Emergence of a high-grade sarcoma in a recurrent meningioma: malignant progression or collision tumor?

Anaplastic meningiomas that resemble sarcomas often reveal clues to their meningothelial differentiation or develop in a plausible setting that confirms their meningothelial origin. Malignant mesenchymal neoplasms without obvious evidence of meningothelial differentiation or origin are more likely to be true primary or metastatic sarcomas. Because of their clinical and biological differences, it is important to distinguish anaplastic meningioma from a sarcoma. We present a 67-year-old woman with multiple meningiomas, who developed a high-grade spindle cell tumor 6 months after the resection of a World Health Organization grade I meningioma. It was not clear whether this tumor represented a malignant transformation of meningioma or a primary sarcoma. Malignant transformation of a meningioma is exceptional within this short period and a coexisting sarcoma and meningioma are equally uncommon. Even though these malignant neoplasms are rare in general, they appear to be more prevalent in patients with multiple meningiomas including those with neurofibromatosis type 2.

The effects of systemic and intratumoral interleukin-12 treatment in C6 rat glioma model.

OBJECTIVE: Cytokine based immunotherapy has long been an exciting field for many investigators aiming to provide an effective alternative treatment modality for glioma management. Among these cytokines, interleukin-12 (IL-72) plays a crucial role in mediating inflammatory and antitumoral activity on the host defence. We have investigated the therapeutic role of systemic and local delivery of IL-12 in C6 rat glioma model and compared these two modalities. METHODS: The donor C6 glioma cells were injected stereotactically to 32 Wistar rats and right frontal tumor formation was established in all subjects. The rats were evenly divided into four groups as intratumoral (i.t.) control group (Group IA), intraperitoneal (i.p.) control group (Group IB), i.t. treatment group (Group II) and i.p. treatment group (Group III). Magnetic resonance imaging were performed to 72 rats (three from each group) on the seventh post-inoculation day. Recombinant mouse IL-12 (rmIL-12) was administered via i.t. (0.1 microg 5 microl/day/rat) and i.p. (0.1 microg 20 microl/day/rat) routes to treatment groups between days 9 and 11 following tumor inoculation, for 3 consecutive days. The rats which were unresponsive to the external stimuli, unable to feed themselves or having severe neurological impairment were decapitated and the specimens were histopathologically examined. RESULTS: The subjects of Group ILL (i.p.) showed a statistically significant prolongation in survival time (mean = 39 days) when compared to the control group (mean = 31.7 days) (p = 0.035) and Group II (i.t.) (mean = 24.5 days) (p = 0.005). Histopathologic examination of Group III revealed markedly increased intratumoral and peritumoral lymphocyte infiltration compared with the other groups. CONCLUSION: This study demonstrated that systemic administration of IL- 12 in C6 glioma model in rats prolongs the survival, probably by stimulating the cellular immunity leading to lymphocytic infiltration.

C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in meningiomas and high-grade gliomas.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) plays a role in DNA biosynthesis, methylation and repair in actively dividing cells by acting on folate metabolism. A common C677T polymorphism in the gene for MTHFR leads to an enzyme with decreased activity. MTHFR polymorphisms have been studied in various cancers but not in primary brain tumors. The purpose of this case-control study was to explore a possible association between MTHFR C677T polymorphism and primary brain tumors. MATERIALS AND METHODS: The MTHFR C677T genotype was determined in 74 patients with histologically-verified primary brain tumors and 98 cancer-free control subjects. RESULTS: The MTHFR 677T variant genotype was observed in 49% of cases and 46% of controls. Although the difference was not significant (p =0. 194), the homozygous TT genotype was found at a higher frequency in high-grade glioma (HGG) patients compared to controls (15.4% and 7.1%, respectively). The MTHFR genotype was not associated with meningioma patients. Defining patients with the CC genotype as reference, the relative risk of HGG for subjects with the T allele (CT+ TT genotype) was 1.17. CONCLUSION: In spite of the established effect of the MTHFR 677 TT genotype on DNA hypomethylation with concomitant inadequate folate levels, the MTHFR 677 TT genotype is not associated with individual susceptibility to HGG.

In vitro investigation of heat transfer in calf spinal cord during polymethylmethacrylate application for vertebral body reconstruction.

The objective of this experimental study was to investigate the temperature variations within the spinal cord of calf cadavers during polymethlymethacrylate (PMMA) application for vertebral body reconstruction. Cervical spines including the cervical spinal cord of ten fresh cadavers were used. Corpectomy and laminectomy were performed and dura was exposed at the same level for proper placement of thermal sensors. Sensors were placed in multiple holes in the spinal cord at depths of 3, 6, 9 and 12 mm, respectively. Whether the thermal sensors were placed in the gray or white matter was determined by computerized tomography. The white and gray matters of the spinal cord exhibited different thermal properties. The white matter was more conductive and absorbed less heat than the gray matter. The heat sensor nearest to PMMA exhibited temperatures of 42-44 degrees C. The second heat sensor placed at 9 mm depth within the gray matter showed 44 degrees C. The third sensor, which was placed at 6 mm depth within the spinal cord recorded the same temperature as the first, i.e., nearest to PMMA sensor. The fourth heat sensor, which was at the farthest location from PMMA demonstrated 37-39 degrees C. The temperature distribution within the gray matter was inversely proportional to the distance from the heat source. The temperature at the dorsal white matter, which was distant from the heating source, remained nearly constant and was not elevated. Our data suggest that thermal injury to the spinal cord during PMMA application may be expected to be more significant in the gray matter when compared with other neural tissues.

Paraoxonase 192 gene polymorphism and serum paraoxonase activity in high grade gliomas and meningiomas.

The purpose of this study was to demonstrate the relationship between serum PON1 activity and PON 192 polymorphism in brain tumours. The distribution of PON 192 polymorphism in 42 high grade gliomas and 42 meningiomas were determined by polymerase chain reaction--based restriction fragment length polymorphism analysis and compared with 50 healthy control subjects. Serum paraoxonase1 activities were also measured and compared in the same population. We found that in both tumour groups serum PON1 activity was significantly lower than the control group (p < 0.001), but did not differ between meningiomas and high grade gliomas. There was no significant difference either in distribution of the AA, AB and BB genotypes or in the allelic frequencies, between the patient group and control subjects (p > 0.05). Our results suggest that serum PON1 as a part of the lipid peroxidation scavenging systems might be involved in the tumourigenesis of brain tumours.

Detection of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both cerebrospinal fluid and serum of patients after aneurysmal subarachnoid hemorrhage.

OBJECT: The aim of this study was to explore whether levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in the cerebrospinal fluid (CSF) and serum of patients after aneurysmal subarachnoid hemorrhage (SAH). METHODS: This prospective clinical study focused on 21 patients who had recently suffered an SAH due to aneurysmal rupture and 15 control patients with hydrocephalus who had no other central nervous system disease. Cerebrospinal fluid and serum samples obtained within the first 3 days and on the 5th and 7th days of SAH were assayed for ICAM-1 and VCAM-1 by using quantitative enzyme-linked immunosorbent assays. Levels of soluble forms of ICAM-1 (p = 0.00001) and VCAM-1 (p = 0.009) in the patients' CSF and those of ICAM-1 (p = 0.00001) and VCAM-1 (p = 0.00001) in their serum were found to be elevated after SAH compared with levels in the CSF and serum of control patients with hydrocephalus. In addition, when the authors compared the increased levels of adhesion molecules in the CSF and serum of patients after SAH, the only statistically insignificant difference that they found was between the levels of VCAM-1 in serum obtained on Days 5 and 7 after SAH (p = 0.27). CONCLUSIONS: Adhesion molecules are a group of macromolecules that may participate in the inflammatory process, a common pathway leading to vasospasm after SAH. Leukocyte adherence to the vascular endothelium, which is induced by adhesion molecules, has been believed to be the initial signal of the development of vasospasm. The authors have demonstrated the synchronized elevation of two adhesion molecules in both CSF and serum following aneurysmal SAH. Blocking of ICAM-1 as well as VCAM-1 by monoclonal antibodies post-SAH may provide a beneficial effect on vasospasm.

Bilateral peninsula-shaped linear craniectomy for mild degrees of craniosynostosis: indication, technique and long-term results.

OBJECTIVE: The goals of surgery in craniosynostosis are to reduce increased intracranial pressure and to achieve a good aesthetic result with minimal mortality and morbidity. A new type of strip craniectomy according to these principles is presented. PATIENTS: The technique was applied to seven cases of oxycephaly and three cases of scaphocephaly under 5 years of age. None of them had major cranial base involvement, facial deformity or marked psychomotor retardation. There was no syndromic case of craniosynostosis included in this group. METHODS: A curvilinear parasagittal craniectomy was combined with coronal and lambdoid craniectomies bilaterally. These craniectomies were curved postero- and antero-inferiorly, respectively, in order to create bilateral 'peninsula-shaped' parieto-temporal bones with their neck still attached to the temporal bone. A linear craniectomy, crossing the superior sagittal sinus and combining right and left curvilinear craniectomies was added. RESULTS: The operative time varied between 45 min and 1h, without any complications. Correction of the skull shape was successful in all cases. CONCLUSION: This technique is simple and effective. But, it is only applicable to a minority of craniosynostoses. Patient selection is the key to better results.

Surgical treatment of intracranial epidermoid tumors.

Intracranial epidermoid tumors are rare, potentially curable, benign lesions that are sometimes associated with perioperative complications, and tend to recur if not completely removed. Histologically benign epidermoid tumors may also develop into highly malignant tumors. This study evaluated on 28 cases of intracranial epidermoid tumor treated over a 13-year period by radical resection with microneurosurgical techniques. The majority of patients underwent computed tomography and/or magnetic resonance imaging within the first 24 hours postoperatively to confirm the results of surgery. Radical surgical resection was achieved in 21 of the 28 cases, and there was no operative mortality. The most common postoperative complication was transient paresis of various cranial nerves. During a mean follow up of 6 years, only one tumor became malignant. Radical surgical resection should be the goal in treating these benign lesions, but if not possible, every effort should be made to minimize the amount of tumor tissue that remains.

Nitric oxide levels in rat cortex, hippocampus, cerebellum, and brainstem after impact acceleration head injury.

Nitric oxide (NO) is a potential mediator of secondary brain injury in the settings of cerebral ischemia and inflammation. Traumatic brain injury (TBI) alters the levels of stable end products of NO metabolism. We investigated these changes and attempted to identify brain regions that were unique with regard to NO production in the period immediately after TBI. The experiment involved assaying nitrite-nitrate concentrations in the rat cortex, cerebellum, hippocampus, and brainstem after impact-acceleration head injury. Five rats comprised the sham-operated (control) group, five sustained mild head injury (MHI), and five sustained severe head injury (SHI). There was a uniform decline in the tissue concentrations of NO metabolites in all four brain regions in both injured groups. There were no significant differences in the concentrations of NO metabolites among the various sites tested in the MHI group; however, there appeared to be a relationship between degree of decline in NO levels and amount of trauma sustained by a given region in the SHI group. In these rats, NO dropped to the lowest levels in the brain region where the direct trauma was most severe. The results suggest that nitrite-nitrate levels in these four brain regions fall below normal in the first 5 min after impact trauma. This decrease may, in part, be related to reduced activity of all nitric oxide synthase isoforms, which would cause a drop in the levels of NO metabolites. We believe that this decline may be linked to, and may even cause, the global decrease in cerebral blood flow that occurs in the initial stages of TBI.

A medical class lost at Gallipoli.

In 1915, the second year of the First World War, one of the big battles was the Gallipoli Campaign. Many students of the Istanbul Darulfunun (today Istanbul University) and of the Istanbul Men's High School joined the second battalion to participate in the defence of the Dardanelles as volunteers. All of the soldiers of that battalion died in 19 May 1915. The Medical School of Darulfunun, which lost all of the students of the class of 1915, had no student to graduate in 1921.

Intracerebral Whipple disease: unusual location and bone destruction. Case report.

Whipple disease is a rare systemic bacterial infection characterized by migratory polyarthralgia and chronic diarrhea. In 5 to 20% of patients with Whipple disease, the infection may present initially with or eventually develop symptoms related to the central nervous system (CNS). Although CNS involvement is a known feature of systemic Whipple disease, intracerebral mass lesions are uncommon. Mass lesions in these cases are typically deep seated and multifocal. Corticosubcortical regions are unusual sites of CNS involvement in cases of Whipple disease. In the present paper, the authors describe the first case of Whipple disease to feature a single corticosubcortical solid frontoparietal mass lesion that displayed homogeneous contrast enhancement on neuroimaging and was associated with bone destruction of the calvaria. Although CNS involvement has been observed in the form of deep-seated mass lesions in cases of systemic Whipple disease, unusual manifestations should be kept in mind during diagnosis and follow-up review in these patients.

An association between mesial temporal lobe epilepsy with hippocampal sclerosis and human leukocyte antigens.

PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is one of the medically intractable epilepsies that may be remediable with surgery. Although the pathogenesis of HS still remains obscure, genetics may play a role as a predisposing factor, with the genetically controlled immune system as one of its aspects. Our aim in this study was to investigate whether there is any association between human leukocyte antigens (HLAs) that are related to chromosome 6 and this specific type of epilepsy. METHODS: HLA class I and II typing were performed with the microlymphocytotoxicity method on 65 Turkish patients with MTLE-HS and on 184 healthy controls. RESULTS: Our study revealed a significantly high frequency of class II antigens HLA-DQ2, -DR4, and -DR7 alleles and the combination of HLA-DR4-DQ2, and DR7-DQ2 alleles. CONCLUSIONS: The HLA alleles that occur with increased frequency in many HLA- associated conditions appear to serve as risk factors that increase susceptibility but are not essential for disease expression. Our data support the role of genetic factors in the development of HS, possibly related to early childhood events that may act as a trigger factor to initiate the cascade in genetically prone patients with specific HLA types to give rise to MTLE eventually.