Tissue Thiol Concentration in High-Grade Gliomas: Is There any Association Between IDH1 Mutation Presence and Tumoral Cellular Antioxidant Defense?

AIM: To assess and compare the antioxidant capacities of high-grade gliomas (HGG) according to their grades and the presence of isocitrate dehydrogenase 1 (IDH1) mutation using tissue thiol level measurement. MATERIAL AND METHODS: Tissue thiol concentrations were measured in 41 HGG samples and 21 healthy brain tissues obtained from autopsy procedures, which were performed within the first 4 hours of death. All samples were stored at ?80°C, and a thiol quantification kit was used in evaluating tissue thiol levels. The Number Cruncher Statistical System was used for statistical analyses to detect the differences between the control group and the HGG group, which was also divided into subgroups according to their grade and IDH1 mutation presence. RESULTS: The tissue thiol levels of HGGs were found to be higher than the control group (p=0.001). Although the median thiol levels of Grade 4 gliomas were higher than those of Grade 3, no statistically significant difference was noted (p=0.076). When all tumors were compared according to the IDH1 mutation presence, IDH1-negative (IDH1-) HGGs had higher thiol contents than IDH1 mutant (IDH1+) HGGs (p=0.001). The thiol levels of Grade 4 IDH1- gliomas were statistically significantly higher than of Grade 3 gliomas (p=0.023), but no statistically significant difference between the thiol levels of Grade 3 and Grade 4 IDH1+ tumors was noted (p=0.459). CONCLUSION: We have demonstrated the higher thiol concentrations of HGGs, particularly IDH1- ones. The sulfhydryl contents of gliomas as an indicator of tumoral antioxidant capacity may be responsible for the treatment resistance of IDH1- gliomas, the mechanism of which is not clear. Thiols can be a novel target for treatment, considering the unsatisfactory results of current modalities for HGGs.

Thymoquinone ameliorates delayed cerebral injury and cerebral vasospasm secondary to experimental subarachnoid haemorrhage.

AIM OF THE STUDY: Among subarachnoid haemorrhage (SAH) patients, delayed cerebral injury (DCI) and infarction are the most important causes of death and major disability. Cerebral vasospasm (cVS) and DCI remain the major cause of death and disability. Thymoquinone (TQ) is the substance most responsible for the biological activity of nigella sativa (NS) and is useful in the treatment of ischaemic and neurodegenerative diseases, oxidative stress, inflammatory events, cardiovascular and neurological diseases. We conducted an experimental study aimed to investigate the preventive and corrective effects of TQ. MATERIALS AND METHODS: 24 Sprague-Dawley rats were randomly divided into three groups. The first was the control group which was a sham surgery group. The second group was the SAH group where the double haemorrage SAH protocol was used to induce vasospasm. The third group was the SAH+TQ group, where cVS was induced by the SAH protocol and the animals received oral 2 cc thymoquinone solution for seven days at a dose of 10 mg/kg, after the induction of SAH. The rats were euthanised seven days after the first procedure. The degree of cerebral vasospasm was evaluated by measuring the basilar artery luminal area and arterial wall thickness. Apoptosis was measured by the western blot method at brainstem neural tissue. Oxidative stress was measured by the Erel Method. Endothelin-1 was measured with ELISA analysis at blood. Statistical analysis was performed. RESULTS: Endothelin-1 values were found to be statistically significantly lower in the control and SAH+TQ groups compared to the SAH group (P < 0.001). Mean lumen area values were significantly higher in the control and SAH+TQ groups than in the SAH group (P < 0.001). In the control and SAH+TQ groups, wall thickness values decreased significantly compared to the SAH group (P < 0.001). OSI values were significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001). Apoptosis was significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001). CONCLUSION: Our results show that post-SAH TQ inhibits/improves DCI and cVS with positive effects on oxidative stress, apoptosis, ET-1, lumen area, and vessel wall thickness, probably due to its anti-ischaemic, antispasmodic, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective effects.

ABO and Rh Blood Groups and Risk of Myelomeningocele.

AIM: To investigate the relationship between the distribution of ABO or Rhesus (Rh) blood group antigens and the incidence of myelomeningocele. MATERIAL AND METHODS: A retrospective data was reviewed for all myelomeningocele patients operated at a tertiary academic hospital between years 2014 and 2019. Age, sex, delivery method, physical and neurological examination findings, and radiological findings alongside with blood type of each patient were recorded. The data of blood group distribution among the study patients was compared to the data of healthy individuals in the same region. RESULTS: Patients with group B and AB showed a higher chance of developing myelomeningocele. Rh-positive blood group was associated with high incidence of myelomeningocele (93.5%), whereas Rh-negative blood group showed least association (6.5%). Rh-positive blood group was also found to be more frequent in patients with myelomeningocele with hydrocephalus and Chiari malformation. CONCLUSION: The findings of this study show that ABO and Rh blood groups have an effect on the development of myelomeningocele under the influence of environmental or genetic factors.

Association between parity and lumbar spine degenerative disorders in young women.

Introduction: Estrogen helps to maintain the health of collagen-containing tissues including the intervertebral disc. Estrogen deficiency after menopause negatively affects the quality of vertebral end plates and induces development of degenerative disc disease (DDD). However, there is no study examining the relationship between parity and spinal degeneration in young women. The aim of this study was to define the relationship between parity and development of vertebral endplate signal changes and DDD in young premenopausal women.Materials and methods: This case-control case study included 224 patients aged 20-40 years with a history of low back pain for at least 3 months. Pfirrmann's grade, Modic changes (MCs), and Schmorl's nodes (SNs) were graded based on magnetic resonance images. Patients' parity, demographics, body mass index, physical activity level, and disability scores were assessed using a questionnaire.Results: The prevalence of abnormal total Pfirrmann's score (>10) and MCs was higher in primiparous patients than multiparous and grand-multiparous; however, it was not statistically significant. The presence of SN was statistically significantly associated with low parity. According to multivariate logistic regression analysis, it was found that the number of births increases by 1 unit, the abnormality in Pfirrmann's score decreases by 1.36 times.Conclusions: This cross-sectional study shows that parity is associated with DDD and vertebral end plate changes. SNs were significantly associated with parity. Modic changes and DDD were less common in grand multipara and multipara young women than in primipara women. These results indicate that low parity may possibly be associated with the development of spinal degeneration.

The effect of high mobility group box-1 protein on cerebral edema, blood-brain barrier, oxidative stress and apoptosis in an experimental traumatic brain injury model.

Traumatic brain injury (TBI) is one of the important reason of morbidity and mortality. While the primary injury due to mechanical impact is unavoidable, the secondary injury which is formed as a result of primary injury and thought to occur due to neuroinflammation in the forefront can be prevented and by this way mortality and morbidity can be reduced. High mobility group box-1 (HMGB1) is a protein that triggers the neuroinflammatory process by being released from the nucleus of necrotic tissues after primary injury. The aim of this study is to investigate the effects of HMGB1 on its receptors TLR4 and RAGE, cerebral edema, blood-brain barrier, oxidative stress and apoptosis causing secondary damage in an experimental traumatic brain injury model. Weighing between 280-320 g, 10 to 12 weeks-old, a total of 30 adult male Sprague-Dawley rats were used for the experiments. The rats were randomly assigned to 3 groups: 1) Control, 2) TBI and 3) TBI + ethyl pyruvate group (n = 10 per group). Right parietal cortical contusion was made by using a weight-dropping TBI method. Brain samples were harvested from pericontusional area at 24 h after TBI. HMGB1, TLR4, RAGE, occludin, claudin-5, ZO-1 levels are investigated by western blot analyses and immunohistochemistry examinations. HMGB-1, TLR4 and RAGE expressions increased after TBI. Major tight junction proteins in the blood-brain barrier: occludin, claudin-5 and ZO-1 expressions decreased after TBI. Brain edema increased after TBI. Also, proapoptotic bax and active caspase 3 expressions increased, antiapoptotic bcl-2 levels decreased after TBI. Total oxidant status and oxidative stress increased, total antioxidant status decreased after TBI. HMGB-1 protein plays a key role in the pathophysiology of traumatic brain injury.

NRGN, S100B and GFAP levels are significantly increased in patients with structural lesions resulting from mild traumatic brain injuries.

OBJECTIVE: To determine whether serum neurogranin (NRGN), glial fibrillary acidic protein (GFAP), and calcium-binding protein S100 beta (S100B) levels are associated with traumatic intracranial lesions compared to computed tomography (CT) findings of patients with mild traumatic brain injury (mTBI). PATIENTS AND METHODS: The cross-sectional study cohort included 48 patients who were admitted to the Emergency Department with a complaint of mTBI, a Glasgow Coma Scale score of 14-15, and at least one symptom of head trauma (i.e., post-traumatic amnesia, nausea or vomiting, post-traumatic seizures, persistent headache, and transient loss of consciousness). Blood samples and CT scans were obtained for all patients within 4 h of injury. Age-matched patients without intracranial traumatic pathology (CT-) were recruited as a control group. Blood samples were measured for NRGN, GFAP, and S100B levels. RESULTS: Of 48 patients, 24 were CT + and had significantly higher serum NRGN (5.79 vs. 2.95 ng/mL), GFAP (0.59 vs.0.36 ng/mL), and S100B (1.72 vs.0.73 µg/L) levels than those who were CT- (p = 0.001, p = 0.026, and p < 0.001, respectively). ROC curves showed that NRGN, GFAP, and S100B levels were sufficient to distinguish traumatic brain injury in patients with mTBI. At the cut-off value for NRGN of 1.87 ng/mL, sensivity was 83.3%, and specificity was 58.3%. At the cut-off value for GFAP of 0.23 ng/mL, sensivity was 75% and specificity was 62.5%. The optimal cut-off value for S100B was 0.47 µg/L (95.8% sensitivity and 62.5% specificity). CONCLUSION: This is the first study to evaluate NRGN in human serum after mTBI. We confirmed that NRGN levels were significantly higher in CT + patients than CT- patients in the mTBI patient population. Future studies of larger populations and different age groups (especially pediatric) can help reduce the number of CT scans as a reliable and noninvasive diagnostic tool for evaluating NRGN protein levels in mTBI patients with a low probability of intracranial lesions.

Effects of Intrathecal Verapamil on Cerebral Vasospasm in Experimental Rat Study.

BACKGROUND: Verapamil, a calcium-channel blocker, has shown promising results on cerebral vasospasm. However, it has not yet been accepted for treatment or prevention purposes because of the associated side effects. Although the effective results of nimodipine and nicardipine's intrathecal administration are well known, intrathecal verapamil has not been considered earlier. We used an experimental subarachnoid hemorrhage-induced vasospasm model for the evaluation of vasodilator and neuroprotective effects of intrathecal verapamil. METHODS: A total of 24 Sprague-Dawley rats were randomly divided into the following 3 groups: group 1 (sham), group 2 (subarachnoid hemorrhage), and group 3 (verapamil). A double hemorrhage method was used. Group 2 did not receive any treatment. Verapamil (Eporon, Dem Ilac, Turkey) at a dose of 1000 µg/kg was given intrathecally to group 3 rats. The animals were euthanized on day 7 of the procedure. Arterial wall thickness and lumen diameter in the basilar arterial cross-sectional areas, endothelin-1 serum level, oxidative stress index, and apoptosis were measured in all groups. RESULTS: In the verapamil group, wall thickness, endothelin-1 level, oxidative stress index, and apoptosis were found to be significantly lower than the subarachnoid hemorrhage group, but the lumen diameter was found to be greater. Intrathecal verapamil was found to decrease vasospasm parameters and apoptosis and increase the antioxidant and antiapoptotic pathways. CONCLUSIONS: Our findings suggest that intrathecal verapamil can prevent vasospasm, oxidative stress, and apoptosis after experimental subarachnoid hemorrhage.

Effects of Modic Type 1 Changes in the Vertebrae on Low Back Pain.

OBJECTIVE: The present study examined the physical extent of Modic type 1 (MT1) changes and other phenotypic magnetic resonance imaging (MRI) findings in the vertebrae of patients with low back pain (LBP) and MT1 changes. We also identified any correlations of these findings with the severity of pain and the Oswestry Disability Index (ODI). The relationship between the presence of pain and MT1 changes has been examined in several studies. However, to the best of our knowledge, no study has assessed the relationships between pain severity and ODI and the total vertebral area of MT1 involvement. METHODS: After excluding any patient with MT2 or MT3 changes, 49 patients with a diagnosis of LBP and MT1 changes demonstrated on MRI were included. MT1 involvement area, disc height, number of Schmorl's nodes, disc degeneration (Pfirrmann grade), and cross-sectional area of the lumbar muscles were obtained via MRI. Additionally, patient demographic data, body mass index, physical activity level, and disability (ODI) scores were assessed. RESULTS: The total vertebral area of MT1 involvement correlated significantly and positively with the ODI (P = 0.001). In the multivariate linear regression model, with ODI as the dependent variable and age, mean Pfirrmann grade, total vertebral area of MT1 involvement, and sex as independent variables, only the total vertebral area of MT1 involvement was significantly associated with the ODI. CONCLUSIONS: A significant positive correlation was noted between the vertebral MT1 involvement extent and changes in the ODI. Other MRI features of patients with LBP were not related to pain severity or ODI.

Single-stage planning for total cure of grade III-V brain arteriovenous malformations by embolization alone or in combination with microsurgical resection.

PURPOSE: There are no established guidelines for treatment of Spetzler-Martin grade III-V brain arteriovenous malformations (bAVMs). The purpose of this study is to report our institutional experience in total obliteration/eradication of grade III-V bAVMs by single-stage planning of embolization combined with microsurgical resection when necessary. METHODS: All patients harboring Spetzler-Martin (S-M) grade III-V bAVMs treated with single-stage planning between January 2006 and January 2018 were retrospectively reviewed. This treatment paradigm is applicable only to surgically accessible bAVMs and does not include deep-seated bAVMs. Indications for treatment, clinical presentation, imaging characteristics, and treatment outcomes were analyzed. Outcomes were assessed based on modified Rankin Scale. RESULTS: A total of 31 patients were identified. Seventeen patients (54.8%) presented with hemorrhage, 10 (32.3%) with seizures, 3 (9.7%) with headaches, and 1 (3.2%) with progressive neurological deficit. Based on S-M grading system, 25 patients (80.6%) harbored grade III bAVM, 5 patients had grade IV bAVMs (16.1%), and 1 patient (3.2%) had a grade V bAVM. There were no treatment-related complications in 24/31 (77.4%) patients. Of the total of seven patients with complications, four patients had clinical deterioration. The long-term (> 6-month), non-disabling morbidity (mRS ≤ 2) rate was 6.5%. The long-term, disabling morbidity rate was 3.2% with a mortality of 3.2%. Complete angiographic obliteration was achieved in 30/31 (96.8%) patients. CONCLUSION: Single-stage treatment strategy can be considered as an alternative to multistage embolization prior to surgery in grade III-V bAVMs. In this study, a high rate of total obliteration with relatively low rates of permanent morbidity and mortality was achieved.

An Exceptional Neurosurgical Presentation of a Patient with Osteopetrosis.

BACKGROUND: Osteopetrosis (OP) is a varied clinical condition caused by malfunction or insufficient development of osteoclasts, or both. Neurologic findings can occur because of osteopetrotic conditions restricting neural foramina through which the spinal cord, cranial nerves, or major vascular structures traverse the skull. Renal tubular acidosis (RTA) is a well-documented condition with OP. However, Chiari I malformation is rarely reported concomitantly with OP. CASE DESCRIPTION: We present a patient with a known RTA who was admitted with a rapid progressive tetraparesis within 24 hours. Clinical and radiologic evaluation of the patient revealed OP with RTA together with Chiari I malformation and holocord hydromyelia. Management of the patient was started with correction of severe hypokalemia (K: 1.4 mEq/L), which resulted in dramatic improvement in tetraparesis. Two days later, a posterior fossa bone decompression with ventriculoperitoneal shunt placement during the same session led to prominent decrease in size of the ventricles and the hydromyelia on long-term follow-up. CONCLUSIONS: Patients with OP can exhibit many clinical conditions. However, our case involved an unusual and rapid progressive tetraparesis, which could confuse the management as necessitating an emergent posterior fossa decompression. Stabilizing the metabolic status of the patient facilitated elective surgery, which further improved patient's neurologic findings and diminished hydromyelia on long-term follow-up.

Expression of miRNA-21, miRNA-107, miRNA-137 and miRNA-29b in meningioma.

OBJECTIVE: Meningiomas are among the most common intracranial tumors, accounting for 30% of all tumors of the central nervous system. Recent studies analyzing microRNA (miRNA) profiles and functions in cancer have provided valuable information about the molecular pathogenesis of several tumor types, including glioblastoma multiforme (GBM), hepatocellular carcinoma, and breast, lung, colon, and prostate cancer. miRNAs are a family of small, endogenous, noncoding RNAs of 18-25 nucleotides. In this study, we carried out a genome-wide array screen comparing miRNA-21, miRNA-107, miRNA-137 and miRNA-29b expression in meningiomas. PATIENTS AND METHODS: A total of 50 meningioma patients (16 men and 34 women) aged between 32 and 80 years were included. The study was conducted at Istanbul Research and Training Hospital Neurosurgery Clinic. RESULTS: Our results have shown a significant increase in miRNA-21 expression with increasing histopathologic grade, while there was a significant reduction in miRNA-107 expression with the increasing histopathological grade. miRNA-137 and miRNA-29b expression did not differ significantly according to histopathologic grade. CONCLUSION: The subject of our study, i.e. the association between miRNA expression and meningioma, is continuously gaining more importance in the wider context of the recent developments in genetic treatments.

Polymorphisms in the Matrix Metalloproteinase-9 Promoters and Susceptibility to Glial Tumors in Turkey.

AIM: Evidence suggests an association between MMP-9 functional gene polymorphisms and several tumors. The aim of this study was to investigate the possible role of single-nucleotide polymorphisms (SNP) at MMP-9 R279Q A/G, P574R G/C and R668Q G/A and R668Q (rs17577) genotypes with glial tumors in Turkey. MATERIAL AND METHODS: The present series consisted of tissue samples obtained from 100 cancer-free controls and 100 patients who had undergone glial tumor resection from 2007 to 2011 at the Cerrahpasa Medical Faculty of Istanbul University. Blood samples were collected to extract the genomic deoxyribonucleic acid (DNA) of each subject by polymerase chain reaction (PCR) and DNA sequencing. The genotypes of MMP-9 P574R, R279Q and R668Q SNPs were determined by using the PCR-RFLP assay. Genotypic distributions between patient and control groups were compared for correlations with glial tumor occurrence. RESULTS: SNPs in MMP-9 were not found to be significantly associated with glial tumor risk among participants except R279Q (G-G) which showed high risk only in multivariate analysis (OR adjusted, 3.15 95% CI, 1.10-9.01). The comparisons between the grade of tumor and the genotypic polymorphisms also showed no significant associations in the case group (all p values > 0.05). CONCLUSION: The current study showed a significant association between the R279Q G/G polymorphism and formation of glial tumor in advanced age. Changed protein features may cause triggering of some subcellular mechanisms that may have a role in activating oncogenic processes over the years. These data add to the growing epidemiological and experimental evidence that MMP-9 may play a role in glial tumors.

Preliminary experience with precipitating hydrophobic injectable liquid in brain arteriovenous malformations.

Advancement in microcatheter design and emergence of new embolic agents offer better results in endovascular treatment of brain arteriovenous malformations (AVMs). Precipitating hydrophobic injectable liquid (PHIL) (Microvention) is a newly introduced dimethyl sulfoxide-based embolic agent for endovascular use. Herein, we present three patients who underwent endovascular treatment of brain AVMs with PHIL, followed by surgical resection. Endovascular features and same-day surgical handling of the new embolic agent PHIL are presented along with histopathologic changes in the acute stage in brain AVMs are presented, and its major differences from Onyx. In our series, PHIL had moderate inflammatory reaction in the acute stage without any associated angionecrosis that is different than Onyx which cause mild inflammatory reaction with angionecrosis. Smallest vessel containing PHIL was 2.9 µm compared to 5 µm with Onyx, which suggests better penetration.

Rapid improvement in visual loss with cabergoline treatment in a giant prolactinoma case: 5 years survey.

Giant prolactinoma is a rare subset of macroadenomas. Limited studies demonstrated which therapy could be successfully used in the first-line therapy of giant prolactinoma. We presented a case with a 54 × 40 × 40 mm pituitary adenoma and optic chiasmatic compression with left sphenoid sinus invasion. The tumor caused a loss of visual field of the right side. Cabergoline treatment was started with dose of 1.5 mg/week. Fifteen days later, the clinical visual acuity examination showed a significant improvement in the patient with visual field defect. After the five years follow-up magnetic resonance imagining showed reduction of the adenoma size (17 × 12 mm) was significant. Our findings suggest that, cabergoline can be used as a first-line therapy in giant prolactinomas because tumoral shrinkage without a surgical procedure and rapid improvement in visual field defect is achieved with this medical treatment.

Tissue and plasma thioredoxin reductase expressions in patients with glioblastoma multiforme.

BACKGROUND AND STUDY AIMS: Thioredoxin reductase (TrxR) is a redox protein that is considered to play a role in tumor progression. The purpose of this study was to assess the expression of TrxR in blood and tumor samples of glioblastoma multiforme (GBM) patients. PATIENTS: TrxR levels were evaluated in blood and GBM tissues extracted from 27 patients, in normal brain tissues of 12 autopsy cases, and in blood samples of 12 healthy subjects. The results were compared between tumor and control groups. RESULTS: The mean level of TrxR in GBM tissues (74.5 ± 14.9 U/g wet tissue) was remarkably higher than in normal brain tissues (14.8 ± 3.4 U/g wet tissue). The mean TrxR levels in blood were significantly higher in GBM patients (296.3 ± 43.6 U/mL) than in the controls (203.0 ± 11.3 U/mL). CONCLUSIONS: These findings suggest that high levels of TrxR may be related to progression of GBM.

CT angiography evaluation of unusual transorbital penetrating injury: a toothbrush.

Orbital penetrating injuries may cause significant harm to optic nerves and eyeball as well as to the brain and cerebral vasculature. Defining surrounding neurovascular structures by CT angiography (CTA) is important for surgical removal. We present an uncommon case of a 3-year-old child with a penetrating orbital injury caused by a toothbrush. To the best of our knowledge, there is no report orbital injury with a toothbrush so far.

Treatment of homocystinuria-related dystonia with deep brain stimulation: a case report.

A 23-year-old woman with the medical history of homocystinuria that had been diagnosed at the age of 14 has been non-responsive to treatment. The patient presented with the symptoms of dysphonia, dysarthria and severe dystonia of the neck and left extremities. Blood and urine biochemistry revealed high levels of homocystine. Brain magnetic resonance imaging was normal with no detectable pathologies. Medical treatment strategies were used and repeated injections of botulinum toxin A were administered, but the symptoms showed no significant improvement. The patient was then operated, and deep brain stimulators targeting the bilateral globus pallidus internus were implanted. After the activation of the electrodes, dystonia symptoms showed a remarkable improvement. Good outcome was documented during the follow-up period of 7 months. To our best knowledge, this is the first reported case of homocystinuria-related dystonia symptoms that were successfully treated with deep brain stimulation.