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Orbital cavernous venous malformation (OCVM) is a sporadic vascular anomaly of uncertain etiology characterized by abnormally dilated vascular channels. Here, we identify a somatic missense mutation, c.121G > T (p.Gly41Cys) in GJA4, which encodes a transmembrane protein that is a component of gap junctions and hemichannels in the vascular system, in OCVM tissues from 25/26 (96.2%) individuals with OCVM. GJA4 expression was detected in OCVM tissue including endothelial cells and the stroma, through immunohistochemistry. Within OCVM tissue, the mutation allele frequency was higher in endothelial cell-enriched fractions obtained using magnetic-activated cell sorting. Whole-cell voltage clamp analysis in Xenopus oocytes revealed that GJA4 c.121G > T (p.Gly41Cys) is a gain-of-function mutation that leads to the formation of a hyperactive hemichannel. Overexpression of the mutant protein in human umbilical vein endothelial cells led to a loss of cellular integrity, which was rescued by carbenoxolone, a non-specific gap junction/hemichannel inhibitor. Our data suggest that GJA4 c.121G > T (p.Gly41Cys) is a potential driver gene mutation for OCVM. We propose that hyperactive hemichannel plays a role in the development of this vascular phenotype.
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Mutação com Ganho de Função , Malformações Vasculares , Humanos , Células Endoteliais , Junções Comunicantes/genética , Mutação , Veias , Malformações Vasculares/metabolismoRESUMO
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.
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Malformações Arteriovenosas , Hemangioma Cavernoso do Sistema Nervoso Central , Humanos , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Encéfalo , ConvulsõesRESUMO
OBJECTIVE: The characteristics of pregnancy and delivery in patients with moyamoya disease (MMD) remain unclear. We retrospectively investigated perinatal outcomes in patients with MMD to evaluate the risks associated to this condition. MATERIALS AND METHODS: Clinical data of women with MMD who delivered at the University of Tokyo Hospital between 2000 and 2021 were collected. Maternal characteristics including genetic data, obstetric complications, method of delivery and anesthesia, neonatal outcomes, neurological events during pregnancy, delivery, and postpartum course, were reviewed. RESULTS: Thirteen pregnancies with MMD were identified. The median maternal age was 30 years. The initial clinical symptoms were identified as transient ischemic attack, infarction, and headache. Eight patients had a history of bypass surgery. The median gestational age at delivery was 37 weeks. DNA samples were collected from five patients, responsible for six pregnancies. Of these six cases, five had the RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variant. Of the 13 pregnancies, seven had hypertensive disorder of pregnancy (HDP). Additionally, three of five pregnancy cases with RNF213 p.Arg4810Lys heterozygous variant presented with HDP. Nine patients underwent cesarean section, and four delivered vaginally with epidural anesthesia. One case of ischemic stroke was confirmed during the postpartum period. Regarding newborns, neither Apgar scores lower than 7 nor neonatal intensive care unit admissions were reported. CONCLUSIONS: This study suggests that the frequency of HDP is higher in patients with MMD compared to those with normal pregnancies. Strict blood pressure control should be performed in patients with MMD during pregnancy and postpartum period.
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BACKGROUND: Transcarotid artery revascularization (TCAR) has emerged as an alternative to carotid artery stenting (CAS). TCAR demonstrated its superiority by avoiding femoral artery puncture and establishing proximal protection without crossing the stenotic lesion. In the TCAR era, we focused on the possibility of a trans-distal radial approach (DRA). A balloon-guide catheter was navigated via DRA to establish proximal protection before lesion crossing. The forearm subcutaneous vein was used as the flow-reversal circuit. METHODS: Six internal carotid artery stenosis patients underwent CAS using "the forearm flow reversal technique." Every procedure was performed under continuous flow reversal from the common carotid artery to the forearm cephalic vein. RESULTS: Successful revascularization was achieved without ischemic or access-site complications. The distal radial artery was patent at discharge in all cases. CONCLUSIONS: Trans-distal radial CAS with forearm flow reversal is a feasible and less invasive technical option.
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Estenose das Carótidas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/cirurgia , Estenose das Carótidas/complicações , Antebraço/cirurgia , Artéria Radial/cirurgia , Fatores de Risco , Stents/efeitos adversos , Artéria Carótida Primitiva , Resultado do Tratamento , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Procedimentos Endovasculares/efeitos adversosRESUMO
BACKGROUND AND IMPORTANCE: Flow diverters (FDs) provide curative endovascular treatment for wide-necked sidewall aneurysms. The efficacy of FDs for bifurcation or branching sidewall aneurysms is probably limited. We used anatomical flow diversion (AFD) for intractable large cerebral aneurysms. We report our experiences with AFD. METHODS: The concept of AFD is the transformation from the bifurcation or branching sidewall type to the nonbranching sidewall type. Linearization of the parent artery by stenting, intentional branch occlusion, and aneurysmal coil embolization were performed. Furthermore, bypass surgery is performed for patients intolerant to branch occlusions. We evaluated the clinical outcomes of intractable aneurysms treated with AFD. RESULTS: AFD was performed in seven unruptured large aneurysms. Aneurysmal locations were the top of the basilar artery (BA), BA-superior cerebellar artery (SCA), internal carotid artery (IC)-posterior communicating artery (PcomA), and IC terminal. The mean dome diameter was 17.0 ± 4.6 mm. Six patients underwent bypass surgery. The occluded branches were the PCA + SCA, PcomA, and anterior cerebral artery (ACA) A1. An FD was used in three patients and a neck bridge stent in four patients. No intraprocedural complications occurred. Two postprocedural ischemic complications occurred in one patient. Six (86%) patients demonstrated a modified Rankin Scale (mRS) 0 at the 3-month follow-up, and one with an ischemic complication showed an mRS 5. Complete occlusion of all aneurysms was maintained with a median follow-up duration of 60 months. CONCLUSION: AFD is useful for intractable large cerebral aneurysms with high curability, although safety verification is required.
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BACKGROUND: Transvenous embolization (TVE), such as selective shunt occlusion, is the first line treatment for cavernous sinus dural arteriovenous fistula (CSDAVF). Despite the favorable outcomes of TVE, some cases necessitating retreatment due to recurrence or incomplete occlusion persist. Given the physical, psychological, and financial burden of multiple treatments, understanding the predictive factors for recurrence, spontaneous occlusion, or retreatment is important. However, few reports have addressed these factors, complicating decision making regarding the need for retreatment. This study analyzed predictive factors for retreatment and spontaneous occlusion to offer new insights into CSDAVF management. METHODS: This retrospective, observational study was conducted in two acute care hospitals. Patients aged 18-100 years undergoing endovascular treatment for CSDAVF from January 2011 to December 2022 were included. RESULTS: Of 65 patients treated with TVE, 29 experienced immediate complete occlusion. Meanwhile, 22 of 36 patients with incomplete occlusion had spontaneous occlusion, and retreatment was performed in 20% of patients. Additional outlet occlusion was negatively associated with retreatment (P=0.046), and it tended to promote spontaneous occlusion (P=0.056). Favorable functional outcomes were observed in all patients, and approximately 94% of patients showed complete occlusion at the latest follow-up. CONCLUSION: TVE is an effective treatment for CSDAVF. Outlet occlusion, when immediate complete occlusion is unattainable, is important to reduce retreatment and promote spontaneous occlusion. Substantially reducing shunt flow, carefully assessing dangerous drainage routes, and closely monitoring the residual shunt are crucial for preventing intracranial hemorrhage when outlet occlusion is performed.
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BACKGROUND: The supreme anterior connecting artery (SAConnA) is an exceedingly rare anatomical variant. This artery may interconnect bilateral anterior cerebral arteries (ACAs), yet its existence and clinical implications are scarcely discussed in the literature. CASE DESCRIPTION: A 60-year-old man with no significant past medical or family history presented to our emergency department. He exhibited right homonymous hemianopsia and Gerstmann's syndrome. Cranial computed tomography indicated a left parietal lobar hemorrhage, and digital subtraction angiography revealed a flow-related aneurysm in the anterior communicating artery, with the arteriovenous malformation (AVM) receiving blood supply from the anterior, middle, and posterior cerebral arteries. Notably, the angiography also disclosed the presence of a SAConnA. We adopted a treatment approach of staged embolizations followed by resection. During the second session, the SAConnA was utilized for the embolization of feeding arteries within the ACA system. CONCLUSIONS: This case demonstrates that SAConnA can be associated with AVMs and can serve as an access route during AVM embolization. SAConnA may be a remnant artery interconnecting bilateral ACAs formed during early embryogenesis.
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PURPOSE: Some aneurysms remain patent after treatment with flow diverters (FD) due to residual blood flow in the aneurysm. Several studies have proposed that branches and residual flow are associated with delayed aneurysm occlusion. We propose that aneurysm isolation (i.e., the complete disconnection of the aneurysm from surrounding vessels) might be a possible factor facilitating aneurysm occlusion. This study aimed to determine if aneurysm isolation was a factor associated with aneurysm occlusion after FD treatment. METHODS: We reviewed 80 internal carotid artery (ICA) aneurysms treated with FDs between October 2014 and April 2021. Aneurysm isolation was assessed in high-resolution cone-beam computed tomograms at the end of each treatment. Aneurysms with incorporated branches and those with connections to other branches due to stent malapposition were deemed to be nonisolated. Other factors, such as patient age, sex, anticoagulant use, aneurysm size, adjunct coil use, and the presence of incorporated branches, were considered. The degree of aneurysm occlusion (complete or incomplete) was assessed by follow-up angiograms 12 months after treatment. RESULTS: Complete occlusion was achieved in 57 of 80 aneurysms (71%). Completely occluded aneurysms had a significantly higher ratio of isolation compared to incompletely occluded aneurysms (91.2% vs. 69.6%, Pâ¯= 0.032). Multivariate logistic regression analysis showed that aneurysm isolation was the sole significant predictor of complete aneurysm occlusion (odds ratio, OR 19.38; 95% confidence interval, CI 2.280-164.657; Pâ¯= 0.007). CONCLUSION: Aneurysm isolation is a significant factor contributing to complete occlusion after FD treatment.
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Doenças das Artérias Carótidas , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/terapia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Stents , Resultado do Tratamento , Masculino , FemininoRESUMO
OBJECTIVE: Prevention of rebleeding events is crucial for patients with hemorrhagic moyamoya disease (MMD), as these increase the risk of mortality. Bypass surgery is effective in preventing subsequent hemorrhage, particularly in patients with posterior hemorrhage, but its efficacy in those with anterior hemorrhage remains unclear. We analyzed the effects of surgical intervention, stroke risk factors, and radiological features on rebleeding events. METHODS: Patients with hemorrhagic-onset MMD who were followed at our institution between 2000 and 2022 were included (41 adult patients, 45 hemispheres). Baseline characteristics and radiological features (anterior or posterior hemorrhagic site, Suzuki grade, posterior cerebral artery involvement, and periventricular anastomosis) were thoroughly reviewed. RESULTS: Of the 45 hemispheres, hemorrhage developed in 9 (20%) hemispheres, with a median duration until rebleeding of 38 (range: 1-44) months. Rebleeding rates were significantly lower in the surgical group than in the nonsurgical group (odds ratio: 0.09; 95% confidence interval [CI]: 0.01-0.79; P = 0.011), and Kaplan-Meier analysis revealed a significantly longer interval between bleeding events in the surgical group (1.3%/y vs. 5.3%/y; P = 0.002), especially in the anterior hemorrhage group (1.3%/y vs. 5.1%/y; P = 0.019). The hazard ratio of surgical intervention for rebleeding with initial anterior hemorrhage was 0.11 (95% CI: 0.01-0.98; P = 0.048). In the nonsurgical group, the presence of hypertension shortened the time to subsequent hemorrhage (P = 0.004). CONCLUSIONS: Surgical intervention may decrease the risk of rebleeding in hemorrhagic onset MMD patients, even in those presenting with anterior hemorrhage. Hypertension was a significant risk factor for rebleeding in nonsurgical patients.
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Revascularização Cerebral , Hipertensão , Doença de Moyamoya , Adulto , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Hemorragia Cerebral/etiologia , Resultado do Tratamento , Revascularização Cerebral/efeitos adversos , Hipertensão/complicaçõesRESUMO
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.
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Revascularização Cerebral , Doença de Moyamoya , Neoplasias , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Idoso , Doença de Moyamoya/cirurgia , Estudos Retrospectivos , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Revascularização Cerebral/efeitos adversosRESUMO
PURPOSE: Arteriovenous fistulas (AVFs) adjacent to the clivus, such as cavernous sinus dural AVFs (CSDAVFs) and condylar AVFs, sometimes have an intraosseous shunted pouch and recruit blood supply from transosseous feeders. Precise analysis of transosseous feeders regarding the clival lesion has not yet been performed. Therefore, this study aimed to clarify the characteristics and identity of transosseous feeders in clival lesions. METHODS: Patients with CSDAVFs and condylar AVFs, who underwent high-resolution cone-beam computed tomography or three-dimensional rotational angiography in our institute, were included. The frequency, type of branch, penetrating point, and termination of intraosseous feeders were retrospectively evaluated. RESULTS: A total of 31 patients with 36 lesions in CSDAVFs and 8 patients with 8 lesions in condylar AVFs underwent angiography. For CSDAVFs, 38 transosseous feeders were detected in 23 out of 31 patients, including 22 in the pharyngeal branch of the ascending pharyngeal artery (APhA), 6 in the hypoglossal branch of the APhA, 6 in the accessory meningeal artery, 3 in the meningohypophyseal trunk (MHT), and 1 in the anterior branch of the middle meningeal artery. For condylar AVFs, 24 transosseous feeders were detected in all 8 patients, including 11 in the pharyngeal branches of the APhA, 7 in the hypoglossal branch of the APhA, 6 in the segmental artery from the vertebral artery, and 2 in the MHT. CONCLUSION: Transosseous feeders of AVFs around the clivus, which are frequently seen in AVFs of this area, mainly arise from ventral clival branches and from pharyngeal branches of the APhA.
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Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Humanos , Angiografia Cerebral/métodos , Estudos Retrospectivos , Artérias , Malformações Vasculares do Sistema Nervoso Central/terapia , Fossa Craniana Posterior/diagnóstico por imagem , Fossa Craniana Posterior/cirurgia , Embolização Terapêutica/métodosRESUMO
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.
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Revascularização Cerebral , Doença de Moyamoya , Adulto , Criança , Humanos , Masculino , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/genética , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/genética , Isquemia/complicações , Revascularização Cerebral/efeitos adversosRESUMO
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.
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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.
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Neoplasias Meníngeas , Meningioma , Neurofibromatose 2 , Humanos , Macrófagos , Neoplasias Meníngeas/genética , Meningioma/genética , Neurofibromatose 2/complicações , Neurofibromatose 2/genética , Estudos RetrospectivosRESUMO
Background: Despite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies. Case presentation: We report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach. Conclusion: Gene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.
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BACKGROUND: The transradial artery approach to cerebral angiography can reduce both patient stress following examination and the risk of major complications due to hematoma. Recently, the distal radial artery approach (DRA) has garnered attention in cardiology as a minimally invasive method. DRA is also considered applicable to neurosurgery, although concerns about procedural difficulty and complications persist. Therefore, this study aimed to evaluate the efficacy of the DRA in cerebral angiography and neuroendovascular treatment. METHODS: We retrospectively selected 30 consecutive patients for whom the DRA was attempted for cerebral angiography at our hospital. The patients' age, sex, height, weight, and medical history information was collected and correlated with successful puncture and complications. The diameter of the distal radial artery (RA) was measured using ultrasonography. RESULTS: The median patient age was 67 years (range, 32-87 years) and 21 (70%) were men. The median diameter of the distal RA was 2.3 mm (range, 1.7-3.2 mm). Distal RA puncture was successful in 23 patients (77%) and no complications were noted; however there was no significant correlation between successful puncture and any of the patient factors. Carotid artery stenting and preoperative tumor embolization were performed via DRA in six and three cases, respectively. Although puncture site hematoma occurred in only one case, all treatments were successful, and no major complications were observed. CONCLUSION: DRA can be safely used for cerebral angiography and neuroendovascular treatment.
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Stenotic developmental venous anomalies (DVAs) often present with neurological deficits. In addition, cerebral capillary telangiectasia (CCT) coexisting with DVA is rarely encountered, and its pathophysiology, including the underlying genetics, and appropriate management remain uncertain. A 46-year-old man without any medical history of note was referred to our hospital with gradually worsening cerebellar ataxia. Two months after symptom onset, ataxic dysarthria and gait emerged. Brain magnetic resonance imaging showed CCT occupying the pons and left cerebellar peduncle. Subsequent catheter angiography demonstrated a DVA leading from the mass into the cavernous sinus with marked outlet stenosis and flow stagnation. We hypothesized that venous congestion was the source of gradual neurological deterioration and therefore initiated anticoagulation. Symptoms showed mild improvement, and his neurological status has remained stable as of 1 year after symptom onset. Whole-exome sequencing of germline DNA did not reveal any rare variants in genes previously reported as pertinent to vascular malformations. Anticoagulation may be a useful option in patients with non-thrombotic, stenotic DVA for whom neurological status did not improve under expectant management. Genetic analysis of this patient did not reveal any pathogenic mutations, and further investigation of somatic mutations is necessary to elucidate potential genetic causes.
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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.
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Neoplasias Meníngeas , Meningioma , Criança , Homozigoto , Humanos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/terapia , Meningioma/genética , Meningioma/patologia , Meningioma/terapia , Deleção de Sequência , Organização Mundial da SaúdeRESUMO
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.
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The relationship between RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variants and clinical manifestation in patients with Moyamoya disease (MMD) remains unclear. We performed a retrospective cohort analysis to clarify the genotype-phenotype correlation of this RNF213 hotspot variant in MMD patients, especially between wild-type (GG) and heterozygous (GA) genotypes. Clinical and genetic data were obtained from patients diagnosed with MMD in our institutions between October 2011 and November 2020. Clinical data included age, sex, neurological status at diagnosis, medical history, smoking history, alcohol intake, and family history. Of the 225 enrolled patients, 160 (71.1%) were symptomatic, 3 (1.3%) had the homozygous variant, and 149 (66.2%) had the heterozygous variant (GA). Analysis of all enrolled patients showed that the GA group was prone to present bilateral symptoms (p = 0.008) and progressive status (Suzuki grade ≥ 4; p = 0.017). Analysis limited to symptomatic patients revealed that the GA group had bilateral symptoms (p = 0.017), younger age at onset (p = 0.043), and, in particular, a higher proportion of onset before 25 years of age (p = 0.021). Multivariate logistic regression analysis of overall patients revealed that earlier age at diagnosis (p < 0.001, OR 0.936, 95% CI 0.914-0.959) and GA group (p = 0.017, OR 3.326, 95%CI 1.237-8.941) were significantly associated with bilateral symptoms. MMD patients diagnosed at a young age with the RNF213 heterozygous variant should be followed up with consideration of possible contralateral stroke if one hemisphere is already symptomatic or of early cerebrovascular events if bilateral hemispheres are asymptomatic.