Melike Mut

Is diffusion-weighted imaging useful in grading and differentiating histopathological subtypes of meningiomas?

PURPOSE Meningiomas are mostly benign, however atypical or malignant subtypes with more aggressive clinical course and higher recurrence rates can also be seen. The purpose of this study was to determine whether histopathological subtypes of meningiomas could be assessed preoperatively using apparent diffusion coefficient (ADC) values. MATERIALS AND METHODS Conventional magnetic resonance (MR) and diffusion-weighted (DW) imaging of 177 adult patients with pathologically proven meningiomas were retrospectively evaluated. Tumor size and the degree of associated edema were noted. The signal intensity of the lesions on DW imaging was evaluated and graded. Mean ADC values were obtained as the mean of measurements from three regions of interests within the mass. ADC ratios of meningioma/contralateral normal appearing subcortical parietal white matter were also calculated. RESULTS The histopathological analysis revealed 135 benign, 37 atypical and 5 malignant lesions. With classification according to the subtype, the mean ADC values and ratios of benign meningiomas were as 0.99±0.12×10(-3) mm(2)/s and 1.22±0.07, respectively. ADC values for atypical and malignant groups were both 0.84±0.1×10(-3) mm(2)/s. The ADC ratios were 1.05±0.1 and 0.96±0.2 for atypical and malignant subtypes, respectively. There was no statistically significant difference between the mean ADC ratios of the three subtypes (ANOVA test; P≥0.05). Gender, age of the patients and tumor size showed no statistically significant difference between the different histological groups. CONCLUSION DW MR imaging was not found to have any additional value in determining histological behaviour nor in differentiating histopathological subtypes of meningiomas.

Multilevel myelopathy in Maroteaux-Lamy syndrome and review of the literature

An 18-year-old male with Maroteaux-Lamy syndrome was presented with spastic quadriparesis. Magnetic resonance imaging of whole spinal canal revealed stenosis at multiple levels of cervical, thoracic and lumbar regions. By the guidance of combined evaluations of neurological examination, neuroradiological and electrophysiological findings, the most responsible spinal segment was detected each time he developed myelopathy and he underwent craniocervical, cervical and thoracolumbar decompressions consecutively. Ligamentum flavum hypertrophy was found to be the principal pathology responsible for the cord compression and myelopathy for all levels. The etiology of myelopathy and priority of the level for which decompression should be done in diffuse spinal stenosis were discussed with the literature review of Maroteaux-Lamy syndrome.

The efficacy of silver-embedded polypropylene-grafted polyethylene glycol-coated ventricular catheters on prevention of shunt catheter infection in rats

PurposeCatheter-related infection is a major complication of ventriculoperitoneal shunt in children. The aim of this study is to determine inflammatory response and the efficacy of polypropylene-grafted polyethylene glycol (PP-g-PEG) copolymer and silver nanoparticle-embedded PP-g-PEG (Ag-PP-g-PEG) polymer-coated ventricular catheters on the prevention of catheter-related infections on a new experimental model of ventriculoperitoneal shunt in rats.MethodsThirty six Wistar albino rats were divided into six groups: group 1, unprocessed sterile silicone catheter-embedded group; group 2, sterile PP-g-PEG-coated catheter group; group 3, sterile Ag-PP-g-PEG-coated catheter group; group 4, infected unprocessed catheter group; group 5, infected PP-g-PEG-coated catheter group; and group 6, infected Ag-PP-g-PEG-coated catheter group, respectively. In all groups, 1-cm piece of designated catheters were placed into the cisterna magna. In groups 4, 5, and 6, all rats were infected with 0.2 mL of 10 × 106 colony forming units (CFU)/mL Staphylococcus epidermidis colonies before the catheters were placed. Thirty days after implantation, bacterial colonization in cerebrospinal fluid and on catheter pieces with inflammatory reaction in the brain parenchyma was analyzed quantitatively.ResultsSterile and infected Ag-PP-g-PEG-covered groups revealed significantly lower bacteria colony count on the catheter surface (ANOVA, 0 ± 0, p < 0.001; 1.08 ± 0.18, p < 0.05, respectively). There was moderate inflammatory response in the parenchyma in group 4, but in groups 5 and 6, it was similar to that of the sterile group (ANOVA, 16.33 ± 3.02, p < 0.001; 4.00 ± 0.68, p < 0.001, respectively).ConclusionsThe PP-g-PEG, especially Ag-PP-g-PEG polymer-coated ventricular catheters are more effective in preventing the catheter-related infection and created the least inflammatory reaction in the periventricular parenchyma.

Surgical treatment of brain metastasis: A review

Brain metastasis is the most common intracranial tumor in adults. Currently, treatment of brain metastasis requires multidisciplinary approach tailored for each individual patient. Surgery has an indispensible role in relieving intracranial mass effect, improving neurological status and survival while providing or confirming neuropathological diagnosis with low mortality and morbidity rates. Besides the resection of a single brain metastasis in patients with accessible lesions, good functional status, and absent/controlled extracranial disease; surgery is proven to play a role in management of multiple metastases. Surgical technique has an impact on the outcome since piecemeal resection rather than en bloc resection and leaving infiltrative zone behind around resection cavity may have a negative influence on local control. Best local control of brain metastasis can be accomplished with optimal surgical resection involving current armamentarium of preoperative structural and functional imaging, intraoperative neuromonitoring, and advanced microneurosurgical techniques; followed by adjunct therapies like stereotactic radiosurgery, whole brain radiotherapy, or intracavitary therapies. Here, treatment options for brain metastasis are discussed with controversies about surgery.

Cintredekin besudotox in treatment of malignant glioma

Background: Interleukin-13 (IL-13) receptors are overexpressed in glioblastoma multiforme (GBM). The presence of IL-13 binding sites in GBM and their absence in normal brain tissue validates IL-13 receptor as an important target in human GBM. Objective: This review discusses the bench-to-bedside experience with a recombinant cytotoxin composed of human IL-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR), delivered via convection-enhanced delivery (CED), in GBM treatment. Methods: The authors review publications regarding the laboratory research and clinical development of IL-13-directed therapies and summarize the future of IL-13-targeted cytotoxin. Conclusion: The IL-13 receptor remains an important potential target in GBM, and preliminary experience with the IL-13–PE38QQR cytotoxin (also called cintredekin besudotox) has helped to pave the way for study of CED as an important means of drug delivery to malignant gliomas. Ongoing analysis of recently completed clinical trials will determine the future of this agent and its potential therapeutic targets.

Both mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (ERK) 1/2 and phosphatidylinositide-3-OH kinase (PI3K)/Akt pathways regulate activation of E-twenty-six (ETS)-like transcription factor 1 (Elk-1) in U138 glioblastoma cells

Epidermal growth factor (EGF) and its receptor (EGFR) have been shown to play a significant role in the pathogenesis of glioblastoma. In our study, the EGFR was stimulated with EGF in human U138 glioblastoma cells. We show that the activated mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (ERK) 1/2 pathway phosphorylated the E twenty-six (ETS)-like transcription factor 1 (Elk-1) mainly at serine 383 residue. Mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, UO126 and ERK inhibitor II, FR180204 blocked the Elk-1 phosphorylation and activation. The phosphatidylinositide-3-OH kinase (PI3K)/Akt pathway was also involved in the Elk-1 activation. Activation of the Elk-1 led to an increased survival and a proliferative response with the EGF stimulation in the U138 glioblastoma cells. Knocking-down the Elk-1 using an RNA interference technique caused a decrease in survival of the unstimulated U138 glioblastoma cells and also decreased the proliferative response to the EGF stimulation. The Elk-1 transcription factor was important for the survival and proliferation of U138 glioblastoma cells upon the stimulation of EGFR with EGF. The MAPK/ERK1/2 and PI3K/Akt pathways regulated this response via activation of the Elk-1 transcription factor. The Elk-1 may be one of the convergence points for pathways located downstream of EGFR in glioblastoma cells. Utilization of the Elk-1 as a therapeutic target may lead to a novel strategy in treatment of glioblastoma.

Effects of curcumin-loaded PLGA nanoparticles on the RG2 rat glioma model

BACKGROUND Curcumin, the active ingredient of turmeric, has a remarkable antitumor activity against various cancers, including glioblastoma. However, it has poor absorption and low bioavailability; thus, to cross the blood-brain barrier and reach tumor tissue, it needs to be transferred to tumor site by special drug delivery systems, such as nanoparticles. OBJECTIVE We aimed to evaluate the antitumor activity of curcumin on glioblastoma tissue in the rat glioma-2 (RG2) tumor model when it is loaded on poly(lactic-co-glycolic acid)-1,2-distearoyl-glycerol-3-phospho-ethanolamine-N-[methoxy (polyethylene glycol)-2000] ammonium salt (PLGA-DSPE-PEG) hybrid nanoparticles. METHODS Glioblastoma was induced in 42 adult female Wistar rats (250-300g) by RG2 tumor model. The curcumin-loaded nanoparticles were injected by intravenous (n=6) or intratumoral route (n=6). There were five control groups, each containing six rats. First control group was not applied any treatment. The remaining four control groups were given empty nanoparticles or curcumin alone by intravenous or intratumoral route, respectively. The change in tumor volume was assessed by magnetic resonance imaging and histopathology before and 5days after drug injections. RESULTS Tumor size decreased significantly after 5days of intratumoral injection of curcumin-loaded nanoparticle (from 66.6±44.6 to 34.9±21.7mm3, p=0.028), whereas it significantly increased in nontreated control group (from 33.9±21.3 to 123.7±41.1mm3, p=0.036) and did not significantly change in other groups (p>0.05 for all). CONCLUSION In this in vivo experimental model, intratumoral administration of curcumin-loaded PLGA-DSPE-PEG hybrid nanoparticles was effective against glioblastoma. Curcumine-loaded nanoparticles may have potential application in chemotherapy of glioblastoma.

ON THE REPORT OF THE FIRST SUCCESSFUL SURGICAL TREATMENT OF BRAIN ABSCESS IN THE OTTOMAN EMPIRE BY DR. CEMIL TOPUZLU IN 1891

IN 1891, Dr. Cemil Topuzlu operated on a brain abscess that originated as a complication of a depression fracture of the cranial inner table. The patient presented with Jacksonian seizures on his left side after a sharp trauma resulting in a 15 cm-long scalp laceration and underlying linear cranial fracture in the right parietal bone. Dr. Topuzlu attributed Jacksonian epilepsy to the fracture irritating the motor area in the right hemisphere and attempted a craniotomy based on his measurements to localize the Rolandic fissure. The operation was complicated by a brain abscess, and Dr. Topuzlu reoperated to drain the abscess. He successfully treated the brain abscess and Jacksonian seizures and then presented this case in the Royal Society of Medicine of the Ottoman Empire and in the International Surgery Congress in Lyon in 1894. The case report was published in his surgery book in 1905. The case was not only the first case of brain abscess to be treated successfully with surgical intervention in the Ottoman Empire, it was also one of the first cases of neurological surgery performed using contemporary anesthesiological and surgical techniques, which reveals the importance of neurological examination and cerebral localization techniques in the era before x-rays. Dr. Topuzlu was the founder of modern surgery in the Ottoman Empire and deserves to be credited for his novel applications in the 19th century.

Bilateral Epidural Hematoma in a Pyknodysostotic Child

Pyknodysostosis is a rarely encountered disease. It is characterized by abnormal facial development, fragility of the bones with relatively mild trauma, cranial abnormalities including widely opened sutures and fontanels frontal bossing, wrinkled skin, finger and nail abnormalities. In the literature, pyknodysostosis was reported only as case reports. Here, we describe a pyknodysostotic child with a bilateral parietal epidural hematoma, caused by a relatively mild head trauma. He was operated on, and the hematoma was evacuated through two different parietal craniotomies. We reported this case, since pyknodysostosis is a rare disease, and our case is the first one who had a surgical intervention as well as being the first with an epidural hematoma in pyknodysostosis.

Unmet needs in the treatment of glioblastoma.

Glioblastoma multiforme (GBM) is among the most difficult of tumors to treat and, despite all efforts, median overall survival (mOS) remains at approximately 12 months [1]. Neurological morbidity at diagnosis and progression of disease is high. The established therapies for GBM include surgery, radiotherapy (RT) and local or systemic chemotherapy. Significant progress has been achieved in the past decade in the understanding of the molecular biology of GBM histology and, as a consequence, there is renewed clinical trial activity in this area focused on improving quality of life, treatment-related morbidity and outcomes [2]. In this review, we discuss several controversies and unmet needs in the diagnosis and treatment of GBM.