The 5-Factor Modified Frailty Index as a More Useful Associated Factor Than Chronological Age After Unruptured Cerebral Aneurysm Surgery: A Nationwide Registry Study.

BACKGROUND: Although chronological age is associated with mortality and morbidity after surgery for unruptured cerebral aneurysms (UCAs), there is little evidence regarding an association between the simplified 5-factor modified frailty index (mFI-5) and postoperative outcomes based on age group. OBJECTIVE: To investigate the association of the mFI-5 score with worse outcomes, mortality, and complications in patients after surgery for UCA by chronological age groups using a Japanese national database. METHODS: This study included 32 902 patients with UCAs enrolled in a Japanese national database between 2011 and 2015. Age group (younger than 65 years, 65-74 years, and 75 years or older), sex, UCA location, treatment, medications, Barthel Index (BI), medical history, mFI-5 score, and in-hospital mortality and complications were evaluated. We identified risk factors for worsening BI score, in-hospital mortality, and overall postoperative complications in each age group. RESULTS: In total, 14 465 patients were enrolled in this study. Multivariable analysis showed that elderly groups and patients with an mFI-5 score ≥2 items were associated with worsening BI scores (odds ratio 1.95; 95% CI 1.52-2.51) and in-hospital complications (odds ratio 1.79; CI 1.49-2.15), despite having no association with in-hospital mortality. Multivariable analysis by age groups showed that the mFI-5 score ≥2 items was associated with in-hospital complications in all age groups, unlike chronological age in patients younger than 74 years. CONCLUSION: The mFI-5 score was a more useful associated factor of in-hospital complications than chronological age in patients younger than 74 years undergoing surgery for UCA.

Perioperative Surgical Risks in Patients With Hemangioblastomas: A Retrospective Nationwide Review in Japan.

BACKGROUND: The perioperative risk of sporadic hemangioblastomas (HBs) and von Hippel-Lindau disease (VHL)-associated hemangioblastomas (VHL-associated HBs) remains unclear due to the rare prevalence of HB. Therefore, this study aimed to clarify risk factors for better surgical management of patients with HBs. METHODS: A retrospective analysis of surgically treated HB patients registered in the Diagnosis Procedure Combination database of Japan, between 2010 and 2015, was performed. Age, sex, sporadic HBs or VHL-associated HBs, medical history, tumor location, hospital case load, postoperative complications, and Barthel index (BI) deterioration were assessed. We also evaluated the outcomes and factors of perioperative BI deterioration. RESULTS: In total, 676 patients with 609 intracranial lesions, 64 spinal lesions, and 3 with both types were eligible. Among them, 618 and 58 patients had sporadic HBs and VHL-associated HBs, respectively. The rates of perioperative BI deterioration were 12.5% and 12.2% for sporadic HBs and VHL-associated HBs, respectively. Perioperative mortality was 1.8% and 0% for sporadic HBs and VHL-associated HBs, respectively. Male sex, old age, high hospital case load, and medical history of diabetes mellitus were significantly associated with perioperative BI deterioration in all cases and sporadic HBs. Only medical history of diabetes mellitus was a significant risk factor for perioperative BI deterioration in VHL-associated HBs. CONCLUSIONS: No differences in perioperative BI deterioration rates between sporadic HBs and VHL-associated HBs were found. However, different risk factors for perioperative BI deterioration were identified. Consideration of these risk factors is recommended in all patients undergoing surgery for HB.

A nationwide registry study: The 5-factor modified frailty index of meningioma surgery in non-elderly and elderly patients.

OBJECTIVES: The simplified 5-factor modified frailty index (mFI-5) is a useful indicator of outcome for patients undergoing surgeries as frailty is considered an important risk factor in elderly patients. However, its usefulness has not been validated based on age groups. Therefore, we aimed to investigate risk factors, including the mFI-5, across age groups for complications and worse outcomes in meningioma surgery using data obtained from the nationwide database in Japan. METHODS: We extracted data from the nationwide registry database in Japan between 2010 and 2015. Age (< 65, 65-74, and ≥ 75 years), sex, Barthel Index (BI), mFI-5 scores, and complications were evaluated. Multivariate logistic regression analyses identified risk factors for worsening BI scores and complications after surgery across all age groups. RESULTS: Among 8138 included patients, an mFI-5 score ≥ 2 items was a significant risk factor for worsening BI scores in patients aged < 65 years (odds ratio: 2.3; 95 % confidence interval: 1.5-3.4), but not in patients aged 65-74 years and those aged ≥ 75 years, contrary to chronological age. Similar results were noted for any complications in patients aged < 65 years (2.5; 1.8-3.6) and aged 65-74 years (1.5; 1.1-2.1), but not in patients aged ≥ 75 years. CONCLUSION: Although the mFI-5 scores could predict the risk of in-hospital worsening outcomes, mortality, and complications, it was more useful in non-elderly patients aged < 65 years rather than in elderly patients aged ≥ 75 years, contrary to chronological age. Further prospective studies should be performed in the future to clarify the utility of the mFI-5.

Effect of region-wide use of prehospital stroke triage scale on management of patients with acute stroke.

BACKGROUND: Prehospital stroke triage scales help with the decision to transport patients with suspected stroke to suitable hospitals. OBJECTIVE: To explore the effect of the region-wide use of the Japan Urgent Stroke Triage (JUST) score, which can predict several types of stroke: large vessel occlusion (LVO), intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral infarction other than LVO (CI). METHODS: We implemented the JUST score and conducted a retrospective and prospective multicenter cohort study at 13 centers in Hiroshima from April 1, 2018, to March 31, 2020. We investigated the success rate of the first request to the hospital, on-scene time, and transport time to hospital. We evaluated the door-to-puncture time, puncture-to-reperfusion time, and 90-day outcome among patients with final diagnoses of LVO. RESULTS: The cohort included 5141 patients (2735 before and 2406 after JUST score implementation). Before JUST score implementation, 1269 strokes (46.4%) occurred, including 140 LVO (5.1%), 394 ICH (14.4%), 120 SAH (4.4%), and 615 CI (22.5%). The JUST score was used in 1484 (61.7%) of the 2406 patients after implementation, which included 1267 (52.7%) cases of stroke (186 LVO (7.7%), 405 ICH (16.8%), 109 SAH (4.5%), and 567 CI (23.6%)). Success rate of the first request to the hospital significantly increased after JUST score implementation (76.3% vs 79.7%, p=0.004). JUST score implementation significantly shortened the door-to-puncture time (84 vs 73 min, p=0.03), but the prognosis remained unaltered among patients with acute LVO. CONCLUSIONS: Use of prehospital stroke triage scales improved prehospital management and preparation time of intervention among patients with acute stroke.

Utility of intraoperative magnetic resonance imaging for giant cell tumor of bone after denosumab treatment: a pilot study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate but locally aggressive neoplasm. Current treatment of high-risk GCTB involves administration of denosumab, which inhibits bone destruction and promotes osteosclerosis. However, denosumab monotherapy is not a curative treatment for GCTB and surgical treatment remains required. Denosumab treatment complicates surgery, and the recurrence rate of GCTB is high (20%-30%). PURPOSE: To examine the utility of intraoperative magnetic resonance imaging (iMRI) for detection and reduction of residual tumor after denosumab treatment and to investigate the utility of iMRI, which is not yet widely used. MATERIAL AND METHODS: We enrolled five patients who received denosumab for a median period of eight months (range 6-12 months). Surgery was performed when the degree of osteosclerosis around the articular surface was deemed appropriate. We performed iMRI using a modified operation table to identify residual tumor after initial curettage and evaluated the rate of detection of residual tumor by iMRI, intraoperative and postoperative complications, exposure time of iMRI, and operation time. RESULTS: Suspected residual tumor tissue was identified in all five cases and was confirmed by histopathology after additional curettage. The rate of detection of residual tumor by iMRI was 100%. Residual tumor was located in sites which were difficult to remove due to osteosclerosis. The iMRI was performed safely and without trouble. During the median follow-up period of 10 months (range 6-24 months), no adverse events or recurrences occurred. CONCLUSION: Intraoperative MRI could contribute to the reduction of residual tumor tissue and it may prevent recurrence of GCTB after denosumab therapy.

The Japan Neurosurgical Database: Statistics Update 2018 and 2019.

Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.

Initiating an epilepsy surgery program with limited resources in Indonesia.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures were 9, 11 and 11 years (95% CI: 8.170-9.830, 10.170-11.830, and 7.265-14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.

In-Hospital Complications After Surgery in Elderly Patients with Asymptomatic or Minor Symptom Meningioma: A Nationwide Registry Study.

BACKGROUND: Asymptomatic or minor symptom meningiomas (AMSMs) in the elderly are incidental findings, with no consensus reached on the optimal management strategy. In the present study, we aimed to determine the surgical risk factors for elderly patients with AMSMs using a nationwide registry database in Japan. METHODS: We identified patients with surgically treated AMSMs using the Diagnosis Procedure Combination database from 2010 to 2015 and reviewed the medical records for age (<65 years; pre-elderly, 65-74 years; and elderly, ≥75 years), sex, Barthel index (BI) score, medical history, tumor location, and complications. An AMSM was defined by a BI score of 100 points at admission. The risk factors for all stroke complications, BI deterioration at discharge, and in-hospital mortality were determined using multivariate logistic regression analyses. RESULTS: From a total of 10,535 patients with meningioma, 6628 were included. Advanced age was a significant risk factor (odds ratio, 3.54; 95% confidence interval, 2.80-4.46) for BI deterioration but not for all-stroke complications or in-hospital mortality. Midline and posterior fossa tumors, diabetes mellitus, and chronic heart disease were significant risk factors for in-hospital mortality. CONCLUSIONS: For elderly patients with surgically treated AMSMs, advanced age was a prominent risk factor for functional decline at discharge. Our study identified several factors that should be evaluated before proceeding with surgery for AMSMs in elderly and pre-elderly patients. These findings could, not only improve decision-making among clinicians treating patients with AMSMs, but also help in predicting the results of surgery for elderly patients with AMSMs.

Detecting non-germinomatous germ cell tumor component by arterial spin labeling perfusion-weighted MR imaging in central nervous system germ cell tumor.

PURPOSE: Differentiating between germinoma and non-germinomatous germ cell tumor (NGGCT) is important because sensitivity to chemotherapy and/or radiotherapy is quite different between these two subgroups. In this study, we evaluated whether the arterial spin labeling (ASL) based perfusion-weighted imaging (PWI) could provide additional information for the differential diagnosis between germinoma and NGGCT. METHOD: Between 2011 and 2018, 20 patients with central nervous system (CNS) germ cell tumor (GCT) who underwent preoperative MR imaging including ASL-PWI were enrolled in this study. Relative tumor blood flow (rTBF) was evaluated on ASL-PWI by manually placing regions of interest at gadolinium enhanced part of the tumors and normal subcortical white matter. Presence of intratumoral T1 hyperintense foci and apparent diffusion coefficient (ADC) were also evaluated. The final diagnosis was made by the combination of tumor markers and the histological diagnosis. RESULTS: Among 20 patients of CNS-GCT, 11 were diagnosed as germinoma and 9 were diagnosed as NGGCT. In the germinoma subgroup, the rTBF ranged from 0.90 to 1.71 (mean 1.21, median 1.09), while it ranged from 1.14 to 5.75 (mean 3.91, median 3.31) in NGGCT subgroup. The receiver operating characteristic (ROC) curve showed that calculating rTBF is useful for differentiating between germinoma and NGGCT (area under the curve (AUC) 0.929, P = 0.0012) compared to intratumoral T1 hyperintense foci (AUC 0.788, P = 0.0304) and ADC (AUC 0.919, P = 0.0016). CONCLUSIONS: High rTBF obtained by ASL-PWI implied the presence of NGGCT component. This information might help in deciding the chemotherapy/radiotherapy intensity.

Spinal Osseous Epidural Arteriovenous Fistula with Intradural Reflux: A Case Report.

The authors report a rare case of spinal osseous epidural arteriovenous fistula (AVF) with intradural reflux. A 71-year-old lady with a past history of a T12 compression fracture and neurofibromatosis type 1 presented with progressive paraparesis. Magnetic resonance (MR) images of the thoracolumbar spine showed edema of the spinal cord and flow voids. Catheter angiography revealed segmental arteries from T11 to L1 feeding an AVF in the epidural space. The AVF drained not only into the epidural venous plexus but also into the perimedullary veins. Of note, there was an intraosseous drainage route that involved the basivertebral vein of T12. Under the diagnosis of spinal osseous epidural AVF with intradural reflux, surgical interruption of the intradural arterialized draining vein was performed. Spinal osseous epidural AVF with intradural reflux is rare with only four cases reported in the past. We believe that spinal osseous epidural AVF should be recognized as a variant of spinal epidural AVF.

Effects of Preservation of the Semispinalis Cervicis Inserted into C2 on Craniocervical Alignment After Laminoplasty.

OBJECTIVE: The preservation of nuchal musculature is essential for preventing axial pain and cervical malalignment after laminoplasty. A few studies have examined the effect of preservation of nuchal musculature on the degenerative progression after laminoplasty. We aimed to clarify the influence of preservation of the semispinalis cervicis inserted into C2 on cervical degenerative change and alignment after laminoplasty. METHODS: We retrospectively reviewed 106 consecutive patients who underwent C3-7 laminoplasty for cervical spondylotic myelopathy during 2006-2017. Patients were classified into 2 groups according to the preservation (P-group; n = 33) or detachment (D-group; n = 73) of the Semispinalis cervicis muscles inserted into the C2 spinous process. Parameters of cervical sagittal alignment, range of motion, and progressive degenerative changes next to or within the range of laminoplasty were evaluated in cervical spine radiographs, and magnetic resonance images obtained during follow-up period. RESULTS: In the D-group, the postoperative C2-7 Cobb angle significantly decreased (-0.06°/month), while the O-C2 Cobb angle significantly increased (0.07°/month). In addition, the C2-7 range of motion significantly decreased in the D-group (-0.12°/month). Degenerative changes in the laminoplasty range were found in 5 patients per group. Three patients from the D-group developed retroodontoid pseudotumors (P < 0.001). CONCLUSIONS: To maintain horizontal gaze, the craniocervical segment can compensate for the loss of lordosis by increasing the Cobb angle. Excessive compensation may exert mechanical stress on the atlantoaxial junction, contributing to the development of a retroodontoid pseudotumor. Preservation of the semispinalis cervicis inserted into C2 is critical for the prevention of malalignment after laminoplasty.

Radiological and Immunostaining Characteristics of H3.3 G34R-Mutant Glioma: A Report of 3 Cases and Review of the Literature.

INTRODUCTION: H3.3 G34R/V mutation is predominantly identified in the supratentorial nonmidline tumors. However, this tumor is not yet categorized as an entity in 2016 WHO CNS classification. More information is necessary to further determine the characteristics of this tumor. CASE PRESENTATION: Three cases of adolescent hemispheric glioma were treated in our institution. All tumors showed the characteristics of huge tumor size with mild peritumoral edema on T2WI/FLAIR, hyperintense on DWI, and slight partial enhancement by gadolinium. The single-voxel proton MR spectroscopy revealed characteristics of high choline peak, marked decrease in N-acetyl aspartate peak, and small lactate peak. The histopathological diagnosis, based on 2007 WHO CNS classification, was high-grade glioma in 2 cases and a PNET. Immuno-staining revealed that the tumor cells were positive against H3.3 G34R, H3K27me3, and p53 antibodies and negative against H3K27M, IDH1-R132H, ATRX, and Olig2 antibodies. Pyrosequencing analysis confirmed H3.3 G34R mutation, IDH-wildtype, and BRAF-wildtype. CONCLUSION: Radiological and immunostaining findings are characteristic in our 3 cases of H3.3 G34-mutant glioma. It is essential to consider H3.3 G34-mutant glioma as a differential diagnosis particularly in pediatric and adolescents and young adult hemispheric tumors.

Ion Channels and Their Role in the Pathophysiology of Gliomas.

Malignant gliomas are the most common primary central nervous system tumors and their prognosis is very poor. In recent years, ion channels have been demonstrated to play important roles in tumor pathophysiology such as regulation of gene expression, cell migration, and cell proliferation. In this review, we summarize the current knowledge on the role of ion channels on the development and progression of gliomas. Cell volume changes through the regulation of ion flux, accompanied by water flux, are essential for migration and invasion. Signaling pathways affected by ion channel activity play roles in cell survival and cell proliferation. Moreover, ion channels are involved in glioma-related seizures, sensitivity to chemotherapy, and tumor metabolism. Ion channels are potential targets for the treatment of these lethal tumors. Despite our increased understanding of the contributions of ion channels to glioma biology, this field remains poorly studied. This review summarizes the current literature on this important topic.

Cerebrospinal fluid ctDNA and metabolites are informative biomarkers for the evaluation of CNS germ cell tumors.

Serum and cerebrospinal fluid (CSF) levels of α-fetoprotein and ß-subunit of human chorionic gonadotropin are used as biomarkers for the management of central nervous system (CNS) germ cell tumors (GCTs). However, additional discriminating biomarkers are required. Especially, biomarkers to differentiate non-germinomatous germ cell tumors (NGGCTs) from germinomas are critical, as these have a distinct prognosis. We investigated CSF samples from 12 patients with CNS-GCT patients (8 germinomas and 4 NGGCTs). We analyzed circulating tumor DNA (ctDNA) in CSF to detect mutated genes. We also used liquid chromatography-mass spectrometry to characterize metabolites in CSF. We detected KIT and/or NRAS mutation, known as frequently mutated genes in GCTs, in 3/12 (25%) patients. We also found significant differences in the abundance of 15 metabolites between control and GCT, with unsupervised hierarchical clustering analysis. Metabolites related to the TCA cycle were increased in GCTs. Urea, ornithine, and short-chain acylcarnitines were decreased in GCTs. Moreover, we also detected several metabolites (e.g., betaine, guanidine acetic acid, and 2-aminoheptanoic acid) that displayed significant differences in abundance in patients with germinomas and NGGCTs. Our results suggest that ctDNA and metabolites in CSF can serve as novel biomarkers for CNS-GCTs and can be useful to differentiate germinomas from NGGCTs.

Preoperative sensory aura predicts risk for seizure in temporal lobe epilepsy surgery.

BACKGROUND: Patients with temporal lobe epilepsy (TLE) often report viscerosensory and experiential auras, with substantial epilepsy localization. However, few previous studies have investigated the epileptic preoperative aura, particularly with regard to its effect on surgical outcomes in patients with drug-resistant epilepsy. OBJECTIVE: This study investigated the potential role of preoperative aura in predicting outcomes after surgery for TLE. MATERIAL AND METHODS: This study included consecutive patients diagnosed with TLE who underwent anterior temporal lobectomy (ATL) for drug-resistant TLE during the period from January 1999 to December 2017. Data pertaining to patient age at the time of surgery, sex, age at initial seizure onset, duration of epilepsy, presence of preoperative aura, comprehensive clinical semiology, side of surgery, and type of pathology were analyzed. Preoperative auras were classified as autonomic, sensory, mental and affective, or multiple manifestations. Patients were followed at 3 and 12 months after surgery and at regular intervals thereafter. RESULTS AND CONCLUSIONS: A total of 498 patients were included in the study. Positive preoperative aura was observed in 386 patients (77.51%). The correlation of each variable with seizure outcomes was analyzed, and the only variable found to correlate with seizure outcome was the presence of preoperative aura. Compared with those with negative preoperative aura, those with positive preoperative aura were 1.74-fold more likely to be seizure-free after surgery for TLE. The analysis of patient data suggested a later onset of initial seizure in those with positive preoperative aura, compared with those without (p = 0.04, 95% confidence interval (CI): 0.55-3.24). Patients with a shorter duration of disease prior to TLE surgery were more likely to achieve seizure-free status postoperatively. Preoperative sensory aura was a good predictor that a patient would be seizure-free during follow-up (p = 0.022).

Risk Factor for Poor Outcome in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage Based on Post Hoc Analysis of the Modified WFNS Scale Study.

OBJECTIVE: There is currently no precise guide for the treatment and management of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). Thus, the aim of this study was to clarify the factors of poor outcome and mortality in elderly patients with aSAH. METHODS: In the modified World Federation of Neurosurgical Societies (mWFNS) scale study, 1124 patients were divided into 2 groups, elderly (age ≥65 years) and non-elderly (age <65 years), with aSAH investigated between October 2010 and March 2013 in Japan. The odds ratio (OR) and 95% confidence interval (CI) of each risk factor was calculated through multivariate logistic regression analysis for poor outcomes, as indicated by the modified Rankin Scale (mRS) score ≥3 and mortality at 3 months after onset in each group. RESULTS: Both groups demonstrated that the mWFNS scale was significant as a grade order risk factor for poor outcomes and mortality associated with disease. In the elderly group, risk factors for poor outcomes at 3 months after onset were older age (OR 1.10, 95% CI 1.06-1.14), male sex (OR 2.03, 95% CI 1.10-3.73), and severe cerebral vasospasm category (OR 10.13, 95% CI 4.30-23.87). Risk factors for mortality at 3 months after onset were older age (OR 1.06, 95% CI 1.01-1.11) and severe vasospasm category (OR 2.17, 95% CI 1.00-4.72). CONCLUSIONS: The mWFNS scale is a useful prognostic predictor for both non-elderly and elderly patients with aSAH. Elderly male patients with aSAH presenting with severe vasospasm should be managed more carefully.

Radiology Profile as a Potential Instrument to Differentiate Between Posterior Fossa Ependymoma (PF-EPN) Group A and B.

OBJECTIVE: Posterior fossa ependymoma (PF-EPN) was categorized into PF-EPN-A and PF-EPN-B subgroups based on the DNA methylation profiling. PF-EPN-A was reported to have poorer prognosis compared with PF-EPN-B. In this study, we particularly evaluated preoperative imaging to distinguish PF-EPN-A from PF-EPN-B. METHODS: Sixteen cases of PF-EPN were treated in our institution from 1999 to 2018. The patients were divided into PF-EPN-A and PF-EPN-B groups based on H3K27me3 immunostaining positivity. We evaluated progression-free survival, overall survival, as well as preoperative magnetic resonance imaging and computed tomography scan images in both groups. Based on T1WI and Gd-T1WI magnetic resonance images, the tumor contrast rate was determined from dividing the volume of gadolinium enhanced tumor by the overall tumor volume. RESULTS: Nine cases (4 male, 5 female) were grouped as PF-EPN-A, and 7 (4 male, 3 female) as PF-EPN-B. The median age of PF-EPN-A and PF-EPN-B were 4 and 43 years old, respectively. In the PF-EPN-A group, the progression-free survival median value was 32.6 months, and the overall survival median was 96.9 months. In contrast, PFS in PF-EPN-B did not reach a median value (P < 0.05) and all the patients were alive (P < 0.05) at the end of the study. With imaging, tumor contrast rate in PF-EPN-B was more than 50% and significantly different from PF-EPN-A (P = 0.0294). Calcification was mainly observed in PF-EPN-A, whereas cystic formation was only seen in PF-EPN-B. CONCLUSIONS: Contrast rate less than 50%, based on the magnetic resonance images, was characteristic in the PF-EPN-A group. Comparatively, cystic component and absence of calcification were more characteristic in the PF-EPN-B group.

Surgery for Radiologically Normal-Appearing Temporal Lobe Epilepsy in a Centre with Limited Resources.

Approximately 26-30% of temporal lobe epilepsy (TLE) cases display a normal-appearing magnetic resonance image (MRI) leading to difficulty in determining the epileptogenic focus. This causes challenges in surgical management, especially in countries with limited resources. The medical records of 154 patients with normal-appearing MRI TLE who underwent epilepsy surgery between July 1999 and July 2019 in our epilepsy centre in Indonesia were examined. The primary outcome was the Engel classification of seizures. Anterior temporal lobectomy was performed in 85.1% of the 154 patients, followed by selective amygdalo-hippocampectomy and resection surgery. Of 82 patients (53.2%), Engel Class I result was reported in 69.5% and Class II in 25.6%. The median seizure-free period was 13 (95% CI,12.550-13.450) years, while the seizure-free rate at 5 and 12 years follow-up was 96.3% and 69.0%, respectively. Patients with a sensory aura had better seizure-free outcome 15 (11.575-18.425) years. Anterior temporal lobectomy and selective amygdala-hippocampectomy gave the same favourable outcome. Despite the challenges of surgical procedures for normal MRI TLE, our outcome has been favourable. This study suggests that epilepsy surgery in normal MRI TLE can be performed in centres with limited resources.

Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone.

PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.