Impact of atherosclerotic etiology on technical and clinical outcomes of mechanical thrombectomy with a stent retriever: subanalysis of the Japan Trevo Registry.

BACKGROUND: The safety and effectiveness of stent retriever use for patients with acute large vessel occlusion (LVO) due to intracranial atherosclerotic disease (ICAD) is not well established. We investigated the differences in clinical outcomes in patients with and without ICAD. METHODS: We analyzed the Japan Trevo Registry, a nationwide registry which enrolled patients with acute LVO who underwent endovascular therapy (EVT) using the Trevo retriever alone or in combination with an aspiration catheter. We compared the technical and clinical outcomes of EVT between the ICAD and No-ICAD groups. The primary outcome was effective reperfusion and the secondary outcome was modified Rankin scale (mRS) score 0-2 at 90 days. Safety outcomes were worsening of neurologic symptoms within 24 hours, any intracranial hemorrhage within 24 hours, vessel dissection/vessel perforation related to using the Trevo retriever and mortality at 90 days. RESULTS: A total of 835 patients (45 in the ICAD group and 790 in the No-ICAD group) were analyzed. In the ICAD group, more men (68.9% vs 50.8%, P=0.02) and a lower median National Institutes of Health Stroke Scale score at admission (11 vs 18, P<0.0001) were observed. The primary outcome was significantly more common in the No-ICAD group (92.5%) than in the ICAD group (80.0%) (adjusted odds ratio (aOR) 0.21, 95% CI 0.09 to 0.50). The proportion of patients with mRS score 0-2 at 90 days was significantly lower in the ICAD group (44.4% vs 42.4%, aOR 0.49, 95% CI 0.23 to 1.00, P=0.0496). Other secondary and safety outcomes were not significantly different between the two groups. CONCLUSIONS: Patients with LVO with ICAD had a lower rate of effective reperfusion than those with No-ICAD.

Perioperative Antiplatelet Management in the Flow-Diverter Treatment for Unruptured Cerebral Aneurysms: A Single-Center, Retrospective Analysis.

BACKGROUND: Although periprocedural antiplatelet therapy for the treatment of unruptured intracranial aneurysms (UIAs) using flow-diverter stents (FDSs) is necessary to avoid thromboembolic complications, a definite antiplatelet therapy has not been established. We aimed to evaluate the safety and efficacy of periprocedural antiplatelet management in UIA treatment with FDS. METHODS: A single-center retrospective analysis of consecutive patients with UIAs treated with FDSs between September 2013 and January 2022 was conducted. Patients received dual antiplatelet therapy (DAPT) (aspirin and clopidogrel) for 14-day before and 3-6 months after FDS placement. Platelet aggregation was evaluated prior to treatment using light transmission aggregometry, which was classified into 3 grades; 1-3: promoted, 4-6: appropriate, and 7-9: non-responder, for adenosine diphosphate (ADP) and collagen. By this classification, the antiplatelet regimen was modified. Outcome included hemorrhagic and ischemic events. RESULTS: 193 patients with 200 UIAs underwent 213 FDSs placement. The median platelet aggregability grade before treatment was 5 for ADP and 4 for collagen. Antiplatelet therapy modification was performed in 62 patients (32.1%). The median postoperative DAPT duration was 94 days. Antiplatelet medicine-related hemorrhagic events occurred in 4 patients (2.1%) and ischemic events occurred in 6 patients (3.1%). These patients had no morbido-mortality. CONCLUSIONS: Periprocedural antiplatelet management based on the value of platelet aggregability was relatively safe and effective for treating UIA with FDS.

Endovascular therapy for acute intracranial large vessel occlusion due to atherothrombosis: Multicenter historical registry.

BACKGROUND: Atherothrombotic stroke-related large vessel occlusion (AT-LVO) is caused by two etiologies, the intracranial artery occlusion due to in situ occlusion (intracranial group) or due to embolism from cervical carotid occlusion or stenosis (tandem group). The prognosis and reocclusion rate of each etiology after endovascular therapy (EVT) is unclear. METHODS: We conducted a historical multicenter registry study at 51 Japanese centers to compare the prognoses of AT-LVO between two etiologies. The primary outcome was the incidence of recurrent ischemic stroke or reocclusion of the treated vessels within 90 days after EVT. Each of the primary outcome means the incidence of recurrent ischemic stroke and reocclusion of the treated vessels within 90 days after EVT. RESULTS: We analyzed 582 patients (338 in the intracranial group and 244 in the tandem group). Patients in the intracranial group were younger (mean 71.9 vs 74.5, p=0.003), more of them were female and fewer of them were current smokers than those in the tandem group. In the tandem group, the patients' National Institutes of Health Stroke Scale score on admission was higher (13 vs 15, p=0.006), onset to puncture time was shorter (299 [145-631] vs 232 [144-459] minutes, p=0.03) and Alberta Stroke Program Early CT Score (ASPECTS) was lower (8 [7-9] vs 8 [6-9], p=0.0002). The primary outcome was higher in the intracranial group (22.5% vs 8.2%, p<0.0001). However, any ICH and death were not significantly different in the two groups. CONCLUSIONS: The incidence of recurrent ischemic stroke or reocclusion after EVT for AT-LVO was higher in the intracranial group.

Characteristics of Calcification and Their Association with Carotid Plaque Vulnerability.

BACKGROUND: Carotid plaque vulnerability is one of the important features for evaluating the risk of subsequent ischemic stroke. Although magnetic resonance imaging (MRI) is the gold standard modality for evaluating plaque vulnerability, some patients cannot undergo MRI because of physical or economic issues. Computed tomography (CT) is more readily available. The purpose of this study was to establish a new category of calcification on CT and to assess its usefulness for detecting vulnerable plaque. MATERIALS AND METHODS: We retrospectively evaluated consecutive patients who underwent plaque imaging using CT and MRI before carotid revascularization at our institute. Calcifications were classified into 4 types according to the new calcium classification. The patients were divided into 2 groups, the double layer sign (DLS)-positive group and the DLS-negative group. Signal intensity ratio (SIR) of carotid plaque was measured on MRI for evaluating plaque vulnerability and compared between type of calcification and SIR. RESULTS: Among the 132 patients evaluated, 50 patients (62.5%) in DLS positive group and 16 patients (30.8%) in DLS negative group had calcification with vulnerable plaque (SIR > 1.47) (P < 0.01). Substantial interobserver agreement of type of calcification was observed (kappa, 0.79; P < 0.01). Multivariate analysis showed that DLS (odds ratio 3.03; 95% confidence interval 1.35-6.8; P < 0.01) and male sex (odds ratio 3.15; 95% confidence interval 1.02-9.68; P = 0.04) were independent predictors of vulnerable plaque. CONCLUSIONS: DLS in our new classification of calcification on CT reliably detects vulnerable plaque and could thus be used in patients who cannot undergo MRI.

Intravenous Administration of Human Amniotic Mesenchymal Stem Cells in the Subacute Phase of Cerebral Infarction in a Mouse Model Ameliorates Neurological Disturbance by Suppressing Blood Brain Barrier Disruption and Apoptosis via Immunomodulation.

Neuro-inflammation plays a key role in the pathophysiology of brain infarction. Cell therapy offers a novel therapeutic option due to its effect on immunomodulatory effects. Amniotic stem cells, in particular, show promise owing to their low immunogenicity, tumorigenicity, and easy availability from amniotic membranes discarded following birth. We have successfully isolated and expanded human amniotic mesenchymal stem cells (hAMSCs). Herein, we evaluated the therapeutic effect of hAMSCs on neurological deficits after brain infarction as well as their immunomodulatory effects in a mouse model in order to understand their mechanisms of action. One day after permanent occlusion of the middle cerebral artery (MCAO), hAMSCs were intravenously administered. RT-qPCR for TNFα, iNOS, MMP2, and MMP9, immunofluorescence staining for iNOS and CD11b/c, and a TUNEL assay were performed 8 days following MCAO. An Evans Blue assay and behavioral tests were performed 2 days and several months following MCAO, respectively. The results suggest that the neurological deficits caused by cerebral infarction are improved in dose-dependent manner by the administration of hAMSCs. The mechanism appears to be through a reduction in disruption of the blood brain barrier and apoptosis in the peri-infarct region through the suppression of pro-inflammatory cytokines and the M2-to-M1 phenotype shift.

Wall Redness of Enlarged Unruptured Cerebral Aneurysm.

OBJECTIVES: The wall of enlarged unruptured cerebral aneurysm (EUCA) is thought to be reddish, thin, and fragile. This study aimed to evaluate the EUCA wall redness based on quantitative signal intensity method and to compare the clinical and radiological characteristics between EUCA and non-EUCA. MATERIALS & METHODS: In this retrospective analysis, red (R), green (G), blue (B), and RGB signal intensities of aneurysm were quantitatively measured using an intraoperative digital picture in 150 cases. Color intensities were measured by two independent investigators. Aneurysm redness was defined as an R/RGB ratio since the brightness of the operative field differed by each surgery or angle of the microscope. RESULTS: The median aneurysm size was 4.9 mm (IQR 3.9-5.9 mm). Median color intensity of R, G, B, RGB, and R/RGB ratio were 206 (185-215), 129 (107-150), 136 (115-157), 157 (140-174), and 1.26 (1.20-1.38), respectively. The intraclass correlation coefficient for R/RGB ratio was 0.73 (P<0.0001). The proportion of female sex was significantly higher for EUCA (p = 0.019). Median R/RGB ratio in GUCA was significantly larger than that of non-EUCA (OR 1.25, 95% CI 1.19-1.35) (p = 0.035). Even after adjustment of female sex, a R/RGB ratio ≧1.36 was related to EUCA (OR 3.02, 95% CI 1.30-7.02). CONCLUSIONS: The present study showed that a R/RGB ratio could be calculated easily and a larger R/RGB ratio was related to EUCA. When EUCA is managed by surgical treatment, more careful manipulation should be needed compared to non-EUCA due to a "red" wall of EUCA.

[Tips for Selecting Balloons or Stents for Cerebral Aneurysms: Effective Use of Each Device].

We introduce typical use cases and the appropriate use of balloon catheters and neck bridge stents for coil embolization of cerebral aneurysm. There are two types of balloon catheters: single-lumen and double-lumen catheters. They are also classified into compliant and super-compliant balloons by softness. Neck bridge stents are classified into two types: open-cell and closed-cell stents. Balloon- and stent-assisted techniques are both useful for wide-neck aneurysms. The complication rates of these methods are similar but the stent-assisted technique requires long-term administration of antiplatelets after the procedure. Both techniques have the challenge that the microcatheter is fixed during coil embolization. The semi-jailing technique, in which the stent is partially deployed during coil insertion, solves this problem. Open-cell stents seem more suitable for this technique because they fit better to the vessel wall even in the curved part. It is important to understand the characteristics of each device for safe and effective treatments.

Outcome of retreatment for recurrent saccular cerebral aneurysms: a propensity score-matched analysis.

Although endovascular or surgical treatment has been performed for preventing the rupture of saccular cerebral aneurysms (sCA), in some patients, the aneurysms may recur and require retreatment. We aimed to investigate the clinical and radiological outcomes of treating recurrent sCA. We retrospectively evaluated the data of 52 patients with 60 recurrent sCAs who were retreated and 1534 patients with 1817 sCAs who received initial treatment. The primary outcome was a recurrence of the aneurysm. Secondary outcomes were an additional treatment, rupture after treatment, and a neurological worsening, which was defined as an increase of 1 or more scores using the modified Rankin Scale at 12-month. Safety outcomes included postoperative ischemic and hemorrhagic complications. We compiled the 120 (60 each) propensity score-matched cohort based on a propensity score for the treatment of recurrent sCA. In the propensity score-matched cohort, recurrence after treatment was observed in 25% and 6.7% of cases in the retreatment and initial treatment groups, respectively. The odds ratio of recurrence after treatment was 4.7 (95% CI, 1.4-15; P = 0.011). The secondary and safety outcomes were not significantly different between the two groups. This study showed that the treatment of recurrent sCA was a risk factor for recurrence after treatment but not for additional treatment, rupture after treatment, or neurological worsening. Although decision-making regarding the treatment varies depending on the institutional protocols and personal experience of the physicians, endovascular or surgical retreatment could be performed without hesitation.

Intracranial vascular feature changes in time of flight MR angiography in patients undergoing carotid revascularization surgery.

PURPOSE: To characterize the intracranial vascular features extracted from time of flight (TOF) images and their changes from baseline to follow-up in patients undergoing carotid revascularization, using arterial spin labeling (ASL) cerebral blood flow (CBF) measurement as a reference. METHODS: In this retrospective study, brain TOF and ASL images of 99 subjects, acquired before, within 48 h, and/or 6 months after, carotid revascularization surgery were analyzed. TOF images were analyzed using a custom software (iCafe) to quantify intracranial vascular features, including total vessel length, total vessel volume, and number of branches. Mean whole-brain CBF was calculated from ASL images. ASL scans showing low ASL signal in the entire flow territory of an internal carotid artery (ICA), which may be caused by labeling failure, were excluded. Changes and correlations between time points were analyzed separately for TOF intracranial vascular features and ASL CBF. RESULTS: Similar to ASL CBF, TOF vascular features (i.e. total vessel length, total vessel volume and number of branches) increased dramatically from baseline to post-surgery, then returned to a level slightly higher than the baseline in long-term follow-up (All P < 0.05). Correlation between time points was observed for all three TOF vascular features but not for ASL CBF. CONCLUSION: Intracranial vascular features, including total vessel length, total vessel volume and number of branches, extracted from TOF images are useful in detecting brain blood flow changes induced by carotid revascularization surgery.

Comparison of angioscopy and histopathology for the evaluation of carotid plaque characteristics: an ex vivo validation study.

Intravascular angioscopy is widely used for evaluating plaque characteristics through the plaque color in the coronary artery. This study evaluated whether angioscopy is capable of identifying various plaque morphologies, including necrotic core and intraplaque hemorrhage (IPH) in the carotid artery. Nine patients underwent carotid endarterectomy for carotid artery stenosis, and these specimens were imaged ex vivo by angioscopy within 6 h. An angioscopic examination of carotid plaque evaluated its color intensity as follows: white, yellow, or red. The IPH area, necrotic core area, and fibrous cap thickness was measured on histological sections at each site. A total of 7 plaques were graded as white plaques, 10 as yellow, and 8 as red by angioscopy. The IPH area and the percent area occupied by IPH were larger in red and yellow plaques than in white plaques (10.7 ± 9.3 mm2, 9.4 ± 7.8 mm2, and 2.2 ± 1.7 mm2, respectively, P = 0.074; and 25 ± 10%, 19 ± 13%, and 7 ± 5%, respectively, P = 0.008). Furthermore, the thickness of the fibrous cap was significantly thinner in red plaques than in yellow and white plaques (128 ± 34 µm, 328 ± 136 µm, and 285 ± 102 µm, respectively, P = 0.002). The ROC analysis for predicting a presence of red plaques identified that the optimal cutoff value of fibrous cap thickness was 181 µm (area under the curve = 0.987, 100% sensitivity, 90% specificity). The prevalence of red plaques on intravascular angioscopy may represent the existence of plaques containing relatively larger necrotic core and IPH with a thin fibrous cap.

Presence of Plaque Neovascularization on Optical Frequency Domain Imaging Predicts Progression of Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: Neovascularization (NV) is regarded to be one of the important features of vulnerable plaque. The purpose of this study was to evaluate associations between the presence of NV, detected using optical frequency domain imaging (OFDI), and ischemic events and the progress of carotid artery stenosis. MATERIALS AND METHODS: Carotid artery plaques were evaluated using an OFDI system before angioplasty. NV was defined as no-signal tubuloluminal structures recognized on at least 3 consecutive images. The total number of NVs was compared between symptomatic and asymptomatic plaques and between progressive and nonprogressive plaques. Carotid plaque was diagnosed as "progressive" when peak systolic velocity increased between serial carotid duplex scans. RESULTS: A total of 36 patients (17 symptomatic, 16 progressive) were included. The percentage of patients with smoking habits was significantly higher with progressive carotid plaque than with nonprogressive carotid plaque (P = 0.003). NV was detected in 34 patients (94%), and the total number of NVs was significantly higher with progressive carotid plaque (10.2 ± 4.8 vs. 3.7 ± 2.8; P < 0.0001). There was no relationship between the number of NVs and ischemic events (symptomatic 6.0 ± 5.1 vs. asymptomatic 7.1 ± 5.0; P = 0.47). In multivariate logistic regression analysis, the number of NVs was an independent predictor of progressive carotid plaque (odds ratio 1.64 per 1 increase [95% confidence interval 1.19-2.64]; P = 0.0005). CONCLUSIONS: NV was more frequently observed in progressive carotid plaques. Evaluation of NV using OFDI may be useful in predicting progressive carotid plaques.

Coil Embolization for Cerebral Aneurysms Using a Semi-Jailing Technique and Open-Cell Stent.

BACKGROUND: Numerous reports have described the semi-jailing technique (SJT) using a closed-cell stent for stent-assisted coil embolization, revealing issues including poor expansion and thrombotic complications in curved vessels. This paper reports preliminary experience with SJT using an open-cell stent, a novel type of stent allowing stent placement from a microcatheter. METHODS: First, this research investigated differences between open- and closed-cell types in SJT using silicone vessel models. Next, 43 patients who underwent SJT for the internal carotid artery were divided into 2 groups to investigate treatment outcomes: 24 patients with placement of an open-cell stent (open-cell group) and 19 patients with closed-cell stents (closed-cell group). RESULTS: In the silicone vessel model, coils could be placed with the open-cell stent deployed with a shorter length than the closed-cell stent. No significant differences were found between groups in terms of maximum diameter of the aneurysm or dome-neck ratio. The open-cell group showed a trend toward higher complete embolization immediately after surgery (54.2% vs. 26.3%, P = 0.06), with few cases of stent malapposition (0% vs. 31.6%, P < 0.01). However, 1 case of ischemic complication in the closed-cell group and 1 case of hemorrhagic complication in open-cell group occurred. All cases of modified Rankin Scale scores at discharge were 0-1. CONCLUSIONS: Although the open-cell stent carries the disadvantage of an unresheathable design, coil placement with a shorter stent deployment length may be advantageous during SJT for internal carotid artery aneurysm embolization with favorable consequences for excellent vessel wall apposition.

Relationship between Hemorrhagic Complications and Target Vessels in Acute Thrombectomy.

PURPOSE: Intracranial hemorrhage after thrombectomy using a catheter to treat acute major cerebral artery occlusion is known to exacerbate patient outcomes. This study was performed to determine the relationship between middle cerebral artery (MCA) tortuosity and postoperative hemorrhage. METHODS: We examined 111 consecutive patients who underwent acute thrombectomy for major intracranial artery occlusion in the anterior circulation at our hospital between September 2013 and June 2016. Patients in whom intracranial hemorrhage or subarachnoid hemorrhage was seen on head computed tomography 12-24 hours after surgery were assigned to the hemorrhagic group, whereas all the other patients were assigned to the nonhemorrhagic group. The groups were compared for tortuosity of the MCA, which was evaluated by finding the top-to-bottom (TB) distance of the M1 segment on anterior-posterior view angiograms. A modified Rankin scale score of 0-2 at 3 months after onset was considered a favorable prognosis. RESULTS: The hemorrhagic group comprised 28 patients (25.2%) and the nonhemorrhagic group comprised 83 patients (74.8%). No significant difference in patient characteristics was seen between the groups. The hemorrhagic group displayed significantly fewer patients with a favorable prognosis (17.9% versus 43.4%, P = .016). The TB distance was significantly greater in the hemorrhagic group (hemorrhagic group, 9.7 mm; nonhemorrhagic group, 7.6 mm; P = .002); multivariate analysis also identified a TB distance over 8.8 mm as a factor independently associated with postoperative intracranial hemorrhage (P = .001). CONCLUSIONS: Post-thrombectomy hemorrhage was significantly correlated with TB distance. A solution is needed for selecting and combining devices used in patients with a TB distance over 8.8 mm.

Concomitant Cushing's Disease and Marked Hyperprolactinemia: Response to a Dopamine Receptor Agonist.

A 38-year-old woman was admitted to our hospital because of amenorrhea, multiple bone fractures, and a Cushingoid appearance. Endocrinological investigations revealed that she had co-existing Cushing's disease and prolactinoma, with a serum level of prolactin (PRL) at 1,480 ng/mL, corticotropin (ACTH) at 81.3 pg/mL, and cortisol at 16.6 µg/dL. Due to the lack of indication for transsphenoidal surgery, cabergoline monotherapy was initiated. A 6-month course of treatment resulted in only subtle amelioration of hypercortisolism, while hyperprolactinemia was dramatically improved. In 5 cases of bihormonal (ACTH/PRL) pituitary macroadenoma reported in the English literature, 2 were initially treated with dopaminergic agonists with substantial effectiveness for both PRL and ACTH. We herein report an extremely rare case of bihormonal macroadenoma in which only PRL was responsive to treatment.

High-Intensity Signal in Carotid Plaque on Routine 3D-TOF-MRA Is a Risk Factor of Ischemic Stroke.

BACKGROUND: Carotid atherosclerotic disease is recognized as an important risk factor for brain ischemic events. However, high-grade stenosis does not always cause ischemic strokes, whereas moderate-grade stenosis may often cause ischemic strokes. It has been reported that there is an association between carotid intraplaque hemorrhage (IPH) and new cerebral ischemic events. The purpose of this study was to elucidate the relationship between high-intensity signals (HIS) on maximum intensity projection (MIP) images from routine 3-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and prior ischemic strokes in the patients with moderate carotid stenosis. MATERIALS AND METHODS: Sixty-one patients with moderate carotid artery stenosis (50-69% stenosis based on North American Symptomatic Carotid Endarterectomy Trial criteria) were included. Carotid IPH was defined as the presence of HIS in carotid plaques on MIP images detected by 3D-TOF-MRA using criteria we previously reported. We analyzed the relationship between the presence of HIS in plaques and prior ischemic strokes defined as ischemic lesions on diffusion-weighted brain images. RESULTS: HIS in carotid plaques were present in 27 (44%) of 61 patients. Prior ipsilateral ischemic strokes occurred more frequently in the HIS-positive group than the HIS-negative group (67 vs. 9%, p < 0.001). Furthermore, there were more smokers in the group with ischemic stroke than without it (62 vs. 25%, p = 0.005). In multivariate logistic regression analysis, HIS in carotid plaque (OR 23.4, 95% CI 4.62-118.3, p < 0.001) and smoking (OR 5.44, 95% CI 1.20-24.6, p = 0.028) were independent determinants of prior ischemic strokes after adjustment for age. CONCLUSIONS: HIS in carotid plaques on 3D-TOF-MRA MIP images are independent determinants of prior ischemic strokes in patients with moderate carotid artery stenosis, and they can potentially provide a reliable risk stratification of patients with moderate carotid artery stenosis.

Usefulness of PRESTO magnetic resonance imaging for the differentiation of schwannoma and meningioma in the cerebellopontine angle.

The principles of echo-shifting with a train of observations (PRESTO) magnetic resonance (MR) imaging technique employs an MR sequence that sensitively detects susceptibility changes in the brain. The effectiveness of PRESTO MR imaging was examined for distinguishing between cerebellopontine angle (CPA) schwannomas and meningiomas in 24 patients with CPA tumors, 12 with vestibular schwannomas, and 12 with meningiomas. Histopathological study of surgical specimens showed that 11 of the 12 schwannomas contained hemosiderin deposits and all had microhemorrhages. One meningioma contained hemosiderin deposits and two involved microhemorrhages. Abnormal vessel proliferation, and dilated and thrombosed vessels were observed in all schwannomas and in 4 meningiomas. In addition to MR imaging with all basic sequences, PRESTO MR imaging and computed tomography were performed. PRESTO imaging showed significantly more schwannomas (n = 12) than meningiomas (n = 2) exhibited intratumoral spotty signal voids which were isointense to air in the mastoid air cells (p < 0.001). These spotty signal voids were significantly associated with histopathologically demonstrated hemosiderin deposits (p < 0.001), microhemorrhages (p < 0.01), and abnormal vessels (p < 0.04). The visualization of spotty signal voids on PRESTO images is useful to distinguish schwannomas from meningiomas.