An analysis of 170 glioma patients and systematic review to investigate the association between IDH-1 mutations and preoperative glioma-related epilepsy

Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between IDH (isocitrate dehydrogenase) mutations and glioma-related epilepsy only recently been studied. The authors aimed to examine the correlations between IDH mutations in glioma patients with preoperative seizures and tumor location. A series of 170 glioma samples were analyzed for IDH1 R132H mutations (amino acid change from arginine to histidine at codon 132) with immunohistochemistry (IHC) staining and for IDH mutations with direct DNA sequencing when the IHC results were negative. If either the IHC or direct DNA sequencing result was positive, the IDH status was defined as mutated. The results of the IDH mutation examinations were used to analyze the relationship between mutations and glioma-related epilepsy. The study population consisted of 64 (37.6%) World Health Organization (WHO) grade II gliomas, 58 (34.1%) grade III, and 48 (28.3%) grade IV gliomas. A total of 84 samples with IDH1 mutations were observed in our study, and 54 of these presented with seizures as the initial symptoms, whereas 28 of the patients with wild-type IDH status presented with seizures (p = 0.043 for the WHO grade II gliomas, p = 0.002 for the grade III gliomas and p = 0.942 for the grade IV gliomas, chi-squared tests). Among the WHO grade II and III gliomas, IDH1 mutations were significantly associated with preoperative seizures, but no significant relationship between IDH mutations and preoperative seizures was found with glioblastoma multiforme.     

IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy

ObjectiveIsocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II–IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency.MethodsThis was a retrospective study. Patients with grades II–IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A — postoperative seizure freedom; Group B — 1–11 seizures over 12 months (less than one seizure per month); and Group C — greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data.ResultsOne hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12 months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p = 0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p = 0.032) and Group B (RR 9.70, p = 0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p = 0.004).SignificanceIn patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy.     

Overexpression of tissue microRNA10b may help predict glioma prognosis

We investigated the relationship between microRNA-10b (miR-10b) expression and prognosis in human glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-10b in 128 glioma and 20 normal brain tissues. Clinical information – age, sex, Karnofsky Performance Status (KPS) and World Health Organization (WHO) grade – were also collected. The associations between miR-10b expression and the clinicopathological factors and outcome of glioma patients were statistically analyzed. Expression levels of miR-10b in glioma tissue were significantly higher than in normal brain tissue (P < 0.001). High-grade glioma (WHO grade III and IV) had much higher miR-10b expression levels than low-grade tumors (WHO grade I and II). Additionally, the increased miR-10b expression in the glioma tissues was significantly associated with a low KPS (P = 0.03). Kaplan–Meier survival curves and Cox regression analyses showed that overexpression of miR-10b (P = 0.01) and high grade (P = 0.02) were independent factors predicting poor outcome for glioma patients. Furthermore, subgroup analyses showed that the miR-10b expression level was significantly associated with poor overall survival in glioma patients with high grades (P < 0.001). Up-regulation of miR-10b may have value in predicting clinical outcome in glioma patients, particularly for those with high pathological grades.     

Outcome of resection of WHO Grade II meningioma and correlation of pathological and radiological predictive factors for recurrence

This study investigated whether extent of surgical resection (Simpson and Shinshu grade) along with pathological and radiological factors influence the tumor control and recurrence-free survival (RFS) of patients with World Health Organization (WHO) grade II meningiomas. The clinical, radiological and surgical notes on the 59 patients with WHO grade II meningioma managed at our institution over 20 years were retrospectively reviewed. In this study, median survival time was 41 months. The overall recurrence rate in Simpson grades I and II resection was 31%. In grades III and IV, the overall recurrence rate was 73%, and this high recurrence rate in these groups was confined within 5 years. In Cox regression analysis, combined data of grades (I and II)/complete resection showed a significant difference in RFS compared to grades (III and IV)/subtotal resection (p = 0.0001). A similar trend of RFS (p = 0.0001) was observed with the Shinshu grading system of resection. In addition, a Ki-67% marker for proliferation less than 15% (p = 0.029), absence of certain radiological features including heterogeneous enhancement, cyst formation and peritumoral edema (p = 0.006), and repeat surgery for recurrent meningioma was associated with better survival (p = 0.014). However, radiosurgery did not have a beneficial role in the treatment of recurrence of atypical meningioma. The Simpson grading system is the primary predictor of recurrence of WHO grade II meningioma after resection. In addition, certain pathological and radiological features need to be considered as possible factors of recurrence after resection. Lastly, depending on the likely risks and surgical morbidity, repeat surgical resection should be performed for recurrent atypical meningioma.     

P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for seizure prophylaxis after glioma resection surgery: A meta-analysis

PurposeThe prognoses of seizure treatment with P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs after glioma resection surgery were investigated across several clinical studies. However, the results of these studies are inconsistent. We examined the relevant studies and conducted a meta-analysis of these two types of anti-epileptic drugs.MethodsA bibliography search using the EMBASE, MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials databases was performed to identify potentially relevant articles and conference abstracts that investigated the effects of non-enzyme-inducing antiepileptic drugs (NEIAEDs) and enzyme-inducing antiepileptic drugs (EIAEDs) on the seizure prognoses of glioma patients.ResultsOne RCT study and five observational studies were included. Pooled estimates of the relative risks (OR) and 95% confidence intervals (CI) were calculated. The pooled odds ratio for NEIAEDs vs. EIAEDs for patients with glioma was 1.12 (95% CI = 0.70–2.10). The pooled odds ratio for NEIAEDs vs. EIAEDs for low-grade gliomas was 1.77 (95% CI = 0.71–4.40). The pooled odds ratio for LEV vs. PHY was 1.459 (95% CI = 0.731–2.910).ConclusionsNo significant difference between the efficacies of P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for prophylactic late seizure treatment was observed. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.     

Seizure prognosis of patients with low-grade tumors

PurposeSeizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management.MethodsPatients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification.ResultsOf the 73 patients with low grade tumors and median follow up of 3.8 years (range 1–20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p = 0.03) and radiation therapy (p = 0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction.DiscussionSeizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and radiation therapy have a favorable impact on seizure outcome. Additional epilepsy surgery is effective.     

磁共振表观弥散系数及多体素磁共振波谱与脑胶质瘤增殖活性的相关性研究

目的探讨磁共振弥散加权成像(DWI)的表观弥散系数(ADC)值及多体素氢质子磁共振波谱(1H-MRS)所示代谢物比值与不同级别胶质瘤增殖活性的相关性及其应用价值。方法 2009年12月至2011年9月术前行DWI及多体素1H-MRS检查、术后病理学结果为脑胶质瘤病人40例,按照WHO标准分为低级别胶质瘤组(Ⅰ~Ⅱ级)与高级别胶质瘤组(Ⅲ~Ⅳ级),各20例;对比分析胶质瘤实质部位主要代谢物N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)比值(NAA/Cr、Cho/Cr、NAA/Cho)及ADC值、相对ADC(rADC)值在不同级别胶质瘤的变化及其与在相应肿瘤组织中Ki-67表达的相关性。结果高级别胶质瘤组Ki-67表达水平、Cho/Cr比值明显高于低级别胶质瘤组(P<0.01),而其ADC值、rADC值、NAA/Cr比值和NAA/Cho比值则明显低于低级别胶质瘤组(P<0.01)。相关分析表明,Cho/Cr值与Ki-67标记指数呈正相关(r=0.849,P<0.01);而NAA/Cho与NAA/Cr比值、ADC和rADC值均与Ki-67标记指数呈负相关(r分别为-0.944、-0.919、-0.935和-0.938,P<0.01)。结论多体素1H-MRS及DWI检查均能有效反应脑胶质瘤的增殖活性,其中瘤体的NAA/Cho比值的诊断价值最高,其联合瘤体的rADC值筛检可大幅提升MR对胶质瘤细胞增殖活性的诊断敏感性。     

Spinal ependymomas: Benefits of extent of resection for different histological grades

Although the World Health Organization (WHO) categorizes spinal ependymomas into three histological grades, difference in surgical outcomes between WHO grades I and II tumors are unclear. For these benign tumors, prognosis may be best determined by factors other than tumor grade alone, such as extent of resection. To analyze the effects of the extent of resection on different grades of spinal ependymomas, we performed a comprehensive literature review to identify adult spinal ependymoma patients who received surgical resection with a clearly identifiable WHO grade. A total of 175 patients were identified. While grade III tumors carried the worst prognosis as expected (p < 0.001), grade I and II tumors did not differ significantly in outcomes following surgery. Overall, gross total resection (GTR, 68.7%, 114/166) provided significantly improved progression-free survival (PFS, p < 0.001) and overall survival (OS, p = 0.022) compared to the subtotal resection group. Surprisingly, the highest GTR rate was achieved for grade II tumors (78.8%, 78/99; p < 0.001) followed by grade I (58.9%, 33/56) and grade III tumors (27.3%, 3/11). Interestingly, PFS was significantly improved by GTR for grade II tumors (p < 0.001), but not for grade I (p = 0.705). Similar trends, although not statistically significant, were found for OS. Our results show that while GTR provides the best overall outcomes, GTR is most effective for classic grade II ependymomas, but not for grade I ependymomas. Despite having a lower WHO grade, myxopapillary ependymomas have a lower GTR rate, and benefit less from GTR.     

Hippocampal-sparing radiotherapy: The new standard of care for World Health Organization grade II and III gliomas?

The neurocognitive effects of cranial radiotherapy in patients with gliomas are well-recognised and may be related to the dose delivered to the hippocampi. Intensity modulated radiotherapy (IMRT) is a radiotherapy technique that can be used to selectively spare the hippocampi without compromising the dose delivered to the tumour. This study aimed to evaluate if hippocampal-sparing IMRT is achievable in patients with World Health Organization (WHO) grade II and III gliomas. A retrospective review of consecutive patients with WHO grade II and III gliomas treated with IMRT at our institution between January 2009 and August 2012 was performed. Hippocampal-sparing was defined as a mean dose to at least one hippocampus of less than 30 Gy. The dose delivered to the tumour was never compromised to achieve the hippocampal dose constraint. Logistic regression analyses were performed to identify predictive factors for achieving hippocampal-sparing treatment. Eighteen patients were identified and hippocampal-sparing was achieved in 14 (78%). The median dose prescribed was 59.4 Gy in 33 fractions and 11 patients had WHO grade III gliomas. The mean dose to the contralateral hippocampus was 24.9 Gy. Planning target volumes less than 420.5 cm³ were more likely to enable hippocampal-sparing treatment to be given (hazard ratio 1.7, p = 0.03) and there was a trend with oligodendrogliomas and anaplastic oligodendrogliomas. Hippocampal-sparing radiotherapy is feasible in patients with WHO grade II and III gliomas. Oncologic outcomes are yet to be assessed prospectively. The relationship between hippocampal dose and neurocognitive function in adults is currently under investigation.     

Correlation of preoperative seizures with clinicopathological factors and prognosis in anaplastic gliomas: A report of 198 patients from China

PurposeSeizures are a common manifestation of many diseases and play an important role in the clinical presentation and quality of life (QOL) in patients with gliomas. The purpose of the present study was to investigate the possible correlation between tumor-related seizures and clinicopathological factors that influence preoperative seizure characteristics and relevant survival outcomes.MethodsWe retrospectively investigated the correlation of preoperative seizures with clinicopathological factors and prognosis in a cohort of 198 Chinese patients with anaplastic gliomas. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures. Survival function curves were calculated using the Kaplan–Meier method.ResultsOf the 198 patients, 68 (34.3%) patients had preoperative seizures. Among the patients with seizures, 26 (38.2%) had generalized seizures, 38 (55.9%) had simple partial seizures, and four (5.9%) complex seizures. There was a higher proportion of epidermal growth factor receptor (EGFR) amplification, frontal lobe involvement, left cerebral hemisphere involvement, and lower Ki-67 expression in patients with preoperative seizures in both univariate and multivariate analyses. Patients with preoperative seizures had a longer overall survival (OS) time compared with those without (median: 1924 days vs. 923 days, P = 0.048).ConclusionThe current study updates existing information on tumor-related seizures and clinicopathological factors in anaplastic gliomas, and suggests two putative biomarkers for preoperative seizures; Ki-67 expression and EGFR amplification. These factors may provide insights for developing effective treatment strategies aimed at prolonging patient survival.     

低级别胶质瘤复发再次术后癫痫预后危险因素分析

目的 探讨首次术后诊断为低级别胶质瘤复发并再次手术治疗后癫痫预后的危险因素。方法 回顾性分析2012年4月至2015年4月收治的复发并再次手术治疗的81例胶质瘤的临床资料。结果 81例中,43例再次术后病理诊断仍为低级别胶质瘤（无恶性转变组）,38例进展为高级别胶质瘤（恶性转变组）。再次术后12个月,无恶性转变组29例（35.8%）完全无癫痫发作（EngelⅠ级）,恶性转变组为26例（32.1%）。多因素Logistic 回归分析结果表明,肿瘤全切除是恶性转变组癫痫预后的良好指标（OR=0.171,95% CI为0.031~0.941,P=0.042）,肿瘤全切除（OR=0.09,95% CI为0.013~0.613;P=0.014）和Ki-67低表达（OR=0.064,95% CI为0.007~0.610;P=0.017）是无恶性转变组癫痫预后良好指标,而年龄≤38岁（OR=8.899,95% CI为1.615~60.667;P=0.013）是无恶性转变组癫痫预后不良指标。结论 肿瘤全切除、年龄>38岁以及Ki-67低表达是预测复发性低级别胶质瘤术后癫痫完全控制的良好因素,而在进展为高级别的胶质瘤中,仅有肿瘤全切除有助于癫痫完全控制。     

Symptom resolution in infiltrating WHO grade II-IV glioma patients undergoing surgical resection

Past studies of morbidity in patients with infiltrating gliomas have focused on the impact of surgery on quality of life. Surprisingly, little attention has been given to the rate at which the presenting symptoms improve after surgery, even though this is often the patient’s first concern. This study is an initial effort to provide useful information about symptom resolution and factors predicting persistence of symptoms in glioma patients who undergo surgery. We conducted a retrospective analysis on patients who underwent surgery for World Health Organization (WHO) grade II-IV astrocytoma/oligodendroglioma/oligoastrocytoma at our institution. All patients were seen 2–4 months postoperatively, and asked about the persistence of symptoms they experienced preoperatively. Symptoms reported in clinic were assessed against symptoms reported prior to surgery. Our study includes 56 consecutive patients undergoing surgery for gliomas. Of patients who experienced symptoms initially, headache resolved in 18/27 postoperatively, weakness resolved in 8/14 postoperatively, altered mental status resolved in 8/12 postoperatively, vision problems resolved in 7/11 postoperatively, nausea resolved in 5/7 postoperatively, and ataxia resolved in 4/5 postoperatively. Headache was more likely to resolve in patients with frontal or temporal tumors (p = 0.02). Preoperative Karnofsky Performance Scale (KPS) of 70 or less was associated with longer postsurgical hospital stay (p < 0.01). Younger patients were more likely to experience a resolution of altered mental status (p = 0.04). Our analysis provides data regarding the rate at which surgery alleviates patient symptoms and considers variables predicting likelihood of symptom resolution. Some patients will experience symptom resolution following resection of WHO grade II-IV gliomas in the months following surgery.     

Quality of life,mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group

ObjectiveBrain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated.Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n = 19) treated with Levetiracetam as an add-on.MethodsWe recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3 months and at 6 months.This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28–70) with uncontrolled partial-onset seizures treated with LEV as add-on.The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency.ResultsTwelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400 mg/die (mean final dose 300 mg/die). Four patients dropped out due to poor compliance and 1 for inefficacy.In the historical control group treated with LEV (mean final dose 2000 mg/die) 12 patients had high-grade gliomas, and 7 had low grade gliomas. Thirteen patients were in monotherapy and 6 in polytherapy with AEDs.In the 22 patients evaluable of 25 patients treated with LCM, we observed at final follow-up 7 patients seizure free, 12 with a significant reduction of seizures ≥ 50%, 2 stable and 1 patient with number of seizures increased.Mean seizure frequency at baseline compared with baseline period: the mean number of seizures significantly decreased from baseline (9.4) to final follow-up (1.2) (P = 0.005). The Responder Rate was 86.4%.Comparing responder rate of 22 evaluable patients with LCM with responder rate of 19 patients with LEV we didn't observe significant differences (p = 0.31).In our patients treated with LCM we didn't observe significant difference at 3 and 6 months in QoL tests results; we observe a significant reduction in the mean score of Karnofsky Performance Status (KPS) and Barthel Index (BI) between baseline and 6 months of follow-up (KPS p = 0.003; BI p = 0.007).No clinical side effects were observed.ConclusionComparing the LCM with the historical group treated with LEV in add-on, we observed that LCM seems to have a higher clinical efficacy than LEV.In our patients, we did not observe any significant changes in QoL tests, indicating stability in all quality of life domains explored, despite the objective worsening in their functional status. Although this is a small series with a relatively short follow-up, our data indicates that LCM in add-on in patients with BTRE appears to be as effective as LEV in add-on, without impact on mood and quality of life.     

TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas

Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein which is associated with tumor development and progression in a variety of epithelial carcinomas, while its expression and role in gliomas have not been considered. The aim of the study was to investigate TROP2 expression in malignant gliomas with different World Health Organization (WHO) classification and its correlation with tumor proliferation and angiogenesis. Immuohistochemistry was used to determine TROP2 and Ki-67 expression and microvessel density (MVD) in tumor specimens and normal brain tissues from 69 glioma patients and the relationship between TROP2 and Ki-67 and MVD was investigated. Immunohistochemistry results showed that the TROP2 expression was found in 59 (85.5 %) of the 69 tumor specimens, but no expression in normal brain tissues. Furthermore, TROP2 expression is significantly higher in WHO grade III (P = 0.025) and WHO grade IV (P = 0.011) gliomas than in WHO grade II gliomas. TROP2 expression correlates with Ki-67 (r = 0.676, P = 0.012) and MVD (r = 0.365, P = 0.035), but not with gender or age in human gliomas. These results suggested that the TROP2 correlated with malignancy, proliferation and angiogenesis in human gliomas. This is the first study describing TROP2 expression in gliomas and its proliferation and angiogenesis-related characteristic may serve as a potential therapeutic target for glioma treatment.     

IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom

IntroductionSeizures are the most common initial symptom in patients with low-grade glioma and their occurrence strongly depends on the tumor location. The majority of low-grade gliomas reveal mutations in the genes encoding isocitrate-dehydrogenase 1 (IDH1) or 2 (IDH2). These mutations are associated with metabolic changes that are potentially epileptogenic. We investigated the correlation between IDH1/2 mutations and tumor localization and seizure as the initial symptom.Materials and methodsThis retrospective study included patients with a diagnosis of WHO grade II astrocytoma and cortical infiltration and in whom initial symptoms were documented and biopsy tissue was available for IDH1/2 analysis. IDH1/2 mutation analysis was performed by direct sequencing or by immunohistochemistry with an antibody which detects mutated protein IDH1 R132H. Sequencing was carried out if immunohistochemistry was negative. IDH1/2 status was defined as mutated if either of these investigations were positive.ResultsSeventy-nine patients were included. IDH1 or IDH2 mutation was present in 63 (80%) patients who on average were younger than patients without IDH1/2 mutation (40 vs. 47 years, p = 0.0331, t-test). IDH1/2 mutations were associated with frontal tumor location (p = 0.0202). All 12 tumors in the insula revealed IDH1/2 mutations. Seizure as the initial symptom was recorded in 57 (72%) patients and was associated with IDH1 or IDH2 mutation by multivariate analysis (OR 22.563, p = 0.0019).ConclusionIn WHO grade II astrocytomas, IDH1/2 mutations mostly occur in tumors infiltrating the frontal lobe. Seizure as the initial symptom is associated with IDH1 or IDH2 mutation.     

胶质瘤中P53、EGFR、Ki-67及MGMT 的表达及临床意义

目的 探讨不同级别胶质瘤中P53、EGFR、Ki-67 及MGMT 的表达及临床意义.方法 应用免疫组织化学方法检测152 例胶质瘤中P53、EGFR、Ki-67 及MGMT 表达,统计分析上述蛋白的表达差异.结果 P53 在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为71.4%,73.1%和60.0%.95 例EGFR 阳性,其阳性表达率与染色强度均与病理级别呈正相关(P ＜0.01).Ki-67 均为阳性表达,Ki-67LI 在高级别胶质瘤中明显高于其在低级别胶质瘤中的表达水平(P ＜0.01).MGMT 阳性84 例,阴性68 例,在低级别胶质瘤和高级别胶质瘤之间的MGMT 表达无明显差异(P ＞0.05).结论 EGFR 和Ki-67 表达与肿瘤病理级别呈正相关,与胶质瘤恶性进展及预后差密切相关.P53 和MGMT 与肿瘤病理级别无明显相关性.检测有助于评估胶质瘤侵袭能力、增殖性,预测胶质瘤对放、化疗敏感性及判断分子靶向药物治疗是否有效.     

El insomnio y la pobre calidad de sueño se asocian a un mal control de crisis en pacientes con epilepsia

ObjectivesThis study aimed to assess the presence of sleep disorders in patients with epilepsy and to analyse their association with seizure control.MethodsWe performed a cross-sectional study of patients with epilepsy, recruited consecutively between September 2017 and December 2018. Patients were classified as having good seizure control (no seizures in the last 4 weeks) or poor seizure control (at least one seizure in the last 4 weeks). We performed intergroup comparisons for demographic and clinical data, insomnia (Insomnia Severity Index [ISI]), excessive daytime sleepiness (Epworth Sleepiness Scale [ESS]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), depression (Beck Depression Inventory-II [BDI-II]), and quality of life (Quality of Life in Epilepsy Inventory-10 [QOLIE-10]).ResultsThe sample included a total of 123 patients, of whom 31.7% had excessive daytime sleepiness (ESS ≥ 10), 50.4% had insomnia (ISI ≥ 10), and 53.6% had poor sleep quality (PSQI ≥ 5). According to our multivariate analysis, presence of seizures was associated with unemployment (odds ratio [OR] = 4.7; 95% confidence interval [CI], 1.36-19.2; P = .02), a higher number of antiepileptic drugs (OR = 5.87; 95% CI, 1.81-27.1; P < .001), insomnia (OR = 1.9; 95% CI, 1.1-9.3; P = .04), and poor sleep quality (OR = 2.8; 95% CI, 1.9-10.32; P = .01).ConclusionsSleep disorders are common in patients with epilepsy. Insomnia and poor sleep quality were associated with poor seizure control. These findings support the hypothesis that sleep disorders constitute a significant comorbidity of epilepsy, especially in patients with poor seizure control.     

Hemangiopericytoma: Radical resection remains the cornerstone of therapy

Hemangiopericytomas (HPC) are mesenchymal tumors with a propensity towards chronicity and metastasis. This study aimed to reflect a single institution experience with both World Health Organization (WHO) grade II and III HPC. Pathology records from the years 1990–2013 at the University of Washington were searched to identify tumors unequivocally classified as HPC. Electronic chart review was then utilized to collect pertinent patient data. Of the WHO grade II HPC, there were four men and two women (average age 52 years) while the grade III HPC group had eight men and two women (average age 51 years). Sixty-six percent of WHO grade II tumors were located in the middle or posterior fossa as compared to none of the grade III tumors. Survival analysis revealed a significant survival benefit for patients who underwent complete resection (223 months) versus those with subtotal resection (138 months, p < 0.05). Factors such as age, sex, the use of up-front radiation, and whether the patient had a recurrence did not show statistical significance related to overall survival or progression free survival. Radiation in the form of external beam radiotherapy given at the time of the first recurrence did trend towards improved progression free survival (56 months) compared to those patients who were not radiated (22 months, p = 0.09) All patients with radical resection went on to never have a recurrence. Our results indicate that HPC are tumors with limited response to radiation and best treated with aggressive resection. Future studies will determine whether molecular-based therapies may provide added adjuvant benefit.