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.

A new surgical path planning framework for neurosurgery.

BACKGROUND: Despite using a variety of path-finding algorithms that use tracts, the most significant advancement in this study is considering the values of all brain areas by doing atlas-based segmentation for a more precise search. Our motivation comes from the literature's shortcomings in designing and implementing path-planning methods. Since planning paths with curvatures is a complex problem that requires considering many surgical and physiological constraints, most path-planning strategies focus on straight paths. There is also a lack of studies that focus on the complete structure of the brain with the tracks, veins, and segmented areas. Instrument dependence is another inadequacy of the methods proposed in the literature. AIMS: The aim of this study is to design a new surgical path planning framework that helps to plan the surgical path independently of the instrument, considers the entire structure of the brain, and allows curvilinear surgical paths. Thus, neurosurgeons can generate patient-specific possible optimal surgical pathways before the neurosurgical procedure. MATERIALS & METHODS: The proposed framework includes different path-finding algorithms (Dijkstra, A*, and their aggressive variants) that find optimal paths by taking the risk scores (surgeons assessed all the segmented regions, considering the extent of damage. In this evaluation, scores ranged from "0 to 10," with the most critical areas receiving a score of "10," while the least possible affected areas were assigned a score of "0") for sensitive brain areas into consideration. For the tract image processing the framework includes fractional anisotropy (FA), relative anisotropy (RA), spherical measure (SM), and linear measure (LM) methods. RESULTS: This is the first paper to handle tracts and atlas-based segmentation of the human brain altogether under a framework for surgical path planning. The framework has a dynamic structure that gives the flexibility to add different path-finding algorithms and generate different widths of surgical pathways. Moreover, surgeons can update the score table to guarantee minimally invasive surgery. The output file format of all the extracted surgical paths is NRRD, so it can be easily visualised, analysed, or processed over the third part software tools. DISCUSSION: In this study, we generated many possible surgical pathways then these pathways were evaluated by the surgeons the results were impressive because the framework could identify surgical pathways used in real-world surgery that correspond to the standard pathways such as anterior transsylvian, trans sulcal, transgyral, and sub-temporal. CONCLUSION: This study proposes a new surgical path planning framework for neurosurgery. Moreover, in the future by adding/adopting different parameters (such as operation time, and short and long-term complications after surgery) to the proposed framework, it would be possible to find new surgical pathways for difficult surgical conditions.

Oxidative Stress Level in Patients with Subarachnoid Hemorrhage.

BACKGROUND: One of the antioxidant mechanisms is the dynamic balance between thiol and disulfide, which, in subarachnoid hemorrhage and other chronic diseases, is disrupted in favor of the latter. The two most commonly used oxidative stress (OS) biochemical markers are the oxidative stress index (OSI) value, which indicates the total oxidant status (TOS) and total antioxidant status (TAS) balance, and the thiol-disulfide (TDS) value, which indicates the total thiol (TT) and native thiol (NT) balance. High OS levels require further investigations. We aimed to investigate the OS level in aneurysmal SAH (aSAH) patients. METHODS: In this clinical prospective study, blood samples were collected from 50 consecutively treated patients with aSAH and 50 volunteers. Serum TOS, TAS, TT, and NT levels were measured using Erel's method via a spectrophotometer. The Glasgow Coma Scale (GCS) scores, Fisher grades, length of hospital stay (LOS), and the Glasgow Outcome Scale (GOS) scores were recorded. Consequently, the OSI and TDS values were calculated in all participants. RESULTS: A statistically significant difference was observed in the TAS, TOS, OSI, and TDS values between the aSAH patients and the controls. The TT and NT values were significantly lower in aSAH patients than in the controls. A correlation was identified between the OSI values and the GCS scores. Although a correlation was observed between the TDS values and the LOS, no correlation was found between the OSI and the TDS values. CONCLUSION: The OSI and TDS, which are OS indicators, might serve as the additional objective nominal data to evaluate the treatment efficacy and follow-up for SAH patients. Moreover, decreasing the OSI values and increasing the TT values can be used as improvement indicators in the treated aSAH patients. If we can reduce the OS at the early stage of SAH, it could improve the prognosis by reducing both the morbidity and mortality rates. Further randomized investigations are required to prove the findings in this prospective study.

Machine Learning-Based Surgical Planning for Neurosurgery: Artificial Intelligent Approaches to the Cranium.

Objectives: Artificial intelligence (AI) applications in neurosurgery have an increasing momentum as well as the growing number of implementations in the medical literature. In recent years, AI research define a link between neuroscience and AI. It is a connection between knowing and understanding the brain and how to simulate the brain. The machine learning algorithms, as a subset of AI, are able to learn with experiences, perform big data analysis, and fulfill human-like tasks. Intracranial surgical approaches that have been defined, disciplined, and developed in the last century have become more effective with technological developments. We aimed to define individual-safe, intracranial approaches by introducing functional anatomical structures and pathological areas to artificial intelligence. Methods: Preoperative MR images of patients with deeply located brain tumors were used for planning. Intracranial arteries, veins, and neural tracts are listed and numbered. Voxel values of these selected regions in cranial MR sequences were extracted and labeled. Tumor tissue was segmented as the target. Q-learning algorithm which is a model-free reinforcement learning algorithm was run on labeled voxel values (on optimal paths extracted from the new heuristic-based path planning algorithm), then the algorithm was assigned to list the cortico-tumoral pathways that aim to remove the maximum tumor tissue and in the meantime that functional anatomical tissues will be least affected. Results: The most suitable cranial entry areas were found with the artificial intelligence algorithm. Cortico-tumoral pathways were revealed using Q-learning from these optimal points. Conclusions: AI will make a significant contribution to the positive outcomes as its use in both preoperative surgical planning and intraoperative technique equipment assisted neurosurgery, its use increased.

Follow-Up of High-Grade Glial Tumor; Differentiation of Posttreatment Enhancement and Tumoral Enhancement by DCE-MR Perfusion.

PURPOSE: To search for the utility of DCE-MRP to differentiate between posttreatment enhancement (PT) and tumoral enhancement (TM) in high-grade glial tumors. MATERIALS AND METHODS: Thirty-four patients with glioma (11 grade 3; 23 grade 4) were enrolled. Enhancement in the vicinity of the resection cavity demonstrated by DCE-MRP was taken into consideration. Based on the follow-up scans, reoperation or biopsy results, the enhancement type was categorized as PT or TM. Measurements were performed at the enhancing area near the resection cavity (ERC), nearby (NNA) and contralateral nonenhancing areas (CLNA). Perfusion parameters of the ERC were also subtracted from NNA and CLNA. Intragroup comparison (paired sample t-test) and intergroup comparison (Student's t-test) were made. RESULTS: There were 7 PTs and 27 TMs. In the PT, the subtracted values of Ve and IAUC from the CLNA and NNA and the subtracted value of Kep from NNA were statistically different. In TM, all metrics were significantly different comparing the CLNA and NNA. Comparing PT with TM, Ktrans, IAUC, Kep, and subtracted values of Ktrans and IAUC from both NNA and CLNA were significantly different. CONCLUSIONS: In PT, only Ktrans values did not reveal any difference comparing NNA and CLNA. To differentiate PT from TM, Ktrans, Kep, IAUC, and subtracted values of Ktrans and IAUC from NNA and CLNA can be used. These findings are in concordance with literature.

A Rare Presentation of Neurobrucellosis in a 6-Year-Old Pediatric Patient with Sagittal Sinus Thrombosis.

Brucellosis is one of the most common zoonosis worldwide. It is still endemic in many regions of the world. A 6-year-old female was admitted to the emergency department (ED) due to a sudden change in consciousness, urinary incontinence, vomiting, and difficulty in walking. Neurological examination demonstrated abducens nerve paralysis, mild-to-moderate motor deficit in hemiparesis in the left arm. Brain magnetic resonance imaging showed a hemorrhagic focus at the right frontal lobe and thrombosis in the superior sagittal sinus of the brain. The diagnosis of neurobrucellosis was confirmed by identifying Brucella spp. in the blood culture on the day 6 of pediatric intensive care unit admission; thus, trimethoprim-sulfamethoxazole and rifampicin, and ceftriaxone were promptly initiated. Despite neuroprotective management and acetazolamide, the patient's neurological problems and high intracranial pressure (ICP) persisted. An external ventricular drainage tube and a Codman ICP monitor were placed to be on the consent vigilance of the patient's neurological condition. The patient's ICP continued to increase despite the current treatment regimen; therefore, a decompressive bitemporal craniectomy was performed. The ICP level of the patient returned to its normal range immediately after the craniectomy. The patient did not have any notable neurologic sequelae at the first-year follow-up. Neurobrucellosis is a rare complication of systemic brucellosis and may present as meningitis, encephalitis, myelitis, radiculitis, and/or neuritis. Herein, we describe a six-year-old girl with brucellosis complicated with cerebral vein thrombosis. This case illustrates the need for close monitoring of patients with unexplained neurological signs or symptoms for brucellosis in endemic areas.

The Role of Staged Cryosurgery and Three-Dimensional Computed Tomography Integrated Navigation System in the Surgical Management of Severe Involvement of Craniofacial Polyostotic Fibrous Dysplasia.

Fibrous dysplasia (FD) is a developmental bone disorder caused by the hamartamatous proliferation of bone-forming cells. A 29-year-old male patient with diagnosis of FD was admitted to our clinic with the symptoms of severe craniomaxillofacial involvement of FD beginning from last year. Neurological examination revealed diplopia, horizontal nystagmus, conductive hearing loss, and partial vision loss. In his medical history, it was reported that he had undergone intramedullary nailing operation in his left femur due to a pathological fracture approximately 8 years ago in the orthopedics clinic of our institution. The patient underwent 3 consecutive surgeries by our plastic and neurosurgical team. The patient was followed-up in the neuro-intensive care unit between the surgical sessions and 1 week after the last operation. Afterwards, he was transferred to the neurosurgical department. No postoperative complication was detected. The preoperative signs were recovered. During his 6th month follow-up control-visit, all his preoperative symptoms were improved. In addition, the patient was satisfied with his postoperative cosmetic improvement. In conclusion, virtual surgical planning and intraoperative surgical navigation systems can make the challenging cases possible to operate with increasing the safety margin of the surgical procedures for polyostotic FD.

Serum SUR1 and TRPM4 in patients with subarachnoid hemorrhage.

Neuroinflammation plays an important role in neuronal injury after aneurysmal subarachnoid hemorrhage (aSAH). Sulfonylurea receptor 1 (SUR1) and transient receptor potential cation channel subfamily M member 4 (TRPM4) receptors play an important role in the pathogenesis of several neural injuries, such as neural edema, spinal cord damage, stroke, and neuronal damage in aSAH. This study aimed to investigate the relationship of serum SUR1 and TRPM4 levels with the neurological status within the first 15 days after aSAH. In this prospective study, blood samples were collected from 44 consecutive patients on the 1st, 4th, and 14th days after aSAH. Serum SUR1 and TRPM4 levels were measured using an enzyme-linked immunosorbent assay kit. Glasgow coma scale and World Federation of Neurosurgical Societies (WFNS) scores upon presentation and Glasgow outcome scale (GOS) score on the 14th day were recorded. Serum SUR1 and TRPM4 levels on the 1st, 4th, and 14th days were significantly higher in patients with aSAH than in normal individuals. This increase in the levels varied among the 1st, 4th, and 14th days. On the first day, a correlation was observed between serum SUR1, but not TRPM4, levels and the WFNS score. Moreover, on the 14th day, an association of serum SUR1 and TRPM4 levels with the GOS score was noted. Serum SUR1 and TRPM4 levels were significantly upregulated in the peripheral blood samples. Further study is warranted to establish the utility of SUR1 and TRPM4 as biomarkers in patients with aSAH.

Comparison of Subtracted Computed Tomography from Computed Tomography Perfusion and Digital Subtraction Angiography in Residue Evaluation of Treated Intracranial Aneurysms.

BACKGROUND: Assessing clipped intracranial aneurysms for residues or incomplete occlusions is critical. Digital subtraction angiography (DSA) has been the gold standard for this. Previously, we presented subtracted computed tomography angiography (sub-CTA) from computed tomography perfusion as a more effective noninvasive technique for clipped aneurysms. The aim of this study was to compare effectiveness of sub-CTA with DSA in residue evaluation. METHODS: A retrospective study of 17 patients with aneurysmal subarachnoid hemorrhage operated on at our institution between November 1, 2016, and December 31, 2018, was performed. Residue aneurysms were evaluated with both sub-CTA and DSA. Positive predictive value and negative predictive value were calculated. Correlation between techniques was determined by the McNemar test and κ value. RESULTS: Sensitivity of sub-CTA in residue evaluation was low in aneurysms ≤3 mm (positive predictive value = 60%). DSA detected residue aneurysm in 29% (5/17) of patients, whereas sub-CTA detected residue aneurysm in 11% (2/17). Only 40% of aneurysms (2/5) were demonstrated by sub-CTA, all >3 mm; 60% (3/5) were missed, all ≤3 mm. CONCLUSIONS: This is the first study comparing the effectiveness of sub-CTA from computed tomography perfusion with DSA in residue aneurysm evaluation. Our results were suggestive, but not conclusive. DSA is still the gold standard in residue evaluation. Sub-CTA from computed tomography perfusion can be a reliable method in evaluation of residual aneurysm >3 mm.

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.

Correlation Between DTI Findings and Volume of Corpus Callosum in Children with AUTISM.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex developmental disorder in which neurological basis is largely unknown. The Corpus Callosum (CC) is the main commissure that connects the cerebral hemispheres. Previous evidence suggests the involvement of the CC in the pathophysiology of autism. AIM: The aim of our study is to assess whether there were any changes in Corpus Callosum (CC) area and volume and to reveal the relationship between Diffusion Tensor Imaging (DTI) features in genu and splenium of corpus callosum in children with ASD. METHODS: Eighteen patient and 15 controls were recruited. The volumetric sagittal TI images were used to provide measurements of midsagittal corpus callosum surface area while FA, MD, RD, and ADC values were extracted from genu and splenium of corpus callosum after which the correlation in the area and volume in ASD children was examined. RESULTS: CC area and volume in children with ASD were decreased than controls. FA values obtained from the genu and splenum of CC were significantly lower and RD values were significantly higher. A positive correlation was observed between the FA of the genu and splenium and area and volume of the CC. There was a negative correlation between ADC, MD and RD of CC and area and volume measurements. CONCLUSION: The conclusions in the interrelations of morphometric and DTI data may demonstrate a likelihood of damages in the axons and cortical neurons. The results showed that there existed microstructural damages from the DTI findings. Furthermore, the decrease in FA could be a representation of the reduction in the myelination in nerve pathways, impaired integrity, reduced axonal density, and organization. Indeed, the changes in volumetric and microstructural of CC could be useful in evaluating underlying pathophysiology in children with autism.

Investigation of Brain Impairment Using Diffusion-Weighted and Diffusion Tensor Magnetic Resonance Imaging in Experienced Healthy Divers.

BACKGROUND The aim of this study was to understand the changes of decompression illness in healthy divers by comparing diffusion-weighted (DWI) and diffusion tensor MRI findings among healthy professional divers and healthy non-divers with no history of diving. MATERIAL AND METHODS A total of 26 people were recruited in this prospective study: 11 experienced divers with no history of neurological decompression disease (cohort) and 15 healthy non-divers (control). In all study subjects, we evaluated apparent diffusion coefficient (ADC) and type of diffusion tensor metric fractional anisotropy (FA) values of different brain locations (e.g., frontal and parieto-occipital white matter, hippocampus, globus pallidus, putamen, internal capsule, thalamus, cerebral peduncle, pons, cerebellum, and corpus callosum). RESULTS ADC values of hippocampus were high in divers but low in the control group; FA values of globus pallidus and putamen were lower in divers compared to the control group. DWI depicted possible changes due to hypoxia in different regions of the brain. Statistically significant differences in ADC values were found in hypoxia, particularly in the hippocampus (p=0.0002), while FA values in the globus pallidus and putamen were statistically significant (p=0.015 and p=0.031, respectively). We detected forgetfulness in 6 divers and deterioration in fine-motor skills in 2 divers (p=0.002 and p=0.17, respectively). All of them were examined using neuro-psychometric tests. CONCLUSIONS Repeated hyperbaric exposure increases the risk of white matter damage in experienced healthy divers without neurological decompression illness. The hippocampus, globus pallidus, and putamen are the brain areas responsible for memory, learning, navigation, and fine-motor skills and are sensitive to repeated hyperbaric exposure.

Comparison of TOF MRA, Contrast-Enhanced MRA and Subtracted CTA from CTP in Residue Evaluation of Treated Intracranial Aneurysms.

AIM: To compare effectiveness of contrast-enhanced MRA (CE-MRA), 3D-Time-of-flight MRA (3D-TOF-MRA) and subtracted CTA from CTP (sub-CTA) in residue evaluation of intracranial aneurysms treated either with coiling or clipping. MATERIAL AND METHODS: Sixteen treated aneurysms, which were evaluated with three methods within two weeks after the operation, were enrolled. The success of each imaging techniques in demonstration of residue aneurysm and nearby vessels was compared by Fisher\'s Exact Test. The differences among three was evaluated by Cochran\'s Q test (p ≤ 0.05). RESULTS: Perfusion abnormality was noted in % 81 of clipped and none of coiled patients. Vessel visualization in the vicinity of aneurysm was better in sub-CTA, followed by CE-MRA. In clipped aneurysms, sub-CTA revealed residue aneurysms in % 16,7 of the patients while 3D-TOF-MRA and CE-MRA revealed none. In coiled aneurysms, CE-MRA revealed residue aneurysms in 100 %, and TOF-MRA in 33,3 % while sub-CTA revealed none. Although dramatic differences were noted in the evaluation of residue aneurysm as well as nearby vessel visualization, no statistical significance noted due to very few patients in subcategories Conclusion: This is first study comparing the effectiveness of CE-MRA, 3D-TOF MRA and sub-CTA in residue aneurysms evaluation. Vessel visualization in the vicinity of aneurysm was better in sub-CTA in all regardless of coiling or clipping. Residue aneurysms were more commonly revealed by CE-MRA in coiled patients and more commonly and better shown by sub-CTA in clipped patients in addition of showing perfusion abnormality that's is more common in clipped patients.

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.