Prabin Shrestha

Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells

Glioblastoma is characterised by invasive growth and a high degree of radioresistance. Survivin, a regulator of chromosome segregation, is highly expressed and known to induce radioresistance in human gliomas. In this study, we examined the effect of survivin suppression on radiosensitivity in malignant glioma cells, while focusing on centrosome aberration and chromosome instability (CIN). We suppressed survivin by small interfering RNA transfection, and examined the radiosensitivity using a clonogenic assay and a trypan blue exclusion assay in U251MG (p53 mutant) and D54MG (p53 wild type) cells. To assess the CIN status, we determined the number of centrosomes using an immunofluorescence analysis, and the centromeric copy number by fluorescence in situ hybridisation. As a result, the radiosensitisation differed regarding the p53 status as U251MG cells quickly developed extreme centrosome amplification (=CIN) and enhanced the radiosensitivity, while centrosome amplification and radiosensitivity increased more gradually in D54MG cells. TUNEL assay showed that survivin inhibition did not lead to apoptosis after irradiation. This cell death was accompanied by an increased degree of aneuploidy, suggesting mitotic cell death. Therefore, survivin inhibition may be an attractive therapeutic target to overcome the radioresistance while, in addition, proper attention to CIN (centrosome number) is considered important for improving radiosensitivity in human glioma.

Expression of vascular endothelial growth factor in dura mater of patients with moyamoya disease

Vascular endothelial growth factor (VEGF) has been found to be involved in vasculogenesis in different intracranial lesions. We investigated meningeal cellularity and VEGF expression in dura mater of patients with and without moyamoya disease. Nine dural specimens from nine cerebral hemispheres of seven patients with moyamoya disease and four control dural specimens from four non-moyamoya patients were collected during surgery and investigated. Dural specimens were immunohistochemically stained with VEGF antibody, and then meningeal cellularity and VEGF expression in dural tissue were analyzed. The mean ± standard error (SE) of total number of meningeal cells (meningeal cellularity) in dural tissue was 21.5 ± 3.0 in the moyamoya disease patients, whereas it was 2.7 ± 0.7 in control patients. The mean ± SE of VEGF expression was 51.1 ± 4.9% in the moyamoya disease patients, whereas it was 13.8 ± 5.9% in control patients. The meningeal cellularity and VEGF expression were statistically significantly higher in the moyamoya group in comparison to control group (p < 0.0001). Meningeal cellularity and VEGF expression are significantly increased in dura mater of the patients with moyamoya disease.

Role of PROPELLER diffusion weighted imaging and apparent diffusion coefficient in the diagnosis of sellar and parasellar lesions

OBJECTIVE To evaluate the role of the apparent diffusion coefficient (ADC) using periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) diffusion weighted imaging (DWI) in the differentiation between sellar and parasellar mass lesions. MATERIALS AND METHODS The study protocol was approved by our institutional review board. We retrospectively studied 60 patients with sellar and parasellar lesions who had undergone PROPELLER DWI on a 3-T MR imager. Conventional MRI findings were expressed as the ratio of signal intensity (SI) in the lesions to the normal white matter and the degree of contrast enhancement. ADC values were calculated as the minimum (ADC-MIN), mean (ADC-MEAN), and maximum (ADC-MAX). All patients underwent surgery and all specimens were examined histologically. Logistic discriminant analysis was performed by using the SI ratios on T1- and T2-weighted images (T1-WI, T2-WI), the degree of enhancement, and absolute ADC values as independent variables. RESULTS ADC-MIN of hemorrhagic pituitary adenomas was lower than of the other lesions with similar appearance on conventional MRI (non-hemorrhagic pituitary adenomas, craniopharyngiomas, Rathkes cleft cysts; accuracy 100%); the useful cut-off value was 0.700 x 10(-3)mm(2)/s. ADC-MAX of meningiomas was lower than of non-hemorrhagic pituitary adenomas (accuracy 90.3%; p<0.01). ADC-MIN of craniopharyngiomas was lower than of Rathkes cleft cysts (accuracy 100%; p<0.05). CONCLUSION As PROPELLER DWI is less sensitive to susceptibility artifacts than single-shot echoplanar DWI, it is more useful in the examination of sellar and parasellar lesions. Calculation of the ADC values helps to differentiate between various sellar and parasellar lesions.

Geminin: A good prognostic factor in high‐grade astrocytic brain tumors

Geminin is a nuclear protein that belongs to the DNA replication inhibitor group. It inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance protein onto chromatin, as is required for DNA replication. For this study, the authors investigated geminin expression in high‐grade astrocytic tumors, including anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), with a view to predicting clinical outcomes on this basis in patients with these malignant brain tumors.

Intrathecal baclofen therapy in severe head injury, first time in Nepal, a technique suitable for underdeveloped countries

Intrathecal baclofen (ITB) has been found to be helpful not only for spasticity but also for unconsciousness in a vegetative patient. This is the first case of ITB in Nepal, and here we discuss the effectiveness of ITB for spasticity in a patient in vegetative state. We also discuss about a simple technique for ITB used in Nepal where baclofen pump is not available. Here, we present a case of a 40-year-old male patient who had severe head injury with diffuse axonal injury treated conservatively. He went on to a vegetative state and subsequently developed severe spasticity of all the limbs. ITB was started under the guidance of one of the authors , Prof. Taira. Baclofen was injected to the spinal intrathecal space through a catheter which is used for spinal anesthesia. Spasticity improved significantly and his higher mental function also showed signs of improvement. He finally became fully conscious and well oriented. ITB is very useful in cases of severe spasticity and vegetative condition, a state of unconsciousness lasting longer than a few weeks. Even with a simple technique in the absence of baclofen pump, ITB can be used with its optimum effect.

Social norms and women's risk of intimate partner violence in Nepal

Social norms increasingly are the focus of intimate partner violence (IPV) prevention strategies but are among the least examined contextual factors in quantitative violence research. This study assesses the within-community, between-community, and contextual effect of a new measure of social norms (PVNS: Partner Violence Norms Scale) on womens risk of IPV. Data come from baseline surveys collected from 1435 female, married, reproductive-age participants, residing in 72 wards in three districts (Chitwan, Kapilvastu, Nawalparasi) in Nepal who were enrolled in a cluster randomized trial testing the impact of a social behavioral change communication intervention designed to prevent IPV. Results of unconditional multilevel logistic regression models indicated that there was cluster-level variability in the 12-month prevalence of physical (ICC = 0.07) and sexual (ICC = 0.05) IPV. Mean PVNS scores also varied across wards. When modeled simultaneously, PVNS scores aggregated to the ward-level and at the individual-level were associated with higher odds of physical (ORind = 1.12, CI = 1.04, 1.20; ORward = 1.40, CI = 1.15, 1.72) and sexual (ORind = 1.15, CI = 1.08, 1.24; ORward = 1.47, CI = 1.24, 1.74) IPV. The contextual effect was significant in the physical (0.23, se = 0.11, t = 2.12) and sexual (0.24, se = 0.09, t = 2.64) IPV models, suggesting that the ward-level association was larger than that at the individual-level. Adjustment for covariates slightly attenuated the ward-level association and eliminated the contextual association, suggesting that individual perceptions and the collective community phenomena were equally strong predictors of womens risk of IPV and should be taken into consideration when planning interventions. PVNS is a promising measure of social norms underpinning womens risk of IPV and warrants further psychometric testing.

Complete Excision of Giant Dumbbell Schwannoma without Neurophysiological Monitoring

Schwannomas are the most common tumors of spine. Dumbbell schwannomas are more commonly found in cervical spine. Complete excision of swchnnoma is mandatory to prevent its recurrence. However, at times it becomes diffi cult and rather impossible in certain cases of giant schwannomas. It is more so when there is no intraopertive neurophysiological monitoring. In this regard here we present 11-year-old boy with giant dumbbell schwannoma at the level of C2 cervical spine. The boy presented with progressive left upper limb weakness. He started having a lump, which got more prominent with time, on the back surface of left upper neck. MRI showed mass at C2 starting from left intradural space extending to extraforaminal space. The mass was giant measuring about 100 mm and was homogenously enhanced with contrast (Figure 1). Surgery was planned through extraforaminal approach. A curvilinear incision was given with the vertical limb of incision in the midline. Extraforaminal giant mass was approached fi rst. Surrounding dissection of the mass was done. Foramen was approached and foraminotomy was done along with small hemilaminotomy of C2 on left side. Total mass was excised in block through the foramen doing durotomy. Neurophysiological monitoring is essential intraoperatively while operating on such cases to minimize possible neurological defi cit.2 However, in our context, Complete Excision of Giant Dumbbell Schwannoma without Neurophysiological Monitoring Prabin Shrestha, MD, PhD Department of Neurosurgery B&B Hospital, Gwarko Lalitpur, Nepal

Management of brain tumor in Nepal

Abstract Management of brain tumors in developing countries displays a different perspective compared to developed nations. The difference starts from the presentation, which is always grossly advanced before the patient seeks treatment. Also, the surgeons must diagnose and plan surgery with the minimum number of diagnostic tools, while the majority of the time operating on the information gained from CT alone. Since cerebral angiography is rarely done, there is chance of vascular damage leading to profound bleeding or brain swelling. Due to the lack of medical insurance, the patient has to pay his/her own bill, a major deciding factor for surgery. Lack of social security is a further concern when morbidity is involved since postoperative disability can lead to further family suffering. Despite these constraints, we provide neurosurgical care to brain tumor patients with modification of surgical indications along with techniques meeting our socio-economic need. Here we present our experience in dealing with brain tumors in Nepal. We discuss the presentation, mode of investigation, the surgical tools and techniques adapted to meet these goals. We also discuss some peculiar differences in the presentation of brain tumors. Such differences in the biological nature of the tumor could be a subject of future study.