[Aberrant methylation of NF2, TIMP-3 and THBS1 genes and their diagnostic values in meningiomas].

OBJECTIVE: To explore the functions of NF2, TIMP-3 and THBS1 genes in the tumorigenesis or progression of meningiomas and analyze the values of these genes in early diagnosis, therapy and prognostic evaluation in meningiomas. METHODS: A total of 66 cases with histological sections of meningiomas, including solitary (SMs, n = 30) and multiple meningiomas (MMs, n = 36), were retrieved from our departmental archives. All cases were regrouped as benign, atypical and anaplastic (malignant) by hematoxylin & eosin staining according to the recently published WHO classification of nervous system tumors. Genomic DNA was extracted from tumor sections and methylation-specific polymerase chain reaction (MSP) performed to detect the CpG methylation status. Normal brain tissue was used as the control group. And then the differences of methylation rate between SMs and MMs tissues and among different subgroups were analyzed by statistical analyses. RESULTS: The results of methylation in different types of meningiomas demonstrated that the rates of NF2, TIMP-3 and THBS1 methylation were 26.7% (8/30), 16.7% (5/30) and 36.7% (11/30) in 30 SMs tissues and 30.6% (11/36), 22.2% (8/36) and 22.2% (8/36) in 36 MMs tissues respectively. But no aberrant methylation of NF2, TIMP-3 and THBS1 genes was found in normal brain tissue. No significant differences in three types of gene methylation rates existed between SMs and MMs in the I-III grade meningiomas. Nevertheless, there was great difference between grades I, II and III in SMs and MMs while no significant difference was found between grades II and III. CONCLUSION: The methylation of NF2, TIMP-3 and THBS1 is correlated with the tumorigenesis of meningiomas (grade II and III). As an important pathogenetic cause of meningiomas, it may be used as a clinical tool for an early diagnosis of meningiomas.

[Expression and significance of MMP-9, PR, Ki-67 and Survivin in multiple meningiomas].

OBJECTIVE: To detect the expressions of matrix metalloproteinase-9(MMP-9), progesterone receptor(PR), Ki-67 and Survivin in the multiple meningiomas (MMs) and explore its genesis, diagnosis and bionomics features. METHODS: A total of 66 cases with histological sections of meningiomas retrieved from the archives of Department of Pathology of our hospital, including 30 cases of solitary meningiomas (SMs) and 36 cases MMs, were regrouped as benign, atypical and malignant by hematoxylin and eosin staining according to the World Health Organization classification of nervous system tumors. Immunohistochemistry was performed to detect the expressions of MMP-9, PR, Ki-67 and Survivin in 36 cases of MMs and 30 cases of SMs. And normal brain tissue was selected as a control group. The staining intensity was analyzed quantitatively for the differential expressions of MMP-9, PR, Ki-67 and Survivin between SMs and MMs. RESULTS: No expression of MMP-9, PR, Ki-67 and Survivin was detected in 5 normal brain tissues, but the expression rates were 100%, 53%, 23% and 88% respectively for significant difference comparing with normal tissue. The result of statistical analysis showed that there was significant difference in the expression intensity of MMP-9 and PR between two groups. The expression intensity MMP-9 in multiple group was significantly higher in MMs than that in SMs (P < 0.01) while PR was lower in MMs than that in SMs (P < 0.05). But no significant difference was found for the expression of Ki-67 or Survivin between two groups. CONCLUSION: The detections of MMP-9, PR, Ki-67 and Survivin are helpful in the clinical diagnosis and early detection of meningioma.

Study on surgical approaches and electrode implantation of oculomotor nerve and inferior obliquus in beagle dogs.

OBJECTIVES: To study the surgical anatomy and approaches of intracranial oculomotor nerve (OMN) and inferior obliquus (IO), and the methods of their electrode implantation in dogs. METHODS: The research was performed on 30 adult beagle dogs at Shanghai Jiaotong University Medical College, Shanghai, China from November 2007 to August 2008. All animals were subjected to a right transfrontotemperal approach to intracranial OMN, a transconjunctival route to IO, and the neuro-stimulating and recording electrode implantation under general anaesthesia. The OMN was stimulated and the electromyography of IO recorded and analyzed with the Powerlab System. The security and reliability of the implanted electrodes were investigated. RESULTS: The surgical anatomy and approaches of both the OMN from its exit from midbrain to the entrance into cavernous sinus and the IO were described. Moreover, the implantation methods of OMN stimulating electrode and the electromyographic recording electrode of IO were displayed. The implanted electrodes were safe and reliable. Some electrophysiologic data of IO were obtained in the healthy dogs. Also, some perioperative precautions for intracranial and ophthalmic surgical procedures in dog were exhibited. The mortality rate of the dogs was 0%, and no operative complications were observed. CONCLUSION: With the data provided, these surgical approaches and the methods of electrode implantation offer a choice to construct an animal model for studying various aspects of OMN regeneration.

The dual role of tumor necrosis factor-alpha in the pathophysiology of spinal cord injury.

Recent studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) is one of the most important mediators in spinal cord injury (SCI). However, the role of TNF-alpha in this process is still under debate due to conflicting evidence. Here, we utilized TNF-alpha transgenic (tg) rats and wild-type (wt) littermates to further investigate the role of TNF-alpha in SCI. We observed that, in the acute phase post-SCI (< or =3 days), TNF-alpha tg rats showed higher expression of TNF-alpha protein and more apoptotic cells in the spinal cord than wt rats, while in the chronic period (> or =7 days), TNF-alpha tg rats exhibited persistent baseline level of TNF-alpha protein, better tissue healing, and more activated astrocytes in the border of the lesion than wt rats. These data further demonstrate that TNF-alpha plays a dual role in SCI and its role probably depends on when it is released after SCI and on which cellular population it acts on.

Meningioma without dural attachment: case report, classification, and review of the literature.

BACKGROUND: The primary occurrences of meningiomas without attachment to the dura are rare. Clinical considerations and pathophysiologic mechanisms about these tumors have not been sufficiently explored, and a complete classification has not been accomplished. CASE DESCRIPTION: A 16-year-old adolescent boy presented with epileptic seizure for 9 years. Neurologic deficits were not found on admission. Magnetic resonance imaging revealed a 25 x 23-mm mass lesion without dural attachment located in the parietooccipital region. The tumor was iso-intense on T1-weighted and hyperintense on T2-weighted images, and became clearly and heterogenously enhanced with gadolinium. During surgery, a right parietooccipital craniotomy revealed the tumor was completely buried in the sulcus occipitalis anterior. Total removal of the tumor was accomplished. Histologic examination indicated that the lesion was an atypical meningioma. CONCLUSION: According to sites of the tumor, supratentorial meningiomas without dural attachment are classified into 5 varieties, and posterior fossa meningiomas without dural attachment into 4 categories. Except for intraventricular ones, meningiomas without dural attachment predominantly occur in males. The average age is about 20 years younger than that of meningiomas in general. Fibroblastic meningiomas constitute the major subtype. Intraparenchymal or subcortical meningiomas should be considered as one type, which may arise from arachnoid cells of the pia mater within brain sulcus.

Epidermoid cyst with infiltrative malignant melanoma in the cerebellopontine angle.

We report a patient with an intracranial epidermoid cyst associated with malignant melanoma in the cerebellopontine angle. The CT, MRI and histopathological findings showed an intracranial epidermoid cyst with an adjacent infiltrating melanoma. Immunohistochemical staining of the solid tumour was positive for the melanoma marker HMB45 and negative for GFAP and cytokeratin. Both CT and MRI were helpful in this patient but the diagnosis could only be made on histopathology.

Secreted Protein Acidic and Rich in Cysteine Modulates Molecular Arterial Homeostasis of Human Arterial Smooth Muscle Cells In Vitro.

Secreted protein acidic and rich in cysteine (SPARC) is widely expressed in the vascular smooth muscle cells (VSMCs) of human intracranial aneurysms (IAs), but the effect and underlying mechanism of SPARC on VSMCs during the formation and progression of IAs needs to be probed. Human umbilical arterial smooth muscle cells (HUASMCs) were treated with a gradient concentrations of SPARC in vitro for different time. Cell counting kit-8 (CCK-8) assay, cell cycle, and cell apoptosis were used to investigate the effect of SPARC on HUASMCs. After exposure to 2 and 4 µg/ml SPARC, cell viability were 89.3 ± 2.00 %, and 87.57 ± 2.17 % (P < 0.05 vs. control), respectively. Induced by 2 µg/ml SPARC, the proportion of cells in G0/G1 phase was 74.77 ± 1.33 % (P < 0.05 vs. control), and the early and late apoptosis ratio were 7.38 ± 1.25 % and 4.86 ± 0.81 % (P < 0.01 vs. control), respectively. After exposure to 2 µg/ml SPARC for 2, 6, 12, 24, and 48 h, Western blot analysis showed that the protein level of p21 was upregulated significantly at 2-12 h (P < 0.05 vs. control), while the expression of p53 remained stable within 48 h. The expression of Bax protein increased markedly and peaked at 24 (P < 0.01 vs. control), while Bcl2 protein decreased significantly at 48 h (P < 0.01 vs. control). Cleaved caspase3 was also upregulated dramatically and peaked at 24 h (P < 0.05 vs. control). The protein level of MMP2 increased significantly and peaked at 24 h (P < 0.01 vs. control), while TIMP2 remained stable and even reduced at 48 h (P < 0.05 vs. control). Taken together, SPARC could arrest HUASMCs in G0/G1 phase by overexpression of p21 and induce mitochondria-mediated apoptosis in vitro, which could result in the decreased cell viability. Besides, SPARC might also lead to the activation of MMP2 instead of MMP9. These results indicated SPARC could reduce the self-repair capability and increase injury of media layer and internal elastic lamina of intracranial artery, which would disrupt the normal homeostatic mechanism controlling vascular repair, thus promoting the formation and progression of IAs.

[Clinicopathologic characteristics and microsurgical treatment of glioma of limbic and paralimbic system].

OBJECTIVE: To explore the features of the clinical manifestations, imaging, pathology and microsurgery on the patients with gliomas of limbic and paralimbic system. METHODS: The clinical data of 28 patients with gliomas of limbic and paralimbic system were analyzed respectively. RESULTS: Seizure was the most common symptom, presented in 24 cases. CT scans showed hypodensity in 19 cases and isodensity in 9 cases. MRI scans were achieved in 23 cases, showing hypointense signal on T(1)WI and hyperintense signal on T(2)WI. Total resection was achieved in 19 cases, subtotal in 6 cases and partial in 3 cases. All patients had excellent postoperative recovery, except 5 patients who developed temporary frontal aphasia and 6 patients who developed contralateral hemiplegia. The patients had a postoperative follow-up ranging from 6 months to 5 years, and 23 cases still survived. CONCLUSION: High-resolution CT and MRI may reveal the size, location, confines and sharp demarcation of the tumors. Gliomas can be microsurgically removed with considerable results.

Traumatic subdural hydroma developing into chronic subdural hematoma.

OBJECTIVE: To probe the incidence, pathogenesis and clinical characteristics of traumatic subdural hydroma (TSH) developing into chronic subdural hematoma (CSDH). METHODS: We retrospectively analyzed the clinical data of 32 patients with TSH developing into CSDH and reviewed related literature. RESULTS: 16.7% of TSH developed into CSDH in this study. The time of evolution was from 22 to 100 days after head injury. All the patients were cured with hematoma drainage. CONCLUSIONS: TSH is one of the origins of CSDH. The clinical characteristics of TSH developing into CSDH follow that the ages of the patients are polarized, that the evolution often happens in the patients with small chronic hydromas and being treated conservatively, that the patients are usually injured deceleratedly and that the accompanying cerebral damage is often very mild.

[Type and its clinical characteristics of traumatic subdural hydroma].

OBJECTIVE: To explore the types and clinical characteristics of traumatic subdural hydroma (TSH). METHOD: One hundred and ninety-two cases of TSH were classified into four types: The types of resolution, steadiness, development and evolution on the basis of their clinical characteristics and dynamic observation of CT scanning. RESULTS: The patients in the resolution type often occurred in the prime of life. They had normal intracranial pressure and good prognoses using the conservative therapy. The majority of the elderly patients was in the steadiness type. Their main clinical manifestations included headache, dizziness, nausea, vomit, abnormal mentality and so on. Generally, there was no positive nervous systemic sign related to TSH. The prognoses of patients with the steadiness type treated by conservative therapy were satisfactory. The development type was common in the babies and children. This was mainly manifested as progressive increased intracranial pressure, mild hemiplegia, aphasia and abnormal mentality. The patients with development type often needed surgical treatment and might die once in a while due to accompanying cerebral parenchymal damage or postoperative complications. The evolution type was characterized by the polarized age, chronic increased intracranial pressure, often happening between 22 and 100 days after TSH and in the cases of small hydromas treated conservatively and mild accompanying cerebral damage, which always have a good prognosis by the treatment of surgery. CONCLUSIONS: The mechanism, clinical characteristics, treatment methods and prognoses varied with different types of TSH.

[Multiple meningiomas: report of 32 cases].

OBJECTIVE: To explore the genesis and classification and diagnosis as well as the treatment of multiple meningiomas. METHODS: Retrospective study of the materials of 32 cases of multiple meningiomas, simultaneously review of the related articles. RESULTS: All patients were divided into 5 groups, primary 18 cases, postoperative 7 cases, accompanied by neurofibromatosis (NF) 4 cases, meningiomatosis 1 case, accompanied with other intracranial tumor 2 cases, one with pituitary adenoma and the other with glioma. All the patients accepted operation, cured 25 cases, improved 7 cases. CONCLUSIONS: The cytogenesis of different type of multiple meningiomas probably varied. Estrogen may play an important role in the genesis of multiple meningiomas. One stage resection of all the tumors was feasible to most cases and advocated. Most cases had strong tolerance to several times of operation, staging operation was permitted. The prognosis and principle of treatment of different group varied.

[Diagnosis and treatment of cystic acoustic neuroma].

OBJECTIVE: To study the clinical features and treatment of cystic acoustic neuroma. METHODS: Twenty-two patients with cystic acoustic neuromas were diagnosed by CT and MRI preoperatively, and the tumors were resected by retrosigmoid approach, and verified by pathological studies. RESULTS: Of the 22 patients, 18 had tumors totally resected (postoperative house Brackman facial nerve grading: grade II in 4 patients, III in 7, IV in 3, V in 2, VI in 2) and 4 had tumors subtotally resected. CONCLUSION: Because of its specific clinical features and poor operative results, cystic acoustic neuroma should be regarded as a specific subtype.

Four patients with painful tic convulsive and a brief review of surgical treatment.

We present four patients with unusual painful tic convulsive: three were due to neurovascular compression; one was secondary to a cerebellopontine angle epidermoid cyst. We discuss these patients and those in the literature to determine the appropriate therapy for this rare disease.

Radiofrequency thermocoagulation rhizotomy for recurrent trigeminal neuralgia after microvascular decompression.

BACKGROUND: Microvascular decompression (MVD) is a well accepted surgical treatment strategy for trigeminal neuralgia (TN) with satisfying long-term outcome. However, considerable recurrent patients need more effective management. The purpose of this study was to evaluate the effectiveness of radiofrequency thermocoagulation rhizotomy (RTR) on patients with recurrent TN after MVD. METHODS: Totally 62 cases of recurrent TN after MVD undergoing RTR from January 2000 to January 2010 were retrospectively evaluated. Based on surgical procedures undertaken, these 62 cases were classified into two subgroups: group A consisted of 23 cases that underwent traditional RTR by free-hand; group B consisted of 39 cases that underwent RTR under the guidance of virtual reality imaging technique or neuronavigation system. The patients in group A were followed up for 14 to 70 months (mean, 40 ± 4), and those in group B were followed up for 13 to 65 months (mean, 46 ± 7). Kaplan-Meier analyses of the pain-free survival curves were used for the censored survival data, and the log-rank test was used to compare survival curves of the two groups. RESULTS: All patients in both groups A and B attained immediate pain relief after RTR. Both groups attained good pain relief rate within the first two years of follow-up: 92.3%, 84.6% and 82.6%, 69.6% respectively (P > 0.05). After 2 years, the virtual reality or neuronavigation assisted RTR group (group B) demonstrated higher pain relief rates of 82.5%, 76.2% and 68.8% at 3, 4 and 5 years after operation respectively, while those in group A was 57.2%, 49.6%, and 36.4% (P < 0.05). Low levels of minor complications were recorded, while neither mortalities nor significant morbidity was documented. CONCLUSIONS: RTR was effective in alleviating the pain of TN cases suffering from unsuccessful MVD management. With the help of virtual reality imaging technique or neuronavigation system, the patients could attain better long-term pain relief.

Surgical management and evaluation of prognostic factors influencing postoperative visual outcome of suprasellar meningiomas.

OBJECTIVE: To study the microsurgical technique and the prognostic factors influencing postoperative visual outcome in patients with suprasellar meningiomas (SMs). METHOD: The clinical materials of 45 patients with SMs treated microsurgically between January 2002 and October 2008 were analyzed retrospectively. Patients received ophthalmologic and radiologic assessment before and after operation. Follow-up ranged from 12 to 93 months (median, 39 months). As far as monocular vision was concerned, univariate and multivariate statistical analysis was performed among factors that might influence postoperative visual outcome. RESULTS: In this group, the mean age of the patients was 51 years. Median tumor size was 3.5 cm. The duration of symptoms ranged from 10 days to 35 years (median, 18 months). Total tumor resection was achieved in 40 cases (88.9%) and subtotal in 5 cases (11.1%). With respect to visual outcome of the 90 eyes, 54 eyes (60%) improved, 24 (26.7%) remained unchanged, and 12 (13.3%) had worsened. It has been illustrated that the postoperative visual improvement was determined by various factors, including age, recurrence, duration and severity of visual disturbance, preoperative condition of optic disc, tumor size, location, peritumoral edema, involvement with optic canal, arachnoid membrane interface, and extent of tumor removal. However, the multivariate analysis showed that recurrence, preoperative condition of optic disc, duration of impaired vision, and peritumoral edema are the most influential factors. CONCLUSIONS: Skillful microsurgical techniques are key to resect SMs while getting the desired visual outcome. The recurrence, preoperative condition of optic disc, duration of impaired vision, and peritumoral edema might be the most important factors influencing postoperative visual outcome.

Construction of double suicide genes system controlled by MDR1 promoter with targeted expression in drug-resistant glioma cells.

The multiple drug resistance protein (MDR1) is frequently overexpressed in human glioma. The aim of this study is to clone the MDR1 promoter from C6/ADR, construct the double suicide genes expressive vector controlled by MDR1 promoter, and explore its targeted expression in C6/ADR cells. MDR1 promoter from C6/ADR genomic DNA, which was linked with T vector, was amplified by using Polymerase chain reaction (PCR). After cut by NdeI and HindIII, MDR1 promoter was cloned into pcDNA3-TK (thymidine kinase) plasmid. The cytosine deaminase (CD) gene from pcDNA3-CD-TK plasmid was directly cloned into the above vector to construct pcDNA3-MDR1-promoter-CD-TK vector. Then this vector was transfected into C6 and C6/ADR cells respectively by liposome. After selection by G418, the tumor cell lines were stably established. Then these cell lines were examined through PCR and RT-PCR to respectively detect the integration and expression of TK and CD genes. The results showed the length and sequence of MDR1 promoter amplified by PCR were confirmed by DNA sequencing. The pcDNA3-MDR1-promoter-CD-TK expression vectors were constructed successfully. PCR indicated the double suicide genes were integrated into C6 and C6/ADR cells. RT-PCR revealed that CD and TK genes expressed in C6/ADR/CD-TK cells, whereas not in C6/CD-TK cells. In conclusions, construction of expressive vector containing double suicide genes controlled by MDR1 promoter with targeted expression in C6/ADR will provide a sound basis for targeted gene therapy for multidrug resistance (MDR) glioma.