廣瀬 雄一

Background: Cerebral amyloid angiopathy-related inflammation (CAA-I) presents with slowly progressive nonspecific neurological symptoms, such as headache, cognitive function disorder, and seizures. Pathologically, the deposition of amyloid-β proteins at the cortical vascular wall is a characteristic and definitive finding. Differential diagnoses include infectious encephalitis, neurosarcoidosis, primary central nervous system lymphoma, and glioma. Here, we report a case of CAA-I showing acute progression, suggesting a glioma without enhancement, in which a radiological diagnosis was difficult using standard magnetic resonance imaging. Case Description: An 80-year-old woman was admitted due to transient abnormal behavior. Her initial imaging findings were similar to those of a glioma. She presented with rapid progression of the left hemiplegia and disturbance of consciousness for 6 days after admission and underwent emergent biopsy with a targeted small craniotomy under general anesthesia despite her old age. Intraoperative macroscopic findings followed by a pathological study revealed CAA-I as the definitive diagnosis. Steroid pulse therapy with methylprednisolone followed by oral prednisolone markedly improved both the clinical symptoms and imaging findings. Conclusion: Differential diagnosis between CAA-I and nonenhancing gliomas may be difficult using standard imaging studies in cases presenting with acute progression. A pathological diagnosis under minimally invasive small craniotomy may be an option, even for elderly patients.

The authors report the first cases of fluorescence-guided spinal surgery of schwannomas using near-infrared fluorescence imaging with the delayed window indocyanine (ICG) green (DWIG) technique for accurate real-time intraoperative tumor visualization. Patients with intradural spinal schwannomas received 0.5 mg/kg ICG at the beginning of surgery. After 1 hour, using the DWIG technique, near-infrared spectroscopy (NIRS) detected the spinal schwannomas, showing the exact tumor location and boundaries. DWIG with NIRS microscopy confirmed the exact location of spinal schwannomas before and after opening of the dura mater, thereby facilitating successful tumor dissection from the surrounding tissues, tumor resection, and confirmation of tumor removal. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21158.

BACKGROUND: Mechanical stimulation may lead to internal carotid artery (ICA) dissection and aneurysm. CASE DESCRIPTION: We encountered a rare case of ICA dissection and aneurysm with prolonged styloid process (SP) fracture. A 37-year-old sales worker presented with right-sided amaurosis fugax. After admission to a nearby optical clinic, he was admitted to our hospital. Computed tomography angiography (CTA) and digital subtraction angiography showed dissection and apparent aneurysmal change in the right cervical portion of the ICA. CTA also showed elongated SPs, so we diagnosed Eagle's syndrome, and fracture of the right-side process. After 2 weeks of antiplatelet therapy, the aneurysm enlarged and dissection remained, so we treated the patient with coil embolization and stenting. CONCLUSION: We encountered a rare case of ICA dissection and aneurysm with Eagle's syndrome. Endovascular treatment was performed because the SP was fractured.

<title>Abstract</title> <sec> <title>Background</title> Adjuvant treatment with Gliadel wafers may prolong overall survival (OS) for malignant glioma patients without increasing toxicity. In Japan, the long-term OS of these patients treated with Gliadel 7.7 mg implants has not been studied. We evaluated OS and prognostic factors that might affect OS in Japanese patients with malignant glioma who received the Gliadel 7.7 mg implant. </sec> <sec> <title>Methods</title> This observational, long-term, postmarketing surveillance was an extension of a previous surveillance. Data were collected through case report forms at 2 and 3 years after Gliadel implant. Up to 8 Gliadel wafers (61.6 mg of carmustine) were placed over the tumor resection site. Primary endpoints were OS and prognostic factors that may influence OS. </sec> <sec> <title>Results</title> Among the 506 patients analyzed, 62.6% had newly diagnosed disease, and 37.4% had recurrent disease; 79.1% had glioblastoma histological type and 79.6% had World Health Organization Grade IV disease. Patients received a median of 8 wafers. The median OS was 18.0 months; OS rates were 39.8% and 31.5% at 2 and 3 years, respectively. Age ≥65 years (hazard ratio [HR]: 1.456; P = .002), lower resection rate (HR: 1.206; P &amp;lt; .001), recurrence (HR: 2.418; P &amp;lt; .001), and concomitant radiotherapy (HR: 0.588; P &amp;lt; .001) were identified as significant prognostic factors. </sec> <sec> <title>Conclusions</title> This study confirmed the 2- and 3-year OS of Japanese malignant glioma patients with varied backgrounds after Gliadel implant. With a careful interpretation of indirect comparisons with previously reported data, the results suggest that prognosis could be improved with Gliadel implants. </sec> <sec> <title>Clinical Trial Registration</title> NCT02300506 </sec>

BACKGROUND: We aimed to clarify the relationship between epicardial adipose tissue (EAT) volume and the presence of severe stenoses (SS) on coronary computed tomography angiography (CTA) for risk stratification of the patients with carotid artery stenoses. METHODS: We prospectively performed CTA for 125 consecutive patients (72.4 ± 8.1 years, 85% men) without a history of coronary artery disease (CAD), who were scheduled for carotid artery revascularization from 2014 to 2020. SS was defined as ≥70% luminal stenosis on CTA. EAT was quantified automatically as the total volume of tissue with -190 to -30 HU. RESULTS: Of 125 patients, 76 had SS. Between the patients with and without SS, there were significant differences in coronary artery calcium score (CACS), left ventricular ejection fraction (LVEF), dyslipidemia, and EAT, despite no differences in carotid echocardiography findings. After adjustment for age, gender, and dyslipidemia, EAT was an independent factor associated with SS (p=0.011), as well as CACS and LVEF. The addition of EAT to a baseline model including age, gender, dyslipidemia, LVEF, and CACS achieved both net reclassification improvement (0.505, p=0.003) and integrated discrimination improvement (0.059, p=0.003). CONCLUSIONS: In patients with carotid stenoses, EAT is associated with CAD and is useful for additional risk stratification. Epicardial fat may have a specific role in the development of CAD in patients with suspected systemic atherosclerosis.

OBJECTIVE: Glioma is the most common type of central nervous system tumor reported worldwide. Current imaging technologies have limitations in the diagnosis and assessment of glioma. The present study aimed to confirm the diagnostic efficacy and safety of anti-1-amino-3-[18F]fluorocyclobutane carboxylic acid (18F-fluciclovine; anti-[18F]FACBC) as a radiotracer for patients undergoing combined positron emission tomography and computed tomography (PET/CT) for suspected glioma. METHODS: Combined data from two multicenter, open-label phase III clinical trials were evaluated for this study. The two trials enrolled patients with suspected high- or low-grade glioma on the basis of clinical symptoms, clinical course, and magnetic resonance imaging findings, and who were scheduled for tumor resection surgery. Patients fasted for ≥ 4 h and received 2 mL of 18F-fluciclovine (radioactivity dose 78.3-297.0 MBq), followed by a 10-min PET scan 10-50 min after injection. The primary efficacy endpoint was the positive predictive value (PPV) of the gadolinium contrast-enhanced T1-weighted image negative [Gd (-)] and 18F-fluciclovine PET-positive [PET ( +)] area of the scans, using the histopathological diagnosis of the tissue sampled from that area as the standard of truth. All adverse events reported during the study were recorded for safety analysis. RESULTS: A total of 45 patients aged 23-89 years underwent 18F-fluciclovine PET; 31/45 patients (68.9%) were male, and 30/45 patients (66.7%) were suspected to have high-grade glioma. The PPV of 18F-fluciclovine PET in the Gd (-) PET ( +) area was 88.0% (22/25 areas, 95% confidence interval: 70.0-95.8). The extent of planned tumor resection was modified in 47.2% (17/36 cases) after 18F-fluciclovine PET scan, with an extension of area in 30.6% (11/36 cases) and reduction in 16.7% (6/36 cases). Furthermore, tissue samples collected from PET ( +) areas tended to have a higher malignancy grade compared with those from PET (-) areas. Overall, 18F-fluciclovine was well tolerated. CONCLUSION: 18F-fluciclovine PET/CT is useful for determining the extent of tumor resection at surgical planning, and may serve as a safe and effective diagnostic tool for patients with suspected glioma. TRIAL REGISTRATION: These trials were registered in the Japan Pharmaceutical Information Center Clinical Trials Information (JapicCTI-152986, JapicCTI-152985).

BACKGROUND: We investigated the ability of magnetic resonance imaging (MRI) to distinguish primary central nervous system vasculitis (PCNSV) from glioblastoma to facilitate the development of an appropriate treatment for PCNSV. METHODS: We enrolled patients who were treated for PCNSV or glioblastoma at our center between January 2007 and August 2018. We compared the diagnoses of the 2 conditions by retrospectively reviewing patients' data for contrast-enhanced MRI, perfusion MRI, flow-sensitive black-blood (FSBB) imaging, and 1H-magnetic resonance spectroscopy (MRS). RESULTS: We evaluated 108 patients (6 PCNSV; 102 glioblastoma). We found a statistically significant correlation between diagnosis and the contrast pattern on MRI. Perivascular enhancement was observed in all cases of PCNSV as follows: ring-like, homogeneous, and irregular patterns were observed in 53 (60%), 18 (20%), and 17 (19%) cases of glioblastoma, respectively. We identified a statistically significant correlation between diagnosis and cerebral blood volume (CBV) in 3 patients with PCNSV who underwent perfusion MRI; and all had low CBVs. Among the 55 patients with glioblastoma who underwent perfusion MRI, low and high CBVs were detected in 3 and 52 patients, respectively. There was no significant correlation between diagnosis and FSBB findings. Evaluation of 1H-MRS data showed statistically significant differences between PCNSV and glioblastoma as functions of neuronal amino acid levels on long echo time MRS, with a slightly different amino acid profile, including glutamine + glutamate on short echo time MRS. CONCLUSIONS: Contrast-enhanced MRI, perfusion MRI, and quantitative analysis of 1H-MRS are valuable techniques for distinguishing PCNSV from glioblastoma before surgery.

BACKGROUND: Thromboembolic complications (TECs) are frequent during the endovascular treatment of unruptured aneurysms. To prevent TECs, dual antiplatelet therapy using aspirin and clopidogrel is recommended for the perioperative period. In patients with a poor response, clopidogrel is a risk factor for TECs. To prevent TECs, our study assessed the stratified use of prasugrel. METHODS: Patients who underwent endovascular therapy for unruptured cerebral aneurysms from April 2017 to August 2019 were enrolled in this clinical study and given premedication with aspirin and clopidogrel for 2 weeks prior to the procedure. P2Y12 reaction units (PRU) were measured using the VerifyNow assay on the day before the procedure (tailored group). In subgroups with PRU <240, the clopidogrel dose was maintained (CPG subgroup). In subgroups with PRU ≥240, clopidogrel was changed to prasugrel (PSG subgroup). We compared the occurrence of TECs with retrospective consecutive cases from January 2015 to March 2017 without PRU assessments (non-tailored group). The frequency of TECs within 30 days was assessed as the primary endpoint. RESULTS: The tailored and non-tailored groups comprised 167 and 50 patients, respectively. TECs occurred in 11 (6.6%) and 8 (16%) patients in the tailored and non-tailored groups (P=0.048), respectively. The HR for TECs was significantly reduced in the tailored group (HR 0.3, 95% CI 0.11 to 0.81); P=0.017) compared with the non-tailored group. CONCLUSION: The results suggest that tailored dual antiplatelet therapy medication with PRU significantly reduces the frequency of TECs without increasing hemorrhagic complications.

Seizures are common neurological emergencies that occasionally cause prolonged impairment of consciousness. The aim of this retrospective single-center study is to clarify factors associated with prolonged impairment of consciousness for admitted adult patients investigating patient backgrounds, blood tests, electroencephalographic patterns, and MRI findings. The patients who were admitted to the hospital due to epileptic seizures were classified into two groups: (1) early recovery group, in which patients recovered their consciousness within 6 hr, and (2) delayed recovery group, in which patients showed impairment of consciousness more than 6 hr. Factors associated with prolonged impairment of consciousness were compared between these groups. In this study, 42 cases (33 patients), with a mean age of 67.8 years, were included. Fifteen cases (13 patients) and 27 cases (20 patients) were classified into the early and delayed recovery groups, respectively. The populations of older patients and patients from a nursing home were significantly higher in the delayed recovery group. With regard to radiological analyses, a high grade of periventricular hyperintensity (PVH), high Evans index score, and enlarged bilateral atrial widths were significantly associated with prolonged impairment of consciousness. Multivariable analyses showed that a high grade of PVH was significantly associated with delayed recovery of consciousness independent of age and status epilepticus. In conclusion, we proposed that diffuse white matter degeneration around the lateral ventricles contributes to prolonged impairment of consciousness.

Schwannomas of the trochlear nerve are relatively rare, and most patients present with preoperative diplopia because of trochlear nerve palsy. We describe the case of a 61-year-old male patient with a trochlear nerve schwannoma and no pre- and postoperative diplopia, despite his trochlear nerve being cut during the operation. We aimed to investigate the frequency of postoperative diplopia associated with intraoperative trochlear nerve disturbance by reviewing previous case reports, wherein postoperative diplopia did not occur after the trochlear nerve was cut intraoperatively. We recorded the frequency of diplopia because of intraoperative trochlear nerve disturbance, such as the trochlear nerve being cut, in cases without pre- and postoperative diplopia. We searched the PubMed, Medline, and Google Scholar databases for works published from 1976 to 2020 and followed the preferred reporting items for systematic reviews and meta-analyses guidelines. We reviewed 36 publications and found 92 cases of trochlear nerve schwannoma. Surgical resection was performed for 43 patients, of whom 40 were kept under observation and 9 were treated with radiation therapy. Of the 43 cases, 9 without preoperative diplopia underwent gross total resection. We analyzed ten cases (including ours) without preoperative diplopia to check for postoperative diplopia. In total, four cases, including ours, did not display postoperative diplopia despite the trochlear nerve being cut. This may be attributed to the preoperatively acquired motor and sensory fusion in the patient's vision because of tumor progression. Our findings may benefit neurosurgeons who treat patients with schwannomas and help them predict patients' outcomes.

Digital subtraction angiography (DSA) assesses the necessity of preoperative embolization in meningioma cases but entails complication risks. Previous studies evaluating meningiomas' angiographic vascularity using perfusion-weighted imaging (PWI) have performed subjective visual assessments, not managing to assess the need for preoperative embolization. We objectively assessed the angiographic stain of meningiomas and examined the usefulness of two parameters of dynamic susceptibility contrast (DSC)-PWI, normalized cerebral blood volume (nCBV) and cerebral blood flow (nCBF), in predicting vascularity and the necessity of preoperative embolization. We retrospectively examined 52 patients who underwent surgery for primary meningioma and preoperative DSA and DSC-PWI. We calculated the normalized luminance (nLum) of the tumor stain in DSA. In 29 meningioma cases with a single feeding artery, we determined the DSC-PWI parameter that correlated with meningioma angiographic vascularity and predicted the necessity of preoperative embolization. We also compared vascularity between meningiomas with single and multiple feeding arteries and between convexity and skull-base meningiomas. nCBF (cut off: 3.66, P = 0.03, area under the curve [AUC] = 0.80) alone could predict the necessity of preoperative embolization and was more significantly correlated with the nLum than nCBV (P = 0.08, AUC = 0.73). Vascularity did not differ between meningiomas with single and multiple feeding arteries; skull-base meningiomas were more vascularized than convexity meningiomas (P = 0.0027). Our objective, quantitative assessments revealed nCBF as the most suitable parameter for evaluating meningioma vascularity. Tumor vascularity assessment using nCBF values and CBF images may aid predicting the necessity of preoperative DSA.

Primary central nervous system lymphomas (PCNSLs) rarely exhibit intratumoral hemorrhage. The differential diagnosis of hemorrhagic neoplasms of the central nervous system (CNS) currently includes metastatic carcinomas, melanomas, choriocarcinomas, oligodendrogliomas, and glioblastomas. Here we present the clinical, radiological, pathological, and molecular genetic features of six cases of PCNSL associated with intratumoral hemorrhage. The median age of patients was 75 years, with male predominance. While conventional PCNSLs were associated with low cerebral blood volume (CBV), perfusion magnetic resonance imaging (MRI) revealed elevated CBV in three cases, consistent with vascular proliferation. All six cases were diagnosed pathologically as having diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell-like (non-GCB) phenotype; marked histiocytic infiltrates and abundant non-neoplastic T-cells were observed in most cases. Expression of vascular endothelial growth factor and CD105 in the lymphoma cells and the small vessels, respectively, suggested angiogenesis within the neoplasms. Neoplastic cells were immunohistochemically negative for programmed cell death ligand 1 (PD-L1), while immune cells in the microenvironment were positive for PD-L1. Mutations in the MYD88 gene (MYD88) (L265P) and the CD79B gene (CD79B) were detected in five and one case, respectively. As therapeutic modalities used for PCNSLs differ from those that target conventional hemorrhagic neoplasms, full tissue diagnoses of all hemorrhagic CNS tumors are clearly warranted.

Isocitrate dehydrogenase (IDH) wild-type diffuse astrocytic tumors tend to be pathologically diagnosed as glioblastomas (GBMs). We previously reported that myoinositol to total choline (Ins/Cho) ratio in GBMs on magnetic resonance (MR) spectroscopy was significantly lower than that in IDH-mutant gliomas. We then hypothesized that a low Ins/Cho ratio is a poor prognosis factor in patients with GBMs, IDH-wild-type. In the present study, we calculated the Ins/Cho ratios of patients with GBMs and investigated their progression-free survival (PFS) and overall survival (OS) to determine their utility as prognostic marker. We classified patients with GBMs harboring wild-type IDH (n = 27) into two groups based on the Ins/Cho ratio, and compared patient backgrounds, pathological findings, PFS, OS, and copy number aberrations between the high and low Ins/Cho groups. Patients with GBMs in the low Ins/Cho ratio group indicated shorter PFS (P = 0.021) and OS (P = 0.048) than those in the high Ins/Cho group. Multivariate analysis demonstrated that the Ins/Cho ratio was significantly correlated with PFS (hazard ratio 0.24, P = 0.028). In conclusion, the preoperative Ins/Cho ratio can be used as a novel potential prognostic factor for GBM, IDH-wild-type.

BACKGROUND: In vestibular schwannoma (VS) patients treated with stereotactic radiosurgery (SRS), radiation-induced pseudoaneurysm is a rare long-term complication. To the best of our knowledge, there has been only one report of direct surgery in ruptured cases, and the optimal strategy for direct surgery is yet to be clarified. This case report describes a case of ruptured VS-related SRS-induced pseudoaneurysm that was successfully treated by direct surgery. CASE PRESENTATION: A 57-year -old man underwent SRS for VS, and the tumour was well controlled after the SRS. Nine years after the SRS, however, he developed subarachnoid haemorrhage, and a SRS-induced distal anterior inferior cerebellar artery aneurysm was detected on the surface of the tumour. During the trapping surgery, the aneurysm was embedded in the tumour, and it was difficult to separate the aneurysm and tumour. Besides, the facial nerve and tumour restricted exposure of the parent artery. The parent artery proximal to the aneurysm could only be exposed by resecting caudal part of the tumour. The aneurysm was trapped with permanent clips and it was pathologically diagnosed as pseudoaneurysm. CONCLUSION: It was suggested that the VS-related SRS-induced pseudoaneurysm is tightly adhered with surrounding structures and exposure of the parent artery could be limited due to the tumour and facial nerve. In this case report, we describe detailed intraoperative findings that will be useful for developing strategies for trapping surgery in future.

BACKGROUND: The World Federation of Neurosurgical Societies (WFNS) scale is widely accepted for predicting outcomes for subarachnoid hemorrhage (SAH) patients. However, it is difficult to definitely predict outcomes for the most poor grade, WFNS grade 5. The present study aimed to investigate the prognostic ability of a novel classification using computed tomography perfusion (CTP) findings, called the cortical blood flow insufficiency (CBFI) scores. METHODS: CTP was performed on admission for aneurysmal SAH followed by radical treatments within 72 hours of onset. Twenty-four cerebral cortex regions of interest (ROIs) were defined. CBFI was defined as Tmax > 4 s in each ROI, and CBFI scores were calculated based on the total number of ROIs with CBFI. Using the optimal cutoff value based on receiver operating characteristics (ROC) analysis to predict patient functional outcomes, CBFI scores were divided into "high" or "low" CBFI scores. Patient functional outcomes at 90 days were categorized based on modified Rankin Scale scores (0-3, favorable group; 4-6 unfavorable group) (0-4, non-catastrophic group; 5-6, catastrophic group). RESULTS: Fifty-seven patients were included in this study, of whom 21 (36.8%) and 13 (22.8%) were in the unfavorable and the catastrophic groups, respectively. A factor predicting unfavorable and catastrophic outcomes was CBFI score cutoff value of 7 points (area under the curve, 0.73 and 0.81, respectively). In multivariable logistic regression analysis for unfavorable outcome, high CBFI scores (odds ratio (OR), 8.6; 95% confidence interval (CI), 1.1-65.4; P = 0.04) and WFNS grade 5 (OR, 30.0; 95% CI, 4.5-201.0; P < 0.001) remained as independent predictors, while for catastrophic outcome, high CBFI scores (OR, 25.3; 95% CI, 3.3-194.0; P = 0.002) and age (OR, 1.1; 95% CI, 1.0-1.2; P = 0.02) remained as independent predictors. Conversely, WFNS grade 5 was not an independent predictor of catastrophic outcomes (OR, 3.8; 95% CI, 0.6-24.0; P = 0.15). In high CBFI scores, the OR of the delayed cerebral ischemia (DCI) occurrence was 9.6 (95% CI, 1.5-61.4; P = 0.02) after adjusting for age. CONCLUSION: High CBFI scores could predict unfavorable and catastrophic outcomes for aneurysmal SAH patients and DCI occurrence.

BACKGROUND: Although it is known that diploic veins frequently communicate with the dural venous sinuses, the role of diploic veins in patients with venous sinus invasion from meningiomas remains unknown. METHODS: We retrospectively examined the medical records of 159 patients who underwent their first craniotomies for intracranial meningiomas. Contrast-enhanced magnetic resonance imaging was used to evaluate diploic vein routes, and digital subtraction angiography (DSA) was used to evaluate diploic vein blood flow. When high blood flow was visualized concurrently with the venous sinuses, the veins were classified as of the "early type." Diploic vein routes were classified into five routes. RESULTS: DSA was performed in 110 patients, with 14 showing superior sagittal sinus (SSS) invasion (SSS group) and 23 showing non-SSS venous sinus invasion (non-SSS group). The proportion of early type diploic veins was significantly higher in the SSS group (27.1%) than in other patients (patients without venous sinus invasion, 2.1%; non-SSS, 4.3%) (p < 0.01). In patients not in the SSS group, diploic veins were sacrificed during craniotomy in 76 patients, including four patients with veins of the early type. No patients demonstrated new neurological deficits postoperatively. In the SSS group, diploic veins were sacrificed in all patients, and early type diploic veins were cut in five patients. Two of these five patients showed postoperative neurological deficits. CONCLUSIONS: In the SSS group, diploic veins may function as collateral venous pathways, and attention is recommended for their interruption. In patients without SSS invasion, diploic veins, even of the early type, can be sacrificed.

Resistance to temozolomide and intratumoral heterogeneity contribute to the poor prognosis of glioma. The mechanisms of temozolomide resistance can vary within a heterogeneous tumor. Temozolomide adds a methyl group to DNA. The primary cytotoxic lesion, O6-methylguanine, mispairs with thymine, leading to a futile DNA mismatch repair cycle, formation of double-strand breaks, and eventual cell death when O6-methylguanine DNA methyltransferase (MGMT) is absent. N7-methylguanine and N3-methyladenine are repaired by base excision repair (BER). The study aim was to elucidate temozolomide resistance mechanisms and identify methods to overcome temozolomide resistance in glioma. Several temozolomide-resistant clones were analyzed. Increased homologous recombination and mismatch repair system deficiencies contributed to temozolomide resistance. Inhibition of homologous recombination resensitized resistant cells with high homologous recombination efficiency. For the mismatch repair-deficient cells, inhibition of BER by PARP inhibitor potentiated temozolomide-induced cytotoxicity. Dianhydrogalactiol is a bifunctional DNA-targeting agent that forms N7-alkylguanine and inter-strand DNA crosslinks. Dianhydrogalactiol reduced the proliferation of cells independent of MGMT and mismatch repair, inducing DNA double-strand breaks and apoptosis in temozolomide-resistant cells. Further, inhibition of chk1 or homologous recombination enhanced dianhydrogalactiol-induced cytotoxicity in the cells. Selecting treatments most appropriate to the types of resistance mechanisms can potentially improve the prognosis of glioma.

Pial arteriovenous fistulas (AVFs) are rare vascular lesions; their exact pathophysiology is largely unknown. Pial AVFs have been reported to develop within capillary malformation-arteriovenous malformation (CM-AVM); however, only a few cases have been reported. Variants in the RASA1 gene have been reported as a cause of CM-AVM. We report the case of an adult patient with pial AVF, who carried variants in the RASA1 and COL4A2 genes. The patient in the current report was likely to have been affected by CM-AVM and the RASA1 variant seemed to be the primary factor in the pathogenesis of pial AVF. However, COL4A2 may have also contributed to the development of pial AVF because the COL4A2 and RASA1 variants have a common pathophysiology, wherein the patient develops lesions due to collagen type IV deficiency.

Seizures are common in patients with gliomas; however, the mechanisms of epileptogenesis in gliomas have not been fully understood. This study hypothesized that analyzing quantified metabolites using magnetic resonance spectroscopy (MRS) might provide novel insights to better understand the epileptogenesis in gliomas, and specific metabolites might be indicators of preoperative seizures in gliomas. We retrospectively investigated patient information (gender, age at diagnosis of tumor, their survival time) and tumor information (location, histology, genetic features, and metabolites according to MRS) in patients with gliomas. The data were correlated with the incidence of seizure and analyzed statistically. Of 146 adult supratentorial gliomas, isocitrate dehydrogenase (IDH) mutant tumors significantly indicated higher incidence of preoperative seizures than IDH wild-type gliomas. However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamate was not associated with high frequency of preoperative seizures in patients with gliomas. Instead, increased total N-acetyl-L-aspartate (tNAA) was significantly associated with them. Moreover, multivariable analysis indicated that increased level of tNAA was an independent predictor of preoperative seizures. According to MRS analysis, tNAA, rather than glutamate, might be a useful to detect preoperative seizures in patient with supratentorial gliomas.

The trigeminal nerve is often displaced by petroclival meningioma (PCM) compression, making it difficult to locate during PCM surgery. This study investigated whether the deviated position of the trigeminal nerve could be easily predicted using the main tumor feeding artery. We retrospectively examined 32 patients who underwent surgery for primary PCM. The deviation of the trigeminal nerve was classified as either Type 1 (displacement toward the back of the cerebellar tentorium), Type 2 (toward the back of the superior petrosal sinus), Type 3 (toward the back of the petrous apex dura), Type 4 (toward the inferior aspect of the tumor), or Type 5 (toward the surface of the brain stem). The main feeding artery was determined by preoperative angiography. The trigeminal nerve was classified as Type 2 in 60% of cases where the proximal tentorial artery (TA) was the main feeding vessel. The nerve was Type 5 where the distal portion of the TA was the main feeding vessel (60% of the cases). The nerves were Type 3 and Type 4 where the proximal inferior lateral trunk (ILT) (60%) and distal ILT (75%), respectively, were the main feeding vessels. In 66.7% of the cases where the dorsal meningeal artery was the main feeding vessel, the nerve was Type 3. Type 1 classification applied in all cases where the ascending pharyngeal artery was the main feeding artery. The main feeding artery can be used to predict trigeminal nerve transposition during PCM surgery.

OBJECTIVE: As chemotherapy and radiotherapy have developed, the role of a neurosurgeon in the treatment of metastatic brain tumors is gradually changing. Real-time intraoperative visualization of brain tumors by near-infrared spectroscopy (NIRS) is feasible. The authors aimed to perform real-time intraoperative visualization of the metastatic tumor in brain surgery using second-window indocyanine green (SWIG) with microscope and exoscope systems. METHODS: Ten patients with intraparenchymal brain metastatic tumors were administered 5 mg/kg indocyanine green (ICG) 1 day before the surgery. In some patients, a microscope was used to help identify the metastases, whereas in the others, an exoscope was used. RESULTS: NIRS with the exoscope and microscope revealed the tumor location from the brain surface and the tumor itself in all 10 patients. The NIR signal could be detected though the normal brain parenchyma up to 20 mm. While the mean signal-to-background ratio (SBR) from the brain surface was 1.82 ± 1.30, it was 3.35 ± 1.76 from the tumor. The SBR of the tumor (p = 0.030) and the ratio of Gd-enhanced T1 tumor signal to normal brain (T1BR) (p = 0.0040) were significantly correlated with the tumor diameter. The SBR of the tumor was also correlated with the T1BR (p = 0.0020). The tumor was completely removed in 9 of the 10 patients, as confirmed by postoperative Gd-enhanced MRI. This was concomitant with the absence of NIR fluorescence at the end of surgery. CONCLUSIONS: SWIG reveals the metastatic tumor location from the brain surface with both the microscope and exoscope systems. The Gd-enhanced T1 tumor signal may predict the NIR signal of the metastatic tumor, thus facilitating tumor resection.

Abstract Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.

BACKGROUND: The extent of resection has been reported to be associated with overall survival in gliomas. The use of 5-aminolevulinic acid (5-ALA) has been recognized to increase the extent of tumor resection. OBJECTIVE: To evaluate what factors affect the intraoperative fluorescence after administration of 5-ALA in gliomas. METHODS: Correlation of intraoperative fluorescence and several clinical, radiographic, molecular biologic, and histopathologic characters was retrospectively evaluated in 104 patients (53 males and 51 females; mean age 54.2 yr) with gliomas at our institution. To clarify the mechanisms that mutant isocitrate dehydrogenase (IDH) affect the intraoperative fluorescence, in Vitro experiments using genetically engineered glioma cells harboring mutant IDH1 were performed. RESULTS: Intraoperative fluorescence was observed in 82 patients (78.8%). In addition to age, magnetic resonance imaging enhancement, World Health Organization grades, and MIB-1 index, the status of IDH was revealed to be correlated with intraoperative fluorescence. In Vitro assay revealed that mutant IDH indirectly reduced the amount of exogenous 5-ALA-derived protoporphyrinogen IX in glioma cells by increasing activity of ferrochelatase and heme oxygenase 1. CONCLUSION: Mutant IDH1/2-induced metabolite changes of exogenous 5-ALA were suggested to contribute to the lesser intraoperative fluorescence in gliomas with mutant IDH1/2 than in those without.

The CIC-DUX4 translocation is the most common genetic alteration of small round cell sarcomas without EWSR1 rearrangement. These "Ewing-like sarcomas" usually occur in peripheral soft tissues, and rare primary central nervous system (CNS) tumors have been described. We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3-C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 10 months. Target RNA sequencing analysis revealed the CIC-DUX4 fusion gene. Methylation array analysis resulted in a diagnosis of "methylation class CNS Ewing sarcoma family tumor with CIC alteration". Although this tumor lacked characteristic histological features such as lobular structures in association with desmoplastic stroma, relatively uniform nuclei with prominent nucleoli and eosinophilic cytoplasm, which are often found in CIC-rearranged sarcomas of soft tissue, were identified. Recently, many CNS and soft tissue tumors require genetic analysis for precise diagnosis. To consider certain molecular testing, careful histological examination is essential.

Mechanical thrombectomy using a retrograde approach is performed for tandem occlusion of the internal carotid artery (ICA). In our patient, a guiding catheter was easily passed by the stenosed lesion despite severe stenosis at the ICA origin. Therefore, we aimed to recanalize the occlusion of the terminal ICA without angioplasty for the stenosed lesion. When contrast was injected, a massive extravasation of contrast from the C2 portion of the ICA was observed. It was speculated that the bleeding was caused by rupture of an aneurysm at that site due to increased intra-arterial pressure caused by the contrast injection to a blind alley, which was created by a wedged guiding catheter at severe stenosis at the ICA origin and the occlusion of the terminal ICA. Our simulation experiment using a silicon vascular model in this situation demonstrated that the elevation of intra-arterial pressure in such blind alley reached over 50, 100, and 200 mmHg by injection of contrast from a microcatheter, a 4-Fr inner catheter, and a 9-Fr balloon-guiding catheter, respectively. When a retrograde approach is planned for tandem occlusion of the ICA, even when the proximal lesion is easily passed, prior angioplasty for the proximal lesion should be considered to avoid wedging by catheter.

Background: Meningiomas often invade venous sinuses, but intravenous sinus meningiomas remain within the intracranial cavity. This case report describes an extremely rare case of tentorial meningioma with venous sinus invasion, extending intraluminally into the lower part of the internal jugular vein in a 59-year-old man.Case presentation: The patient's initial surgery involved the supratentorial component of a right tentorial meningioma, which invaded the right transverse and sigmoid sinuses. The supratentorial component of the tumour did not enlarge during the 2-month waiting period for the first surgery. The patient received postoperative radiation therapy for the residual tumour in the intravenous sinus. Despite radiation, the residual tumour developed caudally and ultimately extended into the right internal jugular vein. The average regrowth speed of the extracranial mass was 3.6 mm/month. The patient underwent surgery for the recurrent tumour located in the transverse sinus, sigmoid sinus, jugular bulb, and internal jugular vein, 46 months after the initial surgery. The pathological features of both surgeries were the same; WHO grade I meningothelial meningioma.Conclusions: To the best of our knowledge, there have been few case reports of benign meningioma with intraluminal extension into the internal jugular vein, and there have been no reports of long-term observation of such cases. Detailed observation of the present case suggests that the difference in growth speed between the intracranial and venous cavity depends on the surrounding environment.

According to the 2016 World Health Organization (WHO) classification of central nervous system tumors, diffuse astrocytic and oligodendroglial tumors are differentiated by the presence of isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation and the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q co-deletion). IDH-mutant astrocytoma often has p53 and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutation, showing the alternative lengthening of telomeres (ALT) phenotype, while IDH-mutant and 1p/19q-co-deleted oligodendroglioma often have wild-type p53 and telomerase reverse transcriptase (TERT) promoter mutation, showing telomerase activation. This study analyzed IDH, ATRX, and TERT promoter mutations, and the correlation between them. Immortalized cells overcome the telomere-related crisis by activating telomerase or ALT. In glioma, telomerase is mainly activated by TERT promoter mutation, while ALT is usually associated with ATRX mutation. Although the mechanism of how ATRX mutation induces ALT remains unclear, ATRX loss alone is believed to be insufficient to induce ALT. Treatments targeting telomere maintenance are promising.

BACKGROUND/AIM: Temozolomide (TMZ) induces prolonged arrest of human glioma cells in the G2/M phase and inhibition of the G2 checkpoint intensifies the effect of TMZ. These findings suggest that the G2 checkpoint is linked to DNA repair mechanisms. MATERIALS AND METHODS: To clarify the mechanism of TMZ resistance, we established TMZ-resistant (TR) clones by serial treatment of U87MG cells with TMZ. We evaluated TMZ-induced cell cycle arrest and the effect of various G2 checkpoint inhibitors. RESULTS: We observed that longer exposure (over 6 months) to TMZ enriched the proportion of TR clones that underwent only minimal G2 arrest following TMZ treatment compared to short exposure (4 months) to TMZ. Expression of MSH6 was reduced in these clones. None of the G2 checkpoint inhibitors could resensitize TR clones to TMZ. CONCLUSION: Longer drug treatment may induce resistance of cells to DNA damaging agent(s) by means of mismatch repair modification.

PURPOSE: Glioblastoma is an aggressive central nervous system tumor with a 5-year survival rate of < 10%. The standard therapy for glioblastoma is maximal safe resection, followed by radiation therapy and chemotherapy with temozolomide. New approaches to treatment of glioblastoma, such as targeting metabolism, have been studied. The object of this study is to evaluate whether asparagine could be a new target for treatment of glioblastoma. METHODS: We investigated a potential treatment for glioblastoma that targets the amino acid metabolism. U251, U87, and SF767 glioblastoma cells were treated with L-asparaginase and/or 6-diazo-5-oxo-L-norleucine (DON). L-asparaginase hydrolyzes asparagine into aspartate and depletes asparagine. L-asparaginase has been used for the treatment of acute lymphoblastic leukemia. DON is a glutamine analog that inhibits several glutamine-utilizing enzymes, including asparagine synthetase. RESULTS: Cell viability was measured after 72 h of treatment. MTS assay showed that L-asparaginase suppressed the proliferation of U251, U87, and SF767 cells in a dose-dependent manner. DON also inhibited the proliferation of these cell lines in a dose-dependent manner. Combined treatment with these drugs had a synergistic antiproliferative effect in these cell lines. Exogenous asparagine rescued the effect of inhibition of proliferation by L-asparaginase and DON. The expression of asparagine synthetase mRNA was increased in cells treated with a combination of L-asparaginase and DON. This combined treatment also induced greater apoptosis and autophagy than did single-drug treatment. CONCLUSION: The results suggest that the combination of L-asparaginase and DON could be a new therapeutic option for patients with glioblastoma.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Cortical blindness (CB) due to contrast-induced encephalopathy is a rare complication in endovascular procedure. Although exact mechanism is not known, disruption of blood-brain barrier (BBB) by contrast agent is supposed to be caused. We report two cases of contrast-induced encephalopathies after coil embolization of unruptured aneurysm. A 68-year-old woman with unruptured basilar artery aneurysm was treated with endovascular stent-assisted coil embolization. The procedure was successfully accomplished within 172 min using about 160 ml of contrast medium (iopamidol). However, she manifested with CB 3 h after the procedure and seizure on the next day. Immediate computed tomography revealed the cortical enhancement in both occipital lobes. Diffusion-weighted imaging-magnetic resonance imaging and fluid-attenuated inversion recovery sequence 1 day after the procedure revealed edema in both occipital lobes with no findings of ischemia or hyperperfusion. Electroencephalography showed sharp and slow waves in both occipital lobes. She required endotracheal intubation on day 2 to maintain airways and breathing. Her sensorium improved 4 days after the procedure with administration of steroid and anticonvulsant. She was extubated on day 4 after the procedure. She was discharged with persisting CB as a sequel.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. Background: We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. Methods: Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. Results: All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. Conclusions: The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

Abstract BACKGROUND The pharmacokinetics of temozolomide in patients with severe renal impairments (creatinine clearance less than 36 mL/min/m2) or in hemodialysis patients has not been investigated. Temozolomide and its metabolic products are mainly excreted in urine, as retention of these in the body may result in increased adverse events in hemodialysis patients harboring a high-grade glioma. METHODS Eight hemodialysis patients with high-grade gliomas from seven institutions were included in the study. Patient characteristics, treatment schedule, clinical course, pathological/molecular findings, and adverse events were evaluated. RESULTS The histopathological diagnoses were Isocitrate dehydrogenase (IDH) wild-type glioblastoma in four cases, Not other specified (NOS) glioblastoma in two cases and IDH-mutant anaplastic astrocytoma in one case. Five of the seven patients completed radiotherapy (48–60 Gy) with concomitant temozolomide (75 mg/m2) followed by adjuvant 5-day temozolomide (150 mg/m2) every 28 days. During the entire course of treatment with temozolomide, severe (Common Terminology Criteria for Adverse Events (CTCAE) more than grade 3) lymphocytopenia occurred in 57%(41.7–61%: non hemodialysis patients data, the same as below), neutropenia in 0%(1–15.4%) and thrombocytopenia in 14%(0–16.7%) of the patients. Generally, the frequency and degree of myelosuppression do not increase in hemodialysis patients with high-grade gliomas. Two of the seven (28.5%) patients died of infectious disease despite having no direct correlation to myelosuppression that is similar rate of 21.9% of the death results from infection in hemodialysis patients in Japan. CONCLUSIONS The high-grade glioma patients under study on hemodialysis did not require decreasing doses of Temozolomide during concomitant radiochemotherapy and maintenance therapy. However, careful clinical and hematological observation is required to avoid critical hematotoxicity and infection.

OBJECTIVE: To investigate the characteristics of materials used as prostheses for microvascular decompression surgery (MVDs) in Japan and their possible adverse events (AEs) to determine preferable materials for MVDs. METHODS: A questionnaire was sent to all members of the Japanese Society for MVDs, and answers were obtained from 59 institutions. RESULTS: Among a total of 2789 MVDs, 1088 operations for trigeminal neuralgia, 1670 for hemifacial spasm, and 31 others, including 117 reoperations, were performed between April 2011 and March 2014. Nonabsorbable material was used in 96.5% of MVDs, including polytetrafluoroethylene (PTFE) (80.5%), polyurethane (11.9%), expanded PTFE (2.1%), and silk thread (1.47%). The use of absorbable materials, including fibrin glue (87.5%), cellulose (13.5%), gelatin (4,77%), and collagen (1.76%), was reported. The major combinations were PTFE with fibrin glue (58.7%) followed by PTFE alone (7.60%). Eighty-eight AEs in 85 (3.2%) cases were reported among 2672 first operations. AEs included 51 central nervous system dysfunctions, 15 wound infections/dehiscence, and 10 others, which were presumed to be related to the intraoperative procedure. Among relatively high-, moderate-, and low-volume centers, there were no significant differences in the frequency of AEs (P = 0.077). Tissue-prosthesis adhesion and/or granuloma formation were reported in 13 cases of 117 reoperations. The incidence of adhesion-related recurrence was 11.1% of all reoperations. CONCLUSIONS: The number of AEs was quite low in this survey, and intradural use of any prosthesis reported in this paper might be justified; however, further development of easily handled and less-adhesive prosthesis materials is awaited.

OBJECTIVE: Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) and meningioma exhibit similar radiographic features; however, they differ in their prognoses. Preoperative differentiation between them is important for determining the treatment and follow-up plan. The aim of this study was to determine the factors that can be used to differentiate SFT/HPC from meningioma and World Health Organization (WHO) grade I from grade II meningioma. METHODS: The analysis included 84 cases: 5 of SFT/HPC, 72 of WHO grade I meningioma, and 7 of WHO grade II meningioma. Clinical characteristics and conventional magnetic resonance imaging, perfusion magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) LCModel parameters were evaluated via multivariate logistic regression analysis to identify the factors that distinguish SFT/HPC from meningioma. RESULTS: Patients with SFT/HPC were mostly men and were younger than those with meningioma. The percentage of T2-weighted images in meningioma was greater than that in SFT/HPC. There were significant differences between SFT/HPC and meningioma in levels of glutamate, phosphocholine, myo-inositol, or glycerophosphocholine + phosphocholine derived from long echo-time MRS, and myo-inositol derived from short echo-time MRS. Stepwise logistic regression analysis revealed that the age of <45 years and myo-inositol in short echo-time MRS of ≧6.347 were associated with a diagnosis of SFT/HPC with high sensitivity and specificity. However, no factors were found that differentiated WHO grade I meningioma from WHO grade II meningioma. CONCLUSIONS: Age and myo-inositol level calculated from MRS are useful factors for distinguishing SFT/HPC from meningioma preoperatively.

The genetic features of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade gliomas (LGGs; World Health Organization grades II and III) are not well defined. This study analyzed the genetic and other features of IDH-wt LGGs to develop a subclassification that can be used to predict their prognosis. Clinical, histopathological, and genetic features of 35 cases of diffuse IDH-wt astrocytoma and IDH-wt anaplastic astrocytoma were analyzed. The following genetic factors were examined: mutations of B-rapidly accelerated fibrosarcoma, telomerase reverse transcriptase promoter (TERTp), histone 3 family 3A, and alpha-thalassemia/mental retardation syndrome, X-linked; and copy number aberrations. In the univariate analysis, the following factors were associated with poor overall survival (OS): the histopathological diagnosis, TERTp mutation, the gain of chromosome 7 (+ 7), and the loss of chromosome 10q (- 10q). In the multivariate analysis, + 7, - 10q, and TERTp mutation were independent prognostic factors associated with poor OS. The median OS was significantly worse for patients who harbored at least one of these factors than for those without any of them (18.5 vs. 54.5 months, P = 0.002). The subclassification of IDH-wt LGGs according to the genetic factors + 7, - 10q, and TERTp mutation is potentially useful for predicting the prognosis.

BACKGROUND: Although the treatment strategies for malignant lymphomas and gliomas differ, it is usually difficult to preoperatively distinguish between them. Magnetic resonance spectroscopy (MRS) was recently reported to be useful for preoperative diagnoses; however, MRS data analysis using LCModel, which is a quantitative and objective method, was performed in only a few of the existing reports. METHODS: The clinical characteristics, conventional magnetic resonance imaging findings, and MRS parameters using LCModel were evaluated to identify the factors that can help distinguish between malignant lymphomas and enhanced gliomas. RESULTS: In total, 59 cases were evaluated, including 13 cases of malignant lymphoma, 1 case of pilocytic astrocytoma, 5 cases of grade Ⅱ glioma, 5 cases of grade Ⅲ glioma, and 35 cases of glioblastoma. There was no correlation between clinical characteristics (sex and age) and diagnosis. Neither T1- nor T2-weighted image was useful for differentiation between the 2 forms of tumors, but the apparent diffusion coefficient minimum value was useful for distinguishing malignant lymphomas from gliomas, with an area under the curve (AUC) value of 0.852. MRS analysis using LCModel revealed differences in glutamate (Glu), N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG), Glu + glutamine, and Lipid (Lip) 13a + Lip13b between malignant lymphomas and gliomas. The largest AUC was 0.904, which was obtained for the Glu level, followed by 0.883 and 0.866 for NAA + NAAG and Lip13a + Lip13b, respectively. CONCLUSIONS: Quantitative analysis of proton-MRS using LCModel is considered to be a valuable method for distinguishing between gliomas and malignant lymphomas.

Recent advance in molecular characterization of gliomas showed that patient prognosis and/or tumor chemosensitivity correlate with certain molecular signatures however, this information is available only after tumor resection. If molecular information is available by routine radiological examinations, surgical strategy as well as overall treatment strategy could be designed preoperatively.With the aim to establish an imaging scoring system for preoperative diagnosis of molecular status in lower-grade gliomas (WHO grade 2 or 3, LrGGs), we investigated 8 imaging features available on routine CT and MRI in 45 LGGs (discovery cohort) and compared them with the status of 1p/19q codeletion, IDH mutations, and MGMT promoter methylation. The scoring systems were established based on the imaging features significantly associated with each molecular signature, and were tested in the another 52 LrGGs (validation cohort).For prediction of 1p/19q codeletion, the scoring system is composed of calcification, indistinct tumor border on T1, paramagnetic susceptibility effect on T1, and cystic component on FLAIR. For prediction of MGMT promoter methylation, the scoring system is composed of indistinct tumor border, surface localization (FLAIR), and cystic component. The scoring system for prediction of IDH status was not established. The 1p/19q score ≥ 3 showed PPV of 96.2% and specificity of 98.1%, and the MGMT methylation score ≥ 2 showed PPV of 77.4% and specificity of 67.6% in the entire cohort.These scoring systems based on widely available imaging information may help to preoperatively design personalized treatment in patients with LrGG.