Ulceration location is associated with clinical course in carotid stenosis.

OBJECTIVE: Plaque ulceration in carotid artery stenosis is a risk factor for cerebral ischemic events; however, the characteristics that determine plaque vulnerability are not fully understood. We thus assessed the association between plaque ulceration sites and cerebrovascular ischemic attack. METHODS: We retrospectively collected the clinical data of 72 consecutive patients diagnosed with carotid artery stenosis with plaque ulcers. After excluding patients with pseudo-occlusion, a history of previous carotid endarterectomy (CEA) or carotid artery stenting (CAS) before the ulcer was first discovered, follow-up data of less than 1 month, or CEA or CAS performed within 1 month after the ulcer was first discovered, 60 patients were ultimately included. Patients were divided into proximal and distal groups based on the ulcer location relative to the most stenotic point. The primary endpoints were ipsilateral cerebrovascular ischemic events ("ischemic events"), such as amaurosis fugax, transient ischemic attack, or ischemic stroke due to carotid artery stenosis with plaque ulceration. The association between ulcer location and ischemic events was also assessed. RESULTS: In the patients with plaque ulcer, more patients had proximal than distal plaque ulcers (39 vs. 21, p=0.028). The median follow-up duration was 3.8 (interquartile range: 1.5-6.2) years. Nineteen patients (32%) experienced ischemic event. Ischemic events occurred more frequently in the distal than in the proximal group (18% vs. 59%; p=0.005). Kaplan-Meier curves demonstrated a significantly shorter event-free time in the distal group (log-rank p=0.021). In univariate analysis, distal ulcer location was associated with ischemic events (odds ratio [OR]: 2.94, 95% confidence interval [CI]: 1.13-7.65, p=0.03). Multivariate analysis using two different models also showed that distal ulcer location was independently associated with ischemic events (Model 1, OR: 3.85, 95%CI: 1.26-11.78, p=0.03; Model 2, OR: 4.31, 95%CI: 1.49-12.49, p=0.009). CONCLUSIONS: Patients with carotid artery stenosis and plaque ulcers located distal to the most stenotic point are more likely to experience cerebrovascular ischemic attacks. Therefore, carotid plaques with ulcers located distal to the most stenotic point may be a potential indication for surgical treatment.

One-Stage Combined Open and Endovascular Treatment Using a Hybrid Operating Room is Safe and Effective for Distal Middle Cerebral Artery Aneurysms.

BACKGROUND: Aneurysms located in the distal middle cerebral artery (DMCA) are relatively rare and lack an established treatment strategy. For DMCA aneurysms, we performed a one-stage combined procedure of endovascular parent artery occlusion (PAO) with coils and superficial temporal artery to middle cerebral artery (STA-MCA) bypass in a hybrid operating room (HOR). The aim of this study was to evaluate the safety and efficacy of this procedure. METHODS: Cases of unruptured DMCA aneurysms treated with the one-stage combined PAO and STA-MCA bypass in HOR were retrospectively examined, and patients' and aneurysmal backgrounds, surgical procedures, and treatment outcomes were analyzed. RESULTS: Six patients were included in the study. The average maximum diameter of the aneurysms was 14.4 mm. One aneurysm was located at M2 and five at M3. All aneurysms had a fusiform shape. No cases were associated with infection, trauma, or malignant tumors. In all 6 cases, the combined PAO and STA-MCA bypass was successfully completed. No postoperative hemorrhagic complications occurred. A symptomatic ischemic complication occurred in 1 case whose symptom disappeared in a week. Three months after surgery, complete obliteration of the aneurysm and patency of the bypass was confirmed in all cases. CONCLUSIONS: The one-stage combined PAO and STA-MCA bypass in the HOR is safe and effective for DMCA aneurysms, potentially serving as a treatment option for this complex aneurysm.

A Review of Current Flow Diverters.

Flow diverter (FD) devices are new-generation stents placed in the parent artery at the aneurysmal neck to obstruct intra-aneurysmal blood flow, thus favoring intra-aneurysmal thrombosis. In Japan, about eight years have passed since health insurance approval was granted for FD devices, and FD placement to treat aneurysms has become widespread. Treatment indications have also been expanded with the introduction of novel devices. At present, three types of FD (Pipeline, FRED, and Surpass Streamline) are available in Japan. This report represents a compilation of available FD technologies and describes the current consensus on this treatment.

Pathological changes in the lenticulostriate artery indicate the mechanisms leading to intracranial hemorrhage in Moyamoya disease: a case report.

This case report details the pathological findings of a vessel wall identified as the bleeding point for intracranial hemorrhage associated with Moyamoya disease. A 29-year-old woman experienced intracranial hemorrhage unrelated to hyperperfusion following superficial temporal artery-middle cerebral artery bypass surgery. A pseudoaneurysm on the lenticulostriate artery (LSA) was identified as the causative vessel and subsequently excised. Examination of the excised pseudoaneurysm revealed a fragment of the LSA, with a disrupted internal elastic lamina and media degeneration. These pathological findings in a perforating artery, akin to the circle of Willis, provide insights into the underlying mechanisms of hemorrhage in Moyamoya disease.

Vitamin D deficiency promotes intracranial aneurysm rupture.

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.

Plaque Ulcerations are Associated with Recurrence in Symptomatic Low-Grade Carotid Stenosis.

OBJECTIVE: Surgical indications for low-grade carotid stenosis have not yet been established. This study aimed to clarify the characteristics of low-grade carotid stenosis refractory to medical treatment. METHODS: We retrospectively analyzed 48 patients with symptomatic low-grade carotid stenosis (<50%). Recurrence was defined as an ipsilateral ischemic event in the symptomatic lesions during the follow-up period. Patient demographics and imaging findings were compared between the recurrence and nonrecurrence groups to investigate risk factors associated with medical treatment. RESULTS: The mean age was 74.1 (58-90 years), and the mean follow-up period was 35.4 months (2.0-97 months). Recurrence occurred in 15 of the symptomatic patients. Ulceration was significantly associated with recurrence under medical treatment (P = 0.001). The median time to recurrence was 26.1 months in patients with ulcers and 54.3 months in those without ulcers (P = 0.04). Pathological study with recurrence showed plaque rupture with multilayered lesions, indicating lesions refractory to medical treatment. CONCLUSIONS: In cases of low-grade carotid stenosis, lesions with ulcerations are likely refractory to medical therapy. Consideration of the indications for surgical treatment may be warranted for lesions with ulceration, even if the degree of stenosis is low.

Irreversible postoperative cognitive impairment after unruptured intracranial aneurysm treatment in the elderly.

PURPOSE: Postoperative cognitive dysfunction and recovery remain unclear in older patients undergoing interventional therapies for unruptured intracranial aneurysms (UIAs). This study aimed to compare changes in postoperative cognitive function between younger and older patients and to detect factors associated with non-recovery from postoperative cognitive dysfunction. METHODS: This study reviewed 59 consecutive patients with UIAs who underwent interventional therapies, including microsurgical clipping or endovascular treatment, from 2021 to 2022. All patients were divided into the older (aged ≥ 70 years) and younger (aged < 70 years) groups. Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) were performed within 2 months before interventions, at 1 week postoperatively (POW1), and 3-6 months postoperatively (POM3-6). RESULTS: MMSE and FAB scores decreased more frequently in the older group than in the younger group at POW1 (older vs. younger: MMSE: 48% vs. 21%, p < 0.05; FAB: 56% vs. 18%, p < 0.01). In the older group, the FAB Z-score decreased in POW1 and recovered by POM3-6 (p < 0.01), while the MMSE Z-score continued to decrease (p = 0.04). Age and the preoperative MSME Z-score were significantly associated with non-recovery from decreased MMSE score at POM3-6 (recovery vs. non-recovery, age: 62 years old vs. 72 years old, p = 0.03, preoperative MMSE Z-score: 0.16 vs. - 0.90, p < 0.01). CONCLUSIONS: This retrospective study found that older patients were more likely to have a postoperative cognitive decline after UIA treatment and implicated that global cognitive function tended to decline more than executive function in the long term. In addition, this study demonstrated that lower preoperative cognitive function was associated with inadequate postoperative cognitive recovery. The findings potentially contribute to the establishment of indications for treating UIAs in older patients.

Impact of tailored multimodal treatment for unruptured brain arteriovenous malformation: comparison with a randomized trial of unruptured brain arteriovenous malformations.

PURPOSE: The first randomized controlled study on unruptured brain arteriovenous malformations (bAVM), the ARUBA trial, demonstrate the superiority of medical management; however, it failed to completely rule out the efficacy of therapeutic interventions due to several limitations. This study aimed to examine the outcomes of multimodal interventional treatment for bAVM in terms of safety and efficacy. METHODS: We reviewed 226 consecutive patients with unruptured bAVM admitted to our institute between 2002 and 2022. Treatment methods were divided into medical management and therapeutic intervention, including microsurgery, stereotactic surgery, and endovascular intervention. First, the choice of therapeutic modalities was assessed in the pre-ARUBA (before February 2014) and post-ARUBA (after March 2014) eras. Second, the incidence of symptomatic stroke or death and functional prognosis with a modified Rankin scale (mRS) score of ≥2 at 5 years was compared between the medical management and therapeutic intervention. RESULTS: In the pre- and post-ARUBA groups, 73% and 84% of patients underwent therapeutic interventions, respectively (p = 0.053). The rate of symptomatic stroke or death was lower in patients who underwent interventional therapies than in those who underwent medical management (9.7% vs. 22%, p = 0.022); however, the opposite was observed in the ARUBA trial (31% vs. 10%). The annual incidence of stroke or death was also lower in the interventional therapy group (4.3%/y vs. 1.8%/year, hazard ratio = 0.45, 95% confidence interval: 0.18-1.08, p = 0.032). The rate of mRS score of ≥2 after a 5-year follow-up was 18% and 6% in the medical treatment and intervention groups (p = 0.14). CONCLUSIONS: The therapeutic intervention rate did not decrease, even after the publication of the ARUBA trial. The rate of stroke or death was lower in the intervention group, indicating that a tailored choice of multimodality is safe and effective for managing unruptured bAVM.

[Changes in Gamma Knife Radiosurgery(GKRS)in Patients with Metastatic Brain Tumors before and after COVID-19].

The spread of coronavirus disease 2019(COVID-19)is a concern as it may delay the detection of malignant tumors due to delayed medical checkups. We examined changes in the treatment of metastatic brain tumors before and after COVID- 19. A retrospective review of 211 patients with metastatic brain tumors who underwent initial gamma knife radiosurgery between July 2019 and December 2021 was conducted. Data collected include patient age, gender, the Karnofsky performance status(KPS), primary tumor control, number, total volume, and outcome during the COVID-19 emergency declaration period and outside of it. The patient number was 164 outside of the emergency period and 47 during the period. Symptomatic cases(KPS<90)and poor control of the primary site increased during the COVID-19 period. The treatment number and volume of brain metastasis did not change. Metastatic control after 4 months of treatment also showed no difference. The number of symptomatic patients increased during the emergency declaration period, suggesting that COVID- 19 may have reduced the rate of asymptomatic patients being seen. However, these were not enough to affect the prognosis at 4 months. Overall, the COVID-19 pandemic had a small impact on the provision of stereotactic radiotherapy for metastatic brain tumors.

Impact of Morphological Factors on the Future Growth of Unruptured Posterior Communicating Artery Aneurysms.

BACKGROUND: No previous study has established the factors associated with intracranial aneurysm growth using imaging data obtained before the appearance of morphological changes. Therefore, we investigated the factors related to future aneurysm growth in posterior communicating artery (Pcom) aneurysms. METHODS: Using a longitudinal database of intracranial aneurysm cases, we reviewed the findings for consecutive patients with unruptured Pcom aneurysms admitted to our institute from 2012 to 2021. Magnetic resonance images obtained over time were used to evaluate aneurysm growth. Aneurysms showing growth over time (group G) and unchanged aneurysms (group U) were compared in terms of background data and morphological factors. RESULTS: 93 Pcom aneurysms (group G: 25 aneurysms, 25%; group U: 68 aneurysms, 75%) were eligible for the present study. Six aneurysm rupture events occurred in group G (24%). Among morphological factors, Pcom diameter (1.2 ± 0.3 mm vs. 0.8 ± 0.7 mm, P < 0.01), bleb formation (group G: 39% vs. group U: 10%; odds ratio, 5.6; P = 0.01), and the lateral projection of the dome (group G: 52% vs. group U: 13%; odds ratio, 3.2; P = 0.023) were significantly different between the 2 groups. The sensitivity and specificity of a cutoff Pcom diameter of 0.73 mm for predicting enlargement were 96% and 53%, respectively. CONCLUSIONS: Pcom diameter, bleb formation, and lateral dome projection were associated with growth of Pcom aneurysms. Aneurysms with these risk factors require careful follow-up imaging, which may facilitate early detection of aneurysm growth and prevention of rupture through therapeutic interventions.

Aspect Ratio Is Associated with Recanalization after Coiling of Unruptured Intracranial Aneurysms.

The rate of recanalization after coil embolization for unruptured intracranial aneurysms (UIAs) is reported to occur around 11.3%-49%. This study aims to investigate the factors that influence the recanalization after coil embolization for UIAs in our institution. We retrospectively investigated 307 UIAs in 296 patients treated at our institution between April 2004 and December 2016. The stent-used cases were excluded. Cerebral angiography and 3D time-of-flight magnetic resonance angiography (TOF MRA) were used for evaluation of the postoperative occlusion status. Volume embolization ratio (VER), aneurysmal size, neck width, and aspect ratio (AR) were compared between the recanalized and non-recanalized groups. The mean follow-up period ranged from 6 to 172 months (mean: 79.0 ± 39.8 months). Recanalization was noted in 78 (25.4%) aneurysms, and 19 (6.2%) aneurysms required retreatment. There was no aneurysmal rupture during the follow-up period. Univariate analysis showed that the aneurysm size (p < 0.001), neck width (p < 0.001), AR (p = 0.003), and VER (p = 0.012) were associated with recanalization. Multivariate logistic regression analysis showed that the AR (p =0.004) and VER (p =0.015) were significant predictors of recanalization. To summarize, a higher AR and a lower VER could lead to recanalization after coil embolization of UIAs. Careful follow-up is required for coiled aneurysms with these features.

Coronary artery aneurysms of unknown origin in a 14-year-old girl.

The case of a 14-year-old girl with acute myocardial infarction due to coronary artery aneurysms (CAAs) of unknown origin, which resembled coronary artery lesions caused by Kawasaki disease, is reported. She was transferred to our hospital due to chest pain with ST-T elevation. She had no history of Kawasaki disease. On the first admission, she was misdiagnosed with acute myocarditis. Then, 54 days later, she experienced chest pain with exertional dyspnea. Her electrocardiogram showed negative T waves in the chest leads. A CAA of the left coronary artery was suspected on two-dimensional echocardiography. Coronary angiograms showed 90% stenosis and multiple CAAs of the left anterior descending artery and the bifurcation of the left coronary artery. Both the right coronary artery and left circumflex artery were occluded. A left ventriculogram showed dyskinesis and an aneurysm at the apex. She underwent triple-vessel coronary artery bypass grafting, and her symptoms improved. In addition, an intracranial aneurysm was also found on cerebral angiography. There were no specific laboratory findings other than SS-A antibodies. It was suspected that the weakness of the vessels was related to the disease. It may have been a different disease that was never previously detected, but her CAAs were Kawasaki-like CAAs.

Impact on Clinical Outcomes of Changes in the Practice of Mechanical Thrombectomy due to the COVID-19 Pandemic.

Objective: To evaluate whether changes in the practice of mechanical thrombectomy could affect the clinical outcomes during the coronavirus disease (COVID-19) pandemic. Methods: Patients who underwent mechanical thrombectomy from April 2019 to March 2021 for anterior circulation proximal large artery occlusion in our institute were divided into two groups of pre- and post-COVID-19, with April 2020 assumed to be the start of the COVID-19 era with the first declaration of a state of emergency. We compared patient characteristics, proportions of patient selection depending on rapid processing of perfusion and diffusion (RAPID) CT perfusion, outcomes including treatment variables such as time and reperfusion status, and patient independence at 3 months. Results: Data for 112 patients (median age, 79 years; 44 females) were included in the analysis. A total of 50 patients were assigned to the pre-COVID-19 group (45%). More patients were selected with RAPID CT perfusion in the post-COVID-19 compared with the pre-COVID-19 (69% vs. 16%; P <0.001). Treatment details and clinical outcomes did not differ between the groups, including the door-to-puncture time (median [interquartile range], 66 [54-90] min vs. 74 [61-89] min; P = 0.15), proportions of significant reperfusion (82% vs. 87%; P = 0.60), and modified Rankin scale score of ≤2 at 3 months (46% vs. 45%; P >0.99). Multivariate logistic regression analysis for the clinical outcome of modified Rankin scale score of ≤2 at 3 months was performed and included the following factors: age, sex, the onset-to-door time, significant reperfusion, and pre- and post-COVID-19. The treatment period did not influence the outcomes (post-COVID-19 group, odds ratio, 0.79; 95% confidence interval, 0.34-1.85, P = 0.59). Conclusion: In the setting of a limited access to emergency MRI during the COVID-19 pandemic, RAPID CT perfusion was performed significantly more often. Changes in the practice of mechanical thrombectomy with the protected code stroke did not bring the different level of treatment and clinical outcomes as before.

Transvenous Coil-plugging Technique for a Symptomatic Giant Varix Associated with Arteriovenous Malformation.

In case of symptomatic varix associated with cerebral arteriovenous malformations (AVM), nidus is usually treated with transarterial embolization (TAE). However, TAE is not always possible due to inaccessible nidus. A man in his 40s presented with numbness and clumsiness in the right hand. Magnetic resonance imaging (MRI) and cerebral angiography revealed a giant varix associated with an AVM nidus in the left parietal lobe. The varix severely compressed the postcentral gyrus with edema. The main feeder was occluded, and tiny collateral vessels fed the nidus. After admission, his symptoms deteriorated rapidly due to the enlarging varix. To extirpate the varix, selective transvenous embolization (TVE) of a small compartment, the varix neck, between the varix and the main cortical drainer with coils was performed. After treatment, the thrombosed varix gradually shrank, and his symptoms improved. The transvenous coil-plugging technique is a potential strategy for symptomatic varix with a varix neck.

Calcium-Binding Protein S100A4 Is Upregulated in Carotid Atherosclerotic Plaques and Contributes to Expansive Remodeling.

Background Carotid plaques with expansive arterial remodeling are closely related to cerebral ischemic events. Although S100A4 (S100 calcium-binding protein A4) is expressed in atherosclerotic lesions, its role in atherosclerotic plaque progression remains unknown. In this study, we examined the association between carotid arterial expansive remodeling and S100A4 expression. Methods and Results Preoperative high-resolution magnetic resonance imaging was used to assess luminal stenosis and vascular remodeling in patients undergoing carotid endarterectomy. To examine murine carotid atherosclerosis, we induced experimental lesions by flow cessation in apolipoprotein E-deficient mice fed a high-fat diet. The role of S100A4 in plaque formation and smooth muscle cell proliferation was investigated in vivo and in vitro, respectively. Human carotid arterial expansive remodeling showed positive correlations with the expression of S100A4, MMP2, and MMP9. S100A4 mRNA levels were positively correlated with those of MMP2, MMP9, and MMP13. S100A4 was expressed in vascular smooth muscle cells (VSMCs) and VSMC-derived foam cells in the plaque shoulder and marginal areas. S100A4 expression increased concomitantly with plaque formation in our animal model. Exogenous recombinant S100A4 protein enhanced the levels of Mmp2, Mmp9, and Mmp13 and the cell proliferation ability in VSMCs. A chemotaxis assay indicated that extracellular S100A4 functions as a chemoattractant for VSMCs. Conclusions S100A4 expression was elevated in human carotid plaques and showed a positive correlation with the degree of expansive remodeling. S100A4-positive VSMC-derived cells are considered to play an important role in carotid expansive remodeling.

Osteoprotegerin Prevents Intracranial Aneurysm Progression by Promoting Collagen Biosynthesis and Vascular Smooth Muscle Cell Proliferation.

Background Decreased extracellular matrix formation and few vascular smooth muscle cells (VSMCs) in cerebral vascular walls are the main characteristics of intracranial aneurysm (IA) pathogenesis. Recently, osteoprotegerin was reported to activate collagen biosynthesis and VSMC proliferation via the TGF-ß1 (transforming growth factor-ß1) signaling. This study aimed to investigate whether osteoprotegerin can prevent IA progression in rats through enhanced collagen expression and VSMC proliferation. Methods and Results IAs were surgically induced in 7-week-old male Sprague-Dawley rats; at 1-week post-operation, recombinant mouse osteoprotegerin or vehicle control was continuously infused for 4 weeks into the lateral ventricle using an osmotic pump. In the osteoprotegerin-treatment group, the aneurysmal size was significantly smaller (37.5 µm versus 60.0 µm; P<0.01) and the media of IA walls was thicker (57.1% versus 36.0%; P<0.01) than in the vehicle-control group. Type-I and type-III collagen, TGF-ß1, phosphorylated Smad2/3, and proliferating cell nuclear antigen were significantly upregulated in the IA walls of the osteoprotegerin group than that in the control group. No significant difference was found in the expression of proinflammatory genes between the groups. In mouse VSMC cultures, osteoprotegerin treatment upregulated the expression of collagen and TGF-ß1 genes, and activated VSMC proliferation; the inhibition of TGF-ß1 signaling nullified this effect. Conclusions Osteoprotegerin suppressed the IA progression by a unique mechanism whereby collagen biosynthesis and VSMC proliferation were activated via TGF-ß1 without altering proinflammatory gene expression. Osteoprotegerin may represent a novel therapeutic target for IAs.