Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy.

BACKGROUND: The role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. METHODS: Patients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. RESULTS: Fifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19-78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10-20 Gy), 27 Gy (range, 18-33 Gy) and 25 Gy (range, 25-30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. CONCLUSION: Our findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

An Investigation into the Relationship of SUR-1TRPM4 Receptor with Peritumoral Edema in High-Grade Glial Tumors.

AIM: To investigate the presence of Sur1-Trpm4 receptors in high-grade glial tumors, and their relationship with edema volumes in preoperative magnetic resonance imaging (MRI) sequences. MATERIAL AND METHODS: MRI sections were extracted from T1-weighted (T1W) and T2-weighted (T2W) sequences and fluidattenuated inversion recovery (FLAIR) images. After that, T1W 3D magnetization-prepared rapid gradient echo (MP-RAGE) sequences were taken with and without contrast medium. Tumor and peritumoral edema volumes were calculated in cubic centimeters. Sur1- Trpm4 receptors were studied by immunohistochemical examination of tissue samples. Relationships between data were analyzed using Spearman's correlation coefficient. RESULTS: In the immunohistochemical examinations, 58% of the samples from patients with high-grade glial tumors were positive for Sur1 and 74% were positive for Trpm4. The volume of tumors was correlated with the volume of peritumoral edema. CONCLUSION: The presence of the Sur1-Trpm4 receptor complex in high-grade glial tumors was confirmed. Further preclinical or clinical studies are required to identify and validate the role of Sur1-Trpm4 in glial tumor subgroups.

Effects of Methylprednisolone in the Treatment of Spinal Cord Injuries by Evaluation of microRNA-21: An Experimental Study.

BACKGROUND AND STUDY AIMS: Spinal cord injury (SCI) is one of the most complicated pathologies that affect active young males. miR-21 primarily regulates several cellular processes. We aimed to elucidate the regulatory role of miR-21 and test methylprednisolone as a disease-modifying agent on experimental SCI tissues. METHODS: A total of 36 8- to 10-week-old adult female Sprague-Dawley rats weighing 250 to 300 g were used. Animals were randomly divided into six groups. Except for groups 1 and 4, the spinal trauma model was applied to all animal groups using the clipping method. In groups 3 and 6, methylprednisolone was given. For real-time polymerase chain reaction (PCR) investigations, rats in groups 1, 2, and 3 were reoperated on after the first postoperative day, whereas those in groups 4, 5, and 6 were reoperated on after postoperative day 7 and spinal cord samples from the laminectomy area were removed for gene expression analysis. Relative gene expression of miR-21, Gfap, Vim, Stat3, Faslg, Pten, Bax, Bcl2, Cox2, and Il6 were determined with quantitative reverse transcription (qRT) PCR. RESULTS: In group 3, the miR-21 expression significantly increased compared with groups 1 and 2. When compared with group 3, a decrease in miR-21 expression was observed in group 6 (p < 0.05). When compared with group 4, group 6 had lower levels of Gfap, Pten, Stat3, and Bax (p < 0.05). CONCLUSIONS: miR-21 supports the beneficial aspects of the body's healing mechanisms following SCI. In the acute phase, the use of methylprednisolone increases miR-21 expression in the early period of trauma. Methylprednisolone increases some astrogliosis and inflammation biomarkers' levels; however, it did not affect the apoptotic biomarkers.

Early stage T1-weighted perfusion magnetic resonance imaging: a factor that predicts local control response in patients with meningioma who underwent gamma-knife radiosurgery.

BACKGROUND: Gamma-knife radiosurgery (GKRS) is an alternative treatment option for selected intracranial meningiomas. The study's aim is to demonstrate the advantages of T1-weighted perfusion magnetic resonance imaging (T1-PMRI) by measuring the volume transfer coefficient (Ktrans) values in the prediction of local response for patients with meningioma who have undergone GKRS consecutively. METHODS: The data of patients diagnosed radiologically with WHO grade 1 intracranial meningiomas was collected prospectively. The patients who were treated consecutively with GKRS at our institution (September 2017-September 2018) were included. After GKRS, the patients were followed up at the defined periods with routine contrast-enhanced MRI and T1-PMRI by measuring the Ktrans. The comparison between the pre-treatment and third-month post-treatment (PO3M) Ktrans was done using the Wilcoxon signed-rank test. RESULTS: Thirty-one patients with 36 tumors have undergone GKRS. Twenty-two patients were female. The mean age was 55.3 years. The mean pre-GKRS volume was 7.67 ccs. The mean 50% radiation isodose was 12.2 Gy. The local tumor control rate was 100%. Fourteen tumors were regressed fully at the last MRI. PO3M Ktrans decreased when compared with the pre-GKRS values (p < 0.0001). However, the numerical decrease in tumor volumes on contrast-enhanced MRI was not statistically significant (p = 0.117). CONCLUSION: Changes between Ktrans on PO3M and pre-GKRS T1-PMRI were more useful in determining the early response to GKRS in patients with meningioma than volumetric changes. Therefore, Ktrans should be taken as a reference to predict the early response to GKRS in follow-up imaging scans.

First Case of MELAS Syndrome Presenting with Local Brain Edema Requiring Decompressive Craniectomy.

Mitochondrial encephalomyopathy, lactic acidosis, and recurrent stroke-like episodes (MELAS) syndrome is a rare but one of the most common maternally inherited multisystem disorder. Although patients with MELAS present a variable clinical profile, strokelike lesions have been detected in 90% of cases, with stroke being the first presenting symptom in 25% of cases. However, cases of local brain edema requiring decompressive craniectomy has not been reported. A 12-year-old male patient was admitted to our pediatric intensive care unit with altered mental status, seizures, and vision loss. The patient was stuporous and presented neck stiffness. Complete blood count, serum electrolytes, biochemistry (including lactate level), acute phase reactants, and repeated blood gas analysis were unremarkable. Brain magnetic resonance imaging (MRI) revealed an edematous stroke-like lesion in the right occipital lobe accompanied by brain swelling. Intravenous ceftriaxone, acyclovir, intravenous immunoglobulin (IVIG), and pulse steroid therapy were started for possible diagnosis of viral/bacterial/autoimmune encephalitis; levetiracetam, phenytoin, and an infusion of sodium thiopental were started for refractory status epilepticus; and a 3% NaCl infusion was started for local brain edema. The results of serum autoimmune encephalitis panel were negative. Further investigations for rheumatic, vascular, and metabolic disorders were unremarkable. Despite these supportive treatments, the patient was clinically decompensated due to brain swelling that progressed to the left midline shift, and he underwent decompressive craniectomy. Histologic examination of brain biopsy specimen revealed non-specific encephalitis findings. A pathogenic variant of the MT-TL1 gene (m.3243A > T), responsible for MELAS, was detected. The patient?s condition dramatically improved after specific treatment for MELAS. If the diagnosis and treatment are delayed, MELAS syndrome can cause serious brain edema, which may ultimately require decompressive craniectomy.

Evaluation of Brainstem Subcortical Auditory Pathways with Diffusion Tensor Imaging After Gamma Knife Radiosurgery in Intracanalicular Vestibular Schwannoma.

OBJECTIVE: To investigate changes in DTI (Diffusion Tensor Imaging) parameters in brainstem subcortical auditory pathways after Gamma Knife Radiosurgery (GKR) in patients with intracanalicular vestibular schwannoma (ICVS) and to analyze the relationship between tumor volume and ADC (apparent diffusion coefficient) and FA (fractional anisotropy) values. METHOD: Seventeen patients with ICVS were evaluated before and after GKR. ADC and FA values of the lateral lemniscus (LL) and inferior colliculus (IC) and tumor volume were calculated. Patients who responded to GKR were classified as Group 1 and those who did not respond adequately as Group 2. The relationship between ADC and FA values and changes in tumor volume were analyzed. RESULTS: Tumor volume significantly decreased after GKR. ADC values obtained from the tumor increased after GKR (p:0.002). There was no significant difference in LL and IC before and after GKR in terms of FA and ADC values (n:17). There was a positive correlation between response to treatment and contralateral LL ADC values after GKR (p=0.005, r:0.652). There was a negative correlation between contralateral IC FA values after GKR and response to treatment (p=0.017, r: -0.568). There was a significant difference between Groups 1 and 2 in regards to contralateral LL ADC (p=0.03) and IC FA values (p=0.017). CONCLUSION: Since the cochlear nerve and subcortical auditory pathways have low regeneration potential after nerve damage, ADC and FA changes in LL and IC may be explained with the presence of intracanalicular tumors prior to GKR. Since GKR does not cause additional damage to the subcortical auditory pathways at the brainstem level, we think that GKR is a noninvasive treatment method that can be used safely in patients with ICVS.

The Effectiveness of Diffusion Tensor Imaging in Determining Radiological Response after Radiosurgery in Patients with Vestibular Schwannoma.

BACKGROUND: The effectiveness of Diffusion Tensor Imaging (DTI) in demonstrating functional changes in the tumor in determining the response to treatment after radiosurgery in patients with vestibular schwannoma (VS) is not clear yet. OBJECTIVE: The study aimed to determine the change in total tumor volume (TTV) in terms of radiological response in patients who had VS and were treated with radiosurgery and investigated the relationship between the TTV, follow-up times and DTI parameters. METHODS: Thirty-one patients were assessed using DTI and MRI. TTV, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were calculated. Patients were divided into three groups: those who responded to the treatment (group 1) (n=11), those who did not (group 0) (n=9) and those who remained stable (group 2) (n=11). RESULTS: The mean duration of follow-up was 28.81±14 months. ADC values increased in patients with VS after radiosurgery (p=0.004). There was no statistical difference in the FA values. A significant reduction in TTV after radiosurgery was detected in group 1 (p=0.003). ADC values increased significantly after radiosurgery in group 2 (p=0.04). Although there were no significant differences, ADC values after radiosurgery increased in group 1 and group 0. CONCLUSIONS: ADC values continuously increase due to radiation damage in the period before the tumor volume shrinks after radiosurgery. We think that it is not appropriate to diagnose inadequate treatment or progression only when TTV is evaluated in terms of response to treatment in the early period after radiosurgery.

Glioblastoma Stem Cells and Comparison of Isolation Methods.

BACKGROUND: Glioblastoma (GBM) is the most aggressive and the most common primary brain tumor. Over the last few years, studies have identified many genetical and phenotypical molecular situations for developing new treatment modalities in patients with GBM. Nevertheless, main problem for the GBM is radio-chemotherapy resistance and relapse after the surgery. The identification of glioma stem cells and microenvironmental influences has created a paradigm shift in targets of therapy. Current studies have shown that glioma stem cell is responsible for aggressiveness, recurrence and resistance to therapy of GBM. GBM stem cell isolated from human GBM multiforme fresh tissue samples is important both for curative therapeutic options and personalized targeted therapy. The purpose of this study was to determine the most suitable isolation method of GBM stem cells (GSCs). METHODS: Tumor tissue sample was obtained during the surgical resection of lesion in patients with the diagnosis of GBM. Tumor stem cell isolation from tissue was performed in three different ways: 1) GBM cell isolation with trypsin; 2) GBM cell isolation with brain tumor dissociation Kit (BTD Kit); and 3) GBM cell isolation with tumor dissociation enzyme (TDE). RESULTS: We showed that GSCs were isolated from tumor specimen using flow cytometry and immunofluorescence staining. Our study showed that isolation with BTD Kit is the most suitable method to isolate GBM tissue-derived glial tumor stem cells. CONCLUSIONS: The development of alternative personalized therapies targeting brain tumor stem cell is urgently needed. It is important to understand the fundamental mechanisms of driving stem cells. If their life cycle mechanisms can be identified, we can control the growth of GBM.

Investigation of cytotoxic, genotoxic, and apoptotic effects of curcumin on glioma cells.

Glioblastoma is a malignant tumor of the brain. The treatment of this tumor is still a challenge. Curcumin has been shown to have therapeutic effects when used to treat malignant diseases. However, the molecular mechanisms of its action are not fully elucidated. We hypothesized that reactive oxygen species (ROS) have a key role in curcumin-induced DNA damage, apoptosis, and cell death. To test our hypothesis, cytotoxic, genotoxic, apoptotic, and ROS-generating effects, as well as mitochondrial membrane potentials of curcumin on rat glioma cells (C-6) and normal fibroblastic cells (L-929) were investigated. We examined concentration-dependent cytotoxic, genotoxic, apoptotic, and ROS generating effects of curcumin at C-6 cells and L-929 cells. The cells were incubated with different doses of curcumin (10-100 µM) for 24 hours. Higher doses of curcumin resulted in greater cellular death of cancer than of normal cells at higher concentrations. Curcumin also induced ROS generation in cancer than normal cells in a concentration-dependent manner. Our results showed that curcumin-induced DNA damage in a dose-dependent manner (p < 0.001). At high curcumin concentration such as 80 µM, the proportions of live cells in cancer and normal cell lines were 11.5 and 44.3, respectively. The higher doses of curcumin resulted in greater apoptosis in cancer than normal cells.This in vitro study provided clear evidence that curcumin induced DNA damage and apoptosis. Cytotoxicity may be due to its pro-oxidant activity in a dose-dependent manner in cancer and normal cells. These activities were higher in cancer cells.

Comparison of the biochemical and radiological criteria for lumbar disc degeneration.

BACKGROUND: The relationship between radiological degeneration criteria on lumbar magnetic resonance imaging (MRI) and both the keratan sulfate (KS) and chondroitin sulfate (ChS) levels was examined in disc material taken from patients undergoing lumbar disc herniation (LDH) surgery. To examine whether the biochemical and radiological degeneration criteria testing the reliability of radiological degeneration findings agreed and to evaluate the contribution of the KS/ChS ratio to disc form (protruding or extruding). METHODS: This was a prospective experimental cohort study. Using enzyme-linked immunosorbent assay, KS and ChS levels were measured in the degenerate nucleus pulposus taken from 71 patients with a diagnosis of LDH who underwent surgery. The degeneration levels and disc form (protruding or extruding) were determined according to the Pfirrmann five-stage grading system on preoperative T2-weighted lumbar MRIs. According to the Pfirrmann system, 28 patients were grade III and 43 were grade IV. The relationship between radiological criteria and the KS/ChS ratio was statistically evaluated. RESULTS: The KS levels (p=0.046) and the KS/ChS ratio (p=0.001) were significantly higher in grade IV patients than in grade III patients. However, there was no difference between the KS and ChS levels and the KS/ChS ratio when patients were classified as protruding or extruding according to their disc structure. Disc structure and biochemical degeneration indicators were not correlated. CONCLUSIONS: The KS level and the KS/ChS ratio were high in patients with marked radiological degeneration on lumbar MRI, demonstrating the sensitivity and reliability of the Pfirrmann five-stage grading system for showing radiological degeneration.

Evaluation of Auditory Pathways Using DTI in Patients Treated with Gamma Knife Radiosurgery for Acoustic Neuroma: A Preliminary Report.

PURPOSE: We aimed to evaluate the change in bilateral auditory pathways using diffusion tensor imaging (DTI) after gamma knife radiosurgery (GKR) and to determine the relationship between the radiosurgical treatment variables and DTI findings. METHODS: In this study 13 patients with unilateral acoustic neuroma and 11 controls underwent routine magnetic resonance imaging (MRI) and DTI. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured from the bilateral auditory pathways in all individuals before and after GKR. RESULTS: Before GKR, subjects' ADC values obtained from the contralateral side were higher at the lateral lemniscus, medial geniculate body and Heschl's gyrus compared to those of the controls. No statistical differences were found in ADC and FA obtained at bilateral auditory pathways before and after GKR. The ADCs measured at the lateral lemniscus were positively correlated with the maximum radiation dose delivered to the brainstem (BS) and the brainstem volume receiving a radiation dose of 10 Gy (BS V10). A negative correlation was found between the FA measured from the inferior colliculus and the maximum radiation dose to the cochlea. The ADCs at the inferior colliculus were positively correlated with the mean radiation dose to the cochlea. CONCLUSION: There were no significant differences in the degree of involvement before and after GKR, revealing that GKR did not significantly affect the auditory pathways at 4 months. The major factors that may lead to microstructural injury to auditory pathways at the brainstem level are associated with maximum brainstem radiation dose, BS V10, and cochlear dose. These findings may suggest that more attention should be paid to anatomical structures including the cochlea and brainstem during treatment planning of GKR.

A Rare Cause of Headache in the Emergency Department: Intraventricular Epidermoid Cyst Rupture With Hydrocephalus.

Lateral intraventricular tumors are not frequently observed. Since these tumors grow linearly rather than exponentially, they grow gradually and thus do not cause mass effects and hydrocephalus. This study is the case report of a rare great volume left intraventricular epidermoid cyst rupture. The tumor was found to be associated with mass effect on neighboring structures and hydrocephalus.