Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data.

PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench. RESULTS: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma. CONCLUSION: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

Organized Chronic Subdural Hematoma (OCSDH) Mimicking Meningioma.

Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease.

Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models.

Hydrogen peroxide (H2 O2 ) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2 O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2 O2 on antitumor immunity remain unclear. To investigate the effects of H2 O2 , especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2 O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2 O2 /RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2 O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2 O2 /RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN-γ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2 O2 /RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2 O2 /RT group. Intratumoral injection of H2 O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H2 O2 /RT therapy combined with cancer immunotherapies, even for advanced cancers.

A Case of High-Grade Glioma in an Eloquent Area Treated with Awake Craniotomy in an 85-year-old Patient.

An 85-year-old woman presented with aphasia due to an occupying lesion in the left frontal lobe near the language area. Complete resection of the contrast-enhancing lesion was performed under awake conditions. The pathological diagnosis was anaplastic astrocytoma, and postoperative radiochemotherapy was administered. Awake surgery is a useful technique to reduce postoperative neurological sequelae and to maximize surgical resection. Although the patient was elderly, which is generally considered high risk, she did not have any severe neurological deficits and had a good outcome. Even in the extreme elderly, awake surgery can be useful for gliomas in language cortices.

Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma.

West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity.

Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma.

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

A Case of Radiation-Induced Osteosarcoma with RB1 Gene Alteration Treated by Skull Base Surgery and Craniofacial Reconstruction.

A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.

The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology.

PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

Mobile endovascular therapy for acute treatment of ruptured vertebral artery dissecting aneurysm in multiple hospitals.

BACKGROUND: The patients with ruptured vertebral artery dissecting aneurysm (rVADA) should be treated as early as possible because VADA carries extremely high risk of rebleeding in the acute phase. We have established a mobile endovascular strategy for the patients with rVADA between our flagship center and its affiliated local hospitals. We introduced and reviewed our mobile endovascular therapy in this study. METHODS: We retrospectively evaluated 98 consecutive patients who underwent endovascular surgery for rVADA from 2000 to 2018 at our institution or five affiliated hospitals. When each patient was initially transported to the local affiliated hospitals, neuroendovascular surgeons traveled directly to the affiliated hospital from the flagship center in order to treat the patient there. Clinical outcomes using modified Rankin Scale at 6 months after treatment, radiological results, and procedure-related complications were reviewed to justify our mobile endovascular strategy. RESULTS: All aneurysms were cured successfully by internal trapping. Favorable outcome was achieved in 61 patients (62.2%) even though 53 patients (54.1%) had presented with severe subarachnoid hemorrhage. Overall mortality rate, treatment-related mortality rate, and treatment related complication rate were 18.4% (18/98), 0%, and 16% (16/98), respectively. There were no differences in clinical and radiological outcomes between the patients treated in the flagship center and those who treated in the affiliated hospitals. Treatment in the affiliated hospital was not a predictive factor of unfavorable outcome in our multivariate analysis, and elderly age (≥ 60) was negatively associated with favorable outcome. CONCLUSIONS: Our results prove the efficacy and safety of mobile endovascular therapy for the treatment of rVADA in the ultra-acute stage. Mobile endovascular therapy may work well in the acute treatment of rVADAs in the certain circumstance.

A case of delayed foreshortening and disconnection of pipeline embolization device detected by chronological cone-beam computed tomography fusion image.

OBJECTIVE: The morphological changes of the pipeline embolization device (PED; Medtronic, Minneapolis, MN, USA), such as delayed migration or foreshortening, can relate to the incomplete occlusion of aneurysms. CASE PRESENTATION: A 30-year-old man with a giant cavernous carotid artery aneurysm was treated with two PEDs using the overlapping technique. Six months after treatment, follow-up angiography showed morphological changes of the PEDs and residual flow into the aneurysm. Chronological cone-beam computed tomography fusion imaging clearly revealed the dynamic foreshortening of the first PED and the disconnection of both PEDs, so we decided to implant an additional PED. CONCLUSION: This case illustrates that a three-dimensional understanding can be useful for assessing the cause of treatment failure or recurrence.

Current Insights into Mesenchymal Signatures in Glioblastoma.

Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives.

A Pediatric Case of Cauda Equina Dermoid Cyst Resected by Minimally Invasive Unilateral Hemilaminectomy.

A 3-year-old boy had difficulty sitting up and walking for several months. Magnetic resonance imaging (MRI) revealed an intradural tumor at the L3-4 level. The tumor was successfully resected by unilateral hemilaminectomy and diagnosed as dermoid cyst. The patient had an uneventful postoperative course without pain, and MRI found no recurrence after surgery. A small bone defect remained that might be favorably reconstructed with autologous and artificial bone. Hemilaminectomy allowed us to resect the cauda equina dermoid cyst with minimal invasiveness. Pediatric patients require follow-up as they are more likely to experience spinal deformity or instability after surgery.

A Rare Case of Idiopathic Spinal Cord Herniation Treated by DuraGen® Collagen Matrix Graft.

We report a rare case of idiopathic spinal cord herniation (ISCH) with a history of cerebrospinal fluid (CSF) leakage. ISCH is a protrusion of the spinal cord through a dural defect. Thin constructive interference in steady-state (CISS) images clearly demonstrated the herniated cord in the present case. The myelopathy worsened and the patient underwent surgery for reduction of herniated spinal cord; the dural defect was filled by placing collagen matrix graft (DuraGen®) between the inner and outer dural layers. The patient's symptoms have improved without relapse for 8 months since surgery. This method may be a good surgical option for cases of spinal cord herniation.

A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification.

Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.

Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands.

Glioneuronal tumor with neuropil-like islands (GNTNI) is a very rare subtype of glioneuronal tumor. We present a case of a 62-year-old man with GNTNI. Two adjacent lesions in the left parietal lobe were removed by left parietal craniotomy. The histological findings were glial cell proliferation and scattered rosettes consisting of synaptophysin-positive and NeuN-positive cells, leading to the diagnosis of GNTNI. Target sequencing revealed a genetic alteration similar to glioblastoma, IDH-wild type, which suggested adjuvant therapies. There are few previous reports on the treatment of this disease, and the patient should be followed carefully.

Treatment outcome of coil embolization for distal anterior cerebral artery aneurysms: A single-center experience.

OBJECTIVE: In recent years, endovascular treatment has become the treatment of choice for distal anterior cerebral artery (DACA) aneurysms. In this study, we report the outcomes of coil embolization for DACA aneurysms. METHODS: Eighteen DACA aneurysms in 16 patients treated with endovascular treatment between January 2010 and December 2020 were included in this study. We retrospectively analyzed patient characteristics, data on aneurysms, the reason for the selection of endovascular treatment, treatment technique, and treatment outcomes. RESULTS: There were 18 procedures in 16 patients. The average age was 65.7 years and 56% of patients were male. The average diameter of the dome was 5.5 mm, and the location of aneurysm was A3 in 83% and A4 in 17%. We mainly selected endovascular treatment for patients with a past history of craniotomy and head trauma, or with systemic comorbidities. The technical success rate was 94%, and adequate obliteration immediately after treatment was achieved in 72%. There were no symptomatic periprocedural complications. The retreatment rate was 11.1%. CONCLUSION: Coil embolization for DACA aneurysms yielded good treatment outcomes. Endovascular treatment for DACA aneurysms will become more common with advances in endovascular devices and the establishment of stable perioperative antiplatelet therapy.

[Evidence of Efficacy of Superficial Temporal Artery-Middle Cerebral Artery Bypass in Japan].

The Japanese EC-IC Bypass Trial(JET)Study demonstrated that a superficial temporal artery-middle cerebral artery(STA-MCA)bypass is effective in preventing the recurrence of ischemic stroke in cases of atherosclerotic internal carotid artery or MCA steno-occlusive lesions with symptoms. The JET-2 Study revealed that the hemodynamic criteria for STA-MCA bypass in the JET Study(rest cerebral blood flow < 80% and cerebrovascular reactivity < 10%)were adequate. An STA-MCA bypass was ranked as recommendation B; the level of evidence was moderate under the conditions of quantitative evaluation of cerebral hemodynamics and low frequency of perioperative complications, as described in the Japanese Guidelines for the Management of Stroke 2021. An education system for the accurate assessment of cerebral hemodynamics, meticulous surgical procedures, and perioperative management for STA-MCA bypass is necessary to hand over evidence of STA-MCA bypass efficacy in Japan to future generations. Simultaneously, new evidence of STA-MCA bypass efficacy should be explored with the advancement of medicine and should be disseminated worldwide.

[Surgical Tips and Precautions for Supratentorial Tumors in Children].

Pediatric brain tumors account for approximately 15% of all pediatric cancers. Approximately half of the cases are malignant, and entail postoperative radiation therapy and chemotherapy. Herein, we describe perioperative tips and precautions for pediatric supratentorial tumors other than suprasellar tumors from our institution. Postoperative cerebrospinal fluid issues are especially prevalent in children, and three representative cases have been presented for discussion. Further, skull closure deems close attention, being crucial for children's future growth, in terms of a cosmetic aspect.

[Visualization of Cerebrospinal Micro-Angioarchitecture].

Researchers have been trying to visualize fine angioarchitecture in cerebrospinal vascular lesions and the positional relationship between vascular lesions and surrounding structures. The aim of this article was to introduce the usefulness of imaging in visualizing the microvascular anatomy in cerebrospinal vascular lesions, such as aneurysm, arterial dissection, arteriovenous malformation, dural arteriovenous fistula(AVF), spinal dural and epidural AVF, and craniocervical junction AVF. For the imaging modality, we used high-resolution magnetic resonance imaging, three-dimensional rotational angiography(3D-RA), slab maximum intensity projection image from 3D-RA, cone-beam computed tomography, and fusion imaging. If fully exploited, imaging can contribute to clinical analysis and surgical treatment and be an essential tool for achieving maximum therapeutic effect without complications.