Concurrent presence of diabetes affects the GLUT3 programming of glucose metabolism in glioblastoma.

OBJECTIVE: Diabetes mellitus (DM)-mediated impaired glucose metabolism increase in the glioblastoma (GB) risk by inducing hyperglycemia and hyperinsulinemia. An integral membrane transport protein, glucose transporter 3 (GLUT3) facilitates glucose transport into GB tumor cells. We aimed to explore the regulation of GLUT3 in GB tumors of patients who were concurrently diagnosed with DM. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from 93 GB patients and retrospectively analyzed. Of the total, 15 patients were concurrently diagnosed with DM (GB-DM). The role of GLUT3 in tumor aggressiveness was evaluated by analyzing its correlation with Ki67, P53 expression, MALAT1 expression, and peripheral blood hemoglobin A1C (HbA1c) level. T98G cells were treated with empagliflozin and metformin to modulate GLUT3. The RNA expression of GLUT3, SOX2, and MALAT1 was analyzed by real-time qPCR. The lactate levels of T98G cells were measured by Cobas c502 analyzer. A scratch wound assay was performed to investigate the migration rate of T98G cells. RESULTS: GLUT3 expression was lower in GB-DM tumors than in GB-only tumors. In GB-DM, the expression of tumoral GLUT3 and peripheral blood glycated hemoglobin (HbA1c) levels were negatively correlated with P53 and Ki67. A decreased GLUT3 shortened the disease-free survival duration in GB-DM patients. Empagliflozin reduced GLUT3, while metformin-induced GLUT3 in T98G cells. The empagliflozin-mediated GLUT3 suppression induced SOX2 and MALAT1 expressions and influenced the migration capacity of T98G cells. CONCLUSIONS: Our findings suggest that the low GLUT3 expression of the tumors of GB-DM patients may induce the production of adenosine triphosphate (ATP) from cellular energy sources other than glucose metabolism. However, further studies are warranted to confirm these results.

Oleuropein modulates glioblastoma miRNA pattern different from Olea europaea leaf extract.

Glioblastoma (GBM) is the most prevalent and deadliest subtype of glioma. Despite current innovations in existing therapeutic modalities, GBM remains incurable, and alternative therapies are required. Previously, we demonstrated that Olea europaea leaf extract (OLE) kills GBM cells by modulating miR-181b, miR-137, miR-153 and Let-7d expression. However, although oleuropein (OL) is the main compound in OLE, its role in the antitumour effect of OLE remains unknown. This study determined the effect of OL on GBM cell line T98G and compared the results with our previous findings regarding the effect of OLE on the same cell line. The antiproliferative activity of OL and its effect on temozolomide (TMZ) response were tested inT98G cells using WST-1 assay. OL inhibition was evaluated using one-way analysis of variance with Tukey's post hoc test. The effect of OL on miR-181b, miR-137, miR-153 and Let-7d expression was assessed using quantitative reverse transcription polymerase chain reaction. Fold differences in expression between untreated, OL or OL + TMZ-treated samples were calculated using 2-ΔCt method. Significance was evaluated using an independent sample t-test. Treatment with 277.5 and 555 µM OL resulted in 39.51% and 75.40% reductions in T98G cells within 24 h. Coadministration of 325 µM TMZ and 277.5 or 555 µM, OL caused 2.08- and 2.83-fold increases, respectively, in the therapeutic effect of TMZ. OL + TMZ significantly increased microRNA expression, particularly Let-7d, than OLE. In conclusion, OL has an antitumour effect on GBM cells mainly via regulation of Let-7d expression. The present results also indicate other minor compounds in OLE play important anticancer roles.

Endovascular treatment of intracranial arteriovenous malformations using detachable-tip microcatheters and Onyx 18®.

PURPOSE: To evaluate clinical and imaging features before embolization, data of embolization procedure and outcome in patients with ruptured or unruptured intracranial arteriovenous malformation (AVM) who were treated by endovascular embolization using detachable-tip microcatheters and Onyx 18®. MATERIAL AND METHODS: Forty-three patients treated with endovascular embolization using a detachable-tip microcatheter and Onyx18® between January 2008 and April 2016 were evaluated. There were 27 men and 16 women with a mean age of 35.9±14.1years (range: 10-68years). Clinical and imaging features, embolization details and post-treatment findings were analyzed. Patients were divided into ruptured AVM and unruptured AVM groups. Death, complications and total embolization rates of each group were assessed. RESULTS: Fifty-one embolization sessions were performed in 43 patients. Total embolization rate was 40% (17/43). There were significant relationships between AVM diameter and total embolization success and AVM diameter and complication rates. The degree of embolization was partial in all patients who had complications. Catheter retention and iatrogenic rupture were not observed in any procedure. No major neurologic deficit was seen in patients who had unruptured AVM and complications after treatment. CONCLUSIONS: Our results show the efficacy of endovascular embolization of AVM using detachable-tip microcatheters and Onyx 18®. A new AVM classification system based on AVM diameter for this embolization technique may be more predictive in terms of total embolization success and complication development.

Assesment of perfusion in glial tumors with arterial spin labeling; comparison with dynamic susceptibility contrast method.

PURPOSE: Arterial spin labeling perfusion imaging (ASL-PI) is a non-invasive perfusion imaging method that can be used for evaluation and quantification of cerebral blood flow (CBF). Aim of our study was to evaluating the efficiency of ASL in histopathological grade estimation of glial tumors and comparing findings with dynamic susceptibility contrast perfusion imaging (DSC-PI) method. METHODS: This study involved 33 patients (20 high-grade and 13 low-grade gliomas). Multiphase multislice pulsed ASL MRI sequence and a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence were acquired for all the patients. For each patient, perfusion relative signal intensity (rSI), CBF and relative CBF (rCBF) on ASL-PI and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) values on DSC-PI were determined. The relative signal intensity of each tumor was determined as the maximal SI within the tumor divided by SI within symetric region in the contralateral hemisphere on ASL-PI. rCBV and rCBF were calculated by deconvolution of an arterial input function. Relative values of the lesions were obtained by dividing the values to the normal appearing symmetric region on the contralateral hemisphere. For statistical analysis, Mann-Whitney ranksum test was carried out. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBF-ASL, rSI-ASL, rCBV and rCBF ratios and grade of gliomas. Their cut-off values permitting best discrimination was calculated. The correlation between rCBV, rCBF, rSI-ASL and rCBF-ASL and glioma grade was assessed using Spearman correlation analysis. RESULTS: There was a statistically significant difference between low and high-grade tumors for all parameters. Correlation analyses revealed significant positive correlations between rCBV and rCBF-ASL (r=0.81, p<0.001). However correlation between rCBF and rCBF-ASL was weaker (r=0.64, p<0.001). CONCLUSION: Arterial spin labeling is an employable imaging technique for evaluating tumor perfusion non-invasively and may be useful in differentiating high and low grade gliomas.

Minimally invasive awake craniotomy using Steiner-Lindquist stereotactic laser guidance.

INTRODUCTION: Awake craniotomy permits the continuous assessment of intraoperative neurological functions. In addition, stereotactic laser guidance aids in performing minimally invasive procedures related to the radical resection of lesions located in eloquent and non-eloquent brain regions. METHODS: Between May 2000 and October 2006, 117 consecutive patients with various intracranial tumoral lesions underwent 141 resection procedures. The eloquent areas were determined with the aid of anatomic landmarks and/or functional MRI (fMRI) examinations. The resection of the lesions was performed under continuous neurological examination. In all cases, postoperative MRI was performed within 24-72 h. RESULTS: Seventy-seven males and 40 females were included in this study. The mean age of the patients was 52.0+/-12.6 years. Most of the lesions were located within the parietal lobe. Of the lesions, 33 (23.4%) were located within the cortex, whereas 108 (76.5%) were subcortical. The most common pathologies were metastasis (70 cases) and glioblastome multiforme (27 cases). In 20 (14.2%) of the patients, fMRI was performed preoperatively. Of 21 patients with multiple lesions, 18 underwent 2 craniotomies and 3 underwent 3 craniotomies. The mean operation time was 72+/-0.3 min, and the mean hospital stay was 3.26+/-1.82 d. The average lesion size was 11.92+/-15.26 cm(3). In 7 cases (4.9%), the surgery caused either new neurological deficits or a worsening of the existing deficits; these deficits were permanent in 2 (1.4%) cases. One patient (0.7%) died due to the development of postoperative intracerebral hemorrhage. CONCLUSIONS: Awake craniotomy with the aid of stereotactic laser guidance is a safe procedure that assists in performing minimally invasive resection of lesions in eloquent and non-eloquent brain regions. Although direct intraoperative stimulation was not performed, detection of the functioning areas of the brain with fMRI decreased additional postoperative neurological deficits. Overall, this method decreased the operation time and hospital stay.

Risk factors and complications of intracranial pressure monitoring with a fiberoptic device.

We prospectively investigated the complications associated with intraparenchymal intracranial pressure (ICP) monitoring using the Camino intracranial pressure device. A fiberoptic ICP monitoring transducer was implanted in 631 patients. About half of the patients (n=303) also received an external ventricular drainage set (EVDS). The durations (mean+/-SD) of ICP monitoring in patients without and with an EVDS were 6.5+/-4.4 and 7.3+/-5.1 days, respectively. Infection occurred in 6 patients with only an ICP transducer (6/328, 1.8%) and 24 patients with an EVDS also (24/303, 7.9%). The duration of monitoring had no effect on infection, whereas the use of an EVDS for more than 9 days increased infection risk by 5.11 times. Other complications included transducer disconnection (2.37%), epidural hematoma (0.47%), contusion (0.47%), defective probe (0.31%), broken transducer (0.31%), dislocation of the fixation screw (0.15%), and intraparenchymal hematoma (0.15%). In conclusion, intraparenchymal ICP monitoring systems can be safely used in patients who either have, or are at risk of developing, increased ICP.

Rupture of a small middle cerebral artery aneurysm into middle fossa arachnoid cyst presenting as a chronic subdural haematoma.

The rupture of an aneurysm into an arachnoid cyst and subdural space is unusual. A 25-year-old man was admitted 2 weeks after having undergone a burr hole drainage for a chronic subdural haematoma elsewhere. An angiogram revealed a small aneurysm at the bifurcation of the middle cerebral artery. The aneurysm was clipped and the cyst communicated with the basal cisterns. To the best of our knowledge, this is the first report of an association of an aneurysm of the middle cerebral artery with an arachnoid cyst presenting as a chronic subdural haematoma.

Spinal dural arteriovenous fistula in a case with lipomyelodysplasia.

Coexistence of a spinal dural arteriovenous fistula within a dysraphic spinal lesion is a very rare situation. We report a 40-year-old man who presented with low back pain and progressive paraparesis. MR images showed an intradural high signal intensity mass at the L2-L3 level containing irregular signal void structures. Spinal angiography revealed extradural arteriovenous fistula with three connections, drained by a tortuous perimedullary vein.

Traumatic epidural haematomas of nonarterial origin: analysis of 30 consecutive cases.

BACKGROUND: The purpose was to analyse the clinical and radiological findings, and management approaches used in 30 consecutive cases of traumatic epidural haematoma of nonarterial origin treated at one centre. METHOD: Medical records for 30 patients surgically treated for epidural haematoma of nonarterial origin between 1997 and 2003 were reviewed. Epidural haematoma of nonarterial origin was diagnosed based on computed tomography (CT) and the bleeding source was confirmed intra-operatively. Admission status, outcome, fracture location, haematoma location/size/volume, and additional intracranial pathology were among the data noted. Two groups were formed for analysis: venous sinus bleeding (group 1) and other venous sources (group 2). FINDINGS: The 30 cases accounted for 25% of the total number of traumatic epidural haematomas (n = 120) treated during the same period. The epidural haematomas of nonarterial origin locations were transverse sigmoid sinus (n = 11; 36.7%), superior sagittal sinus (n = 6; 20%), venous lakes (n = 5; 16.6%), diploë (n = 5; 0.16%), arachnoid granulations (n = 2; 6.7%), petrosal sinus (n = 1; 3.3%). There were 12 postoperative complications in 9 patients: recurrence (n = 4; 13.3% of the 30 total), pneumonia (n = 4; 13.3%), meningitis (n = 2; 6.7%), hydrocephalus (n = 1; 3.3%) and subdural effusion (n = 1; 3.3%). All recurrence cases were re-explored. Six (20%) patients died. Glasgow Outcome Scale (GOS) scores (mean follow-up 13.3 +/- 7.8 months) revealed 22 (73.3%) patients with favourable results (GOS 4-5) and 8 (26.7%) had poor results (GOS 1-3). CONCLUSIONS: Cases of epidural haematoma of nonarterial origin differ from the more common arterial-origin epidural haematomas with respect to lesion location, surgical planning, postoperative complications, and outcome. Epidural haematoma of nonarterial origin should be suspected if preoperative CT shows a haematoma overlying a dural venous sinus or in the posterior fossa and convexity. The sinus-origin group had a high frequency of fractures which crossed the sinuses, and this might be diagnostically and surgically useful in such cases.

Oxidised regenerated cellulose as a cause of paraplegia after thoracotomy: case report and review of the literature.

STUDY DESIGN: Case report. OBJECTIVE: To report an unusual case of paraplegia. SETTING: University Hospital Bursa, Turkey. CASE REPORT: A 22-year-old woman presented with paraplegia following a left-sided thoracotomy. Magnetic resonance imaging showed a dorsal epidural mass at the level of T6. The patient underwent an emergency T6/7 laminectomy and removal of a tuft of oxidised regenerated cellulose, which had migrated through the intervertebral foramen causing spinal cord compression. CONCLUSION: In cases of neurological deficits after surgery at the posterolateral edge of a thoracotomy, the clinician should be aware of the above possibility. Urgent radiological diagnosis and decompressive laminectomy is the treatment of choice.

Brain stem stroke associated with epidermoid tumours: report of two cases.

Two cases of cerebello-pontine angle epidermoid tumour presented with the clinical findings of brain stem stroke. Preoperative imaging showed stretching of branches of the basilar artery. Brain stem stroke as a presenting feature of cerebello-pontine angle epidermoid tumour has not been reported before.

Primary-isolated optic nerve sarcoidosis.

Sarcoidosis is a systemic, idiopathic granulomatous disorder with occasionally surprising clinical presentations. A primary involvement of the optic nerve is particularly important due to visual prognosis. We report here a patient with occult sarcoidosis who presented to us with progressive visual loss as the first and primary manifestation of the disease. The patient underwent surgery for histopathological diagnosis and decompression of the optic nerve. This case demonstrated that sarcoidosis should be considered in the differential diagnosis of any lesion involving the optic nerve.

Details of fibroligamentous structures in the cervical unco-vertebral region: an obscure corner.

Vertebral bone, joints and ligaments on the cervical spine are structures that maintain the stability of the spine and protect the neurovascular structures. Determining the detailed anatomical location of the intervertebral foramen and unco-vertebral (UV) region with respect to the vertebral bone, joint and ligaments is critical when choosing the safest surgical approach to the cervical spine. We studied the microscopic detailed anatomy of the dural covering and posterior longitudinal ligament (PLL) in eight cadaver specimens and the relevance of these structures in the UV region from C4 to C7. The uncinate process (UP) and its covering ligaments are mechanical barriers that prevent the nerve root and the vertebral artery against unintentional surgical damage. Dissection at the posterolateral surface of the UP revealed a separate perivascular fibroligamentous tissue (PVFLT) that originates from the PLL. The recognition of the PVFLT may provide for safe surgery by protecting the neural and vascular structures during decompression in the UV region.

[Monitoring and controlling of intracranial pressure in severe head injury]. / Ciddi kafa travmalarinda intrakranial basincin monitörizasyonu ve kontrol edilmesi.

Uncontrolled intracranial hypertension is an important cause of mortality and morbidity in severely head injured patients. Monitoring intracranial pressure (ICP) and controlling intracranial hypertension are essential in preventing herniation and avoiding ischemic secondary brain injury. Head injured patients may require specific ICP treatment to maintain it below 20 to 25 mmHg and improve cerebral perfusion pressure (CPP) above 70 mmHg. The optimal values of ICP and CPP are vary among patients and over time. A basic goal of neurotrauma intensive care is to develop methods for treatment the various traumatic cerebral conditions for individual patients. Various methods to controlling ICP have evolved over the past two decades. Most of these therapeutic maneuvers are critical to optimizing outcomes beyond simply lowering ICP. Continuous ICP monitoring reflects the brain decompensation, allowing early detection of herniation. The present article aims to define the roles of ICP and CPP monitoring as a methods of the ICP reduction therapy after severe brain injury.