In-house molecular diagnosis of diffuse glioma updating the revised WHO classification by a platform of the advanced medical care system, Senshin-Iryo.

Since the World Health Organization (WHO) 2016 revision, the number of molecular markers required for diffuse gliomas has increased, placing a burden on clinical practice. We have established an in-house, molecular diagnostic platform using Senshin-Iryo, a feature of Japan's unique healthcare system, and partially modified the analysis method in accordance with the WHO 2021 revision. Herein, we review over a total 5 years of achievements using this platform. Analyses of IDH, BRAF, and H3 point mutations, loss of heterozygosity (LOH) on 1p/19q and chromosomes 10 and 17, and MGMT methylation were combined into a set that was submitted to Senshin-Iryo as "Drug resistance gene testing for anticancer chemotherapy" and was approved in August 2018. Subsequently, in October 2021, Sanger sequencing for the TERT promoter mutation was added to the set, and LOH analysis was replaced with multiplex ligation-dependent probe amplification (MLPA) to analyze 1p/19q codeletion and newly required genetic markers, such as EGFR, PTEN, and CDKN2A from WHO 2021. Among the over 200 cases included, 54 were analyzed after the WHO 2021 revision. The laboratory has maintained a diagnostic platform where molecular diagnoses are confirmed within 2 weeks. Initial expenditures exceeded the income from patient copayments; however, it has gradually been reduced to running costs alone and is approaching profitability. After the WHO 2021 revision, diagnoses were confirmed using molecular markers obtained from Senshin-Iryo in 38 of 54 cases (70.1%). Among the remaining 16 patients, only four (7.4%) were diagnosed with diffuse glioma, not elsewhere classified, which was excluded in 12 cases where glioblastoma was confirmed by histopathological diagnosis. Our Senshin-Iryo trial functioned as a salvage system to overcome the transition period between continued revisions of WHO classification that has caused a clinical dilemma in the Japanese healthcare system.

Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid.

Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood-brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.

Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma.

Background: Telomerase reverse transcriptase promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance of TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase (IDH)- and TERTp-wild-type glioblastomas. Methods: Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type IDH. Results: TERTp mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were TERTp-wild-type. Among the TERTp-wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without phosphatase and tensin homolog (PTEN) loss and/or mutation. Patients with TERTp-wild-type glioblastomas with PTEN loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without PTEN loss and/or mutation. We divided the patients with TERTp-wild-type into 3 clusters using unsupervised hierarchical clustering: Good (PTEN and TP53 alterations; lack of CDKN2A/B homozygous deletion and platelet-derived growth factor receptor alpha (PDGFRA) alterations), intermediate (PTEN alterations, CDKN2A/B homozygous deletion, lack of PDGFRA, and TP53 alterations), and poor (PDGFRA and TP53 alterations, CDKN2A/B homozygous deletion, and lack of PTEN alterations) outcomes. Kaplan-Meier survival analysis indicated that these clusters significantly correlated with the overall survival of TERTp-wild-type glioblastoma patients. Conclusions: Here, we report that PTEN loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with IDH- and TERTp-wild-type glioblastomas. The combination of 4 genes, PTEN, TP53, CDKN2A/B, and PDGFRA, is important for the molecular classification and individual prognosis of patients with IDH- and TERTp-wild-type glioblastomas.

Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study.

We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of patients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre- and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger cohorts.

Induction of glioblastoma cell ferroptosis using combined treatment with chloramphenicol and 2-deoxy-D-glucose.

Glioblastoma, a malignant tumor, has no curative treatment. Recently, mitochondria have been considered a potential target for treating glioblastoma. Previously, we reported that agents initiating mitochondrial dysfunction were effective under glucose-starved conditions. Therefore, this study aimed to develop a mitochondria-targeted treatment to achieve normal glucose conditions. This study used U87MG (U87), U373, and patient-derived stem-like cells as well as chloramphenicol (CAP) and 2-deoxy-D-glucose (2-DG). We investigated whether CAP and 2-DG inhibited the growth of cells under normal and high glucose concentrations. In U87 cells, 2-DG and long-term CAP administration were more effective under normal glucose than high-glucose conditions. In addition, combined CAP and 2-DG treatment was significantly effective under normal glucose concentration in both normal oxygen and hypoxic conditions; this was validated in U373 and patient-derived stem-like cells. 2-DG and CAP acted by influencing iron dynamics; however, deferoxamine inhibited the efficacy of these agents. Thus, ferroptosis could be the underlying mechanism through which 2-DG and CAP act. In conclusion, combined treatment of CAP and 2-DG drastically inhibits cell growth of glioblastoma cell lines even under normal glucose conditions; therefore, this treatment could be effective for glioblastoma patients.

Liquid biopsy with multiplex ligation-dependent probe amplification targeting cell-free tumor DNA in cerebrospinal fluid from patients with adult diffuse glioma.

Background: Copy number alterations (CNAs) are common in diffuse gliomas and have been shown to have diagnostic significance. While liquid biopsy for diffuse glioma has been widely investigated, techniques for detecting CNAs are currently limited to methods such as next-generation sequencing. Multiplex ligation-dependent probe amplification (MLPA) is an established method for copy number analysis in pre-specified loci. In this study, we investigated whether CNAs could be detected by MLPA using patients' cerebrospinal fluid (CSF). Methods: Twenty-five cases of adult diffuse glioma with CNAs were selected. Cell-free DNA (cfDNA) was extracted from the CSF, and DNA sizes and concentrations were recorded. Twelve samples, which had appropriate DNA sizes and concentrations, were subsequently used for analysis. Results: MLPA could be successfully performed in all 12 cases, and the detected CNAs were concordant with those detected using tumor tissues. Cases with epidermal growth factor receptor (EGFR) amplification, combination of gain of chromosome 7 and loss of chromosome 10, platelet-derived growth factor receptor alpha amplification, cyclin-dependent kinase 4 amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion were clearly distinguished from those with normal copy numbers. Moreover, EGFR variant III was accurately detected based on CNA. Conclusions: Thus, our results demonstrate that copy number analysis can be successfully performed by MLPA of cfDNA extracted from the CSF of patients with diffuse glioma.

Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma.

Background: Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzing outcomes of patients with IDH wild-type GBM. Methods: Using a custom-made oncopanel, we evaluated PDGFRA gain/amplification in 107 GBM samples harboring wild-type IDH, along with MGMT promoter (MGMTp) methylation status. Results: We detected PDGFRA gain/amplification in 31 samples (29.0%). PDGFRA gain/amplification predicted poor prognosis (P = .003). Compared to unamplified PDGFRA, PDGFRA gain/amplification in GBM was associated with higher patient age (P = .031), higher Ki-67 score (P = .019), and lower extent of surgical resection (P = .033). Unmethylated MGMTp also predicted poor prognosis (P = .005). As PDGFRA gain/amplification and unmethylated MGMTp were independent factors for poor prognosis in multivariate analyses, we grouped GBM cases based on PDGFRA and MGMTp status: poor (PDGFRA gain/amplification and unmethylated MGMTp), intermediate (PDGFRA gain/amplification or unmethylated MGMTp), and good (PDGFRA intact and methylated MGMTp) prognosis. The Kaplan-Meier survival analysis indicated that these groups significantly correlated with the OS of GBM patients (P < .001). Conclusions: Here we report that PDGFRA gain/amplification is a predictor of poor prognosis in IDH wild-type GBM. Combining PDGFRA gain/amplification with MGMTp methylation status improves individual prognosis prediction in patients with IDH wild-type GBM.

Chronic Subdural Hematoma after Craniotomy with Preoperative Embolization of Middle Meningeal Artery: A Case Report.

Endovascular embolization of the middle meningeal artery (MMA) has been reported as an effective method for treating chronic subdural hematoma (CSDH); however, its preventive effect on CSDH following craniotomy is unknown. We present a case in which MMA embolization was ineffective in preventing CSDH following craniotomy. A 56-year-old man who complained of diplopia was diagnosed with sphenoid ridge meningioma with a 3-cm diameter. MMA embolization prior to the operation and total surgical removal of the tumor were performed. Two months postoperatively, the patient complained of headache and hemiparesis of the left side. CSDH with a 15-mm thickness and a midline shift was observed. MMA embolization before inflammation may not play a role in preventing CSDH development because MMA embolization is considered effective in CSDH because it is associated with the blood supply of neovessels that are newly formed due to inflammation. Therefore, MMA embolization might not be effective in preventing the occurrence of CSDH following craniotomy.

Changes in the Relapse Pattern and Prognosis of Glioblastoma After Approval of First-Line Bevacizumab: A Single-Center Retrospective Study.

BACKGROUND: Controversies exist regarding the aggressive recurrence of glioblastoma after bevacizumab treatment. We analyzed the clinical impact of bevacizumab approval in Japan by evaluating the clinical course and relapse pattern in patients with glioblastoma. METHODS: We included 100 patients with IDH-wild-type glioblastoma from September 2006 to February 2018 in our institution. The patients were classified into the pre-bevacizumab (n = 51) and post-bevacizumab (n = 49) groups. Overall, progression-free, deterioration-free, and postprogression survivals were compared. We analyzed the relapse pattern of 72 patients, whose radiographic progressions were evaluated. RESULTS: Significant improvement in progression-free (pre-bevacizumab, 7.5 months; post-bevacizumab, 9.9 months; P = 0.0153) and deterioration-free (pre-bevacizumab, 8.5 months; post-bevacizumab, 13.8 months; P = 0.0046) survivals was seen. These survival prolongations were strongly correlated (r: 0.91, P < 0.0001). The nonenhancing tumor pattern was novel in the post-bevacizumab era (5 of 33). The presence of a nonenhancing tumor did not indicate poor postprogression survival (hazard ratio: 0.82 [0.26-2.62], P = 0.7377). The rate of early focal recurrence was significantly lower (P = 0.0155) in the post-bevacizumab (4 of 33) than in the pre-bevacizumab (18 of 39) era. There was a significant decrease in early focal recurrence after approval of bevacizumab in patients with unresectable tumors (P = 0.0110). The treatment era was significantly correlated with a decreased rate of early focal recurrence (P = 0.0021, univariate analysis; P = 0.0144, multivariate analysis). CONCLUSIONS: Approval of first-line bevacizumab in Japan for unresectable tumors may prevent early progression and clinical deterioration of glioblastoma without worsening the clinical course after relapse.

Efficacy of endoscopic treatment for chronic subdural hematoma surgery.

Endoscopic treatment is a potential therapeutic addition to chronic subdural hematoma (CSDH) surgery. However, the effect of endoscopic treatment remains controversial. Herein, we examined the optimal indication for endoscopic treatment in CSDH surgery. We retrospectively analyzed 380 consecutive patients with CSDH who underwent single burr-hole craniostomy. We defined postoperative rebleeding as radiological re-accumulation or increased computed tomography value of the hematoma. Reoperation was performed following further hematoma accumulation and/or neurological deterioration. Complicated CSDH was radiologically defined as a hematoma with a clot and/or fibrous septum. There were no differences in baseline characteristics or postoperative mortality and morbidity between the endoscope (97 patients) and control (283 patients) groups. The incidence of postoperative rebleeding (9.3% vs 25.1%, respectively; P = 0.001) and reoperation (0% vs 9.2%, respectively; P = 0.004) were significantly lower in the endoscope group versus controls. Multivariate analysis showed that males (odds ratio 2.14, 95% confidence interval 1.19-3.81; P = 0.012) and endoscopy (odds ratio 0.29, 95% confidence interval 0.13-0.59; P = 0.001) were independently associated with postoperative rebleeding. When CSDHs were divided into two types based on hematoma component, 175 patients exhibited complicated CSDH. There was a significant reduction in postoperative rebleeding (6.5% vs 23.0%, respectively; P = 0.010) and reoperation (0% vs 9.7%, respectively; P = 0.027) in complicated CSDH patients. Endoscopic treatment in CSDH surgery does not increase the risk of surgical complications. Complicated CSDH with a clot and/or septum may be an optimal indication for endoscopic treatment in CSDH surgery to reduce postoperative recurrence.

Volumetric study reveals the relationship between outcome and early radiographic response during bevacizumab-containing chemoradiotherapy for unresectable glioblastoma.

PURPOSE: Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBM), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of early radiographic responses in nd-GBM treated with BEV. METHODS: Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. An experienced neuroradiologist interpreted early responses on fluid-attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI). Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response Assessment in Neuro-Oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan-Meier analysis. RESULTS: The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p = 0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist's interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in the RANO criteria. However, even less stringent neuroradiologist interpretation could successfully predict OS prolongation (improved vs. non-improved: p = 0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20-50% (20%, p = 0.0315; 30%, p = 0.087; 40%, p = 0.0456). CONCLUSIONS: Early response during BEV-containing chemoradiation can be a predictive indicator of patient outcome in unresectable nd-GBM.

Mechanical Thrombectomy for Basilar Artery Occlusion Compared with Anterior Circulation Stroke.

OBJECTIVE: To investigate the clinical effectiveness of mechanical thrombectomy (MT) for basilar artery occlusion (BAO) and to ascertain whether outcomes for patients with BAO were comparable to those with anterior circulation large vessel occlusion (ACS). METHODS: A total of 345 patients who underwent MT between 2011 and 2018 were grouped by occlusion site (295 patients with ACS and 50 patients with BAO). Patients' baseline characteristics, procedural times, complications, symptomatic intracranial hemorrhage, modified Rankin Scale score, and mortality at 90 days were analyzed. RESULTS: Male preponderance (66.0% vs. 48.8%; P = 0.0316), younger age (72.5 years [interquartile range (IQR), 64.75-78.5 years] vs. 77 years [IQR 69-84 years]; P = 0.0297), higher National Institutes of Health Stroke Scale score (24.5 [IQR, 13-32] vs. 18 [IQR 13-22]; P = 0.0015) and higher reperfusion rate (100% vs. 84.7%; P = 0.0010) were observed in patients with BAO. We found no significant difference in favorable outcomes (modified Rankin Scale score ≤2) between patients with BAO and patients with ACS (64.3% vs. 49.3%; P = 0.0914). In multivariate analysis, Alberta Stroke Program Early Computed Tomography Score (odds ratio [OR], 1.282; 95% confidence interval [CI], 1.090-1.524; P = 0.0024), time from onset to reperfusion (OTR) (OR, 0.9950; 95% CI, 0.992-0.998; P = 0.0008), successful reperfusion (OR, 6.953; 95% CI, 1.576-48.729; P = 0.0092), and hemorrhagic complication (OR, 0.352; 95% CI, 0.151-0.797; P = 0.0122) were associated with a favorable outcome at 90 days in patients with ACS. In patients with BAO, only OTR (OR, 0.9879; 95% CI, 0.974-0.999; P = 0.0314) was associated with a favorable outcome at 90 days. CONCLUSIONS: MT may be considered the standard care for patients with BAO. OTR was the only common significant predictor for favorable outcomes in both patient cohorts.

A Direct Aspiration First Pass Technique in Japanese Real-World Clinical Setting.

BACKGROUND: It is debatable whether mechanical thrombectomy has benefits in a real-world setting outside the more rigid and selective clinical trial environment. OBJECTIVE: To evaluate clinical outcomes, efficacy, and safety of mechanical thrombectomy in single-center retrospective cohort case series. METHODS: We reviewed prospectively collected data from our large-vessel occlusion stroke database to identify patients undergoing mechanical thrombectomy using Penumbra catheters (Penumbra, Almeida, California) as first-line devices. The primary outcomes were the modified Rankin Scale score at 90 d and recanalization rate. The secondary outcomes included the rates of hemorrhagic complications and mortality. RESULTS: The entire study population included 298 patients. Thrombolysis in Cerebral Infarction Scale ≥2b was achieved in 86.6% of patients. Fifty-five patients (18.5%) were outside the 6 hr time window and 82 patients (27.5%) were over 80-yr old. The posterior circulation thrombectomy rate was 12.4%. At 90 d from onset, 49.3% of patients had favorable outcomes. The parenchymal hemorrhage type 2 (PH2) and subarachnoid hemorrhage rates were 2.3% and 11.7%, respectively. In multivariate analyses, cerebral blood flow/cerebral blood volume mismatch (odds ratio [OR] = 9.418; 95% confidence interval [CI], 3.680-27.726; P < .0001), onset to recanalization time (OR = 0.995; 95% CI, 0.991-0.998; P = .0003), and hemorrhagic complications including PH2 and subarachnoid hemorrhage (OR = 0.186; 95% CI, 0.070-0.455; P = .0002) were associated with favorable outcomes. CONCLUSION: A direct aspiration first pass technique with an adjunctive device demonstrated high recanalization rates in old Japanese patients. Our patient cohort may reflect the application of endovascular techniques in acute ischemic stroke treatment in a real-world setting.

Mechanical Thrombectomy for Acute Anterior Cerebral Artery Occlusion.

BACKGROUND: We sought to examine the presentation, treatment, and outcomes of anterior cerebral artery (ACA) occlusions in patients undergoing mechanical thrombectomy (MT). METHODS: Two-hundred ninety-eight consecutive patients with large-vessel occlusion treated with MT were analyzed to identify all patients with acute ACA occlusion who underwent MT. The primary end point was defined as achieving a thrombolysis in cerebral infarction score ≥2b. The secondary end point included the 90-day modified Rankin Scale (mRS) score and symptomatic intracranial hemorrhage. RESULTS: Nine patients with a median National Institutes of Health Stroke Scale score of 24 presented with acute ACA occlusion. The median time from onset to recanalization was 229 minutes. The ACA occlusion was a primary embolic occlusion in 5 patients, secondary to an interventional maneuver in 4 patients. Recanalization (thrombolysis in cerebral infarction ≥2b) was achieved in 9 of 9 patients (100%) without procedural complications. All patients had a 90-day mRS score ≥3, and 2 patients had an mRS score of 6. Two patients developed hemorrhagic infarction, and 1 patient had subarachnoid hemorrhage. CONCLUSIONS: Although MT can be considered in patients with ACA occlusions, our data suggest that future clinical trials are needed to determine the efficacy of MT for ACA occlusions. Unfavorable outcomes in our study were considered to occur because of a larger infarct volume due to internal carotid artery, middle cerebral artery, and anterior cerebral artery territory infarction. The time from onset to recanalization was longer because MT was performed for occlusions of multiple arteries.

Novel microguidewire-assist (MGA) manoeuver for coil embolisation of an unruptured middle cerebral artery aneurysm.

We describe here a novel yet very simple technique, called microguidewire-assist (MGA) manoeuvre, for coil embolisation of unruptured intracranial aneurysms. A 79-year-old woman with a small, broad-necked middle cerebral artery (MCA) bifurcation aneurysm that incorporated the orifice of the acute-angled M2 superior trunk underwent coil embolisation. Since the balloon assist technique was not feasible, we inserted and retained only the microguidewire through M1 to the M2 superior trunk; subsequently, with appropriate use of the microguidewire, coil embolisation was completed. The MGA manoeuvre resulted in slight vessel straightening and subsequent changes in the angulation of the aneurysmal neck, with which stable placement of the platinum coil was successfully accomplished. For coil embolisation of small, broad-necked MCA aneurysms that partially straddle the M2 trunk, this manoeuvre might provide an effective therapeutic alternative if other techniques are not feasible.

Recurrence in 787 Patients with Chronic Subdural Hematoma: Retrospective Cohort Investigation of Associated Factors Including Direct Oral Anticoagulant Use.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a highly recurrent disorder. Although some predictors including the use of antithrombotic agents such as aspirin and warfarin have been proposed, the pathogenic mechanism involved remains unclear. Moreover, the link between direct oral anticoagulant (DOAC) agent use and CSDH recurrence has not been reported. The aim of this study was to investigate factors including DOAC use that could potentially be associated with CSDH recurrence. METHODS: The authors analyzed 787 patients with CSDH who underwent surgery for CSDH with 1 burr-hole irrigation at Baba Memorial Hospital from January 2012 to November 2017. The patients were divided into recurrence and nonrecurrence groups and anticoagulant, antiplatelet, and control groups. Recurrence was defined as ipsilateral hemorrhage within 90 days from the original operation. Variables with P < 0.1 in the univariate analysis were included in a multivariate logistic regression model. RESULTS: CSDH recurrence was observed in 12.2% of patients, and significantly more men (80.2%) than women experienced recurrence. Age, sex, and warfarin use were entered in the multivariate analysis, and it was revealed that age and male sex were independently associated with CSDH recurrence. Antithrombotic agent use including use of DOACs was not associated with increased CSDH recurrence. CONCLUSIONS: The present study found that age and male sex were independently associated with CSDH recurrence, while the use of antithrombotic agents was not.

Basilar Artery Occlusion with "Seizures" as a Presenting Symptom: Three Cases Treated Using Mechanical Thrombectomy.

BACKGROUND: Basilar artery occlusion (BAO) is a rare, potentially fatal cause of ischemic stroke. It is often challenging to diagnose, especially when the presenting symptom is "seizures". We present 3 cases of patients with BAO presenting with seizures. CASE DESCRIPTION: The first patient was a 53-year-old man with clonic convulsions. On angiography, BAO was detected and mechanical thrombectomy (MT) was performed. The modified Rankin Scale score at 3 months after treatment was 1. The second patient was a 64-year-old man with generalized convulsions. He was diagnosed with BAO and vertebral artery dissection and was treated with MT, percutaneous transluminal angioplasty, and stenting. The modified Rankin Scale score at 3 months after treatment was 3. The third patient was a 77-year-old man with tonic convulsions. He was diagnosed with BAO and treated with MT. However, he did not survive. CONCLUSIONS: BAO is devastating; however, it is a treatable disease. Our report suggests that BAO should be suspected in patients presenting with initial convulsive seizures.

A case of delayed distal coil migration after coil embolization of an unruptured distal azygos anterior cerebral artery aneurysm: A case report and literature review.

Intraprocedural coil migration during endovascular treatment for an aneurysm that might carry serious ischemic complications is well known. On the other hand, delayed coil migration after endovascular treatment for an aneurysm is very rare. A 77-year-old woman was incidentally diagnosed with unruptured aneurysm associated with distal azygos anterior cerebral artery (ACA). The aneurysm was located at the distal bifurcation of the azygos ACA and was wide necked (approximately 7 mm in diameter). Endovascular coil embolization was selected and the aneurysm was occluded successfully, but 29 days after endovascular therapy, follow-up computed tomography (CT) and magnetic resonance (MR) angiography revealed distal coil migration in the peripheral portion of the ACA. In addition, CT on day 57 after therapy revealed the migrated coil had moved more distally. Fortunately, in the course of these events, the patient remained asymptomatic. To the best of our knowledge, this represents the first case of delayed distal coil migration associated with relatively rare azygos ACA aneurysm, and also the first report confirming more distal coil movement over time. In the future, a large number of patients could develop this complication as more aneurysms are aggressively treated with endovascular treatment. Knowledge regarding the possibility of delayed coil migration is thus important.

[Coil Embolization for Very Small Intracranial Aneurysms with Diameter Less than 3mm:A Case Series of 14 Patients and Literature Review].

INTRODUCTION: Many studies describe aneurysms measuring ≤3mm as "very small" or "tiny, " with a risk of intraoperative rupture higher than that of most cerebral aneurysms. We evaluated the results of endovascular coil embolization for very small aneurysms with diameter ≤3mm. MATERIAL AND METHODS: The same interventional neurosurgeon performed coil embolization for 14 tiny aneurysms in 14 patients(8male and 6 females)at our institution between May 2015 and June 2017. Patient age range was 42-88 years(average 65.6 years). Five aneurysms had ruptured and 9 were unruptured. Of the 9 unruptured aneurysms, 3 were associated with a previous ruptured aneurysm. We assessed the procedural complications, type of microcatheter and coils used, total number and length of coils, and angiographic results immediately after the procedure. RESULTS: In 14 aneurysm cases, 8 used only 1 pre-shaped microcatheter, 4 used 2, and 2 used 3;cases using multiple microcatheters added final shaping. Only one case used a helical first coil and the remaining 13 cases used a 3-dimensional coil. The number of coils used was 1 in 3 cases, 2 in 7 cases, 3 in 2 cases, and 4 in 2 cases. The total length of coils inserted was <5 cm in 5 cases, 5-10 cm in 5 cases, and >10 cm in 4 cases. The total length of coils used was <10cm in 70% of cases. Immediately after coil embolization, complete occlusion and a neck remnant were achieved in 11 and 3 cases, respectively. Ballooning was induced by intentionally introducing a balloon-assist technique during surgery in 7 cases, and the balloon was actually inflated in 4 cases. Complications were seen in 2 ruptured cases;1 had an intraoperative rupture, the other had parent artery occlusion, and both patients recovered. CONCLUSION: Coil embolization for tiny aneurysms can be performed comparatively safely by understanding the pitfalls and by using appropriate procedures and tools. Placing the catheter tip at the aneurysm neck is the first step and endovascular treatment is usually performed with ≤3 coils measuring ≤10 cm in total length. Complete embolization should be attempted, but even incomplete embolization is acceptable. More delicate coil embolization is required.

Optimal thresholds for ischemic penumbra predicted by computed tomography perfusion in patients with acute ischemic stroke treated with mechanical thrombectomy.

BACKGROUND AND PURPOSE: Optimal thresholds for ischemic penumbra detected by CT perfusion (CTP) in patients with acute ischemic stroke (AIS) have not been elucidated. In this study we investigated optimal thresholds for salvageable ischemic penumbra and the risk of hemorrhagic transformation (HT). METHODS: A total of 156 consecutive patients with AIS treated with mechanical thrombectomy (MT) at our hospital were enrolled. Absolute (a) and relative (r) CTP parameters including cerebral blood flow (aCBF and rCBF), cerebral blood volume (aCBV and rCBV), and mean transit time (aMTT and rMTT) were evaluated for their value in detecting ischemic penumbra in each of seven arbitrary regions of interest defined by the major supplying blood vessel. Optimal thresholds were calculated by performing receiver operating characteristic curve analysis in 47 patients who achieved Thrombolysis In Cerebral Infarction (TICI) grade 3 recanalization. The risk of HT after MT was evaluated in 101 patients who achieved TICI grade 2b-3 recanalization. RESULTS: Absolute CTP parameters for distinguishing ischemic penumbra from ischemic core were as follows: aCBF, 27.8 mL/100 g/min (area under the curve 0.82); aCBV, 2.1 mL/100 g (0.75); and aMTT, 7.30 s (0.70). Relative CTP parameters were as follows: rCBF, 0.62 (0.81); rCBV, 0.83 (0.87); and rMTT, 1.61 (0.73). CBF was significantly lower in areas of HT than in areas of infarction (aCBF, p<0.01; rCBF, p<0.001). CONCLUSIONS: CTP may be able to predict treatable ischemic penumbra and the risk of HT after MT in patients with AIS.