Association of Genetic Variants with Postoperative Donor Artery Development in Moyamoya Disease: RNF213 and Other Moyamoya Angiopathy-Related Gene Analysis.

Robust postoperative bypass development is a characteristic of moyamoya disease (MMD); however, genetic factors mediating this phenomenon remain incompletely understood. Therefore, we aimed to elucidate the relationship between postoperative donor artery development and genetic variants. We retrospectively enrolled 63 patients (79 hemispheres) who underwent combined revascularization surgery. Postoperative development of the superficial temporal artery (STA), middle meningeal artery, and deep temporal artery (DTA) was assessed using the caliber-change ratio determined from magnetic resonance angiography measurements. We analyzed RNF213 and 36 other moyamoya angiopathy-related genes by whole-exome sequencing and extracted rare or damaging variants. Thirty-five participants carried RNF213 p.Arg4810Lys (all heterozygotes), whereas 5 had RNF213 rare variants (RVs). p.Arg4810Lys was significantly associated with postoperative DTA development, while age at surgery, hypertension, and hyperlipidemia were inversely associated. Multiple regression analysis revealed that age and p.Arg4810Lys held statistical significance (P = 0.044, coefficient - 0.015, 95% confidence interval (CI) - 0.029 to 0.000 and P = 0.001, coefficient 0.670, 95% CI 0.269 to 1.072, respectively). Those with RNF213 RV without p.Arg4810Lys exhibited a significant trend toward poor DTA development (P = 0.001). Hypertension demonstrated a significant positive association with STA development, which remained significant even after multiple regression analysis (P = 0.001, coefficient 0.303, 95% CI 0.123 to 0.482). Following Bonferroni correction for multiple comparisons, targeted analyses of RNF213 and 36 moyamoya angiopathy-related genes showed a significant association of only RNF213 p.Arg4810Lys with favorable DTA development (P = 0.001). A comprehensive analysis of RNF213, considering both p.Arg4810Lys and RVs, may provide a clearer prediction of postoperative DTA development.

Intracranial aneurysm wall displacement depicted by amplified Flow predicts growth.

BACKGROUND: Abnormal intracranial aneurysm (IA) wall motion has been associated with IA growth and rupture. Recently, a new image processing algorithm called amplified Flow (aFlow) has been used to successfully track IA wall motion by combining the amplification of cine and four-dimensional (4D) Flow MRI. We sought to apply aFlow to assess wall motion as a potential marker of IA growth in a paired-wise analysis of patients with growing versus stable aneurysms. METHODS: In this retrospective case-control study, 10 patients with growing IAs and a matched cohort of 10 patients with stable IAs who had baseline 4D Flow MRI were included. The aFlow was used to amplify and extract IA wall displacements from 4D Flow MRI. The associations of aFlow parameters with commonly used risk factors and morphometric features were assessed using paired-wise univariate and multivariate analyses. RESULTS: aFlow quantitative results showed significantly (P=0.035) higher wall motion displacement depicted by mean±SD 90th% values of 2.34±0.72 in growing IAs versus 1.39±0.58 in stable IAs with an area under the curve of 0.85. There was also significantly (P<0.05) higher variability of wall deformation across IA geometry in growing versus stable IAs depicted by the dispersion variables including 121-150% larger standard deviation ([Formula: see text]) and 128-161% wider interquartile range [Formula: see text]. CONCLUSIONS: aFlow-derived quantitative assessment of IA wall motion showed greater wall motion and higher variability of wall deformation in growing versus stable IAs.

POLR2A Mutation is a Poor Prognostic Marker of Cerebellopontine Angle Meningioma.

BACKGROUND AND OBJECTIVES: Recent molecular analyses have shown that the driver genetic mutations of meningiomas were associated with the anatomic location. Among these, POLR2A mutation is common among lesions in the skull base, mainly in the cerebellopontine angle (CPA). The objective of this study was to investigate the efficacy of POLR2A mutation as a prognostic marker for CPA meningiomas. METHODS: We retrospectively analyzed the clinical data of 70 patients who had World Health Organization grade I CPA meningiomas. Somatic DNA was analyzed by Sanger sequencing and microsatellite array to examine for NF2, AKT1, KLF4, SMO, and POLR2A mutations and 22q loss. Genetic and clinical parameters were analyzed to identify the factors related with tumor recurrence. RESULTS: We detected clearly the clinical features of the CPA cases with POLR2A mutation. Compared with cases without POLR2A mutation, cases with POLR2A mutation had more meningothelial type (P = 6.9 × 10-4), and higher rate of recurrence (P = .04). We found that the poor prognostic factors associated with the recurrence of CPA meningiomas were POLR2A mutation (P = .03, hazard ratio [HR] 9.38, 95% CI 1.26-70.0) and subtotal resection (STR) (P = 5.1 × 10-4, HR 63.1, 95% CI 6.09-655.0). In addition, in the group that underwent STR, POLR2A mutation was a poor prognostic factor associated with tumor recurrence (P = .03, HR 11.1, 95% CI 1.19-103.7). CONCLUSION: POLR2A mutation and STR were the poor prognostic markers associated with the recurrence of CPA meningioma. For CPA meningioma cases that underwent STR, only POLR2A mutation was a poor prognostic factor. Detecting POLR2A mutation may be a cost-effective, easy, and useful marker for prognostication.

Imaging Biomarkers and Prevalence of Complex Aortic Plaque in Cryptogenic Stroke: A Systematic Review.

BACKGROUND: Complex aortic plaque (CAP) is a potential embolic source in patients with cryptogenic stroke (CS). We review CAP imaging criteria for transesophageal echocardiogram (TEE), computed tomography angiography (CTA), and magnetic resonance imaging and calculate CAP prevalence in patients with acute CS. METHODS AND RESULTS: PubMed and EMBASE databases were searched up to December 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Two independent reviewers extracted data on study design, imaging techniques, CAP criteria, and prevalence. The Cochrane Collaboration tool and Guideline for Reporting Reliability and Agreement Studies were used to assess risk of bias and reporting completeness, respectively. From 2293 studies, 45 were reviewed for CAP imaging biomarker criteria in patients with acute CS (N=37 TEE; N=9 CTA; N=6 magnetic resonance imaging). Most studies (74%) used ≥4 mm plaque thickness as the imaging criterion for CAP although ≥1 mm (N=1, CTA), ≥5 mm (N=5, TEE), and ≥6 mm (N=2, CTA) were also reported. Additional features included mobility, ulceration, thrombus, protrusions, and assessment of plaque composition. From 23 prospective studies, CAP was detected in 960 of 2778 patients with CS (0.32 [95% CI, 0.24-0.41], I2=94%). By modality, prevalence estimates were 0.29 (95% CI, 0.20-0.40; I2=95%) for TEE; 0.23 (95% CI, 0.15-0.34; I2=87%) for CTA and 0.22 (95% CI, 0.06-0.54; I2=92%) for magnetic resonance imaging. CONCLUSIONS: TEE was commonly used to assess CAP in patients with CS. The most common CAP imaging biomarker was ≥4 mm plaque thickness. CAP was observed in one-third of patients with acute CS. However, high study heterogeneity suggests a need for reproducible imaging methods.

Meningiomas in patients with neurofibromatosis type 2 predominantly comprise 'immunogenic subtype' tumours characterised by macrophage infiltration.

Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm3/year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages.

Cerebrovascular Events During Treatment for Systemic Malignant Tumors in Patients with Moyamoya Disease.

OBJECTIVE: With the increasing incidence of malignancies, the importance of cancer-associated stroke is emphasized. Although moyamoya disease is a leading cause of stroke, no reports have documented cancer-associated stroke in patients with this condition. We aimed to investigate cerebrovascular events during malignancy treatments in patients with moyamoya disease. METHODS: A total of 405 patients with moyamoya disease who visited our hospital between January 2000 and March 2022 were retrospectively examined. We evaluated the management of moyamoya disease, presence of the ring finger protein 213 p.Arg4810Lys variant, treatments for malignant tumors, presence of cerebrovascular events during treatment, and follow-up periods and outcomes. RESULTS: Among the 405 patients, 17 patients with moyamoya disease (4.2%) were diagnosed with malignancies. Among patients aged 60 years and over, 7 out of 67 (10.4%) had malignancies. Of the 17 patients, 11 (64.7%) were symptomatic, and 7 (41.2%) had revascularization surgery. 9 patients were treated with oral antiplatelet drugs. There was no significant difference between the groups with and without malignancy regarding the presence of the ring finger protein 213 p.Arg4810Lys variant (80.0% vs. 62.7%, P = 0.33). All patients underwent surgical treatment, and 7 (41.2%) received chemotherapy. One death due to tumor progression was reported. No cerebrovascular event was observed during malignancy treatments and follow-up periods, which had a mean duration of 6 years. CONCLUSIONS: In our cohort, malignancy treatments in patients with moyamoya disease were safely conducted without cerebrovascular events. However, it is advisable to avoid hypotension, dehydration, hyperventilation, and long-term discontinuation of antiplatelet drugs during the treatment of malignant tumors.

Complete Recanalization in Mechanical Thrombectomy Is Associated with Favorable Functional Outcome for M2 Occlusions.

Objective: There are insufficient coherent reports on mechanical thrombectomy (MT) for occlusion of the second segment of the middle cerebral artery (M2 occlusion) in a real-world clinical setting. We evaluated the efficacy and safety of MT for M2 occlusions and compared the primary thrombectomy strategies (stent retriever, aspiration catheter, and combined technique) to analyze factors predicting good functional outcomes. Methods: We evaluated background factors, preprocedural factors, procedural factors, and procedural time for patients who underwent MT for M2 occlusions from our retrospective cohort. According to the modified Rankin Scale (mRS) score three months after MT, patients were divided into good (mRS ≤2) and poor (mRS ≥3) prognosis groups. Results: A total of 29 patients (median age, 78 years; 11 [37.9%] females) were included in the study. In this cohort, rates of successful reperfusion, thrombolysis in cerebral infarction (TICI) 3, postprocedural hemorrhage (PPH), and symptomatic PPH were 82.8, 34.5, 31.0, and 0%, respectively. Good prognoses were achieved in 13 (45%) cases. A prognostic factor of MT for M2 occlusions is TICI 3 from multivariate analysis (OR, 11.7; 95% CI, 1.003-136; p = 0.0497). There was no statistically significant difference in the functional outcome three months after MT based on the choice of the primary thrombectomy strategy. Conclusion: MT for M2 occlusions is a reliable and relatively safe procedure. The presence of TICI 3 was a prognostic factor in this cohort. Future studies are warranted to investigate the optimal thrombectomy strategy for medium vessel occlusion.

RNF213 p.Arg4810Lys Wild Type is Associated with De Novo Hemorrhage in Asymptomatic Hemispheres with Moyamoya Disease.

Clinical implications of RNF213 genetic variants, other than p.Arg4810Lys, in moyamoya disease (MMD), remain unclear. This study aimed to investigate the association of RNF213 variants with clinical phenotypes in MMD. This retrospective cohort study collected data regarding the clinical characteristics of 139 patients with MMD and evaluated the angioarchitectures of 253 hemispheres using digital subtraction angiography at diagnosis. All RNF213 exons were sequenced, and the associations of clinical characteristics and angiographical findings with p.Arg4810Lys, p.Ala4399Thr, and other rare variants (RVs) were examined. Among 139 patients, 100 (71.9%) had p.Arg4810Lys heterozygote (GA) and 39 (28.1%) had the wild type (GG). Fourteen RVs were identified and detetcted in 15/139 (10.8%) patients, and p.Ala4399Thr was detected in 17/139 (12.2%) patients. Hemispheres with GG and p.Ala4399Thr presented with significantly less ischemic events and more hemorrhagic events at diagnosis (p = 0.001 and p = 0.028, respectively). In asymptomatic hemispheres, those with GG were more susceptible to de novo hemorrhage than those with GA (adjusted hazard ratio [aHR] 5.36) with an increased risk when accompanied by p.Ala4399Thr or RVs (aHR 15.22 and 16.60, respectively). Within the choroidal anastomosis-positive hemispheres, GG exhibited a higher incidence of de novo hemorrhage than GA (p = 0.004). The GG of p. Arg4810Lys was a risk factor for de novo hemorrhage in asymptomatic MMD hemispheres. This risk increased with certain other variants and is observed in choroidal anastomosis-positive hemispheres. A comprehensive evaluation of RNF213 variants and angioarchitectures is essential for predicting the phenotype of asymptomatic hemispheres in MMD.

Validation of multiparametric MRI based prediction model in identification of pseudoprogression in glioblastomas.

BACKGROUND: Accurate differentiation of pseudoprogression (PsP) from tumor progression (TP) in glioblastomas (GBMs) is essential for appropriate clinical management and prognostication of these patients. In the present study, we sought to validate the findings of our previously developed multiparametric MRI model in a new cohort of GBM patients treated with standard therapy in identifying PsP cases. METHODS: Fifty-six GBM patients demonstrating enhancing lesions within 6 months after completion of concurrent chemo-radiotherapy (CCRT) underwent anatomical imaging, diffusion and perfusion MRI on a 3 T magnet. Subsequently, patients were classified as TP + mixed tumor (n = 37) and PsP (n = 19). When tumor specimens were available from repeat surgery, histopathologic findings were used to identify TP + mixed tumor (> 25% malignant features; n = 34) or PsP (< 25% malignant features; n = 16). In case of non-availability of tumor specimens, ≥ 2 consecutive conventional MRIs using mRANO criteria were used to determine TP + mixed tumor (n = 3) or PsP (n = 3). The multiparametric MRI-based prediction model consisted of predictive probabilities (PP) of tumor progression computed from diffusion and perfusion MRI derived parameters from contrast enhancing regions. In the next step, PP values were used to characterize each lesion as PsP or TP+ mixed tumor. The lesions were considered as PsP if the PP value was < 50% and TP+ mixed tumor if the PP value was ≥ 50%. Pearson test was used to determine the concordance correlation coefficient between PP values and histopathology/mRANO criteria. The area under ROC curve (AUC) was used as a quantitative measure for assessing the discriminatory accuracy of the prediction model in identifying PsP and TP+ mixed tumor. RESULTS: Multiparametric MRI model correctly predicted PsP in 95% (18/19) and TP+ mixed tumor in 57% of cases (21/37) with an overall concordance rate of 70% (39/56) with final diagnosis as determined by histopathology/mRANO criteria. There was a significant concordant correlation coefficient between PP values and histopathology/mRANO criteria (r = 0.56; p < 0.001). The ROC analyses revealed an accuracy of 75.7% in distinguishing PsP from TP+ mixed tumor. Leave-one-out cross-validation test revealed that 73.2% of cases were correctly classified as PsP and TP + mixed tumor. CONCLUSIONS: Our multiparametric MRI based prediction model may be helpful in identifying PsP in GBM patients.

Recurrent glioblastoma metastatic to the lumbar vertebra: A case report and literature review: Surgical oncology.

Background: Glioblastoma is a malignant tumor, and its prognosis is as poor as 1.5 to 2 years. Most cases recur within one year even under the standard treatment. The majority of recurrences are local, and in rare cases, metastasize mostly within the centra nervous system. Extradural metastasis of glioma is exceedingly rare. Here, we present a case of vertebral metastasis of glioblastoma. Case presentation: We present a 21-year-old man post total resection of the right parietal glioblastoma, diagnosed with lumbar metastasis. He originally presented with impaired consciousness and left hemiplegia and underwent gross total resection of the tumor. Given the diagnosis of glioblastoma, he was treated with radiotherapy combined with concurrent and adjuvant temozolomide. Six months after tumor resection, the patient presented with severe back pain, and was diagnosed as metastatic glioblastoma on the first lumbar vertebrae. Posterior decompression with fixation and postoperative radiotherapy were conducted. He went on to receive temozolomide and bevacizumab. However, at 3 months after the diagnosis of lumbar metastasis, further disease progression was noted, and his care was transitioned to best supportive care. Comparison on copy number status between primary and metastatic lesions on methylation array analysis revealed more enhanced chromosomal instability including 7p loss, 7q gain and 8 gain in the metastatic lesion. Conclusion: Based upon the literature review and our case, younger age of initial presentation, multiple surgical interventions, and long overall survival seem to be the risk factors of vertebral metastasis. As the prognosis of glioblastoma improves over time, its vertebral metastasis is seemingly more common. Therefore, extradural metastasis should be kept in mind in the treatment of glioblastoma. Further, detailed genomic analysis on multiple paired specimens is mandated to elucidate the molecular mechanisms of vertebral metastasis.

Clinical and Genetic Characteristics of Patients with Moyamoya Disease who Experienced Both Ischemic and Hemorrhagic Events.

OBJECTIVE: Cerebrovascular events in moyamoya disease are mainly classified into ischemic or hemorrhagic onset. It is rare for one patient to develop both ischemia and hemorrhage in moyamoya disease; detailed clinical course and genetic characteristics of such patients have not been elucidated. We aimed to clarify the clinical features of patients with both ischemic and hemorrhagic cerebrovascular events. METHODS: We analyzed the background factors, radiological features, and genotype of ring finger protein 213 c.14429 G > A (p.Arg4810Lys) of patients with moyamoya disease who visited our hospital between 1996 and 2020, and experienced both ischemic and hemorrhagic cerebrovascular events. Additionally, we analyzed factors that caused subsequent hemorrhage in adult-onset ischemic moyamoya disease. RESULTS: Of 262 patients, 12 presented with both ischemia and hemorrhage, of which, 4 exhibited pediatric onset and 8 had adult onset. In pediatric-onset subjects, ischemia was the initial event in all cases. Hemorrhagic events occurred at a median of 24.7 years postoperatively in patients who had undergone bypass surgery. In adult-onset subjects, ischemia preceded hemorrhage in 7 patients. In males, the interval to subsequent hemorrhage was significantly shorter for adult-onset ischemic moyamoya disease, and the hazard ratio for hemorrhagic events was 5.45. The ring finger protein 213 p.Arg4810Lys heterozygous variant was present in 9 patients. CONCLUSIONS: A majority of patients with moyamoya disease with both ischemia and hemorrhage experience an ischemic event first. Patients who developed ischemia in childhood may develop subsequent hemorrhage in approximately 20-25 years after bypass surgery. Male sex is a risk factor for a subsequent hemorrhagic event in adult-onset ischemic moyamoya disease.

Genetics of brain arteriovenous malformations and cerebral cavernous malformations.

Cerebrovascular malformations comprise abnormal development of cerebral vasculature. They can result in hemorrhagic stroke due to rupture of lesions as well as seizures and neurological defects. The most common forms of cerebrovascular malformations are brain arteriovenous malformations (bAVMs) and cerebral cavernous malformations (CCMs). They occur in both sporadic and inherited forms. Rapidly evolving molecular genetic methodologies have helped to identify causative or associated genes involved in genesis of bAVMs and CCMs. In this review, we highlight the current knowledge regarding the genetic basis of these malformations.

Vessel wall MR imaging of aortic arch, cervical carotid and intracranial arteries in patients with embolic stroke of undetermined source: A narrative review.

Despite advancements in multi-modal imaging techniques, a substantial portion of ischemic stroke patients today remain without a diagnosed etiology after conventional workup. Based on existing diagnostic criteria, these ischemic stroke patients are subcategorized into having cryptogenic stroke (CS) or embolic stroke of undetermined source (ESUS). There is growing evidence that in these patients, non-cardiogenic embolic sources, in particular non-stenosing atherosclerotic plaque, may have significant contributory roles in their ischemic strokes. Recent advancements in vessel wall MRI (VW-MRI) have enabled imaging of vessel walls beyond the degree of luminal stenosis, and allows further characterization of atherosclerotic plaque components. Using this imaging technique, we are able to identify potential imaging biomarkers of vulnerable atherosclerotic plaques such as intraplaque hemorrhage, lipid rich necrotic core, and thin or ruptured fibrous caps. This review focuses on the existing evidence on the advantages of utilizing VW-MRI in ischemic stroke patients to identify culprit plaques in key anatomical areas, namely the cervical carotid arteries, intracranial arteries, and the aortic arch. For each anatomical area, the literature on potential imaging biomarkers of vulnerable plaques on VW-MRI as well as the VW-MRI literature in ESUS and CS patients are reviewed. Future directions on further elucidating ESUS and CS by the use of VW-MRI as well as exciting emerging techniques are reviewed.

NF2 Alteration/22q Loss Is Associated with Recurrence in WHO Grade 1 Sphenoid Wing Meningiomas.

Sphenoid wing meningiomas account for 11−20% of all intracranial meningiomas and have a higher recurrence rate than those at other sites. Recent molecular biological analyses of meningiomas have proposed new subgroups; however, the correlation between genetic background and recurrence in sphenoid wing meningiomas has not yet been fully elucidated. In this study, we evaluated the clinical characteristics, pathological diagnosis, and molecular background of 47 patients with sphenoid wing meningiomas. Variants of NF2, AKT1, KLF4, SMO, POLR2A, PIK3CA, TRAF7, and TERT were determined using Sanger sequencing, and 22q loss was detected using multiplex ligation-dependent probe amplification. Alterations were localized at NF2 in 11 cases, had other genotypes in 17 cases, and were not detected in 12 cases. Interestingly, WHO grade 1 meningiomas with NF2 alteration/22q loss (p = 0.008) and a MIB-1 labeling index > 4 (p = 0.03) were associated with a significantly shorter recurrence-free survival, and multivariate analysis revealed that NF2 alteration/22q loss was associated with recurrence (hazard ratio, 13.1). The duration of recurrence was significantly shorter for meningiomas with NF2 alteration/22q loss (p = 0.0007) even if gross-total resection was achieved. Together, these findings suggest that NF2 alteration/22q loss is associated with recurrence in WHO grade 1 sphenoid wing meningiomas.

Advances in Molecular Biological and Translational Studies in World Health Organization Grades 2 and 3 Meningiomas: A Literature Review.

The treatment of World Health Organization (WHO) grades 2 and 3 meningiomas remains difficult and controversial. The pathogenesis of high-grade meningiomas was expected to be elucidated to improve treatment strategies. The molecular biology of meningiomas has been clarified in recent years. High-grade meningiomas have been linked to NF2 mutations and 22q deletion. CDKN2A/B homozygous deletion and TERT promoter mutations are independent prognostic factors for WHO grade 3 meningiomas. In addition to 22q loss, 1p, 14p, and 9q loss have been linked to high-grade meningiomas. Meningiomas enriched in copy number alterations may be biologically invasive. Furthermore, several new comprehensive classifications of meningiomas have been proposed based on these molecular biological features, including DNA methylation status. The new classifications may have implications for treatment strategies for refractory aggressive meningiomas because they provide a more accurate prognosis compared to the conventional WHO classification. Although several systemic therapies, including molecular targeted therapies, may be effective in treating refractory aggressive meningiomas, these drugs are being tested. Systemic drug therapy for meningioma is expected to be developed in the future. Thus, this review aims to discuss the distinct genomic alterations observed in WHO grade 2 and 3 meningiomas, as well as their diagnostic and therapeutic implications and systemic drug therapies for high-grade meningiomas.

Definition and time course of pericavity edema after minimally invasive endoscopic intracerebral hemorrhage evacuation.

BACKGROUND: Perihematomal edema (PHE) volume correlates with intracerebral hemorrhage (ICH) volume and is associated with functional outcome. Minimally invasive surgery (MIS) for ICH decreases clot burden and PHE. MIS may therefore alter the time course of PHE, mitigating a critical source of secondary injury. OBJECTIVE: To describe a new method for the quantitative measurement of cerebral edema surrounding the evacuated hematoma cavity, termed pericavity edema (PCE), and obtain details of its time course following MIS for ICH. METHODS: The study included 48 consecutive patients presenting with ICH who underwent MIS evacuation. Preoperative and postoperative CT scans were assessed by two independent raters. Hematoma, edema, cavity, and pneumocephalus volumes were calculated using semi-automatic, threshold-guided volume segmentation software (AnalyzePro). Follow-up CT scans at variable delayed time points were available for 36 patients and were used to describe the time course of PCE. RESULTS: Mean preoperative, postoperative, and delayed PCE were 21.0 mL (SD 15.5), 18.6 mL (SD 11.4), and 18.4 mL (SD 15.5), respectively. The percentage of ICH evacuated correlated significantly with a decrease in postoperative PCE (r=-0.46, p<0.01). Linear regression analysis revealed a significant relation between preoperative hematoma volume and both postoperative PCE (p<0.001) and postoperative relative PCE (p<0.001). The mean peak PCE was 26.4 mL (SD 15.6) and occurred at 6.5 days (SD 4.8) post-ictus. The 2-week postoperative time course of relative PCE did not fluctuate, suggesting stability in edema during the perioperative period surrounding evacuation and up to 2 weeks after the initial bleed. CONCLUSIONS: We present a detailed and accurate method for measuring PCE volume with semi-automatic, threshold-guided segmentation software in the postoperative patient with ICH. Decrease in PCE after MIS evacuation correlated with evacuation percentage, and relative PCE remained stable after minimally invasive endoscopic ICH evacuation.

Mechanical Thrombectomy for ICA Top Occlusion with Twig-Like MCA: A Case Report.

Objective: We report a case of hemorrhagic complication after mechanical thrombectomy (MT) for internal carotid artery (ICA) occlusion with twig-like middle cerebral artery (MCA). Case Presentation: A 75-year-old man was admitted to our hospital with ICA occlusion. Recanalization was achieved by a direct aspiration first pass technique (ADAPT). The peripheral MCA was twig-like, but operators thought that a thrombus remained in the MCA first segment. The procedure was continued and suspended with perforation of the microguidewire. Conclusion: When performing MT for large vessel occlusion (LVO) with twig-like MCA, it is difficult to proceed a device to the periphery and there is a risk of hemorrhage.

CT Perfusion collateral index in assessment of collaterals in acute ischemic stroke with delayed presentation: Comparison to single phase CTA.

BACKGROUND & PURPOSE: Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients. METHODS: ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS. RESULTS: A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p<0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p = 0.001) and good functional outcome (p = 0.003). CONCLUSION: CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging marker of collateral status in patients with delayed presentation of AIS.

Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis.

Neoplastic programmed cell death ligand 1 (PD-L1) expression, activated by PD-L1 gene alterations, is strongly associated with classic Hodgkin lymphoma (CHL). This association enabled a diagnostic consensus for lymphocyte-depleted CHL (LD-CHL), a previously enigmatic disease. We describe two patients with LD-CHL and primary extranodal disease. One patient was a 92-year-old female (Case #1) with a large mass that involved the uterus combined with swollen lymph nodes in the pelvic cavity. The second patient was a 76-year-old female (Case #2) with human T-cell leukemia virus type 1 (HTLV-1) who initially exhibited massive bone marrow involvement without peripheral lymphadenopathies. Biopsies of these tumors from the cervix uteri and bone marrow, respectively, revealed lesions rich in Hodgkin and Reed-Sternberg (H-RS) cells and diminished populations of other cell populations. Immunohistochemistry demonstrated that these H-RS cells expressed CD30, BOB1, and fascin, but not CD15, CD20, PAX5, or OCT2. They also expressed PD-L1, which led to our preferred diagnosis of LD-CHL in both patients. Epstein-Barr virus was associated with LD-CHL in Case #1, but not in Case #2. Both patients were deemed too frail for treatment. They died of disease at 1 (Case #1) and 15 months (Case #2) after the diagnosis. These findings highlight the abnormal biological behavior of this immune-escape-related lymphoid neoplasm in patients with immunodeficiency due to immune senescence and HTLV1 infection.

Linear Pinched Hemorrhoidectomy: A Retrospective Observational Study (An Innovative, Simplified Hemorrhoidectomy).

OBJECTIVES: There was an urgent need to create a simple, reliable hemorrhoidectomy procedure for high-risk cases in our university hospital. We performed linear pinched hemorrhoidectomy (LPH) and evaluated its effectiveness compared to conventional hemorrhoidectomy (CH). METHODS: We included 215 Goligher grade 3 and 4 hemorrhoid cases in this study. Of these cases, 167 were in the CH group, and 48 patients were in the LPH group. We retrospectively compared the lengths of hospital stay, operative times, blood loss, and complications. RESULTS: The age tended to be higher in the LPH group (mean: CH 60 years, LPH 68 years). In the univariate analysis, LPH had more resections, shorter operative times, and less blood loss. LPH had shorter operative times in the multivariate analysis, less blood loss, and more anticoagulant use. There were no significant differences between the two groups in terms of complications. Five and two patients in the CH and LPH groups, respectively, had postoperative hemorrhage requiring hemostasis. Only the CH group had three and four cases of anal stenosis and wound edema, respectively. CONCLUSIONS: We studied simplified hemorrhoidectomy using an ultrasonic scalpel and cylindrical proctoscope in a university hospital. We found that it a useful procedure with few complications and was easy for residents to learn. We believe that advances in surgical devices will make it possible to perform safer and simpler hemorrhoidectomy in the future.