Prognostic value of EGFR expression in de novo and progressed atypical and anaplastic meningiomas: an immunohistochemical and fluorescence in situ hybridization pilot study.

AIM: The aim of this study was to assess both the epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry and the EGFR gene amplification by fluorescence in situ hybridization in meningiomas of different grade, in order to evaluate their possible role in the development of the disease. EGFR protein belongs to the family of tyrosine kinase growth factor receptors, which also includes HER2, HER3 and HER4. Elevated expression or activity of EGFR has been reported in several cancers, including brain tumours. EGFR activation can enhance the malignant potential of epithelial tissues. METHODS: We investigated whether there was a difference in the EGFR protein expression and the EGFR gene amplification between the so called de novo malignant meningiomas and recurrent meningiomas with or without malignant progression from a previously lower grade tumor. Our goal was to evaluate if EGFR expression was a useful marker to select patients affected by meningioma with a major risk of recurrences. We also assessed the prognostic value of the EGFR expression on overall survival. RESULTS: Progression from benign meningiomas to atypical or anaplastic meningiomas correlated with an increase in the expression of EGFR protein. Our study shows that EGFR immunostaining in meningiomas directly correlates to the tumor's grade. The EGFR expression did not correlate with the overall survival and the recurrence-free survival of the patients affected by meningioma (de novo, recurrent and progressed). CONCLUSION: We submit that the EGFR expression is not a useful prognostic element to identify patients with a major risk of meningioma recurrence.

A rare location of benign osteoblastoma: case study and a review of the literature.

Osteoblastoma is a solitary, benign bone tumor that is rarely localized in the frontal sinus. It consists of hypocellular mineralized tissue that may form large masses or irregular trabeculae. A 31 year old man came to our attention with a 7 month history of diplopia, photophobia, frontal headhaches and progressive exophthalmos with proptosis of the left eye. The patient was submitted to computed tomography (CT) which allowed to appraise the extension of the lesion. The mass expanded inside the left frontal sinus and the upper ethmoidal cells invading the left orbital roof. Considering the extension of the tumor, the site and the connections with contiguous structures, a combination of endoscopic endonasal technique with intraorbital approach was performed. At histological examination typical features of benign osteoblastoma were observed. The sites of predilection for the tumor are the long bones, vertebral column, and small bones of hands and feet. Its occurrence in the skull and jaw bones is relatively rare and represents only 15% of all osteoblastomas. To our knowledge, only 5 cases of osteoblastoma of the frontal sinus have been previously reported in the English-language literature. This report describes a case of benign osteoblastoma in a rare site, namely, the frontal sinus with particular attention about the differential diagnosis and the treatment.    

Cervical spine chondroma arising from C5 right hemilamina: a rare cause of spinal cord compression. Case report and review of the literature.

Chondromas are rare primary spine tumors. Only 12 cases of chondromas located in the cervical spine have been reported in the literature up to now. The authors report a case of a cervical periosteal chondroma in a 38-year-old man presenting with neck pain and a syndrome of spinal cord compression. Magnetic resonance imaging revealed a lesion that was hypo- or isointense on T1-weighted images and iso-hyperintense on T2-weighted images. Administration of Gd-DPTA resulted in margin enhancement on T1-weighted images. CT scans revealed a hyperdense calcified lesion arising from the internal surface of C5 right hemi-lamina. The patient underwent a right C5 hemi-laminectomy, with complete en-bloc removal of the lesion. The authors emphasize that early identification of the initial lesion should be coupled with total surgical resection, as a definitive treatment, in order to prevent malignant transformation.

Phosphatidylcholine synthesis-related enzyme activities of bovine brain microvessels exhibit susceptibility to peroxidation.

In microvessels isolated from bovine brain, microsomal enzyme activities involved in phosphatidylcholine biosynthesis and degradation were determined. The microvessels possessed acyl-CoA:1-acyl-sn-glycero-3-phosphocholine (AT) and glycerophosphocholine phosphodiesterase (GroPChoPDE) activity at a higher level compared with bovine and rat brain or rat liver microsomes whereas they expressed CTP:phosphocholine cytidylyltransferase (CT) and choline phosphotransferase (CPT) activity at a lower level. Each enzyme has been characterized in terms of response to inhibitors or activators revealing properties very similar to those in brain and liver microsomes. In the homogenate prepared from t-butylhydroperoxide-treated microvessels (10 min exposure to 10 microM up to 1 mM concentrations), AT and CPT activities exhibited a significant dose-dependent inhibition. In contrast, GroPChoPDE activity was unaffected. CT was inhibited only at 1 mM concentration. Short treatment of microvessels with Fe2+ (20 microM)-ascorbate (0.25 mM) or 100 microM linoleate hydroperoxide did not have any effect on the activity of the four enzymes. Strong inhibition of all enzymes was noted when the linoleate hydroperoxide system was fortified by Fe2+ ions (100 microM). AT inactivation was also found when oxidized low density lipoprotein was preincubated with microvessels. On the other hand, oxidized LDL left unchanged CPT and GroPChoPDE activities whereas it promoted a slight stimulation of cytidylyltransferase activity. Overall, the results suggest a link between oxygen radical generation and the perturbation of the microvessel membrane structure in which the four enzymes are incorporated, coupled to a direct sulfhydryl protein modification.

Italian multicenter study of reversible cerebral ischemic attacks. Part 5. Risk factors and cerebral atherosclerosis.

As part of a prospective study, the influence of several premorbid and environmental factors on the presence, extent and severity of cerebral vessel atherosclerosis was studied in 462 patients with clinical diagnosis of RIA who underwent cerebral angiography. The extent and severity of atherosclerosis of the cerebral vessels was quantified using extracranial and intracranial cerebrovascular scores (ECS, ICS) based on the number and severity of the lesions in 11 extracranial and 21 intracranial arterial segments. Results of univariate and multivariate analyses indicate that the presence of atherosclerotic changes of cerebral vessels, as shown by angiography, was strongly related with age in both sexes. The lesions were more frequent in males, in particular under age 55. Elevated cholesterol was associated with a higher incidence of atherosclerotic lesions. Smoking was associated with a higher incidence of extracranial lesions. Age, smoking and history of hypertension were the best predictors of the extent and severity of cerebral vessel atherosclerosis.

Diverging projections of the C2 and D2 olivocorticonuclear cerebellar pathways of the rat.

A divergent mediolateral projection to the cerebellar nuclei of the C2 and the D2 olivocorticonuclear cerebellar pathways was found after segregate injections of a tracer (either WGA-HRP or FR or BDA) in the rostral (D2 area) or caudal side (C2 area) of the rat paraflocculus. The C2 olivary area of the cerebellar cortex sends most of its nuclear projection to the nucleus interpositus posterior (classically perceived as the nuclear target of the C2 olivocorticocerebellar pathway) and a smaller contingent of fibres to the parvocellular region of the nucleus lateralis (classically perceived as the nuclear target of the D2 olivocorticocerebellar pathway). The D2 olivary area of the cerebellar cortex sends most of its nuclear projection to the parvocellular region of the nucleus lateralis (classically perceived as the nuclear target of the D2 olivocorticocerebellar pathway) and a smaller contingent of fibres to the magnocellular region of the nucleus lateralis (classically perceived as the nuclear target of the D1 olivocorticocerebellar pathway). The lateral interaction of the D2 and the C2 olivocerebellar pathways could represent the anatomical substrate for the functional integration of different olivocerebellar compartments.

Arachidonate transport through the blood-retina and blood-brain barrier of the rat after reperfusion of varying duration following complete cerebral ischemia.

The permeability-surface area product (PS) of [1-14C]arachidonate at the blood-retina and blood-brain barrier was determined by short carotid perfusion in young Wistar rats 1 or 6 h after recovery period following complete cerebral ischemia induced by temporary cardiac arrest. For the retina and structures of visual system, hypothalamus and olfactory bulb there was no significant difference over sham-operated rats among mean PSs. For cortex, hippocampus and striatum, significant increases were found at both time intervals of recovery after cardiac arrest. The ischemia-reperfusion model was characterized by a significant increase in tissue conjugated diene in the hippocampus and microsomal lysophosphatidylcholine acyltransferase activity in the cortex. Consistent with these findings, we also show ultrastructural evidence mainly represented by partial opening of interendothelial junctions and mild signs of tissue edema in surrounding neuropil, suggesting barrier leakiness predominantly in the cortex, hippocampus and striatum but almost absent in the retina microvessels. Our results indicate that ischemia-reperfusion does affect influex through blood-brain barrier into regional structures of rat central nervous system of arachidonate, a metabolic substrate and lipid mediator rapidly incorporated into microcapillary and brain lipids. The data also suggested that: (i) reactive oxyradicals were moderately generated during the early phase of ischemic-reperfusion process in the rat; (ii) after reperfusion, in vitro susceptibility of different brain regions to iron-induced peroxidation was highest in the hippocampus and lowest in the cortex and striatum; (iii) membrane phospholipid repair mechanisms were activated at the same time.

Receptor-mediated stimulation of inositol phospholipid hydrolysis in human brain.

Stimulation of inositol phospholipid hydrolysis by transmitter receptor agonists was studied in slices from the occipital, temporal and cerebellar cortex that were surgically removed from three patients during ablation of brain tumors. Norepinephrine and the muscarinic acetylcholine agonist carbamylcholine increased the content of [3H]inositol monophosphate (InsP) in all the regions examined, whereas the glutamate receptor agonist quisqualate was effective only in the cerebellar slices. These results provide evidence that neurotransmitter receptors are coupled to inositol phospholipid hydrolysis in human brain tissue.

Arachidonate transport through the blood-retina and blood-brain barrier of the rat during aging.

The permeability-surface area product (PS) of [I-14C]arachidonate at the blood-retina (BRB) and blood-brain barrier (BBB) was determined after short carotid perfusion in Wistar rats at 4, 12 and 28 months of age. For the visual system structures, parietal and frontal cortex, striatum, hypothalamus, hippocampus and olfactory bulb there was no significant difference among mean PSs in any age group. Our results indicate that: (1) arachidonate is able to cross at relevant rate BRB and BBB; (2) in all brain regions except retina, optic tract and hippocampus, blood barriers have a transport capacity for arachidonate significantly higher than that for docosahexaenoate and palmitate as well; (3) aging does not affect influx into retina and other structures of rat central nervous system of the arachidonate, a metabolic substrate rapidly incorporated into microcapillary and brain lipids, and for which simple diffusion transport across the BRB and BBB may be postulated.

Multiloculated hydrocephalus in infants.

The clinical features and the neuroradiological appearance of multiloculated hydrocephalus that followed meningitis and ventriculitis in five newborn infants are presented. Several factors probably involved in the pathogenesis are discussed. Computed tomography is particularly helpful in the recognition of this entity and in the evaluation of its course. However, ventriculograms are advised to document the communication of the septated cavities. Of four infants treated by ventriculoatrial shunting, two died and two are mentally and neurologically disabled. Another infant, who underwent craniotomy and fenestration of the ventricular membranes, died accidentally 3 months after operation. In light of similar cases reported in the literature, the prognosis seems very poor. Craniotomy with fenestration of the ventricular septa seems a promising procedure, although further supportive evidence is needed.

SEM evaluation of endothelial changes following end-to-side microvascular anastomoses in rats.

A scanning electron microscopic (SEM) study was carried out to evaluate the endothelial changes in carotid end-to-side microsurgical anastomoses. This procedure, associated with occlusion of the brachiocephalic trunk, was performed in 24 Sprague-Dawley rats. The animals were sacrificed at time intervals ranging between 15 minutes and 14 days after surgery. The specimens were collected after perfusion-fixation in vivo and treated for SEM observations. The findings show that the first 45 minutes are the most critical time for thrombus formation. Reendothelialization could be detected at 3 days after the microsurgical procedure. Endothelial regeneration occurred earlier on the suture line than on the stitches, documented by the migration and morphological changes of the endothelial cells advancing from the normal endothelium to cover the defect and the suture material. The repair was usually completed within 14 days. Damage of the inner vascular wall, related to minor failures of the microsurgical technique, appears to be a cause of delayed reendothelialization.

Supratentorial hemangioblastoma in a child. Case report.

Hemangioblastomas are rarely seen in the supratentorial region, especially in childhood. The case of a 10-year-old boy with left parieto-occipital cystic hemangioblastoma is reported. The neoplasm was not attached to the dura, nor was it associated with von Hippel-Lindau syndrome or with erythrocythemia. Cerebral angiography showed no evidence of a vascularized tumor, whereas computerized tomography gave more accurate information. The gross and microscopic appearance of the lesion is described, and a review of similar cases previously reported in the literature is presented.

Ossifying fibroma of the skull in a patient with neurofibromatosis type 1. Case report.

Ossifying fibroma is a rare, benign, primary bone tumor that occurs most commonly in the mandible; a cranial vault location is extremely rare. In this report a case of symptomatic frontoparietotemporal ossifying fibroma with intracranial growth and cerebral displacement in a 12-year-old boy with neurofibromatosis type 1 (NF1) is described. Once excised the lesion did not recur. The skeletal system is frequently affected in NF1, and bone abnormalities are present in 50% to 70% of patients with this condition. The etiology of such lesions in NF1 is still controversial. To the authors' knowledge, ossifying fibromas of calvarial bones have not been described in NF1.

Dynamics of endothelial repair in end-to-side microsurgical carotid anastomoses in rats: a scanning electron microscopic evaluation.

A scanning electron microscopic (SEM) investigation of endothelial behavior, following carotid end-to-side microsurgical anastomoses, was carried out in twenty-four Sprague-Dawley rats. From the hemodynamic point of view, the experimental model used in this study involved a bidirectional flow in the recipient vessel. Following surgery, specimens were collected at intervals varying from 15 minutes to 14 days. The thrombus formation was particularly evident in the first 45 minutes, and then gradually disappeared. Evidence showed that the new endothelial cells, covering the defect at the site of the suture, originate from the normal endothelium. Regenerated endothelial cells showed particular morphological features which are expressions of high metabolic rate and of active cell movement. Endothelial repair on the suture line began 3 days after the operation, and was completed there earlier than it was on the stitches. An accurate microsurgical technique is needed to avoid an increased thrombus formation and delayed re-endothelialization.

Early partial reperfusion in a new rat model of focal cerebral ischaemia.

The influence of early partial reperfusion in a new rat model of focal cerebral ischaemia was investigated. Two groups, each of 30 adult male rats, were subjected to permanent occlusion of the right middle cerebral artery. The former, (group A) had an additional permanent occlusion of both common carotid arteries; the latter (group B) had a temporary carotid occlusion lasting for two hours. Mortality rate, evaluated within three days, was 70% in group A and 20% in group B. The mean size of cerebral infarcts was 63% in group A whereas it was 21% in group B. These data suggest that, in this animal model, early partial reperfusion is effective in reducing the mortality rate, and the size of the cerebral infarcts. Furthermore, this experimental model appears suitable for studies elucidating the role of reperfusion and/or other efforts in focal cerebral ischaemia.

Correlation between histological grade, MIB-1, p53, and recurrence in 69 completely resected primary intracranial meningiomas with a 6 year mean follow-up.

Sixty-nine intracranial, totally excised meningiomas were immunostained for MIB-1 and p53 protein expression. According to the 1993 WHO criteria, revised by Perry et al., the 69 meningiomas were classified into: grade I = 54 benign meningiomas, grade II = 10 atypical meningiomas, grade III = 5 malignant meningiomas. The patients were followed until death or for an average of 6.7 years. The 69 meningiomas were divided into two groups, according to the absence (n = 42) or presence (n = 27) of recurrences. In the last group we included 3 patients who died of meningioma recurrence. According to the percentage of MIB-1 positively stained cells, meningiomas were divided into three groups: <1% (n = 36), 1-10% (n = 28), >10% (n = 5). We found the MIB-1 labeling index (LI) <1% in 33 grade I (61%) and in 3 grade II (30%) meningiomas. On the other hand, 7 grade II (70%) and all grade III (100%) meningiomas presented a MIB-1 LI >1%. Correlation between histological grade and MIB-1 LI was statistically significant (p = 0.0006). The correlation between MIB-1 LI and follow-up was also highly significant (p < 0.001): the majority of meningiomas which did not recur (32/42 equal to 76%) were characterized by a low (<1%) MIB-1 LI. In the recurrence group MIB-1 LI was significantly higher than in the disease-free patients' group. Moreover, MIB-1 appeared to be a prognostic parameter not strongly related to the histological grade. In fact, it was significantly higher in recurrent histologically benign meningiomas, as compared with benign meningiomas without recurrence (p = 0.0006). Positive p53 protein expression (>1%) was shown in 26/45 meningiomas (57%), with an LI of 1-10% in 18 (40%) and an LI of >10% in 8 (17%) meningiomas. Although the p53 LI tended to be higher in atypical and malignant meningiomas, no significant correlation was found between the p53 expression and the recurrence (p = 0.05). The authors conclude that quantitative MIB-1 labeling is a useful technique in the routine diagnostic assessment of meningiomas, and helpful in obtaining more information about prognosis and thereby in planning the most suitable treatment.

Cryopreservation of autogeneous bone flap in cranial surgical practice: what is the future? A grade B and evidence level 4 meta-analytic study.

AIM: Autogenous bone flap adequately preserved can be used successfully for repair of iatrogenic cranial bone defects because of its biological and economic advantages. The commonly used techniques of bone preservation are freezing at temperature ranging from -16 to -40 inverted exclamation mark C or subcutaneous pocketing. METHODS: We searched on NLM database querying as subject headings "cranioplasty and autologous bone" and found 7 papers meeting our criteria. For every series we considered the frequency of bone resorption and infection and performed statistical analysis by means of contingency tables carrying out for the chi2 test according to Pearson and considering to be statistically significant p(chi2) <0.05 values. RESULTS: Compared series presented no statistically significant difference with regard to frequency of the complications (chi2=6.43 for critical value of 11.07 (k-1=5) (P>0.25) and chi2=5.48 for critical value of 7.81 (k-1=3) (P>0.10) respectively for infection and resorption. CONCLUSION: Although we did not find any significative difference among the frequencies of the complications of the series, it is our opinion that freezing the bone flap is preferable to abdominal pocketing because it needs no double surgical abdominal time and the bone flap frozen is stronger to mechanical loading than fresh flap. Cryopreservation of autologous bone flap should be the standard technique of preservation for delayed cranioplasty but a multicentric prospective trial is advisable to obtain in short time statistically significant results focusing better on the rate of marginal resorption of the bone flap using new cryoprotectant solutions.