Treatment Outcomes of PED for Unruptured Aneurysms of Internal Carotid Artery: Comparison of PED-Flex and PED-Shield.

There is a lack of data regarding the safety and effectiveness of implanting the Pipeline Embolization Device with Shield technology (PED-Shield) compared with the previous generation of Pipeline (PED-Flex). This retrospective single-center study aimed to compare treatment outcomes between the PED-Shield and PED-Flex for treating unruptured internal carotid artery aneurysms. The PED-Flex was used in 62 procedures (67 aneurysms, 59 patients) and the PED-Shield in 53 procedures (59 aneurysms, 58 patients). The mean aneurysm diameter was significantly lower in the PED-Shield group than in the PED-Flex group (11.9 ± 7.0 mm vs. 15.2 ± 6.9 mm, p < 0.001). At the 12-month follow-up, the complete angiographic occlusion rate was 72.1% and 72.3% in the PED-Flex and PED-Shield groups, respectively (p = 0.9808). Limited to aneurysms larger than 10 mm, 70.6% and 68.0%, respectively (p = 0.8175). The incidence of more than three high signal intensity areas on diffusion-weighted imaging after treatment was significantly lower in the PED-Shield group than in the PED-Flex group (27.7% vs. 67.7%; p < 0.001). Limited to aneurysms larger than 10 mm, 41.1% and 69.6%, respectively (p < 0.0117). Symptomatic ischemic complications occurred within 30 days of four PED-Flex procedures (6.5%) and one PED-Shield procedure (2.0%) (p = 0.2315). Limited to aneurysms larger than 10 mm, 1.8% and 3.2%, respectively (p = 0.6677). The incidence of mRS score worsening at 6 months was 3.2% and 1.9% in the PED-Flex and PED-Shield groups, respectively (p = 0.6534). The PED-Shield can achieve outcomes equivalent to or better than the PED-Flex. Further large-scale studies are warranted to confirm our findings.

Extracranial internal carotid artery-dissecting aneurysm having a re-entry tear and causing lower cranial nerve palsies treated with flow-diverting stent: A case report.

Background: Extracranial internal carotid artery (ICA)-dissecting aneurysms (DAs) rarely cause re-entry tears and lower cranial nerve palsies. The therapeutic strategies for these pathologies are not well established. This report presents a case of an extracranial ICA -DA with a re-entry tear that caused lower cranial nerve palsy. Case Description: A 60-year-old man presented with left neck pain, hoarseness, and dysphagia. Physical examination and laryngoscopy determined palsies of the left cranial nerves IX, X, and XII. Digital subtraction angiography (DSA) revealed a DA in the left extracranial ICA, and three-dimensional DSA showed entry and re-entry tears in the intimal flap. Flow-diverting stents (FDSs) were placed on the lesion that covered the entry and re-entry tears because the symptoms did not improve after five weeks of conservative treatment. A post-procedural angiogram indicated flow stagnation in the DA. Symptoms improved remarkably immediately after the procedure, and the aneurysm was almost completely occluded six months later. Conclusion: Herein, an extracranial ICA -DA with a re-entry tear that caused lower cranial nerve palsy did not improve after five weeks of conservative treatment. FDS placement promptly resolved the aneurysm and symptoms. Thus, FDS placement may be an effective treatment option for extracranial ICA-DAs with re-entry tears or lower cranial nerve palsies.

Association of ADC of hyperintense lesions on FLAIR images with TERT promoter mutation status in glioblastoma IDH wild type.

Background: Although mutations in telomerase reverse transcriptase (TERT) promoter (TERTp) are the most common alterations in glioblastoma (GBM), predicting TERTp mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing TERTp mutation status using magnetic resonance imaging (MRI). Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)-wild-type GBM. The apparent diffusion coefficient (ADC) and volume of CELs and FLAIR hyperintense lesions (FHLs) were determined, and the correlation between MRI features and TERTp mutation status was analyzed. In a subset of cases, FHLs were histopathologically analyzed to determine the correlation between tumor cell density and ADC. Results: TERTp mutations were present in 77 (67.5%) patients. The minimum ADC of FHLs was significantly lower in the TERTp-mutant group than in the TERTp-wild-type group (mean, 958.9 × 10-3 and 1092.1 × 10-3 mm2/s, respectively, P < 0.01). However, other MRI features, such as CEL and FHL volumes, minimum ADC of CELs, and FHL/CEL ratio, were not significantly different between the two groups. Histopathologic analysis indicated high tumor cell density in FHLs with low ADC. Conclusion: The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning.

Human-Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Showed Neuronal Differentiation, Neurite Extension, and Formation of Synaptic Structures in Rodent Ischemic Stroke Brains.

Ischemic stroke is a major cerebrovascular disease with high morbidity and mortality rates; however, effective treatments for ischemic stroke-related neurological dysfunction have yet to be developed. In this study, we generated neural progenitor cells from human leukocyte antigen major loci gene-homozygous-induced pluripotent stem cells (hiPSC-NPCs) and evaluated their therapeutic effects against ischemic stroke. hiPSC-NPCs were intracerebrally transplanted into rat ischemic brains produced by transient middle cerebral artery occlusion at either the subacute or acute stage, and their in vivo survival, differentiation, and efficacy for functional improvement in neurological dysfunction were evaluated. hiPSC-NPCs were histologically identified in host brain tissues and showed neuronal differentiation into vGLUT-positive glutamatergic neurons, extended neurites into both the ipsilateral infarct and contralateral healthy hemispheres, and synaptic structures formed 12 weeks after both acute and subacute stage transplantation. They also improved neurological function when transplanted at the subacute stage with γ-secretase inhibitor pretreatment. However, their effects were modest and not significant and showed a possible risk of cells remaining in their undifferentiated and immature status in acute-stage transplantation. These results suggest that hiPSC-NPCs show cell replacement effects in ischemic stroke-damaged neural tissues, but their efficacy is insufficient for neurological functional improvement after acute or subacute transplantation. Further optimization of cell preparation methods and the timing of transplantation is required to balance the efficacy and safety of hiPSC-NPC transplantation.

Fungal symptomatic intracranial aneurysm treated with a flow diverting stent: A case report.

Background: Intracranial infectious aneurysms (IIAs) are very rare, and fungal aneurysms are infrequently reported. We report a case of an unruptured IIA caused by fungal rhinosinusitis and treated with a flow-diverting stent. Case Description: An 81-year-old woman visited the ophthalmology department with impaired eye movement and ptosis and was placed under follow-up. A week later, she also developed a headache; magnetic resonance angiography revealed an aneurysm measuring 2 mm in the C4 portion of the right internal carotid artery. A 3-week follow-up with contrast-enhanced magnetic resonance imaging showed an increase in its size to 10 mm, and a contrast lesion was observed surrounding the right cavernous sinus. The patient started treatment with voriconazole and steroids on the same day. Ten weeks later, despite improvements in inflammation, the size of the aneurysm was unchanged; we, therefore, treated the aneurysm with a flow-diverting stent. Oculomotor nerve palsy improved, and the patient was discharged to a rehabilitation hospital 28 days after the placement, with a modified Rankin Scale of 4. A 1-year follow-up angiogram showed a partial decrease in the size of the aneurysm, with an O'Kelly-Marotta grading scale of B3. Conclusion: IIAs grow rapidly, and the risk of rupture is high due to the weakening of the aneurysmal wall. To reduce the risks of rupture and recurrence after treatment, the infection should be treated before inserting a flow-diverting stent. Flow-diverting stent placement may be an effective treatment for IIA once the original infection has been cured.

Prediction of MGMT promotor methylation status in glioblastoma by contrast-enhanced T1-weighted intensity image.

Background: The study aims to explore MRI phenotypes that predict glioblastoma's (GBM) methylation status of the promoter region of MGMT gene (pMGMT) by qualitatively assessing contrast-enhanced T1-weighted intensity images. Methods: A total of 193 histologically and molecularly confirmed GBMs at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KANSAI) were used as an exploratory cohort. From the Cancer Imaging Archive/Cancer Genome Atlas (TCGA) 93 patients were used as validation cohorts. "Thickened structure" was defined as the solid tumor component presenting circumferential extension or occupying >50% of the tumor volume. "Methylated contrast phenotype" was defined as indistinct enhancing circumferential border, heterogenous enhancement, or nodular enhancement. Inter-rater agreement was assessed, followed by an investigation of the relationship between radiological findings and pMGMT methylation status. Results: Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the exploratory and 0.55 for the validation cohort, and for "Methylated contrast phenotype," 0.30 and 0.39, respectively. The imaging feature, the presence of "Thickened structure" and absence of "Methylated contrast phenotype," was significantly predictive of pMGMT unmethylation both for the exploratory (p = .015, odds ratio = 2.44) and for the validation cohort (p = .006, odds ratio = 7.83). The sensitivities and specificities of the imaging feature, the presence of "Thickened structure," and the absence of "Methylated contrast phenotype" for predicting pMGMT unmethylation were 0.29 and 0.86 for the exploratory and 0.25 and 0.96 for the validation cohort. Conclusions: The present study showed that qualitative assessment of contrast-enhanced T1-weighted intensity images helps predict GBM's pMGMT methylation status.

Predictors of Middle Meningeal Artery-Related Vascular Diseases Associated with Blunt Head Trauma.

OBJECTIVE: Traumatic middle meningeal artery (MMA)-middle meningeal vein (MMV) fistula (MMA-MMV fistula) and MMA pseudoaneurysm are the 2 main MMA-related vascular diseases occurring after blunt head trauma. These are rare but known causes of delayed intracranial hemorrhage. This study investigated predictors that may aid in the diagnosis of these diseases. METHODS: In our department, screening digital subtraction angiography (DSA) is performed for patients with blunt head trauma accompanied by intracranial hemorrhage and skull or facial bone fracture. This study included 87 patients who underwent screening DSA without craniotomy from January 2019 to June 2023. The patients' clinical characteristics were retrospectively collected from the database. Statistical analysis was performed to examine the associations of various evaluation items with MMA-related vascular diseases. RESULTS: The first DSA examination revealed 34 MMA-MMV fistulas and 1 MMA pseudoaneurysm. The second follow-up DSA examination revealed 13 MMA-MMV fistulas and four MMA pseudoaneurysms. Temporal/parietal bone fracture (odds ratio, 5.33; P = 0.0005; 95% confidence interval, 1.95-14.60) was significantly associated with MMA-related vascular diseases. Endovascular treatments were performed in 9 patients. All procedures were successfully completed without complications; no delayed bleeding was observed. CONCLUSIONS: Temporal/parietal bone fracture in patients with blunt head trauma is a likely predictor of MMA-related vascular diseases. When initial head computed tomography reveals this pathology, we recommend careful imaging follow-up (e.g., DSA) and treatment as needed, while considering the possibility of MMA-related vascular diseases.

Slow-growing WNT medulloblastoma with atypical magnetic resonance imaging findings: illustrative case.

BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.

Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation: a Japanese Pediatric Molecular Neuro-Oncology Group study.

BACKGROUND: One of the most significant challenges in patients with medulloblastoma is reducing the dose of craniospinal irradiation (CSI) to minimize neurological sequelae in survivors. Molecular characterization of patients receiving lower than standard dose of CSI therapy is important to facilitate further reduction of treatment burden. METHODS: We conducted DNA methylation analysis using an Illumina Methylation EPIC array to investigate molecular prognostic markers in 38 patients with medulloblastoma who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with reduced-dose CSI. RESULTS: Among the patients, 23 were classified as having a standard-risk and 15 as high-risk according to the classic classification based on tumor resection rate and presence of metastasis, respectively. The median follow-up period was 71.5 months (12.0-231.0). The median CSI dose was 18 Gy (15.0-24.0) in both groups, and 5 patients in the high-risk group received a CSI dose of 18.0 Gy. Molecular subgrouping revealed that the standard-risk cohort included 5 WNT, 2 SHH, and 16 Group 3/4 cases; all 15 patients in the high-risk cohort had Group 3/4 medulloblastoma. Among the patients with Group 3/4 medulloblastoma, 9 of the 31 Group 3/4 cases were subclassified as subclass II, III, and V, which were known to an association with poor prognosis according to the novel subtyping among the subgroups. Patients with poor prognostic subtype showed worse prognosis than that of others (5-year progression survival rate 90.4% vs. 22.2%; p < 0.0001). The result was replicated in the multivariate analysis (hazard ratio12.77, 95% confidence interval for hazard ratio 2.38-99.21, p value 0.0026 for progression-free survival, hazard ratio 5.02, 95% confidence interval for hazard ratio 1.03-29.11, p value 0.044 for overall survival). CONCLUSION: Although these findings require validation in a larger cohort, the present findings suggest that novel subtyping of Group 3/4 medulloblastoma may be a promising prognostic biomarker even among patients treated with lower-dose CSI than standard treatment.

[Classification and Diagnostics of Pediatric Brain Tumors].

In childhood and young adulthood, a wide variety of brain tumors, such as medulloblastoma and ependymoma, frequently occur. Moreover, high- or low-grade diffuse gliomas, commonly found in adults, also emerge. Recent genomic research has revealed numerous molecular and genetic features of pediatric brain tumors. These molecular and genetic findings have been incorporated into the latest 2021 World Health Organization Classification of Tumors of the Central Nervous System(WHO CNS 5). WHO CNS 5 introduces separate classifications for adult- and pediatric-type diffuse gliomas, which were conventionally diagnosed using the same criteria. Classifying these adult- and pediatric-type gliomas using histopathological properties alone is challenging. Therefore, molecular diagnostics utilizing diverse molecular and genetic information, including variants, copy number alterations, structural abnormalities, and DNA methylation profiles, are imperative. Many molecular and genetic characteristics have been elucidated in the WHO CNS 5. Molecular diagnostics and classification are essential for accurately categorizing pediatric brain tumors, and the significance of molecular and genetic information will continue to grow.

Flow Diverter Stenting for Symptomatic Intracranial Internal Carotid Artery Aneurysms: Clinical Outcomes and Factors for Symptom Improvement.

Flow diverter (FD) stenting is expected to improve cranial nerve symptoms caused by aneurysms via the theoretical reduction of the mass effect by promoting spontaneous thrombosis through the flow diversion effect. However, the factors involved in symptom improvement after treatment remain unclear. This study was performed to identify factors for symptom improvement after FD stenting and the symptom improvement rate of each impaired cranial nerve. We retrospectively evaluated 33 patients who underwent FD stenting for symptomatic internal carotid artery aneurysms at our institution from January 2016 to June 2021. Twenty-three (69.7%) patients had resolved or improved symptoms after 1 year of treatment. The optic nerve was affected in 12 patients; the oculomotor nerve, in 16; the trigeminal nerve, in 2; and the abducens nerve, in 13. There was no statistically significant difference in the symptom improvement rate of each impaired cranial nerve. The patients were classified into the improved and nonimproved groups based on their symptoms after 1 year of treatment, and the factors related to the symptoms were analyzed. The time from onset to treatment was significantly shorter in the improved group than in the nonimproved group (197.1 and 800 days, respectively; p = 0.023). There were no significant differences in age, aneurysm diameter, adjunctive coil embolization, partial thrombosis, change in mass diameter on magnetic resonance imaging, or aneurysm occlusion rate on angiography between the two groups. These results suggest that early treatment after the onset of aneurysm-induced cranial neuropathies increases the likelihood of symptom improvement.

Human induced pluripotent stem cell line (ONHi001-A) generated from a patient with infantile neuroaxonal dystrophy having PLA2G6 c.517C > T (p.Q173X) and c.1634A > G (p.K545R) compound heterozygous mutations.

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease caused mainly by homozygous or compound heterozygous mutations in the PLA2G6 gene. We generated a human induced pluripotent stem cell (hiPSC) line (ONHi001-A) using fibroblasts derived from a patient with INAD. The patient exhibited c.517C > T (p.Q173X) and c.1634A > G (p.K545R) compound heterozygous mutations in the PLA2G6 gene. This hiPSC line may be useful for studying the pathogenic mechanism underlying INAD.

Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy.

Background: New therapies for glioblastoma (GBM) are urgently needed because the disease prognosis is poor. Chimeric antigen receptor (CAR)-T cell therapy that targets GBM-specific cell surface antigens is a promising therapeutic strategy. However, extensive transcriptome analyses have uncovered few GBM-specific target antigens. Methods: We established a library of monoclonal antibodies (mAbs) against a tumor cell line derived from a patient with GBM. We identified mAbs that reacted with tumor cell lines from patients with GBM but not with nonmalignant human brain cells. We then detected the antigens they recognized using expression cloning. CAR-T cells derived from a candidate mAb were generated and tested in vitro and in vivo. Results: We detected 507 mAbs that bound to tumor cell lines from patients with GBM. Among them, E61 and A13 reacted with tumor cell lines from most patients with GBM, but not with nonmalignant human brain cells. We found that B7-H3 was the antigen recognized but E61. CAR-T cells were established using the antigen-recognition domain of E61-secreted cytokines and exerted cytotoxicity in co-culture with tumor cells from patients with GBM. Conclusions: Cancer-specific targets for CAR-T cells were identified using a mAb library raised against primary GBM tumor cells from a patient. We identified a GBM-specific mAb and its antigen. More mAbs against various GBM samples and novel target antigens are expected to be identified using this strategy.

Correlation of T1- to T2-weighted signal intensity ratio with T1- and T2-relaxation time and IDH mutation status in glioma.

The current study aimed to test whether the ratio of T1-weighted to T2-weighted signal intensity (T1W/T2W ratio: rT1/T2) derived from conventional MRI could act as a surrogate relaxation time predictive of IDH mutation status in histologically lower-grade gliomas. Strong exponential correlations were found between rT1/T2 and each of T1- and T2-relaxation times in eight subjects (rT1/T2 = 1.63exp-0.0005T1-relax + 0.30 and rT1/T2 = 1.27exp-0.0081T2-relax + 0.48; R2 = 0.64 and 0.59, respectively). In a test cohort of 25 patients, mean rT1/T2 (mrT1/T2) was significantly higher in IDHwt tumors than in IDHmt tumors (p < 0.05) and the optimal cut-off of mrT1/T2 for discriminating IDHmt was 0.666-0.677, (AUC = 0.75, p < 0.05), which was validated in an external domestic cohort of 29 patients (AUC = 0.75, p = 0.02). However, this result was not validated in an external international cohort derived from TCIA/TCGA (AUC = 0.63, p = 0.08). The t-Distributed Stochastic Neighbor Embedding analysis revealed a greater diversity in image characteristics within the TCIA/TCGA cohort than in the two domestic cohorts. The failure of external validation in the TCIA/TCGA cohort could be attributed to its wider variety of original imaging characteristics.

Quantitative measurement of peritumoral concentrations of glutamate, N-acetyl aspartate, and lactate on magnetic resonance spectroscopy predicts glioblastoma-related refractory epilepsy.

BACKGROUND: Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS). METHODS: Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated. RESULTS: In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p < 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were > 1.25, > 1.09, and > 0.88, respectively. CONCLUSIONS: Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.

Genetic Alteration May Proceed with a Histological Change in Glioblastoma: A Report from Initially Diagnosed as Nontumor Lesion Cases.

Despite recent signs of progress in diagnostic radiology, it is quite rare that a glioblastoma (GBM) is detected asymptomatically. We describe two patients with asymptomatic nonenhancing GBMs that were not diagnosed with neoplasia at first. The patients had brain scans as medical checkups, and incidentally lesions were detected. In both cases, surgical specimens histopathologically showed no evidence of neoplasia, whereas molecular genetic findings were isocitrate dehydrogenase (IDH)-wildtype, O6-methylguanine-DNA methyltransferase promoter (pMGMT) unmethylated, and telomerase reverse transcriptase (TERT) promoter mutated, which matched to GBM. One patient was observed without adjuvant therapy and the tumor recurred 7 months later. Reoperation was performed, and histopathologically GBM was confirmed with the same molecular diagnosis as the first surgical specimen. Another patient was carefully observed, and chemoradiotherapy was begun 6 months after the operation following the extension of the lesion. Eventually, because of disease progression, both patients deceased. We postulate that in each case, the tumor was not lower-grade glioma but corresponded to the early growth phase of GBM cells. Thus far, cases of malignant transformation from lower-grade glioma or asymptomatic GBM with typical histologic features are reported. Nevertheless, to the best of our knowledge, no such case of nonenhancing, nonhistologically confirmed GBM was reported. We conjecture these cases shed light on the yet unknown natural history of GBM. GBM can take the form of radiological nonenhancing and histological nonneoplastic fashion before typical morphology. Molecular genetic analysis can diagnose atypical preceding GBM, and we recommend early surgical removal and adjuvant treatment.

Staged treatment for ruptured wide-neck intracranial aneurysm with intentional partial coiling in the acute phase followed by definitive treatment.

Background: Evidence supports endovascular coiling for ruptured intracranial aneurysms (RIAs). However, in some cases, it is difficult to achieve complete occlusion by coiling, such as with wide-neck aneurysms. We report our experience with intentional staged RIA treatment using targeted endovascular coiling at the rupture point in the acute phase, followed by delayed stent-assisted coiling, flow diverter stenting, or surgical clipping. Methods: Consecutive patients with RIAs treated between April 2015 and June 2021 were retrospectively investigated. Clinical characteristics, treatment complications, and patient outcomes data were collected. Results: Among 108 RIAs treated in our hospital, 60 patients underwent initial coiling; 10 patients underwent staged treatment. The aneurysm locations were the anterior communicating artery (n = 5), internal carotid-posterior communicating artery (n = 3), internal carotid-paraclinoid (n = 1), and vertebral artery-posterior inferior cerebellar artery (n = 1). The mean ± standard deviation aneurysmal diameter was 9.6 ± 5.4 mm and the mean aspect ratio was 1.2 ± 0.7. As the second treatment to obliterate blood flow to the neck area, we performed five stent-assisted coiling, two flow-diverter stentings, and three surgical clippings. Only one minor perioperative complication occurred. The median duration between the first and second treatments was 18 days (range, 14- 42 days). Good clinical outcome (modified Rankin scale score 0-2) at 90 days was achieved in 5 (50%) cases. The median follow-up duration was 6.5 months (range, 3-35 months); no rerupture occurred. Conclusion: Intentional staged treatment with a short time interval for RIA was effective and feasible.

Revisiting the definition of glioma recurrence based on a phylogenetic investigation of primary and re-emerging tumor samples: a case report.

A recurrent tumor is defined as a re-emerging subclone originating from an ancestorial clone of the primary neoplasm. Hence, it should be distinguished from de novo tumor emerging from other clones. Herein, we describe an exceptional case in which the locally re-emerging glioma did not share genetic alterations of the primary tumor. While the initial tumor harbored mutations in IDH1 and TERT genes as well as 1p/19q codeletion, the re-emerging tumor did not present any of these genetic abnormalities. Variant calling for tumor samples using whole-genome sequencing revealed that 1696 mutations within the primary tumor faded in the re-emerging tumor, and that 4591 mutations were newly detected in the re-emerging tumor. These results suggested that the initial and re-emerging tumors did not share same clonal origins, although the second tumor appeared adjacent to the old surgical cavity 5 years after the initial surgery. We finally speculated that the re-emerging tumor could be a "de novo glioma" or "radiation-induced glioblastoma following treatment of a diffuse glioma." This case highlights the importance of molecular re-evaluation of clinically diagnosed "recurrent" glioma lesions.

Correlation Between Genetic Abnormalities in Induced Pluripotent Stem Cell-Derivatives and Abnormal Tissue Formation in Tumorigenicity Tests.

Cell therapy using induced pluripotent stem cell (iPSC) derivatives may result in abnormal tissue generation because the cells undergo numerous cycles of mitosis before clinical application, potentially increasing the accumulation of genetic abnormalities. Therefore, genetic tests may predict abnormal tissue formation after transplantation. Here, we administered iPSC derivatives with or without single-nucleotide variants (SNVs) and deletions in cancer-related genes with various genomic copy number variant (CNV) profiles into immunodeficient mice and examined the relationships between mutations and abnormal tissue formation after transplantation. No positive correlations were found between the presence of SNVs/deletions and the formation of abnormal tissues; the overall predictivity was 29%. However, a copy number higher than 3 was correlated, with an overall predictivity of 86%. Furthermore, we found CNV hotspots at 14q32.33 and 17q12 loci. Thus, CNV analysis may predict abnormal tissue formation after transplantation of iPSC derivatives and reduce the number of tumorigenicity tests.