Urinary 8-hydroxy-2'-deoxyguanosine levels are elevated in patients with IDH1-wildtype glioblastoma and are associated with tumor recurrence in gliomas.

2021 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification includes molecular diagnostic parameters such as isocitrate dehydrogenase (IDH) mutation or 1p19q codeletion status, in addition to the classical histological classification. Several studies have revealed that patients with IDH1 mutation have a longer survival rate compared to wildtype individuals. In glioma cells, increased oxidative stress has been identified. However, till now, the relation between oxidative stress levels and IDH1 mutation status in those patients was not examined. Therefore, the aim of this study was to investigate the urinary levels of oxidatively induced DNA damage products, 8-hydroxy-2'- deoxyguanosine (8-OH-dG), (5'R) and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA) as reliable oxidative stress markers in patients with IDH1-wildtype (n = 20) and IDH1-mutant (n = 22) glioma. Absolute quantification of 8-OH-dG, R-cdA and S-cdA was achieved by liquid chromatography-tandem mass spectrometry with isotope dilution. The levels of 8-OH-dG were significantly greater in IDH1-wildtype glioma patients than those in IDH1-mutant ones (p = 0.017). No statistically significant difference was observed for R-cdA and S-cdA levels. 8-OH-dG levels were positively correlated with patients' tumor recurrence in all patients (r = 0.382, p = 0.014). The mutation status of glioma is well correlated with oxidative stress. Examination of noninvasively measured oxidative DNA damage products along with IDH1 mutation status in glioma patients, might be particularly important in terms of evaluating and monitoring the effectiveness of treatment.

Development and validation of an LC-MS/MS method for D- and L-2-hydroxyglutaric acid measurement in cerebrospinal fluid, urine and plasma: application to glioma.

Aim: IDH mutations have been identified as frequent molecular lesions in several tumor types, particularly in gliomas. As a putative marker of IDH mutations, elevated D-2-HG has been reported in glioma, acute myeloid leukemia and intrahepatic cholangiocarcinoma. Excessive production of L-2-HG has also been described in renal cell carcinoma and 2-hydroxyaciduria. Materials & methods: The authors present a fully optimized stable isotope dilution multiple reaction monitoring method for quantification of D-/L-2-HG using LC-MS/MS. This is the first method validation study performed on cerebrospinal fluid, plasma and urine demonstrating clinical applicability with samples from glioma patients. Results & conclusion: This method validation study showed high accuracy and precision with low limit of detection and limit of quantification values. The authors believe that the presented approach is highly applicable for basic and clinical research on related pathologies.

Minimally Invasive Detection of IDH1 Mutation With Cell-Free Circulating Tumor DNA and D-2-Hydroxyglutarate, D/L-2-Hydroxyglutarate Ratio in Gliomas.

Isocitrate dehydrogenase-1 (IDH1) mutation is accepted as one of the earliest events in tumorigenesis in gliomas. This mutation causes preferential accumulation of D- relative to L-enantiomer of 2-hydroxyglutarate (2-HG). Minimally invasive techniques to detect IDH1 mutation may prove useful for clinical practice. We adopted 2 different diagnostic approaches to detect IDH1 mutation status in glioma patients: Evaluation of D- and L-2-HG levels in cerebrospinal fluid (CSF), urine, and plasma, and identification of IDH1 mutation using cell-free circulating tumor DNA (ctDNA) in CSF and plasma. Forty-nine glioma patients in different stages were included. Levels of D- and L-2-HG were determined using liquid chromatography-tandem mass spectrometry; IDH1 R132H mutation was determined by digital-PCR. D-2-HG levels and D/L-2-HG ratio (rDL) in CSF and rDL in plasma were significantly higher in the mutant group than in the wild-type group (p = 0.029, 0.032, 0.001, respectively). The IDH1 mutation detection rates in CSF- and plasma-ctDNA were 63.2% and 25.0%, respectively. These data indicate that D-2-HG values in CSF and rDL in plasma and CSF can be considered as significant contributors to the identification of IDH1 mutation status. In addition, detection of IDH1 mutation in CSF-ctDNA from glioma patients provides a basis for future use of ctDNA for minimally invasive clinical assessment of gliomas.

Treatment of Intractable Midbrain Tremor with a Pedinculopontine Nucleus Radiofrequency Lesion.

In this report, we present the case of a 21-year-old female with midbrain tremor involving atypical features, treated using a pedinculopontine nucleus lesion. Different targets for the treatment of midbrain tremor using radiofrequency lesion have been reported. In this case, stimulation of the thalamic ventralis intermedius nucleus and subthalamic nucleus produced no satisfactory improvement in tremor frequency and amplitude. A third goal was to obtain a significant response in terms of these outcomes with pedinculopontine nucleus stimulation. According to the literature, this is the first case of midbrain tremor treated with a pedinculopontine nucleus radiofrequency thermocoagulation lesion.

Magnetic Resonance Imaging-guided Stereotactic Biopsy: A Review of 83 Cases with Outcomes.

BACKGROUND: The purpose of this study was to determine the relationship between the radiological and histopathological distribution of the cerebral lesions diagnosed with stereotactic biopsy (STB) procedure and its outcomes. MATERIALS AND METHODS: In the current study, a retrospective analysis of 83 patients that underwent the STB in our clinic from January 2011 to December 2015 was made. T1-weighted contrast-enhanced cranial magnetic resonance imaging examinations were performed on patients on whom Leksell stereotactic frame system was installed. The histopathological and the radiological data derived from the STB procedure were classified. RESULTS: In terms of localization, glial tumor (56.6%) was the most common lesion in all regions, except for the multifocal lesions. Contrary to the common knowledge, lymphoma (14.4%) was found to be the most common lesion among multifocal lesions. The success of obtaining positive STB samples in the current series was 95.2% and the complication rate was 3.6%. CONCLUSION: Had a routine computed tomography scan been performed on each patient in this series, the number of clinically insignificant small intracerebral hematomas would have probably been higher. Nevertheless, the rate of the STB sampling accuracy and the complication rate were similar to those reported in the relevant literature.

MRI-guided frame-based stereotactic brainstem biopsy procedure: A single-center experience.

INTRODUCTION AND OBJECTIVES: This study aims at presenting our experience of the MRI-guided frame-based stereotactic brainstem biopsy method, and evaluating the outcomes of the procedure. PATIENTS AND METHODS: The current study involved 18 cases that underwent MRI-guided frame-based stereotactic biopsy for brainstem lesions between 2011 and 2018 in our clinic. The relevant data regarding the technique of the biopsy procedure, morbidity, histopathological diagnosis it yields and diagnostic accuracy was retrospectively analyzed. RESULTS: Stereotactic biopsy procedure was performed on 18 patients, including 16 adults and two children. MRI was used as guidance for the biopsy procedure in all patients. The adult patients had the biopsy under local anesthesia; as for the pediatric patients local anesthesia plus sedation was used. All patients received diagnosis based on the histopathological examination of their biopsy samples. No equivocal or negative results, and no major morbidity or mortality was seen in the patients after the procedure. CONCLUSIONS: MRI-guided frame-based stereotactic biopsy can be considered as a safe and efficient diagnostic method for brainstem lesions when its diagnostic yield and its morbidity and/or mortality rates are evaluated. Choosing the best trajectory for each lesion, using MRI as guidance for targeting, taking a limited number of biopsy samples are valuable criteria for the decreased morbidity rates in stereotactic brainstem biopsy procedures.

DTI-Based Neuronavigation Guided Eloquent Area Glioma Resection with Awake Craniotomy: Supra-Functional Resection of Eloquent Area Gliomas.

AIM: To present an overview of our awake craniotomy practices performed with complementary use of diffusion tensor imaging (DTI)-based neuronavigation (DTI-bN) and cortical-subcortical electrical stimulation for glioma resection located in eloquent areas, and the clinical outcomes of these practices regarding neurological morbidity and residual tumour volume. MATERIAL AND METHODS: This study was conducted between October 2016 and December 2017 involving 18 cases. The DTIbN method, in addition to cortical-subcortical stimulation, was done with awake craniotomy. Changes in the neurological status of the patients and results of the method regarding residual tumour volume were recorded. This retrospective study use data obtained from patients' records and radiological examinations. RESULTS: Of the 18 patients, a gross total resection was performed on nine patients (50%), a near total resection was performed on seven patients (38.8%) and a subtotal resection was performed on two patients (11.1%). Intraoperative neurological deterioration was observed in 14 of 18 patients during their surgical procedures, and neurological examinations in the sixth post-operative month revealed permanent deficits in two patients. CONCLUSION: This study is one of the rare series to have presented the results of the use DTI-bN method as well as corticalsubcortical stimulation during awake craniotomy, according to literature review. In 88% of cases, tumour resection rates are over 90%.

A Case of Vago-Glossopharyngeal Neuralgia Caused by Choroid Plexus.

Vascular compression has been reported to be the most common reason for vago-glossopharyngeal neuralgia (VGN). The treatment may include medications, ganglion blockade with a radiofrequency ablation, and microvascular decompression (MVD). A review of the literature reveals that VGN may develop due to choroid plexus compression, and the number of reported cases is very limited. The current case is the fifth in the relevant literature. In this paper, choroid plexus compression has been shown intraoperatively during the treatment of rare idiopathic VGN using MVD. Complaints of the patient have been resolved following the choroid plexus excision.

Awake Craniotomy Procedure: Its Effects on Neurological Morbidity and Recommendations.

AIM: To present our experience with the awake craniotomy (AC) method starting from the preoperative period, to report the morbidity and the functional outcomes along with the complications in patients who underwent AC, and to make recommendations for possible problems. MATERIAL AND METHODS: This study involved 46 cases- 2 of which were pediatric cases with lesions localized in the functional area - who were operated with the AC method between September 2011 and January 2016 at our clinic. The age range was 12 to 81 years. The average age was 48 years. Both preoperative and postoperative (1, 3, 6 and 12 months) neurological examinations were recorded. RESULTS: Of the 46 patients who had AC surgery in this series, 17 were observed to have neurological deterioration in the intraoperative period. At the month 1 follow-up, 13 of these 17 patients were observed to have full neurological recovery. Moreover, 4 patients that developed hemiplegia were able to mobilize with support at the month 6 follow-up. All patients were observed to have a return of language skills to baseline preoperative function on month 1 follow-up. CONCLUSION: When the results of the AC method were examined, it was observed that persistent postoperative neurological deficit rates were very low in the follow-up period. Based on our practice presented here, it could be concluded that the precise synchrony between the surgeon, the anesthesia team and the patient is required for successful AC and the preservation of language and motor functions.

Pediatric Awake Craniotomy for Brain Lesions.

Awake craniotomy is a special method to prevent motor deficits during the resection of lesions that are located in, or close to, functional areas. Although it is more commonly performed in adult patients, reports of pediatric cases undergoing awake craniotomy are limited in the literature. In our clinic, where we frequently use awake craniotomy in adult patients, we performed this method in 2 selected pediatric cases for lesion surgery. At an early age, these 2 cases diagnosed with epilepsy presented cerebral lesions, but since the lesions enclosed functional areas, surgical resection was not regarded as a treatment option at this time. In these 2 pediatric cases, we successfully completed lesion surgery with awake craniotomy. The method and the techniques employed during surgery are presented concomitant with other reports in the literature.

Multiple spinal metastases of cranial gliosarcoma: a case report and review of the literature.

Gliosarcoma is a rare brain tumor that consists of both glial and mesenchymal components. We report the case of a 68-year-old female with cranial gliosarcoma metastatic to the spinal cord. Initially, the patient was diagnosed with cranial gliosarcoma and treated with surgical resection followed by radiotherapy. Four months after she completed treatment, she presented with a sudden onset of hemiplegia. MRI (Magnetic Resonance Imaging) scan demonstrated two masses at the thoracic spinal cord. Immediate surgery was performed and the lesions were resected. No further therapy was recommended due to the poor condition of the patient. The patient subsequently died 3 months after diagnosis of the spinal cord metastases. There are about 20 reported cases of metastatic gliosarcoma and most focus on systemic metastases of gliosarcoma. Spinal cord metastases are, however, very rare and here we report such a case. Available literature on metastatic gliosarcoma was also reviewed.

Perfusion and diffusion MR imaging in enhancing malignant cerebral tumors.

OBJECTIVE: Common contrast-enhancing malignant tumors of the brain are glioblastoma multiforme (GBMs), anaplastic astrocytomas (AAs), metastases, and lymphomas, all of which have sometimes similar conventional MRI findings. Our aim was to evaluate the role of perfusion MR imaging (PWI) and diffusion-weighted imaging (DWI) in the differentiation of these contrast-enhancing malignant cerebral tumors. MATERIALS AND METHODS: Forty-eight patients with contrast-enhancing and histologically proven brain tumors, 14 AAs, 17 GBMs, nine metastases, and eight lymphomas, were included in the study. All patients have undergone routine MR examination where DWI and PWI were performed in the same session. DWI was performed with b values of 0, 500, and 1000 mm(2)/s. Minimum ADC values (ADC(min)) of each tumor was later calculated from ADC map images. PWI was applied using dynamic susceptibility contrast technique and maximum relative cerebral blood volume (rCBV(max)) was calculated from each tumor, given in ratio with contralateral normal white matter. Comparisons of ADC(min) and rCBV(max) values with the histological types of the enhancing tumors were made with a one-way analysis of variance and Bonferroni test. A P value less than 0.05 indicated a statistically significant difference. RESULTS: The ADC(min) values (mean+/-S.D.) in GBMs, AAs, lymphomas, and metastases were 0.79+/-0.21 (x10(-3)mm(2)/s), 0.75+/-0.21 (x10(-3)mm(2)/s), 0.51+/-0.09 (x10(-3)mm(2)/s), and 0.68+/-0.11 (x10(-3)mm(2)/s), respectively. The difference in ADC(min) values were statistically significant between lymphomas and GBMs (P<0.05). It was also statistically significant between lymphomas and AAs (P<0.03). However, there were no differences between lymphomas and metastasis, and between GBMs, AAs, and metastasis. The rCBV(max) ratio (mean+/-S.D.) in GBMs were 6.33+/-2.03, whereas it was 3.66+/-1.79 in AAs, 2.33+/-0.68 in lymphomas, and 4.45+/-1.87 in metastases. These values were statistically different between GBMs and AAs (P<0.001), GBMs and lymphoma (P<0.0001). Although there seemed to be difference between GBMs and metastases, it was not statistically significant (P<0.083). CONCLUSION: Combination of DWI and PWI, with ADC(min) and rCBV(max) calculations, may aid routine MR imaging in the differentiation of common cerebral contrast-enhancing malignant tumors.

Old method, new drugs: comparison of the efficacy of sevoflurane, isoflurane, and desflurane in achieving controlled hypotension in spinal surgery.

This study compared the efficacy of isoflurane, sevoflurane, and desflurane in achieving hemodynamic stability in spinal procedures using moderate levels of controlled hypotension. After obtaining ethics committee approval and written informed consent, 32 American Surgical Association I-II patients were randomly allocated to receive isoflurane (n=12), sevoflurane (n=10), or desflurane (n=10) in O2-N2O (1:1) for maintenance of anesthesia. The induction of anesthesia, fentanyl dosage, and initial and maintenance volume replacements were standardized. Blood pressure was invasively monitored and maintained within a target systolic blood pressure (SBP) range of 80 to 90 mm Hg during the study. SBP outside this range was recorded. Volatile anesthetic concentration was adjusted according to the same protocol for all 3 agents. SPB control was maintained better with sevoflurane and isoflurane than desflurane; median SBP was outside the target range during 32% (range, 15%-55%) of study time with isoflurane, 26% (12%-42%) with sevoflurane, and 44% (20%-80%) with desflurane. Total blood loss did not differ among the groups. Sevoflurane and isoflurane administered in 2 L/min fresh gas flow were more effective than desflurane in achieving controlled hypotension in spinal surgery.

Meningitis due to methicillin-resistant Staphylococcus aureus (MRSA): review of 10 cases.

We evaluated retrospectively, 10 MRSA meningitis cases in our hospital that occurred between January 1999 and June 2004. All were post-neurosurgical and were considered to have hospital-acquired meningitis. Fever, leukocytosis, variable conscious levels were the most common findings. Six patients were treated with regimens including teicoplanin, and four with vancomycin. Mean duration of treatment was 23.5+/-18.8 days (range, 3-60 days). One patient died. In cases of MRSA meningitis, intravenous vancomycin is the mainstay of therapy. However, six of these 10 patients were successfully treated with regimens including teicoplanin, suggesting that this agent may be an alternative to vancomycin in the therapy of these cases.

Intravascular papillary endothelial hyperplasia of the central nervous system--four case reports.

Four rare cases of intracranial intravascular papillary endothelial hyperplasia (IPEH) manifesting as cranial nerve disturbances occurred in 16-, 18-, 24-, and 28-year-old females. Magnetic resonance imaging showed all lesions as isointense with strong enhancement on T1-weighted images, and as hyperintense on T2-weighted images. All lesions were removed via craniotomies. Histological examination found vascular structures and papillary spaces lined with endothelial cells showing immunoreactivity for CD31. Complete removal was curative in two cases, whereas incomplete removal resulted in cure in one case and residual deficits in one case. Iatrogenic deficits should be avoided in IPEH treatment by surgery. Differentiation from neoplasm such as angiosarcoma depends on histological characteristics.

Secretory meningiomas.

Secretory meningiomas are a rare meningioma subtype. Among meningiomas, the frequency of secretory meningiomas is 1.6%. Unlike other meningioma types, most of the patients were female (ratio 3:1). No recurrence was reported during the 24-180 months follow-up period of our secretory meningiomas in which, a low level of 0.3% Ki-67 proliferative index was reported. In this meningioma subtype, the percentage of cases with positive progesterone receptor is 33%. With carcinoembryonic antigen, cytokeratin and epithelial membrane antigen, in all the cases positivity was observed in both, the inclusions and the cells surrounding them. With human milk fat globulin 2, a high ratio (92%) of positivity was observed. Majority of the cases were negative with CA125, only three of the cases had suspicious positivity. Distribution of inclusions was irregular and their positive reactions showed varying staining features. Positivity with alpha-1-antitripsin was seen not only in the inclusions but also in some meningothelial cells as well. Ubiquitin was positive in inclusions of the 83% of cases. Staining features of the inclusions pointed out the possibility of them being in a varying age and/or content. Secretory meningiomas are a different type compared to other meningiomas, not only with their histological features but also with their clinical features as well.