authors review the literature concerning GN caused by complex neurovascular conflicts.

Subarachnoid hemorrhage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Although an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbidity and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered for the treatment of cerebral vasospasm. In recent years, the mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia following SAH, have been investigated intensively. A number of pathological processes have been identified in the pathogenesis of vasospasm, including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium. To date, the current therapeutic interventions remain ineffective as they are limited to the manipulation of systemic blood pressure, variation of blood volume and viscosity and control of arterial carbon dioxide tension. In this scenario, the hormone erythropoietin (EPO) has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is administered systemically. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH. In this context, the aim of the current review is to present current evidence on the potential role of EPO in cerebrovascular dysfunction following aneurysmal subarachnoid hemorrhage.

Introduction: Klippel-Feil syndrome is characterized by a congenital fusion of cervical vertebrae. Intracranial teratomas are nongerminomatous germ cell tumors and they account for 0.3 to 0.9% of all intracranial tumors. Teratomas with malignant transformation refer to lesions which give rise to malignant cancer of somatic type. The association between tumors of dermoid origin and Klippel-Feil malformation is extremely rare. Only 23 other cases have so far been reported, and only one case of dermoid tumor with areas of dedifferentiation on squamous cell carcinoma has been described. Case presentation: We report the case of a 72-year-old white man with a 2-year history of gait and balance disturbances. A brain magnetic resonance imaging revealed a fourth ventricle neoplastic process with infiltrative features. He was operated through a suboccipital craniectomy with a C1 laminotomy and bilateral vertebral artery transposition. At 6-months follow-up, magnetic resonance imaging showed an early regrowth of the fourth ventricle tumor, with the same radiological features. Conclusions: Patients with Klippel-Feil malformation could develop posterior fossa dermoid tumors. The malignant potential of such tumors must be considered and surgery is recommended. Particular attention must be focused on the histopathological analysis in order to identify possible foci of malignant transformation.

Introduction: Cavernous angiomas of the spinal cord are rare vascular malformations, which account for approximately 5 to 12 percent of spinal cord vascular lesions. They usually originate in the vertebrae, with occasional extension into the extradural space, and intramedullary cavernomas, even if reported in the literature, are very rare. Case presentation: We report the case of a 34-year-old Caucasian woman affected by a thoracic intramedullary cavernous angioma. Our patient complained of 10-day history of acute dorsal pain, progressive weakness of both lower extremities, worse on the right side, a ‘pins and needles’ sensation in the abdominal region and bladder dysfunction. Magnetic resonance imaging showed, at D5 level, a vascular malformation, which was not documented at spinal angiography. Our patient underwent surgical treatment with total removal of the lesion and her symptoms gradually improved. A histological examination revealed the typical features of a cavernous angioma. Conclusions: Intramedullary cavernous angioma is a rare lesion that should be diagnosed early and surgically treated before rebleeding or enlargement of the lesion can occur.

The resection of tumors within or close to eloquent motor areas is usually guided by the compromise between the maximal allowed resection and preservation of neurological functions. Navigated transcranial magnetic stimulation (nTMS) is an emerging technology that can be used for preoperative mapping of the motor cortex. We performed pre-surgical mapping by using nTMS in 17 patients with lesions in or close to the precentral gyrus. The study was conducted on consecutive patients scheduled for surgical treatment. nTMS allowed to exactly localize the motor cortex in 88.2% of cases. In 70.6% it provided the surgeon with new unexpected information about functional anatomy of the motor area, influencing the pre-operative planning. Moreover, in 29.4% these functional information had a clear impact on surgery, making necessary a change of surgical strategy to avoid damage to the motor cortex. Our results prove that nTMS has a large benefit in the treatment of rolandic brain tumors. It adds important information about spatial relationship between functional motor cortex and the tumor and reduces surgical-related post-operative motor deficits.

Intracranial tumors represent a significant health problem. The annual incidence of primary and secondary central Nervous system neoplasms ranges from 10 to 17 per 100.000 persons. The main histological types of brain tumors in adults include: high-grade (gliomas, primary cerebral lymphomas, medulloblastomas), low-grade (meningiomas, acoustic neuromas, neu‐ rofibromas) and Secondaries (common malignancies spreading to the brain include lung cancer, breast cancer, stomach cancer, prostate cancer, thyroid cancer, colorectal cancer, mel‐ anoma and kidney cancer). In recent years, the diagnosis of brain tumors has considerable progressed due to continuous advances in neuroradiology.

The aim of this study was to evaluate the advantages and limits of virtual magnetic resonance techniques in planning surgery for microvascular decompression in patients with neurovascular conflict.Between December 2010 and December 2011, we prospectively observed 32 patients (30 with trigeminal neuralgia and two with hemifacial spasm), with a suspected clinical diagnosis of neurovascular conflict. To assess the contact between nerve and vessel, magnetic resonance imaging (MRI) by three-dimensional (3D) constructive interference in steady state (CISS) and high-resolution MR angiography (MRA) were performed in all cases. Moreover, we performed presurgical simulation of microvascular decompression using MR two-dimensional image fusion and virtual cisternography. The neuroradiological findings were compared with the surgical findings.In all cases, we demonstrated the anatomical relations between cranial nerves and offending vessels with an optimal correlation between radiological and surgical patterns.Advanced virtual MRI techniques, such as image fusion and virtual cisternography, are able to depict the complex anatomical relationships between neural and vascular structures within the cisternal spaces of the skull base. These techniques can be considered an optimal presurgical tool to support traditional MRI evaluation of this region.

Object The integration of state-of-the-art neuroimaging into treatment planning may increase the therapeutic potential of stereotactic radiosurgery. Functional neuroimaging, including functional MRI, navigated brain stimulation, and diffusion tensor imaging–based tractography, may guide the orientation of radiation beams to decrease the dose to critical cortical and subcortical areas. The authors describe their method of integrating functional neuroimaging technology into radiosurgical treatment planning using the CyberKnife radiosurgery system. Methods The records of all patients who had undergone radiosurgery for brain lesions at the CyberKnife Center of the University of Messina, Italy, between July 2010 and July 2012 were analyzed. Among patients with brain lesions in critical areas, treatment planning with the integration of functional neuroimaging was performed in 25 patients. Morphological and functional imaging data sets were coregistered using the Multiplan dedicated treatment planning system. Treatment planning was initially based on morphological data; radiation dose distribution was then corrected in relation to the functionally relevant cortical and subcortical areas. The change in radiation dose distribution was then calculated. Results The data sets could be easily and reliably integrated into the Cyberknife treatment planning. Using an inverse planning algorithm, the authors achieved an average 17% reduction in the radiation dose to functional areas. Further gain in terms of dose sparing compromised other important treatment parameters, including target coverage, conformality index, and number of monitor units. No neurological deficit due to radiation was recorded at the short-term follow-up. Conclusions Radiosurgery treatments rely on the quality of neuroimaging. The integration of functional data allows a reduction in radiation doses to functional organs at risk, including critical cortical areas, subcortical tracts, and vascular structures. The relative simplicity of integrating functional neuroimaging into radiosurgery warrants further research to implement, standardize, and identify the limits of this procedure.

Several authors have demonstrated that preoperative embolization of meningiomas reduces blood loss during surgery. However, preoperative embolization is still under debate. Aim of this study is the retrospective evaluation of necrosis score, surgical time, and transfused blood volume, on patients affected by intracranial meningiomas treated with preoperative embolization before surgery, compared with a control group treated only with surgery. Twenty-eight patients with meningiomas were subjected to a preoperative embolization with polyvinyl alcohol (PVA). These patients were divided into two groups: group 1, patients with preoperative embolization performed at least 7 days before surgery; and group 2, patients with preoperative embolization performed less than 7 days before surgery. A statistical evaluation was made by comparing necrosis score, surgical time, and transfused blood volume of these groups. Then, we compared these parameters also with group 3, which included patients with surgically treated meningioma who did not undergo preoperative embolization. Surgery time and transfused blood volume were significantly lower in patients who had been embolized at least 7 days before definitive surgery. Furthermore, large confluent areas of necrosis were significantly more frequent in patients with a larger time span between embolization and surgery. Preoperative embolization with PVA in patients with intracranial meningiomas is safe and effective, as it reduces the volume of transfused blood during surgical operation. However, patients should undergo surgery at least 7 days after embolization, as a shorter time interval has been correlated with a longer surgical time and a higher transfused blood volume.

Direct cortical stimulation (DCS) is an intraoperative technique that uses electrodes placed directly on the exposed cortical surface of the brain to stimulate activity of functional areas by simultaneously recording the evoked responses peripherally. DCS is very precise and re‐ liable and can be considered the gold standard in brain mapping and intraoperative func‐ tional monitoring. Nevertheless, the neurosurgeon discovers the spatial relationship between the disease and eloquent cortical surfaces only after having completed a cranioto‐ my and dural opening.

Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities, affecting the central nervous system. CCMs can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes:CCM1(K-Rev interaction trapped 1 (KRIT1)),CCM2(MGC4607), andCCM3(PDCD10). CCMs occur as a single or multiple malformations that can lead to seizures, focal neurological deficits, hemorrhagic stroke, and headache. However, patients are frequently asymptomatic. In our previous mutation screening, performed in a cohort of 95 Italian patients, both sporadic and familial, we have identified several mutations in CCM genes, three of which in three distinct sporadic patients. In this study, representing further molecular screening of the three CCM genes, in a south Italian cohort of CCM patients enrolled by us in the last three years, we report the identification of other four new mutations in 40 sporadic patients with either single or multiple CCM.

We have recently reported that in astrocytoma cells the expression of interleukin-8 (IL-8) is upregulated by prostaglandin E2 (PGE2). Unfortunately, the exact mechanism by which this happens has not been clarified yet. Here, we have investigated whether IL-8 activation by PGE2 involves changes in DNA methylation and/or histone modifications in 46 astrocytoma specimens, two astrocytoma cell lines and normal astrocytic cells. The DNA methylation status of the IL-8 promoter was analyzed by bisulphite sequencing and by methylation DNA immunoprecipitation analysis. The involvement of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), as well as histone acetylation levels, was assayed by chromatin immunoprecipitation. IL-8 expression at promoter, mRNA and protein level was explored by transfection, real-time PCR and enzyme immunoassay experiments in cells untreated or treated with PGE2, 5-aza-2'-deoxycytidine (5-aza-dC) and HDAC inhibitors, alone or in combination. EMSA was performed with crude cell extracts or recombinant protein. We observed that PGE2 induced IL-8 activation through: (1) demethylation of the single CpG site 5 located at position -83 within the binding region for CEBP-β in the IL-8 promoter; (2) C/EBP-β and p300 co-activator recruitment; (3) H3 acetylation enhancement and (4) reduction in DNMT1, DNMT3a, HDAC2 and HDAC3 association to CpG site 5 region. Treatment with 5-aza-dC or HDAC inhibitors of class I HDACs strengthened either basal or PGE2-mediated IL-8 expression. These findings have elucidated an orchestrated mechanism triggered by PGE2 whereby concurrent association of site-specific demethylation and histone H3 hyperacetylation resulted in derepression of IL-8 gene expression in human astrocytoma.

Diffuse and high-grade astrocytomas are invasive neoplasms which grow diffusely into the brain parenchyma. Microglia has been termed the brain's immune system, although its specific role remains uncertain. Objective of this study was to assess in a series of astrocytic neoplasms, the expression of a macrophage marker CD 68 and Major Histocompatibility Complex Class II CR3/43. We examined 10 pilocytic astrocytomas, 13 diffuse astrocytomas and 17 anaplastic astrocytomas. For macrophages we used the CD68 monoclonal mouse antibody. For assessing the presence of MHC Class II complexes we used the specific monoclonal antibody CR3/43. CD68-positive mononuclear cells were observed in perivascular and hypoxic areas, within neoplastic tissue, inside and contiguous to vessel wall. CR3/43 positive complexes were detected in mononuclear elongated elements with amoeboid extensions strictly attached to endothelial cells, or contiguous to perinecrotic areas within neoplastic tissue. We suggest an active involvement of macrophage/microglia infiltrates in neovascularization and malignancy in astrocytomas. Macrophage infiltration and major histocompatibility complex class II complexes reactivity in gliomas could also suggest the occurrence of immune surveillance with a preliminary host's immune response. In addition, macrophages could promote angiogenesis mechanisms and induction of tumor growth.

Meningiomas involving the spinal meninges show a reduced tendency to recur compared to those of the intracranial compartment. Nonetheless, due to the few reports with a significant number of patients, their biological characteristics largely remain to be investigated. With the aim of clarifying the biology of these tumors, we examined in the present paper the clinicopathological features, the estrogen receptor (ER) and progesterone receptor (PR) status, as well as the Ki-67 labeling index (LI) and matrix metallo-proteinase-9 (MMP-9) expression of 58 spinal meningiomas. Ki-67 LI ranged between 1% and 5% (median: 1%); no expression of ER was found in all the cases, whereas PR immunoexpression was found in 86% of the tumors. High MMP-9 expression was encountered in 46% of meningiomas, and it was significantly correlated with the percentage of PR expression. The recurrence rate was 1.7%. The only recurred case showed high MMP-9 expression, absence of PR and low Ki-67 LI. Our findings confirm that spinal meningiomas are indolent tumors with low growth fraction and recurrence rate. In these neoplasms, high MMP-9 expression seems to be associated with the development of recurrences only in the absence of PR expression. Thus, the evaluation of both MMP-9 and PR expression might be of use in the identification of spinal meningiomas at higher risk of relapse.

Chordomas are midline tumors that arise from embryonic remnants of the notochord and are considered to be malignant tumors because of their tendency to invade and destroy the involved bone. Cases of intradural chordomas without bone involvement have been rarely described with a predilection for prepontine location. The absence of bony invasion renders the complete excision of these tumors more feasible and is related to their better prognosis in comparison to conventional chordomas. Herein we report the first intradural chordoma arising in the Meckel's cave. The intradural location of the lesion, outside midline structures, in the absence of bone infiltration, made the differential diagnosis versus other meningeal lesions such as chordoid meningioma challenging. The intense and strong immunohistochemical expression of pan-cytokeratins, S100, cytokeratin-19 and of the notochordal marker brachyury allowed differential diagnosis toward other tumors showing chordoid morphology. The expression of brachyury, which had not been previously analyzed in intradural chordoma, definitely links the histogenesis of this neoplasia to the notochord, similar to that of conventional chordoma. We also show that, different from conventional chordoma, intradural chordoma does not express the metallo-proteinases (MMPs) -2 and -9, which may account for its indolent biological behavior.

Osteoblastic meningioma is a rare variant of meningioma characterized by the presence of a variable number of bone spicules within the tumor parenchyma. Its histogenesis has not been yet fully clarified. Herein we report clinical and histological findings and expression of bone matrix proteins (osteocalcin and ostepontin) observed in seven osteoblastic meningiomas. None of the cases displayed recurrences or significant re-growth after partial resection. In 5/7 cases the osseous component occurred in association with psammoma bodies and dystrophic calcification. Interestingly, foci composed of immature bone trabeculae, mineralized chondroid matrix, and osteoclasts were found in one of the two cases with no psammoma bodies or calcification, suggesting enchondral ossification. Positive staining for osteocalcin, which is a marker of terminal osteoblastic differentiation, was observed within the bone spicules in all meningiomas, but not in the chondroid mineralized matrix. On the other hand, immuno-expression of osteopontin, an early osteogenic marker, was observed in the osteoclasts and in mature and immature bone spiculae, calcification, and psammoma bodies. Even more, osteopontin was extensively expressed by the neoplastic cells of cases without calcification or psammoma bodies, suggesting acquisition of osteoblastic phenotype in these meningiomas. In conclusion, osteoblastic meningioma seems to be an indolent variant of meningiomas characterized by a slow growth and good prognosis. Our histological and immunohistochemical findings suggest that bone formation may occur through two different pathways, i.e., as the final step of calcification or through a metaplastic mechanism in cases with absent calcification or psammoma bodies.

Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities. CCMs can occur as sporadic or familial autosomal dominant form. Familial cases are associated with mutations in CCM1[K‐Rev interaction trapped 1 (KRIT1)], CCM2 (MGC4607) and CCM3 (PDCD10) genes. In this study, a three‐gene mutation screening was performed by direct exon sequencing, in a cohort of 95 Italian patients either sporadic or familial, as well as on their at‐risk relatives. Sixteen mutations in 16 unrelated CCM patients were identified, nine mutations are novel: c.413T > C; c.601C > T; c.846 + 2T > G; c.1254delA; c.1255‐4delGTA; c.1681‐1682delTA in CCM1; c.48A > G; c.82‐83insAG in CCM2; and c.396G > A in CCM3 genes. The samples, negative to direct exon sequencing, were investigated by MLPA to search for intragenic deletions or duplications. One deletion in CCM1 exon 18 was detected in a sporadic patient. Among familial cases 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3, whereas in the remaining 22% no mutations were detected, suggesting the existence of either undetectable mutations or other CCM genes. This study represents the first extensive research program for a comprehensive molecular screening of the three known genes in an Italian cohort of CCM patients and their at‐risk relatives.

The treatment of giant olfactory groove meningiomas (OGMs; maximum diameter ≥ 6 cm) poses special problems and represents a surgical challenge. We discuss the long-term results in a series of 18 patients with giant OGMs and report our experience on a global strategy encompassing the pterional approach to manage the lesion and an extended transbasal approach to treat recurrences.Between February 1991 and December 2007, 18 patients with giant OGMs were surgically managed via a pterional craniotomy. Postoperative follow-up imaging was obtained at one, six, and 12 months and then yearly. In preoperative images, data from tumor volume were assessed. The volume of the residual right frontal porencephalic cave (ipsilateral to the operative side) was compared with the volume of the porencephalic cave measured in the left frontal lobe (internal control) in each case. Comparison between porencephalic cave and the original tumor volume for each side was also performed.At the first operation in 17 of 18 patients (94.4%), the tumor resection was accomplished by a complete macroscopic lesion removal and coagulation of its dural attachment (Simpson grade II). In one patient, a Simpson grade V resection was obtained. The mean follow-up was 93.5 months, ranging from 12 to 214 months. Recurrences were observed in three patients (16.7%) at 103, 102, and 128 months, respectively, from the time of the first operation. These patients were operated on via an extended subfrontal transbasal approach accomplishing a complete (Simpson grade I) resection. No death occurred. The visual deficit improved in seven of 13 patients (53.8%), remained stable in five (38.5%), and worsened in one patient (7.7%). Overall, 17 of 18 patients (94.4%) had a good outcome and returned to their previous occupations. All the tumors presented with a symmetrical growth pattern. The mean meningioma volume was 23.51 ± 1.62 cm(3) for the right portion of the tumor and 23.04 ± 1.35 cm(3) for the left portion. The mean residual porencephalic volume was significantly smaller in the left frontal lobe (mean value 5.7 mL) than in the right frontal lobe (mean value 16.6 mL; P0.05). The mean residual porencephalic volume was significantly smaller than the tumor volume both in the left (P0.01) and in the right side (P0.05).The pterional-transsylvian approach provides two major advantages: first, it minimizes morbidity and mortality through an early neurovascular control and by limiting parenchymal damage as demonstrated by a quantitative analysis; second it is associated with low recurrence rate at a long-term follow-up.

Non-traumatic intradiploic arachnoid cyst is a rare condition. We describe a young man with typical trigeminal neuralgia and intradiploic arachnoid cyst at the greater wing of the sphenoid. The patient was successfully treated with medical therapy. To our knowledge, this is the first case report of a possible correlation between trigeminal neuralgia and intraosseous arachnoid cyst. We describe the clinical case, the possible pathogenetic mechanism and briefly review the literature.

Cerebral arteriovenous malformations (AVMs) represent congenital anomalies of blood vessels composed of a nidus of anomalous arterial and venous vessels without a capillary network. We describe a case of bleeding cerebral AVM in a pregnant women at the second quarter of gestation and diagnosed by digital subtraction angiography showing a large principal arterial nidus supply. The AVM was treated by endovascular embolization at the 27th week of gestation. The post-operative course was uneventful and a caesarean section was performed at the 37th week of gestation. The endovascular approach may represent a safe method in the treatment of this cerebral condition during pregnancy.

Somatostatin anti-proliferative and anti-angiogenic activities, together with the expression of somatostatin receptors (sstrs), account for the use of somatostatin analogues in the treatment of human tumours. In the present study, sstr2A immunohistochemical expression was analyzed in grade II and III meningiomas and was compared with that revealed in grade I meningiomas. Thirty-five formalin-fixed paraffin-embedded meningiomas, comprising 13 grade I, 19 grade II and 3 grade III tumours, according to the WHO 2007 classification, were submitted to immunohistochemical assays for sstr2A. Moreover, in the same cohort of tumours, the immunoexpression of CD105, a specific marker for neo-angiogenesis, as well as the Ki-67 labelling index (LI), reflecting the proliferative activity of the meningiomas, were recorded. Sstr2A immunoreaction was evidenced in 26/35 cases and was localized at the cytoplasm and the plasma membrane in 12 and in 14 cases, respectively. Specifically, a positive staining was found in 7/13 grade I, in 16/19 grade II and in 3/3 grade III tumours, thus demonstrating that sstr2A is frequently expressed in high grade meningiomas. A significantly higher microvessel density (MVD), assessed by CD105 immunostaining and Ki-67 LI were evidenced in high grade meningiomas. A significant correlation was recorded between sstr2A expression and a high MVD of the meningiomas. The existence of a correlation between sstr2A expression and the entity of neo-angiogenesis provides the basis for the use of somatostatin analogue-based therapies in the treatment of meningiomas.

Microsurgical resection, stereotactic aspiration and VP shunt have for years been the choice options for the treatment of colloid cysts of the third ventricle. Recently, endoscopic approaches have aroused increasing interest and gained acceptance. Although safer, this minimally invasive approach is considered less efficacious than microsurgery. Relatively long-term results are now available and some conclusions might be inferred on the usefulness of this procedure. Between 1994 and 2005, 61 patients harbouring a colloid cyst of the third ventricle were treated with neuroendoscopic technique in 11 Italian neurosurgical centres. Cyst diameters ranged from 6 to 32 mm. A flexible endoscope was used in 34 cases, a rigid one in 21, both instruments in six. The technique consisted in cyst fenestrations, colloid aspiration, coagulation of the internal cyst wall and, occasionally, capsule excision. Mean postoperative hospital stay was 6.7 days. Early postoperative neuroimaging revealed a cyst residue in 36 cases (mean diameter 4.3 mm). There were two complications (3.2%). Follow-up varied between 1 and 132 months (mean 32 months, more than 5 years in 17 patients). There were seven asymptomatic recurrences, three of them evolving from a previous residue. The endoscopic approach to the treatment of colloid cysts is safe, effective and well accepted by patients. Although asymptomatic, recurrences (11.4%) cast a persisting shadow on the long-term results, and, therefore, the controversy with the traditional microsurgical treatment remains open.