Reduced Serum sRANKL and sTREM2 Levels in High-Grade Gliomas: Association with Prognosis.

INTRODUCTION: High-grade gliomas (HGG), including Glioblastoma multiforme (GBM), account for the majority of primary brain tumors. Nevertheless, prognostic and diagnostic biomarkers are quite limited for HGG. The objective of this study was to investigate the prognostic value of sRANKL and sTREM2 levels in HGG patients. METHODS: Twelve consecutive patients with HGG, 14 patients with non-glial tumors (non-GT) and 20 age and gender-matched healthy controls were recruited. Overall survival duration of the patients was recorded. Pre-operative serum levels of sRANKL and sTREM2 were measured by ELISA. Tumors of HGG patients were analyzed by immunohistochemical staining for p53 and Ki67 and percentage scores were calculated. RESULTS: Patients with HGG and non-GT showed lower serum sRANKL and sTREM2 levels than healthy individuals. Levels of sRANKL were inversely correlated with the overall survival of patients (p=0.002, R=0.787), while sTREM2 levels were inversely correlated with p53 score (p=0.018, R=-0.666) but not survival. CONCLUSION: Brain tumor patients show suppressed levels of glial activity biomarkers in the peripheral circulation. Serum sRANKL levels may serve as a potential prognostic biomarker for HGG.

Effects of tamoxifen therapy on sciatic nerve crush injury: An experimental study in rats.

OBJECTIVE: This study aimed to determine the effects of tamoxifen on sciatic nerve crush injury in a rat model using histopathological, histomorphometric, and immunohistochemical approaches. METHODS: In this study, 24 male Sprague-Dawley rats aged of 5 to 7 weeks and weighing between 300 g and 400 g were used. The rats were randomly divided into 3 groups: control (group C), sciatic nerve injury (group SNI), and sciatic nerve injury with tamoxifen (group SNT). The sciatic nerve crush injury model was performed using the De Koning's crush force method. In group C, only a skin incision was made and then the skin was sutured. In group SNI, the injury model was performed but no treatment was applied. In group SNT, the injury model was executed, and then 40 mg/kg/day tamoxifen was given for 4 weeks by intraperitoneal methods. At the end of 4 weeks, all animals were killed using high doses of an anesthetic. Approximately, 2-cm sciatic nerve samples were obtained for histopathological, histomorphometric, and immunohistochemical analyses using the old skin incision. RESULTS: In the histopathological examination, vascular congestion and density of vacuolization were significantly lower in group SNT than in group SNI (p<0.05). In the histomorphometric examination, the mean sciatic nerve diameter was 306±62 µm in group C, 510±42 µm in group SNI, and 204±23 µm in group SNT. A significant difference was observed in the sciatic nerve diameter measurements among the 3 groups (p<0.05). In pairwise comparisons, the mean sciatic nerve diameter was significantly lower in group SNT than in group SNI (p=0.00002). Sciatic nerve diameter measurements of both groups were found to be significantly higher than group C (p<0.05). The mean epineurium thickness was 17±0.8 µm in group C, 32±2.5 µm in group SNI, and 17±0.8 µm in group SNT. A significant difference was observed in the epineurium thickness measurements among the 3 groups (p<0.05). In pairwise comparisons, the epineurium thickness was significantly higher in group SNI than in groups SNT and C (p<0.05). In the immunohistochemical analysis, S100 immunoreactivity was found significantly higher in group SNI than in the other 2 groups (p<0.05). CONCLUSION: The histomorphometric, histopathological, and immunohistochemical data obtained from this study have shown that tamoxifen has a beneficial effect on sciatic nerve crush injury in the experimental rat model.

Radioprotective effect of melatonin against radiotherapy-induced cerebral cortex and cerebellum damage in rat.

PURPOSE: The present study aims to investigate the radioprotective effect of melatonin (MEL) against early period brain damage caused by different dose rate beams in the experimental rat model. MATERIALS AND METHODS: Forty-eight Sprague Dawley rats were randomly divided into six groups; the control, only melatonin, low dose rate-radiotherapy (LDR-RT), high dose rate-radiotherapy (HDR-RT) groups and (LDR-RT) + MEL and (HDR-RT) + MEL radiotherapy plus melatonin groups. Each rat administered melatonin was given a dose of 10 mg/kg through intraperitoneal injection, 15 minutes before radiation exposure. The head and neck region of each rat in only radiotherapy and radiotherapy plus melatonin groups was irradiated with a single dose of 16 Gy in LDR-RT and HDR-RT beams. Rats in all groups were examined for histopathology and biochemistry analysis 10 days after radiotherapy. RESULTS: Comparing the findings for LDR-RT and HDR-RT only radiotherapy groups and the control group, there was a statistically significant difference in histopathological and biochemical parameters, however, melatonin administered in radiotherapy plus melatonin groups contributed improving these parameters (p < .05). There was no statistically significant difference between LDR-RT and HDR-RT beams (p > .05). CONCLUSIONS: It was concluded that melatonin applied before LDR-RT and HDR-RT radiotherapy protected early period radiotherapy-induced brain damage. The effects of clinically low and high dose beams on the cerebral cortex and cerebellum were investigated histopathologically for the first time. HDR beams can be safely applied in brain radiotherapy. However, more experimental rat and clinical studies are needed to explain the radiobiological uncertainties about the clinic dose rate on different cancerous and healthy tissues.

Morphometric analysis of cervical intervertebral disc space to reduce neural complications during anterior approaches to the cervical spine.

BACKGROUND: Although neurovascular complications rarely occur during surgical procedures, they have serious consequences. We reviewed the limits of safe surgery to decrease the possibility of neurovascular injuries. METHODS: Four measurements were performed for each patient at the vertebral levels adjacent to the intervertebral discs at C3-C4, C4-C5, C5-C6, and C6-C7. These measurements were: 1)midline anteroposterior diameter of the intervertebral disc, 2)transverse diameter of the intervertebral disc, 3)right and left measurements of the line vertically drawn to the disc anterior from the most lateral point of the dura mater, and 4)measurement of the distance from measurement 3 to the right and left root. RESULTS: Average anteroposterior and transverse vertebral diameters were determined to be 18.11 and 27.15 mm, respectively. Average of the results of the 3rd measurement was 5.51 mm on the right and 5.36 on the left. Average of the 4th measurement was 7.8 mm on the right 7.75 mm on the left. The shortest interval was at the C3-4 level and the longest interval was at the C6-7 level. CONCLUSION: Determining the safe surgery limits will help surgeons evaluating suitable implant sizes and decreasing the perioperative complications during decompression to cervical vertebrae and instrument procedures.

Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats.

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague-Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague-Dawley rats. PTE model was developed by injecting PTZ (30+15+15 mg/kg, 30 min intervals, i.p.) 7 days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100 mg/kg), LEV (50 mg/kg), GBP (100 mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14 days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50 mg/kg LEV and 100 mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

Finite Element Analysis of Short- Versus Long-Segment Posterior Fixation for Thoracolumbar Burst Fracture.

OBJECTIVE: The thoracolumbar (TL) area marks the transition of the rigid thoracic spine into the mobile lumbar spine, and it is considered to be the weakest part of the spine. This study was designed to develop a finite element (FE) model of the TL junction (T9-L3) to provide data that could help the clinician and researcher to answer the question of whether short-segment posterior fixation is sufficient for biomechanical performance. In addition, the aim was to examine whether long-segment posterior fixation carries a greater risk of the development of adjacent segment disease. METHODS: This was a biomechanical finite element model analysis. FE analysis of the spine was conducted with posterior instrumentation under multidirectional loading conditions in order to evaluate the kinematics of the instrumented lumbar spine, as well as stresses in the posterior spinal instrumentation. We analyzed the following: 1) the range of motion of the T9-L3 region; and 2) the von Mises stress nephograms of the pedicle screws, rods, vertebrae, endplates, and intervertebral discs of 2 fixation FE models. RESULTS: Long-segment stabilization was found to be beneficial in terms of reducing total stress on the spine. However, it is possible to reduce the stress on the system by incorporating the spinal fracture into the stabilization system. Therefore, short-segment stabilization is sufficient to create a safe and robust stabilization system and to maintain neighboring intact vertebrae. CONCLUSIONS: Short-segment posterior fixation is sufficient to stabilize fractures at the TL junction, where the spinal fracture is included in the stabilization system.

Morphometric analysis of posterior fossa and craniovertebral junction in subtypes of Chiari malformation.

OBJECTIVES: Chiari malformations (CMs) are a group of disorders defined by anatomic anomalies of the cerebellum, brainstem, and craniovertebral junction (CVJ). In this study, we aimed to investigate morphometry of posterior fossa and CVJ in subtypes of CM and in control group, and to bring up a matter a correlation with demographic data and subtypes of CM. PATIENTS AND METHODS: The study group included patients managed for CM between 2012 and 2016 and control group. Radiological evaluation was studied by special programs and formulas. Intracranial volumes and morphometric datas of posterior fossa and CVJ were recorded retrospectively. RESULTS: Of the 141 patients, 91 had CM and 50 were control group participants. Mean age was 34.75. Patients were classified as CM-0 (n:10), CM-1 (n:45), CM-1.5 (n:21), CM-2 (n:15). There were statistically significance between Chiari subtypes by syringomyelia (SM) presence (p ˂ 0.01), SM localization (p ˂ 0.01), posterior fossa volume (PFV) (p ˂ 0.01), length of clivus (LoC) and length of subocciput (LoSO) (p ˂ 0.01 for both), angle between clivus and subocciput (C-SO angle) (p ˂ 0.01), and clivo-dental angle (C-D angle) (p ˂ 0.01). CONCLUSION: On morphometric comparison of CM subtypes we concluded that etiological differences lead to morphological differences. CM-2 has remarkable differences from both other subtypes and the control group.

Correlation of matrix metalloproteinase (MMP)-1, -2, -3, and -9 expressions with demographic and radiological features in primary lumbar intervertebral disc disease.

Degeneration of IVD is a progressive and irreversible process and can be evaluated with immunohistochemical examination or radiological grading. MMPs are a family of proteolytic enzymes and involved in the degradation of the matrix components of the IVD. We aimed to compare MMP-1, -2, -3, and -9 expressions with demographic features, visual analogue scale (VAS), Oswestry Disability Index (ODI) and radiological (MRI) grades. The study involved 60 participants. We recorded data about age, complaint, radiological imaging, expression levels of MMP-1, -2, -3, and -9, ODI and VAS for back pain retrospectively. Intervertebral disc degeneration was graded on a 0-5 scale according to the Pfirrmann classification. As a result of the study, the median age was 52.09±12.74years. There were statistical significances between age and MMP-1, and MMP-2. There was a close correlation between grade and MMP-9. We found correlation between the VAS and the MMP-9 expression. In addition, there was relationship between expression of MMP-2 and MMP-1, MMP-3, MMP-9. In conclusion, the expressions of MMP-1 and -2 are increased with aging. There was no relationship between radiological evaluation of IVDD and aging. Increased expression of MMPs affected IVDD positively. The relationship with MMPs is not explained. This study adds to our understanding of the interaction between MMPs and IVDD.

The relation of matrix metalloproteinase 1, 2, 3 expressions with clinical and radiological findings in primary and recurrent lumbar disc herniations.

AIM: In this study, our aim was to examine if matrix metalloproteinase expressions (MMP-1, MMP-2, MMP-3) in patients operated with a lumbar disc hernia diagnosis are different in terms of clinical and neuroradiological findings. MATERIAL AND METHODS: The study included 80 patients treated with micro discectomy for lumbar disc hernia. Degeneration was scored via magnetic resonance (MR) images. MMP-1, MMP-2, and MMP-3 antibodies were used for immunohistochemical evaluation of degenerated disc materials. MMP expressions were compared between primary and recurrent cases, and correlation analysis was conducted. RESULTS: Discectomy material showed higher expression of MMP-1 and MMP-3 in cases of recurrent lumbar disc herniation than in primary herniation. There was no significant relationship between MMP expression and MR degeneration score. CONCLUSION: MMP-1 and MMP-3 expressions were significantly higher in recurrent cases in terms of magnetic resonance degeneration score. We assume that the higher co-expression of MMP-1 and MMP-3 might be used in targeted treatment regiemens in patients with recurrent LDH.

Spinal arachnoid cyst associated with arachnoiditis following subarachnoid haemorrhage in adult patients: A case report and literature review.

OBJECTIVE: Arachnoiditis is an inflammatory process resulting with the fibrosis of arachnoid mater. It can vary in severity from mild thickenings to catastrophic adhesions that ruins subarachnoid space. As a result, arachnoid cysts can be formed. Arachnoid cyst induced by symptomatic spinal arachnoiditis is a rare complication of subarachnoid haemorrhages. In this article, we aimed to present a case of spinal arachnoid cyst formation following subarachnoid haemorrhage and examine similar cases in the literature. CASE REPORT: Forty-six years old, previously healthy female patient has been treated medically for headaches due to perimesencephalic subarachnoid bleeding. Approximately two and a half months later, she started to have severe headaches and diplopia. We detected hydrocephalus and performed ventriculoperitoneal shunt surgery. Two months later, she started to have complaints of weakness in her lower extremities. On neurological examination, she had paraparesis and on spinal magnetic resonance imaging she had an arachnoid cyst lengthening from C7 to T2 and compressing the spinal cord posteriorly. We performed partial laminectomy, drainage of arachnoid cyst and replacement of cystopleural T tube shunt. On follow-up, her lower extremity strength has ameliorated. She was taken into a physical therapy and rehabilitation programme. Three months later she was able to walk with a crutch. CONCLUSION: Subarachnoiditis and associated arachnoid cyst can cause severe morbidity. This rare situation (which especially occurs following subarachnoid haemorrhage of posterior fossa) should be known and physicians should keep in mind that it requires urgent surgical procedure.

Spinal intramedullary metastasis of breast cancer.

Objective. Breast cancer accounts for approximately one-third of all cancers in females. Approximately 8.5 % of all central nervous system metastases are located in the spinal cord. These patients have rapidly progressing neurological deficits and require immediate examination. The aim of surgery is decompression of neural tissue and histological evaluation of the tumor. In this paper, we present a case of breast cancer metastasis in thoracic spinal intramedullary area which had been partially excised and then given adjuvant radiotherapy. Case. A 43-year-old female patient with breast cancer for 8 years was admitted to our hospital with complaints of weakness in both legs. Eight years ago, she received chemotherapy and radiotherapy. On her neurological examination, she had paraparesis (left lower extremity: 2/5, right lower extremity: 3/5) and urinary incontinence. Spinal MRI revealed a gadolinium enhancing intramedullary lesion. Pathologic examination of the lesion was consistent with breast carcinoma metastasis. The patient has been taken into radiotherapy. Conclusion. Spinal intramedullary metastasis of breast cancer is an extremely rare situation, but it has a high morbidity and mortality rate. Microsurgical resection is necessary for preservation or amelioration of neurological state and also for increased life expectancy and quality.

Comparison of disc and body volumes in degenerated and nondegenerated lumbar discs: a stereological study.

AIM: To carry out comparison and correlation analyses of the intervertebral disc (IVD) and vertebral body (VB) volumes in magnetic resonance (MR) images of patients with degenerated and nondegenerated lumbar discs. MATERIALS AND METHODS: MR images were examined retrospectively in 93 patients. Lumbar VB and IVD volumes in T1-T2 weighted sagittal MR images were calculated via the Cavalieri method, a stereological method. Volumetric changes in degenerated and nondegenerated discs were compared. RESULTS: The percentages of degenerated IVDs were 12.9%, 12.9%, 28%, 50.5%, and 52% in discs from levels L1 to L5, respectively. There were no differences in VB volumes between the degenerated and nondegenerated groups for all lumbar vertebra levels. However, significant volumetric decreases were observed in degenerated IVDs for all lumbar vertebra levels, as compared to nondegenerated IVDs. Comparisons of VB volume and IVD volume ratios also revealed decreases, but they were significant only for levels L1 and L4. CONCLUSION: Disc volumes were found to be decreased, although vertebral bodies were not affected in degenerated IVD groups. However, using VB and IVD volume ratios may not always yield reliable results.

Spontaneous cervical epidural hematoma with hemiparesis mimicking cerebral stroke.

Aim. Spontaneous cervical epidural hematoma (SCEH) is defined as an epidural hematoma that does not have an etiological explanation. The most common site for SCEH is cervicothoracic area. Early diagnosis and treatment are important for prognosis and good results. In this paper, we aimed to present a case who complains of sudden weakness on right extremities imitating cerebral stroke and that neuroimaging reveals spontaneous cervical epidural hematoma. Case. A 72-year-old woman was admitted to our hospital with acute neck pain and loss of strength on right extremities. On neurological examination, the patient had right hemiparesis. PT, aPTT, and INR results were 50.5, 42.8, and 4.8, respectively. Cranial MRI was in normal limits. Spinal MRI revealed a lesion that extends from C4 to C7 located on the right side and compatible with epidural hematoma. The patient was operated after normalization of INR values. Conclusion. Even though SCEH is a rare condition, it can cause severe morbidity and mortality. Early diagnosis and treatment are quiet important for prognosis. SCEH can easily be mistaken for stroke as with other pathologies and this diagnosis should come to mind especially in patients who have diathesis of bleeding.

The role of a single nucleotide polymorphism of the matrix metalloproteinase-1 gene promoter region in invasion and prognosis of meningiomas.

AIM: The matrix metalloproteinase (MMP) enzyme family has been shown to be active in tumorigenesis and tumor progression. In this study, we analyzed the prevalence of a guanine insertion in the MMP-1 gene promoter region in meningiomas and its effect on invasion and prognosis. MATERIAL AND METHODS: The study was performed with 33 meningioma patients. We also included 33 healthy patients in the study as a control group. The promoter area was amplified by polymerase chain reaction (PCR) following DNA isolation. The polymorphism was detected by restriction fragment length polymorphism (RFLP). RESULTS: According to the WHO classification of meningiomas, 87.9% of the affected patients were grade 1, and 12.1% were grade 2. In total, 72.7% of the meningioma patients (n=24) had at least one copy of the insertion (2G/1G or 2G/2G genotypes) and 27.3% (n=9) did not (1G/1G). There was no significant difference between the meningioma and control groups according to genotype distribution. CONCLUSION: In this study, the polymorphism in the matrix metalloproteinase-1 gene promoter region did not have an effect on the initiation, growth and progression of meningioma.

Spinal intradural hematoma and permanent paraparesis after a lumboperitoneal shunt operation: an unusual complication.

Pseudotumor cerebri is a condition of increased intracranial pressure in the absence of clinical, laboratory or radiological pathology. Spinal intradural hematoma formation after lumboperitoneal shunt (LPS) implantation is very rare, but it can cause sudden and serious deterioration. In this report, we present a patient who developed an intradural hematoma following LPS operation. A 27-year-old male patient suffering from headaches and progressive vision loss was diagnosed with pseudotumor cerebri. He underwent LPS operation in January 2009. Four hours after the operation, he developed urinary and fecal incontinence with paraparesis (1/5). Lumbar magnetic resonance imaging identified an intradural hematoma at the level of L2-L3, and he was reoperated. The intradural hematoma was removed. Physical therapy was started because of paraparesis. Two months later, the patient's muscle strength had increased to 3/5. Surgeons must remember that, LPS implantation can cause a spinal intradural hematoma in a small percentage of patients, with catastrophic results.

Monostotic fibrous dysplasia involving occipital bone: a case report and review of literature.

Fibrous dysplasia (FD) is a progressive systemic bone tumour of young and it can be seen on cranial bones. FD is divided into three types according to radiological features. The second most common subtype is polyostotic subtype. With this article, we aimed to review and present clinical features, radiological examination, differential diagnosis and treatment management of a case of solitary monostotic fibrous dysplasia of occipital bone. 15 years old female patient admitted to our hospital for a bump and in the back of his head that she noticed 1 month ago. Her physical and neurological examination was normal. On cranial CT examination we detected a bony defect. Her gadolinium enhanced cranial MRI revealed bony defect along with massive gadolinium enhancement in adjacent tissue. On histopathologic examination; PANCK, CD68, CD1a were found negative and CD45, S-100, Vimentine were found positive. Ki-67 was 4,8%. In conclusion, fibrous dysplasia is a progressive bone disease of the young patients. Despite its resemblance to a benign lesion by not being symptomatic it can progress and cause severe bony defects and skin lesions. Total surgical resection is necessary and sufficient for total treatment.