Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma.

PURPOSE: The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. METHODS: We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. RESULTS: Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88 years vs. 6.80 years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23 years vs. 10.69 years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). CONCLUSION: Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

T2-FLAIR mismatch sign correlates with 11C-methionine uptake in lower-grade diffuse gliomas.

PURPOSE: The T2-FLAIR mismatch sign is recognized as an imaging finding highly suggestive of IDH-mutant astrocytomas. This study was designed to determine whether the T2-FLAIR mismatch sign correlates with uptake of 11C-methionine in lower-grade gliomas. METHODS: We included 78 histopathologically verified lower-grade gliomas (grade 2: 31 cases, grade 3: 47 cases) in this study. 78 patients underwent 11C-methionine positron emission tomography (MET-PET) scans and magnetic resonance (MR) imaging scans prior to histological diagnosis. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. MR imaging scans were evaluated for the presence of the T2-FLAIR mismatch sign by three independent reviewers. We compared molecular status, the T2-FLAIR mismatch sign and 11C-methionine uptake among patients with different lower-grade glioma molecular types. RESULTS: The 78 lower-grade gliomas were assigned to one of three molecular groups: Group A (IDH-mutant and 1p/19q non-codeleted, n = 22), Group O (IDH-mutant and 1p/19q codeleted, n = 20), and Group W (IDH wildtype, n = 36). T2-FLAIR mismatch was found in 16 cases (20.5%) that were comprised of 8 (36.4%), 0 (0%), 8 (22.2%) cases in the molecular group A, O and W, respectively. The median T/N ratio of MET-PET in tumors with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.83, p < 0.001, Mann-Whitney U test). In the Groups A and W (excluding Group O), the median T/N ratio on MET-PET in groups A and W (but not group O) with T2-FLAIR mismatch was 1.50, which was significantly lower than that of tumors without T2-FLAIR mismatch (1.81, p = 0.002, Mann-Whitney U test). CONCLUSION: The T2-FLAIR mismatch sign correlated with lower 11C-methionine uptake in lower grade gliomas.

Temporal virtual reality-guided, dual-task, trunk balance training in a sitting position improves persistent postural-perceptual dizziness: proof of concept.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a newly defined disorder characterized by functional dizziness. Due to its recent discovery, definitive treatment for PPPD has not been established; therefore, this study aimed to assess the effectiveness of virtual reality (VR)-guided, dual-task, trunk balance training for the management of PPPD using the mediVR KAGURA system. METHODS: We analyzed data of patients who presented with PPPD from January 1, 2021, to February 28, 2021. The VR group included patients who underwent mediVR KAGURA-guided training for 100 tasks (10 min). Patients with PPPD who received standard treatment and rehabilitation were assigned to the control group. Equilibrium tests were performed at baseline and immediately after mediVR KAGURA-guided training to examine its effectiveness in improving static and dynamic balance. Additionally, clinical questionnaires related to balance disorders were administered at baseline and 1 week after mediVR KAGURA-guided training to examine its effects on balance-related symptoms. The primary outcome was improvements in static and dynamic balance and Niigata PPPD Questionnaire (NPQ) scores. RESULTS: VR-guided training using mediVR KAGURA improved objective outcomes, including static and dynamic postural stability, after a single 10-min training session. Additionally, mediVR KAGURA-guided training improved scores on the Hospital Anxiety and Depression Scale and NPQ 1 week after the 10-min training session. CONCLUSION: VR-guided training using mediVR KAGURA represents a viable method for managing balancing ability, anxiety, and symptoms in patients with PPPD. Such training provides a safe and cost-effective solution for PPPD management. Further studies are required to evaluate the clinical efficacy of this strategy. TRIAL REGISTRATION: Institutional Ethics Committee of Kitano Hospital, approval number: 1911003. Registered 18 December 2019, https://kitano.bvits.com/rinri/publish_document.aspx?ID=426 .

TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma.

The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

[A Case of Cerebral Tuberculoma].

Cerebral tuberculoma is a rare and serious form of tuberculosis. Despite advancements in imaging and laboratory diagnostics, it is challenging to diagnose cerebral tuberculoma due to its insidious nature and nonspecific findings. A 56-year-old woman was referred to our hospital for headaches. The patient had previously undergone treatment for pulmonary tuberculosis, which had been completely cured 2 months prior to presentation. Brain MRI revealed an enhanced mass lesion with surrounding edema in the right frontal lobe. Although a mild increase in the serum carcinoembryonic antigen(CEA)level and a moderate accumulation of FDG on FDG-PET indicated inflammatory changes or a malignant brain tumor, other imaging and laboratory findings were nonspecific. The mass lesion was indistinguishable from a brain tumor. Hence, the patient underwent surgical removal, and the pathological diagnosis was tuberculoma. In patients with a history of tuberculosis, cerebral tuberculoma should be considered in the differential diagnosis of intracranial mass lesions, even if the original lesion is completely cured. A mild increase in the serum CEA level and a moderate accumulation of FDG on FDG-PET were considered indicative of intracranial inflammation and consistent with cerebral tuberculoma.

[Clinical Findings of Thalamic and Brainstem Glioma Including Diffuse Midline Glioma, H3K27M Mutant:A Clinical Study].

BACKGROUND: Diffuse midline glioma, H3K27M mutant is a glioma located in the thalamus, brainstem, or spine with the H3K27M mutation, which is a new entity in the 2016 revised WHO classification. The treatment of thalamic glioma(TG)and brainstem glioma(BSG), which includes diffuse midline gliomas, the H3K27M mutant is challenging, and there are no standard therapeutic strategies. It is important to determine the characteristics of these brain tumors. Here, we retrospectively reviewed 31 consecutive patients with TG and BSG who were treated at our institute between January 1994 and May 2018, including methionine-positron emission tomography(MET-PET)data. RESULTS: Fourteen patients had TG, while 17 patients had BSG. Six patients were children, and 25 were adults. Nine patients with TGs and seven with BSG were enhanced by gadolinium. Twenty-seven patients were treated with radiotherapy, and 20 patients were treated with chemotherapy. All 21 tumors that underwent surgery showed wild-type IDH. The H3K27M mutation was present in four TG and two BSG. There was no statistically significant association between methionine uptake and gadolinium contrast enhancement and tumor grade. The median overall survival period(OS)of all cases was 16.9 months, whereas those of TG and BSG were 22.8 and 10.0 months, respectively. CONCLUSION: Because TG and BSG still have poor prognoses, it is necessary to elucidate the pathology of the disease and establish its standard therapy.

[Cerebellar Glioblastoma with Intrathecal Dissemination:A Report of Four Cases].

Primary cerebellar glioblastoma is a rare disease that accounts for 0.4-3.4% of glioblastoma multiforme(GBM)cases. The clinicopathological characteristics and prognosis of primary cerebellar GBM are not well understood due to its rarity and the lack of an established treatment strategy. To elucidate the prognostic factors and dissemination pattern, we retrospectively assessed four cases of cerebellar GBM that we treated between 2003 and 2013. All cases involved men, and the age range was 53 to 76 years(median 69.5 years);each patient underwent surgical removal and received adjuvant chemotherapy or radiotherapy. Every cerebellar GBM patient developed intrathecal dissemination at every stage of cerebellar GBM. Two patients had spinal metastases with tumor recurrence, and no patient had brain stem invasion. IDH1 mutation and MGMT expression were both negative in three cases. The median overall survival of cerebellar GBM patients was 13.8 years, and the median progression-free survival was 5.5 years, which is similar to that reported in previous reports-and similar in terms of results-for supratentorial GBM treated at the same time at our institution. In conclusion, the prognosis of cerebellar GBM appears to be similar to that of supratentorial GBM;however, the pattern of tumor progression, such as intrathecal dissemination, is different. Craniospinal irradiation on cerebellar GBM should be carefully considered with frequent follow-up by whole spine survey using MRI.

[Effectiveness of Color-Coded Doppler Ultrasonography for Detecting the Trajectory in the Surgical Management of Distal ACA Aneurysms].

Distal anterior cerebral artery(DACA)aneurysms are relatively rare. The detection of the surgical trajectory of DACA aneurysmal clipping is difficult because DACA aneurysms are located at various sites in the ACA. The purpose of this study was to evaluate the effectiveness of intraoperative use of color Doppler ultrasonography for the surgery of DACA aneurysms. DACA aneurysms of ten patients(three men, seven women;64.5 years old on median)were examined using intraoperative color Doppler imaging(CDI), which was performed before microscopic procedures, to detect the location of the aneurysms. Among them, six patients had ruptured aneurysms with diameters ranging from 2.5 to 10.8mm, and four of them had intracerebral hematomas. All the aneurysms and surrounding arteries were clearly detected using CDI. Moreover, in larger aneurysms, blood flow dynamics inside the aneurysm were also observed using CDI. As a result, we concluded that the intraoperative use of color Doppler ultrasonography was effective of detecting the trajectory for the DACA aneurysms without causing any damage to the brain by redundant dissections.

[A Rare Case of Radiation-Induced Meningioma that Occurred Only 3 Years and 6 Months after Radiation Therapy for Oligodendroglioma].

We describe an adult case of radiation-induced meningioma(RIM)that was identified within a short interval from the initial treatment for brain tumor. A 45-year-old woman, who had tumor resection followed by radiation therapy for right frontal oligodendroglioma, showed a small enhanced lesion on the right frontal region 3 years and 6 months after the initial radiation therapy. The pathological diagnosis was meningioma(World Health Organization(WHO)grade I)and the Ki-67 labeling index was 3.2%. Most RIMs occur after a long period of time(18.7-24.0 years on average)following radiation therapy. Several studies have suggested that the period before the occurrence of RIM is correlated with both the age of a patient and the radiation dose at the time of radiation therapy. A patient that receives a higher dose of radiation at a younger age has a higher risk of RIM occurrence. In this case, the patient was middle aged;however, she was exposed to a high dose of radiation(54 Gy). High-dose radiation might induce the early onset of RIM. Recently, treatments for glioma have been developed, thus resulting in an increased long-term survival rate among patients. Physicians must pay attention not only to the recurrence of gliomas but also to the occurrence of RIMs.

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas.

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.

LAPTM4B-35 is a novel prognostic factor for glioblastoma.

Lysosome-associated protein transmembrane-4 beta (LAPTM4B)-35, a newly identified cancer-associated gene, is overexpressed in a wide variety of malignant tumors. However, studies of its expression and role in glioma have not yet been reported. This study aimed to investigate the expression and the role of LAPTM4B-35 in glioma and to assess its value as a prognostic factor. Seventy-seven glioma cases (Grade II in 18 patients, Grade III in 16 and Grade IV in 43) were immunohistochemically examined for LAPTM4B-35, pAkt, factor VIII and Ki-67 expressions. The LAPTM4B-35 expression score of Grade II gliomas was lower than those of Grade III-IV gliomas (p < 0.05), while the difference between Grade III and IV gliomas was not statistically significant. Of the 43 patients with glioblastoma (GBM), 27 (62.8%) had high LAPTM4B-35 expression, which was associated with high tumor micro-vessel density and pAkt activation. The median progression-free survival (PFS) of GBM patients with high LAPTM4B-35 expression was 5.13 months, significantly shorter than that of those with low LAPTM4B-35 expression (12.0 months, p < 0.0001). The median overall survival (OS) of GBM patients with high LAPTM4B-35 expression was 12.5 months, again significantly shorter than that of those with low LAPTM4B-35 expression (29.6 months, p < 0.0001). Multivariate analysis indicated LAPTM4B-35 to be an independent prognostic factor for PFS and OS of GBM patients. Our findings show LAPTM4B-35 to be strongly associated with tumor proliferation, tumor angiogenesis and poor outcomes of GBM patients, suggesting LAPTM4B-35 to potentially be applicable as a novel prognostic marker and even to possibly play a role in improving GBM treatment.

Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy.

Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.

Antiangiogenic variant of TSP-1 targets tumor cells in glioblastomas.

Three type-1 repeat (3TSR) domain of thrombospondin-1 is known to have anti-angiogenic effects by targeting tumor-associated endothelial cells, but its effect on tumor cells is unknown. This study explored the potential of 3TSR to target glioblastoma (GBM) cells in vitro and in vivo. We show that 3TSR upregulates death receptor (DR) 4/5 expression in a CD36-dependent manner and primes resistant GBMs to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced caspase-8/3/7 mediated apoptosis. We engineered human mesenchymal stem cells (MSC) for on-site delivery of 3TSR and a potent and secretable variant of TRAIL (S-TRAIL) in an effort to simultaneously target tumor cells and associated endothelial cells and circumvent issues of systemic delivery of drugs across the blood-brain barrier. We show that MSC-3TSR/S-TRAIL inhibits tumor growth in an expanded spectrum of GBMs. In vivo, a single administration of MSC-3TSR/S-TRAIL significantly targets both tumor cells and vascular component of GBMs, inhibits tumor progression, and extends survival of mice bearing highly vascularized GBM. The ability of 3TSR/S-TRAIL to simultaneously act on tumor cells and tumor-associated endothelial cells offers a great potential to target a broad spectrum of cancers and translate 3TSR/TRAIL therapies into clinics.

Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors.

Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic marker for germinoma with syncytiotrophoblastic giant cells (STGC) and choriocarcinoma. Elevated hCG in germinoma is considered to predict less favorable prognosis, and an intensive treatment strategy may accordingly be applied. However, there is some evidence that any germinoma may produce hCG to varying extent. We investigated mRNA expression of the hCG ß subunit (hCGß) using real time quantitative polymerase chain reaction in 94 germ cell tumors (GCTs). Most (93.3 %) GCTs showed higher expression levels compared with that of normal brain tissue (1.09 × 10(0)-1.40 × 10(5) fold). The expression was the highest in GCTs which harbor choriocarcinoma or STGC components. The expression level of hCGß in germinoma was highly variable (1.09 × 10(0)-5.88 × 10(4) fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF correlated with gene expression, especially when GCTs with single histological component were analyzed separately. The expression was not significantly associated with recurrence in pure germinoma. These results suggest that the serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear to have the capacity of producing hCG irrespective of their histology. The clinical significance of ubiquitous hCG expression in GCTs needs further investigation.

Multimechanistic tumor targeted oncolytic virus overcomes resistance in brain tumors.

Only a subset of cancer patients inoculated with oncolytic herpes simplex virus (oHSV) type-1 has shown objective response in phase 1 and 2 clinical trials. This has raised speculations whether resistance of tumor cells to oHSV therapy may be a limiting factor. In this study, we have identified established and patient derived primary glioblastoma multiforme (GBM) stem cell lines (GSC) resistant to oHSV and also to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that has recently shown promise in preclinical and initial clinical studies. We created a recombinant oHSV bearing a secretable TRAIL (oHSV-TRAIL) and hypothesized that oHSV-TRAIL could be used as a cancer therapeutic to target a broad spectrum of resistant tumors in a mechanism-based manner. Using the identified resistant GBM lines, we show that oHSV-TRAIL downregulates extracellular signal-regulated protein kinase (ERK)-mitogen-activated protein kinase (MAPK) and upregulates c-Jun N-terminal kinase (JNK) and p38-MAPK signaling, which primes resistant GBM cells to apoptosis via activation of caspase-8, -9, and -3. We further show that oHSV-TRAIL inhibits tumor growth and invasiveness and increases survival of mice bearing resistant intracerebral tumors without affecting the normal tissues. This study sheds new light on the mechanism by which oHSV and TRAIL function in concert to overcome therapeutic-resistance, and provides an oncolytic virus based platform to target a broad spectrum of different cancer types.

Impact of [11C]methionine PET with Bayesian penalized likelihood reconstruction on glioma grades based on new WHO 2021 classification.

OBJECTIVE: The uptake of [11C]methionine in positron emission tomography (PET) imaging overlapped in earlier images of tumors. Bayesian penalized likelihood (BPL) reconstruction increases the quantitative values of tumors compared with conventional ordered subset-expectation maximization (OSEM). The present study aimed to grade glioma malignancy based on the new WHO 2021 classification using [11C]methionine PET images reconstructed using BPL. METHODS: We categorized 32 gliomas in 28 patients as grades 2/3 (n = 15) and 4 (n = 17) based on the WHO 2021 classification. All [11C]methionine images were reconstructed using OSEM + time-of-flight (TOF) and BPL + TOF (ß = 200). Maximum standardized uptake value (SUVmax) and tumor-to-normal tissue ratio (T/Nmax) were measured at each lesion. RESULTS: The mean SUVmax was 4.65 and 4.93 in grade 2/3 and 6.38 and 7.11 in grade 4, and the mean T/Nmax was 7.08 and 7.22 in grade 2/3 and 9.30 and 10.19 in grade 4 for OSEM and BPL, respectively. The BPL significantly increased these values in grade 4 gliomas. The area under the receiver operator characteristic (ROC) curve (AUC) for SUVmax was the highest (0.792) using BPL. CONCLUSIONS: The BPL increased mean SUVmax and mean T/Nmax in lesions with higher contrast such as grade 4 glioma. The discrimination power between grades 2/3 and 4 in SUVmax was also increased using [11C]methionine PET images reconstructed with BPL.

Combined extradural subtemporal and anterior transpetrosal approach to tumors located in the interpeduncular fossa and the upper clivus.

BACKGROUND: Central skull base lesions in the interpeduncular fossa and the upper clival regions can be challenging to access because of their location anterior to the brainstem. We have modified the anterior transpetrosal approach by combination with the extradural subtemporal route to increase the surgical corridor. METHODS: Thirty-seven patients underwent surgical treatment via the anterior transpetrosal approach from 2002 to 2012. The combined surgical approach was primarily applied when the tumors arose from the upper clival portion and extended to the interpeduncular fossa. The combined approach was used in seven of these patients, comprising four patients with petroclival meningiomas, one patient with sphenoclival meningiomas, one patient with trigeminal schwannoma, and one patient with an epidermoid cyst extending from the interpeduncular fossa to the prepontine cistern. RESULTS: The combined approach permitted excellent visualization of the interpeduncular fossa in addition to the upper clivus and the lateral aspect of the brain stem. Mobilization of the temporal lobe by the entire epidural dissection of the lateral wall of the cavernous sinus facilitates access via the subtemporal route. The transient symptom of the temporal lobe in the dominant site may be the only drawback for this combined approach, although it may disappear immediately after the surgery. CONCLUSION: The present approach combines Dolenc's approach and Kawase's approach, providing a wide exposure to lesions of the interpeduncular fossa and the clivus.

Nonconvulsive status epilepticus characteristics in glioma patients: a retrospective study.

PURPOSE: Epilepsy is a common complication of gliomas. The diagnosis of nonconvulsive status epilepticus (NCSE) is challenging because it causes impaired consciousness and mimics glioma progression. NCSE complication rate in the general brain tumor patient population is approximately 2%. However, there are no reports focusing on NCSE in glioma patient population. This study aimed to reveal the epidemiology and features of NCSE in glioma patients to enable appropriate diagnosis. METHODS: We enrolled 108 consecutive glioma patients (45 female, 63 male) who underwent their first surgery between April 2013 and May 2019 at our institution. We retrospectively investigated glioma patients diagnosed with tumor-related epilepsy (TRE) or NCSE to explore disease frequency of TRE/NCSE and patient background. NCSE treatment approaches and Karnofsky Performance Status Scale (KPS) changes following NCSE were surveyed. NCSE diagnosis was confirmed using the modified Salzburg Consensus Criteria (mSCC). RESULTS: Sixty-one out of 108 glioma patients experienced TRE (56%), and five (4.6%) were diagnosed with NCSE (2 female, 3 male; mean age, 57 years old; WHO grade II 1, grade III 2, grade IV 2). All NCSE cases were controlled by stage 2 status epilepticus treatment as recommended in the Clinical Practice Guidelines for Epilepsy by the Japan Epilepsy Society. The KPS score significantly decreased after NCSE. CONCLUSION: Higher prevalence of NCSE in glioma patients was observed. The KPS score significantly decreased after NCSE. Actively taking electroencephalograms analyzed by mSCC may facilitate accurate NCSE diagnosis and improve the activities of daily living in glioma patients.