The association between calreticulin and glucagon-like peptide-1 expressions with prognostic factors in high-grade gliomas.

OBJECTIVE: The aim of this study is to present the expressions of Calreticulin (CALR) and Glucagon-like peptide-1 (GLP-1) in high-grade gliomas and to further show the relation between the levels of these molecules and Ki-67 index, presence of Isocitrate dehydrogenase (IDH)-1 mutation, and tumor grade. PATIENTS AND METHODS: A total of 43 patients who underwent surgical resection due to high-grade gliomas (HGG) (grades III and IV) were included. The control group comprised 27 people who showed no gross pathology in the brain during the autopsy procedures. Adequately sized tumor samples were removed from each patient during surgery, and cerebral tissues were removed from the control subjects during the autopsy procedures. Each sample was stored at -80°C as rapidly as possible until the enzyme assay. RESULTS: Patients with high-grade gliomas showed significantly higher levels of CALR and significantly lower levels of GLP-1 when compared to control subjects (P = 0.001). CALR levels were significantly higher, GLP-1 levels were significantly lower in grade IV gliomas than those in grade III gliomas (P = 0.001). Gliomas with negative IDH-1 mutations had significantly higher CALR expressions and gliomas with positive IDH-1 mutations showed significantly higher GLP-1 expressions (P = 0.01). A positive correlation between Ki-67 and CALR and a negative correlation between Ki-67 and GLP-1 expressions were observed in grade IV gliomas (P = 0.001). CONCLUSIONS: Our results showed that higher CALR and lower GLP-1 expressions are found in HGGs compared to normal cerebral tissues.

AGR2 Gene Expression in Glioblastoma: A Novel Molecular Potential Target for Diagnosis and Treatment.

AIM: To assess anterior gradient protein 2 (AGR2) gene expression in patients with human glioblastoma (GBM) in comparison to levels in healthy brain tissues. MATERIAL AND METHODS: We evaluated the expression levels of AGR2 gene in 34 tissue samples: 29 of them were derived from patients with glioblastoma (GBM group) and 5 were derived from patients with mesial temporal lobe epilepsy (control group). Moreover, in order to demonstrate the AGR2 gene expression, we performed RNA isolation from tissue samples, cDNA acquisition from RNA via reverse transcription and the demonstration of gene expression via real-time polymerase chain reaction. We therefore confirmed findings of both groups. RESULTS: The mean age of the GBM and control groups were 53.1 ± 12.82 years and 40.4 ± 10.92 years respectively. AGR2 gene expression levels of the GBM group were significantly higher than those of the control group (p < 0.01). There were no significant differences of AGR2 gene expression levels across age groups, levels of glucose, urea, creatinine, white blood cell count (WBC), neutrophil, lymphocyte, hemoglobin, platelet, thyroid-stimulating hormone (TSH), T3 and T4 in GBM group (p > 0.05). CONCLUSION: AGR2 gene expression was significantly higher in patients with GBM. Thus, AGR2 gene can be considered as a potential therapeutic target.

Comparison of Clinical and Radiologic Outcomes between Dural Splitting and Duraplasty for Adult Patients with Chiari Type I Malformation.

BACKGROUND: The most used surgical procedure in the treatment of patients with Chiari type I malformation (CIM) is posterior fossa decompression. However, no consensus has been reached regarding the superiority of either dural splitting or duraplasty. Thus, the aim of this study was to compare clinical and radiologic outcomes between the two techniques used in consecutive patients. METHODS: We retrospectively reviewed 74 adult patients with CIM who were diagnosed and treated surgically between 2015 and 2020 at our neurosurgery department. The patients were divided into two groups: dural splitting in group 1 and duraplasty in group 2. Clinical outcomes based on Chicago Chiari Outcome Scale (CCOS) scores at the last control visits were compared between the groups. Radiologic outcomes were compared in terms of tonsillar regression rate based on 12-postoperative-month magnetic resonance images. RESULTS: Overall improved, unchanged, and worsened neurologic statuses were observed in 75.6% (n = 56), 17.5% (n = 13), and 6.7% (n = 5) of our patients, respectively. The mean last visit CCOS scores in groups 1 and 2 were 12.3 ± 2.1 and 13.5 ± 1.7, respectively. The difference between the groups was statistically significant (p < 0.01). The mean tonsillar regression rates were 34.7 ± 17.0% and 52.1 ± 15.3% in groups 1 and 2, respectively, with a statistically significant difference (p < 0.001). CONCLUSION: Adult patients undergoing duraplasty had better clinical and radiologic outcomes than those treated with dural splitting. Therefore, we recommend decompression with duraplasty for adult CIM patients.

Efficacy of Middle Meningeal Artery Embolization in Treatment Resistant Spontaneous Intracranial Hypotension Caused Subdural Hematoma : Report of Two Cases and Review of the Literature.

Spontaneous intracranial hypotension (SIH) most commonly manifests as bilateral subdural hematoma (SH). SIH cases mostly resolve spontaneously but further treatment would be needed via blind epidural blood patch (EBP). Cerebrospinal fluid (CSF) leakage in EBP-refractory cases can be treated surgically only if the localization of CSF leakage is detectable but it cannot be possible in most of the cases. Also surgical evacuation of SH secondary to SIH (SH-SIH) is not favorable without blocking the CSF leakage. Thus the management of these patients is a challenge and alternative treatment options are needed. Although middle meningeal artery embolization (MMAE) is an effective treatment option in non-SIH SH, there is no report about its application in the treatment of SH-SIH. We present two cases of SH-SIH which their clinical and radiological findings were completely resolved by bilateral MMAE treatment.

Multi-Level Anterior Cervical Decompression in Multi-Level Cervical Spondylotic Myelopathy without Extending the Corpus Resection: A Cadaveric Study of a Novel Surgical Technique.

AIM: To perform three-level decompression with a single-level corpectomy by modifying the fusion with anterior cervical corpectomy (ACC-F) method on a cadaver. MATERIAL AND METHODS: The anterior cervical region of four whole-head cadavers was dissected. The corpectomy was performed under a surgical microscope with a MT4-20+ ultrasonic bone dissector (UBD) tip. Superior and inferior decompression were conducted and viewed with a 70° neuroendoscope using two types (vertically and horizontally oriented) of specially designed 23 mm-long, 90°-angled UBD tips. RESULTS: After neck dissection and the removal of the thyroid and cricoid cartilages, C5 corpectomy and adjacent-level discectomies were performed. Following discectomy and corpectomy, superior and inferior decompression were conducted with specially designed UBD tips and viewed with a 70° neuroendoscope. A three-level anterior cervical decompression was provided with a single-level corpectomy. CONCLUSION: This study demonstrated that two more level decompression is possible with a single-level corpectomy in the cervical region using the new technique.

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.

The Synergistic Effect of Combined Transforaminal and Caudal Epidural Steroid Injection in Recurrent Lumbar Disc Herniations.

Background Recurrent lumbar disc herniation (RLDH) is one of the most common causes of chronic low back and leg pain. Although surgical treatment has high success rates in primary lumbar disc herniations, recurrence is not an uncommon clinic condition after the surgery. Considering the recurrent surgeries have lower success rates and higher risks, such as dural tear and nerve injury, alternative treatment modalities are needed for RLDH patients. Epidural steroid injections (ESI), particularly transforaminal steroid injection (TFESI) and caudal steroid injection (CESI), which are the alternative treatments to surgery, have not shown reasonable results in RLDH separately. In this study, we aimed to investigate the effects of combined TFESI and CESI (TFESI + CESI) treatment, which has been found successful in primary lumbar disc herniation (PLDH) and on pain control and quality of life in RLDH patients for the first time. Materials and methods A total of 71 patients, who had ESI treatment as only TFESI or TFESI + CESI because of RLDH in our clinic between March 2017 and February 2020, were investigated retrospectively. The visual analog scale (VAS) leg, VAS back, and Oswestry disability index (ODI) were used to assess leg pain, low back pain, and limitation of daily routine activities. Each assessment was done before the intervention and repeated at the third week, the third month, and the sixth month of injection, and the results were noted. Results Out of 71 patients, 38 were female and 33 male. Patients were divided into two subgroups according to the applied ESI methods as only TFESI (n = 32) and TFESI + CESI (n = 39). In the only TFESI group, the mean VAS leg score was 7.84, 4.63, 5.40, and 6.19 before, at the third week, the third month, and the sixth month of the injection, respectively. Also, in this group, the mean VAS back score was 8.06, 4.16, 4.88, and 5.97; the mean ODI score was 55.81, 34.31, 37.5, and 49.04 in the same respect. In the TFESI + CESI group, the mean VAS leg score was 8.20, 2.87, 3.64, 4.23; mean VAS back score 8.03, 3.05, 3.90, 4.08; mean ODI score 56.56, 28.05, 30.21, 33.64 before, at the third week, third month, and sixth month of the injection, respectively. The mean of the initial VAS leg, VAS back, and ODI scores was not found to be statistically significantly different between the two groups. The mean of all VAS leg, VAS back, and ODI scores was found to be lower in the TFESI + CESI group than the only TFESI group at each third-week, third-month, and sixth-month controls, and these differences were statistically significant. (p<0.0001 at each controls for VAS leg; p = 0.001 at third week, p = 0.002 at third month and p <0.0001 at sixth month for VAS back; p= 0.0003 at third week, p<0.0001 at third month, p<0.0001 at sixth month for ODI) Conclusion Our study demonstrates that TFESI + CESI treatment is an effective non-surgical treatment for RLDH. Considering the higher risks and lower success rates of recurrent surgeries, TFESI + CESI can be a potential treatment option for RLDH patients.

Assessing the connectional anatomy of superior and lateral surgical approaches for medial temporal lobe epilepsy.

The most common approaches in the treatment of epilepsy, the trans-sylvian selective amygdalohippocampectomy (SAH) and the anterior temporal lobe resection (ATLR) reach the medial temporal lobe through different surgical routes. Our aim was to delineate the white matter (WM) fiber tracts at risk in relation to trans-sylvian SAH and ATLR by defining each fascicle en route to medial temporal lobe during each approach. ATLR and trans-sylvian SAH were performedand related WM tracts en route to medial temporal region were presented in relation to the relevant approaches and surrounding neurovascular structures. The WM tracts most likely to be disrupted during trans-sylvian SAH along the roof of the temporal horn were the UF - and less commonly IFOF - at the layer of the external capsule, anterior commissure, anterior bend of optic radiations, and sublenticular internal capsule. Amygdaloid projections to the claustrum, putamen and globus pallidus, the tail of caudate and the peduncle of the lentiform nucleus were also in close proximity to the resection cavity. Fiber tracts most likely to be impaired during ATLR included the UF, ILF, IFOF, anterior commissure, optic radiations, and, less likely, the vertical ventral segment of the arcuate fascicle. Both ATLR and trans-sylvian SAH carry the risk of injury to WM pathways, which may result in unpredictable functional loss. A detailed 3-D knowledge of the related connectional anatomy will help subside neurocognitive, neuroophtalmologic, neurolinguistic complications of epilepsy surgery, providing an opportunity to tailor the surgery according to patient's unique connectional and functional anatomy.

Chondrosarcoma in the body of the C2 vertebral axis.

Chondrosarcoma, a malignant bone tumor, is rarely encountered in the cervical spine. This article describes a patient whose neck pain and dysphagia were caused by an expansive, destructive lesion with calcification that was located in the body of the axis (C2 vertebra), the first time a chondrosarcoma has been reported in this location.

The Expression of MIR17HG Protein as a Potential Therapeutic Target in Meningioma.

BACKGROUND: MIR17 host gene (MIR17HG) is a potential therapeutic target for some cancer types. The aim of this study was to assess MIR17HG protein levels in patients with meningioma who had not been reported previously in the literature and comparing with normal meninges tissues. METHODS: MIR17HG protein levels were measured in 46 samples including 25 meningioma tissues procured during surgery and 21 normal meninges tissues obtained within 4 hours of death during autopsy procedures. Each sample was stored at -80°C until the evaluation of MIR17HG protein using a sandwich enzyme-linked immunoassay principle. Results were compared between the groups. RESULTS: MIR17HG protein levels were significantly higher in meningioma tissues compared with controls and difference was statistically significant (P = 0.012). Both World Health Organization grade I and grade II meningiomas had higher MIR17HG protein levels compared with controls and differences were statistically significant (P = 0.026 for grade I and P = 0.042 for grade II). Receiver operating characteristic curve analysis was performed to determine the cutoff of MIR17HG protein value in differentiating meningioma and control groups. At the cutoff value for MIR17HG protein of >0.0998 ng/mL, the sensitivity was 73.91%, 71.43%, and 77.78% and area under the curve was 0.756, 0.753, and 0.761 for meningioma group, grade I, and grade II subgroups, respectively, and specificity was 69.23% for each group. CONCLUSIONS: MIR17HG protein expression was found to have a higher level in meningiomas than in normal meninges tissues in our study. Considering the recurrence and irresectability for some meningiomas, which require further treatment, MIR17HG may be a new target for treatment in meningiomas and our study will shed light on further studies.

Can preoperative neutrophil to lymphocyte, lymphocyte to monocyte, or platelet to lymphocyte ratios differentiate glioblastoma from brain metastasis?

This retrospective analysis of patients aims to show the blood levels of preoperative inflammatory markers in patients with glioblastoma and brain metastasis and to provide the diagnostic accuracy of the neutrophil-lymphocyte (NLR), lymphocyte-monocyte (LMR), and platelet-lymphocyte (PLR) ratios between the 2 groups of patients.The retrospective reviews of the neutrophil, lymphocyte, monocyte, and platelet counts were analyzed in 80 patients with newly diagnosed glioblastoma and 70 patients with brain metastasis. The NLR, LMR, and PLR were calculated in each group. The differences in all the parameters were compared between the 2 groups.Although the neutrophil, monocyte, and platelet counts were higher and the lymphocyte count was lower in patients with metastasis, the difference was not significant. A significantly higher PLR (P = .004) and a lower LMR (P = .01) were found in patients with brain metastasis. Although both PLR and LMR had diagnostic accuracy in differentiating glioblastoma from brain metastasis, LMR showed the highest diagnostic accuracy. NLR showed no diagnostic accuracy.Systemic inflammation is more severe in glioblastoma than in brain metastasis, and LMR is more sensitive and/or specific than PLR in differentiating glioblastoma from brain metastasis. Therefore, LMR (less likely PLR) can be used as an index for differentiating between glioblastoma and brain metastasis before surgery.

Preoperative Systemic Inflammatory Markers in Different Brain Pathologies: An Analysis of 140 Patients.

AIM: To analyze preoperative inflammatory markers including neutrophil, lymphocyte and platelet counts and neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios in a group of patients with different brain pathologies and healthy controls. MATERIAL AND METHODS: Above mentioned preoperative inflammatory markers were analyzed in a total of 140 patients included 39 with temporal lobe epilepsy, 37 with glioblastoma multiforme, 32 with grade-I meningioma and 32 with intracranial metastasis. Healthy controls included 30 subjects. The levels were compared between each patient group and between patients and controls. RESULTS: Significant higher neutrophil, platelet counts, NLR and PLR were found in glioma, meningioma and metastasis patients compared to epilepsy (p < 0.05). On the other hand lymphocyte counts were significantly lower than epilepsy (p < 0.05). PLR > 120.78 was suggestive of metastasis rather than GBM. CONCLUSION: Preoperative inflammatory markers increase in different brain pathologies and metastasis show striking changes. PLR can have diagnostic value in differentiating metastasis from GBM.

Surgical Management of Sphenoid Sinus Lateral Recess Cerebrospinal Fluid Leaks: A Single Neurosurgical Center Analysis of Endoscopic Endonasal Minimal Transpterygoid Approach.

OBJECTIVE: To review the results of sphenoid sinus lateral recess (SSLR) cerebrospinal fluid (CSF) leaks treated with the endoscopic endonasal minimal transpterygoid approach (EEMTPA) and to discuss the surgical technique and outcomes. METHODS: We performed a retrospective analysis of 13 cases who underwent SSLR CSF leak repair through the EEMTPA in our clinic between September 2008 and December 2017. Demographic and etiological features with reconstruction and surgical outcomes were examined. Mean follow-up time was 6.1 years. RESULTS: In regard to etiology, the SSLR CSF leaks included 9 patients with spontaneous, 2 patients with traumatic, and 2 with iatrogenic causes. CSF leak was at the left lateral recess in 8 cases and at right lateral recess in 5 cases. Nine patients had empty sella syndrome, and 11 patients had meningoencephaloceles in addition to SSLR CSF leaks. All patients underwent surgery through the EEMTPA, and a multilayer closure with tissue overlay grafts were used for reconstruction. A pedicled nasoseptal flap and/or pedicled middle turbinate flap were applied to the area of the leak in all cases. One patient had a persistent CSF leak and another had recurrence, both of which required revision surgery. Our overall success rate was 100%. CONCLUSIONS: EEMTPA is a safe and effective method that can be used to treat challenging pathologies at the SSLR, including CSF leaks accompanying meningoencephaloceles. Furthermore, the success rate of EEMTPA for SSLR CSF leaks can be increased by applying endoscopic skull base reconstruction techniques such as the pedicled nasoseptal flap and pedicled middle turbinate flap.

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.

Seizure Outcome of Patients with Magnetic Resonance Imaging-Negative Epilepsies: Still An Ongoing Debate.

BACKGROUND: Surgical results regarding MRI-negative epilepsy were presented and related clinical and histopathological parameters were discussed. METHODS: Thirty-six MRI-negative epilepsy patients were retrospectively analyzed. Histopathological specimens were re-reviewed by 2 blind neuropathologists and re-classified based on the current classifications. RESULTS: The mean age at surgery and seizure onset was 24.5 years and 9.3 years, respectively. Eight patients were younger than 18 years. Mean duration of seizures was 15.3 years. All but 2 underwent invasive monitorization. Eighteen patients had hypometabolism on FDG-PET with temporal lobe involvement in majority (66.7%). Hypometabolism was found in all patients with hippocampal sclerosis (HS), which was present in 50% and 66.7% of focal cortical dysplasia (FCD) type I and II patients, respectively. The frontal lobe resection was the most frequent type of operation followed by resections in temporal, parietal and occipital lobes. In 7 patients, multilobar resection was performed. Histopathological diagnosis was FCD type I, II, III, HS, and gliosis in 14, 12, 2, 3 and 2 patients, respectively. The mean follow-up was 5.8 years. Seventeen patients were seizure free and favorable outcome (Engel's I and II) was found in 69.7%. FCD type I tend to have more favorable seizure outcome. Duration of epilepsy and hypometabolism on FDG-PET was significantly related to outcome, whereas involved lobe was not. CONCLUSIONS: Our results suggest it is worth pursuing resective surgery in adults as well as in children with drug-resistant epilepsy with normal MRI.