Optimal endovascular therapy technique for isolated intracranial atherothrombotic stroke-related large vessel occlusion in the acute to subacute stage.

BACKGROUND AND PURPOSE: Reocclusion after treatment is a concern in endovascular therapy (EVT) for isolated intracranial atherothrombotic stroke-related large vessel occlusion (AT-LVO). However, the optimal EVT technique for AT-LVO has not yet been investigated. This study evaluated the optimal EVT technique for AT-LVO in a real-world setting. MATERIALS AND METHODS: We conducted a historical multicenter registry study at 51 centers that enrolled patients with AT-LVO. We divided the patients into three groups based on the EVT technique: mechanical thrombectomy alone (MT-only), percutaneous transluminal angioplasty (PTA), and stent deployment (Stent). MT alone was classified into the MT-only group, PTA and MT-PTA into the PTA group, and MT-Stent, MT-PTA-Stent, PTA-Stent, and Stent-only into the Stent group. The primary outcome was the incidence of reocclusion of the treated vessels within 90 days of EVT completion. RESULTS: We enrolled 770 patients and analyzed 509 patients. The rates in the MT-only, PTA, and Stent groups were 40.7, 44.4, and 14.9%, respectively. The incidence rate of residual stenosis >70% of final angiography was significantly higher in the MT-only group than in the PTA and Stent groups (MT-only vs. PTA vs. Stent: 34.5% vs. 26.3% vs. 13.2%, p=0.002). The reocclusion rate was significantly lower in the PTA group than in the MT-only group (adjusted hazard ratio [95% confidence interval], 0.48 [0.29-0.80]). Of the patients, 83.5% experienced reocclusion within 10 days after EVT. Alarmingly, a substantial subset (approximately 62.0%) of patients underwent reocclusion within 2 days of EVT. The incidence of modified Rankin scale scores of 0-2 90 days after EVT was not significantly different among the three groups. The incidences of symptomatic intracranial hemorrhage (ICH), any other ICH, and death were not significantly different. CONCLUSIONS: The incidence rate of reocclusion was significantly lower in the PTA group than in the MT-only group. We found no significant difference in reocclusion rates between the Stent and MT-only groups. In Japan, GP IIb/IIIa inhibitors are not reimbursed. Therefore, PTA might be the preferred choice for AT-LVOs due to the higher reocclusion risk with MT-only. Reocclusion was likely to occur within 10 days, particularly within 2 days post-EVT. ABBREVIATIONS: EVT = endovascular treatment; LVO = large vessel occlusion; MT = mechanical thrombectomy; PTA = percutaneous transluminal angioplasty; ICH = intracranial hemorrhage; SD = standard deviation; IQR = interquartile range; HRs = hazard ratios; BMI = body mass index; LDL = low-density lipoprotein; HDL = high-density lipoprotein; DAPT = dual antiplatelet therapy; TAPT = triple antiplatelet therapy.

Minimally invasive craniotomy for putaminal hemorrhage using a tubular retractor: A technical note.

Background: Minimally invasive endoscopic and stereotactic surgery have been established as surgical treatments for putaminal hemorrhage. However, facilities that do not have equipment for endoscopic or stereotactic surgery will likely have to perform conventional craniotomy. Using a tubular retractor, we were able to perform minimally invasive surgery, such as endoscopic surgery. Methods: A craniotomy was performed for left putaminal hemorrhage after cerebral infarction treatment. A 3-4 cm craniotomy centered at Kocher's point was performed under general anesthesia. A 2 cm incision was made in the cortex, and a tubular retractor was inserted under a microscope. The hematoma was reached at a position 4-5 cm from the cortex. Results: Thanks to the tubular retractor, it was relatively easy to observe the hematoma, and it was possible to remove it and confirm hemostasis without difficulty. Brain injury caused by the retractor insertion cavity was small, and no hemostasis was required. The surgery was completed by dura mater closure, bone flap fixation, and wound closure as per the standard. Most of the putaminal hemorrhage could be removed, and there was no rebleeding after the operation. The patient is still undergoing rehabilitation because of aphasia and muscle weakness. Manual Muscle Testing was at three points in the upper limb, and four points in the lower limb remained. Conclusion: For putaminal hemorrhage, microscopic craniotomy was performed using a tubular retractor and an approach such as endoscopic surgery. Craniotomy, hematoma removal, and hemostasis operations are also considered to be minimally invasive surgeries.

Expanding the Treatable Imaging Profile in Patients With Large Ischemic Stroke: Subanalysis From a Randomized Clinical Trial.

BACKGROUND: We aimed to examine the boundary of the ischemic core volume in patients undergoing endovascular thrombectomy (EVT) versus those receiving medical management to determine the minimum optimal size for favorable treatment outcomes. METHODS: This is a prespecified substudy of the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial). Patients with large vessel occlusion were enrolled between November 2018 and September 2021 with a National Institutes of Health Stroke Scale score of at least 6 on admission and an Alberta Stroke Program Early Computed Tomography Score value of 3 to 5. We investigated the correlation between optimal quantified ischemic core volume, assessed solely using magnetic resonance diffusion-weighted imaging, and functional outcomes (modified Rankin Scale score, 0-3) at 90 days by predictive marginal plots. Final infarct volume and safety outcomes (symptomatic intracerebral hemorrhage and mortality) were also assessed. RESULTS: Of the 203 cases, 168 patients (85 in the EVT group versus 83 in the medical management group) were included. The median (interquartile range) core volume was 94 (65-160) mL in patients with EVT and 115 (71-141) mL in the medical management group (P=0.72). The predictive marginal probabilities of the 2 groups intersected at 128 mL for estimating functional outcomes. Symptomatic intracerebral hemorrhage and mortality within 90 days had overlay margins through all core volumes in both groups. The median final infarct volume (interquartile range) was smaller in the EVT group (142 [80-223] mL versus 211 [123-289] mL in the medical management group; P<0.001). CONCLUSIONS: In this prespecified analysis of a randomized clinical trial involving patients with large ischemic strokes, patients with an estimated core volume of up to 128 mL on diffusion-weighted imaging benefit from EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702413.

Mode of Imaging Study and Endovascular Therapy for a Large Ischemic Core: Insights From the RESCUE-Japan LIMIT.

BACKGROUND AND PURPOSE: Differences in measurement of the extent of acute ischemic stroke using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) by non-contrast computed tomography (CT-ASPECTS stratum) and diffusion-weighted imaging (DWI-ASPECTS stratum) may impact the efficacy of endovascular therapy (EVT) in patients with a large ischemic core. METHODS: The RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan-Large IscheMIc core Trial) was a multicenter, open-label, randomized clinical trial that evaluated the efficacy and safety of EVT in patients with ASPECTS of 3-5. CT-ASPECTS was prioritized when both CT-ASPECTS and DWI-ASPECTS were measured. The effects of EVT on the modified Rankin Scale (mRS) score at 90 days were assessed separately for each stratum. RESULTS: Among 183 patients, 112 (EVT group, 53; No-EVT group, 59) were in the CT-ASPECTS stratum and 71 (EVT group, 40; No-EVT group, 31) in the DWI-ASPECTS stratum. The common odds ratio (OR) (95% confidence interval) of the EVT group for one scale shift of the mRS score toward 0 was 1.29 (0.65-2.54) compared to the No-EVT group in CT-ASPECTS stratum, and 6.15 (2.46-16.3) in DWI-ASPECTS stratum with significant interaction between treatment assignment and mode of imaging study (P=0.002). There were significant interactions in the improvement of the National Institutes of Health Stroke Scale score at 48 hours (CT-ASPECTS stratum: OR, 1.95; DWIASPECTS stratum: OR, 14.5; interaction P=0.035) and mortality at 90 days (CT-ASPECTS stratum: OR, 2.07; DWI-ASPECTS stratum: OR, 0.23; interaction P=0.008). CONCLUSION: Patients with ASPECTS of 3-5 on MRI benefitted more from EVT than those with ASPECTS of 3-5 on CT.

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.

Cavernous sinus dural arteriovenous fistula treated with transvenous embolization through facial vein: A case report.

Background: Although the inferior petrosal sinus (IPS) is the most common approach route for transvenous embolization (TVE) of cavernous sinus dural arteriovenous fistulas (CSDAVFs), other routes should be chosen in cases which the IPS is occluded. We report a case in which the superior ophthalmic vein (SOV) approach through the facial vein (FV) was the first choice to achieve radical cure of a hemorrhage-onset CSDAVF. Case Description: An 81-year-old female presented with a history of transarterial embolization (TAE) and TVE for the left CSDAVF 27 years ago. She was transported to us with a chief complaint of consciousness disturbance, and head computed tomography (CT) showed subcortical hemorrhage in the right frontal lobe. Cerebral angiography revealed CSDAVF with draining into the right SOV and right superficial middle cerebral vein (SMCV). Angiography, computed tomography venography, and contrast-enhanced magnetic resonance imaging did not show IPS, but the outflow pathways to the SOV, FV, and internal jugular vein were confirmed, so an approach through the FV was selected. Conclusion: The FV was selected through the right femoral vein and thanks to the distal access catheter (DAC) being guided to the SOV, the microcatheter could be easily guided to the SMCV through the cavernous sinus (CS). TVE was performed, complete occlusion was confirmed. When preoperative occlusion of the IPS was confirmed, the FV was useful for the first choice of route, and the use of DAC allowed us to complete the treatment accurately and quickly.

Number of Passes of Endovascular Therapy for Stroke With a Large Ischemic Core: Secondary Analysis of RESCUE-Japan LIMIT.

BACKGROUND: The increased risk of intracranial hemorrhage with multiple passes in endovascular therapy (EVT) for large vessel occlusion with a large ischemic core is a concern. We explored the effect of the number of EVT passes on patients in a randomized clinical trial. METHODS: This post hoc study was the secondary analysis of RESCUE-Japan LIMIT, which was a randomized clinical trial comparing EVT and medical treatment alone for large vessel occlusion with large ischemic core. We grouped patients according to the number of passes with successful reperfusion (modified Thrombolysis in Cerebral Infarction score, ≥2b) in 1, 2, and 3 to 7 passes and failed reperfusion (modified Thrombolysis in Cerebral Infarction score, 0-2a) after any pass in the EVT group, and these groups were compared with medical treatment group. The primary outcome was modified Rankin Scale score of 0 to 3 at 90 days. Secondary outcomes were improvement in National Institutes of Health Stroke Scale score of ≥8 at 48 hours, mortality at 90 days, symptomatic intracranial hemorrhage, and any intracranial hemorrhage within 48 hours. RESULTS: The number of patients who received EVT with successful reperfusion after 1, 2, and 3 to 7 passes and failed reperfusion were 44, 23, 19, and 14, respectively, and 102 received medical treatment alone. The adjusted odds ratios (95% CIs) for the primary outcome relative to medical treatment were 5.52 (2.23-14.28) after 1 pass, 6.45 (2.22-19.30) after 2 passes, 1.03 (0.15-4.48) after 3 to 7 passes, and 1.17 (0.16-5.37) if reperfusion failed. The adjusted odds ratios (95% CIs) for any intracranial hemorrhage within 48 hours relative to medical treatment were 1.88 (0.90-3.93) after 1 pass, 5.14 (1.97-14.72) after 2 passes, 3.00 (1.09-8.58) after 3 to 7 passes, and 6.16 (1.87-24.27) if reperfusion failed. CONCLUSIONS: The successful reperfusion within 2 passes was associated with better clinical outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03702413.

Association Between Alberta Stroke Program Early Computed Tomography Score and Efficacy and Safety Outcomes With Endovascular Therapy in Patients With Stroke From Large-Vessel Occlusion: A Secondary Analysis of the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT).

Importance: Endovascular therapy (EVT) has been found to reduce functional disability in patients with acute stroke due to large-vessel occlusion. However, the extent of the ischemic region, measured using Alberta Stroke Program Early Computed Tomography Scores, may limit the efficacy of EVT. Objective: To compare the efficacy and safety of EVT according to ASPECTS 3 or less vs 4 to 5. Design, Setting, and Participants: The Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT) was an open-label randomized clinical trial conducted from November 2018 to December 2021 at 45 stroke centers across Japan. The trial enrolled adult patients with acute ischemic stroke with a large ischemic region, defined as ASPECTS 3 to 5 primarily determined by magnetic resonance imaging, with occlusion site at the internal carotid artery or middle cerebral artery segment 1. Among 203 enrolled patients, 1 withdrew consent and 202 were included in the original trial and secondary analysis. This secondary analysis was conducted in April 2022. Interventions: Patients were randomly assigned to EVT with medical therapy or medical therapy alone. Main Outcomes and Measures: Modified Rankin Scale (mRS) score at 90 days and symptomatic and any intracranial hemorrhage within 48 hours. Results: Among 202 patients, 106 (52%) had ASPECTS 3 or less (mean [SD] age, 76.7 [9.6] years; 54 female individuals [50.9%]) and 96 had ASPECTS 4 to 5 (mean [SD] age, 75.6 [10.6] years; 36 female individuals [37.5%]). Of patients with ASPECTS 3 or less, 12 (21.4%) in the EVT group and 9 (18.0%) in the no EVT group had an mRS score of 0 to 3 (odds ratio [OR], 1.24; 95% CI, 0.47-3.26). Of patients with ASPECTS 4 to 5, 19 patients (43.2%) in the EVT group and 4 (7.7%) in the no EVT group had an mRS score of 0 to 3 at 90 days (OR, 9.12; 95% CI, 2.80-29.70; interaction P = .01). The ordinal shift across the range of mRS scores toward a better outcome was not significant in those with ASPECTS or 3 or less (common OR, 1.56; 95% CI, 0.79-3.10) but was significant in those with ASPECTS 4 to 5 (common OR, 4.48; 95% CI, 2.07-9.71; interaction P = .046). The risk of intracranial hemorrhage was significantly increased in patients with ASPECTS 3 or less when EVT was conducted (OR, 4.14; 95% CI, 1.84-9.32) and nonsignificantly increased in those with ASPECTS 4 to 5 (OR, 2.05; 95% CI, 0.89-4.73; interaction P = .24). Conclusions and Relevance: In this study, EVT was associated with improved 90-day functional outcomes in patients with acute large vessel occlusive stroke and ASPECTS was 4 to 5 but not in those with ASPECTS 3 or less. Trial Registration: ClinicalTrials.gov Identifier: NCT03702413.

Localized kinking during deployment of a flow redirection lumen device (FRED) could be due to excessive pushing.

BACKGROUND: The safety and efficacy analysis of flow redirection lumen device (FRED) demonstrated the excellent safety profile of FREDs for aneurysm treatment. We describe the first case in which FRED deployment for a paraclinoid aneurysm resulted in in-stent stenosis, necessitating balloon angioplasty, and an additional stent. CASE DESCRIPTION: A 50-year-old woman had a left paraclinoid aneurysm with a maximum diameter of 6.1 mm. We planned FRED deployment. We experienced in-stent stenosis just after the deployment of a FRED. Devices such as guidewires and catheters could not cross the lesion through the FRED because of an obstruction in the FRED. Balloon angioplasty and subsequent stenting resolved thrombosis and kinking. FRED has potential for kinking locally. CONCLUSION: Surgeons should consider this possibility when treating cerebral aneurysm using FRED. Cone-beam computed tomography after deployment of FRED may be useful for evaluating the stent shape.

Endovascular Therapy for Acute Stroke with a Large Ischemic Region.

BACKGROUND: Endovascular therapy for acute ischemic stroke is generally avoided when the infarction is large, but the effect of endovascular therapy with medical care as compared with medical care alone for large strokes has not been well studied. METHODS: We conducted a multicenter, open-label, randomized clinical trial in Japan involving patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) value of 3 to 5 (on a scale from 0 to 10, with lower values indicating larger infarction). Patients were randomly assigned in a 1:1 ratio to receive endovascular therapy with medical care or medical care alone within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images. Alteplase (0.6 mg per kilogram of body weight) was used when appropriate in both groups. The primary outcome was a modified Rankin scale score of 0 to 3 (on a scale from 0 to 6, with higher scores indicating greater disability) at 90 days. Secondary outcomes included a shift across the range of modified Rankin scale scores toward a better outcome at 90 days and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours. RESULTS: A total of 203 patients underwent randomization; 101 patients were assigned to the endovascular-therapy group and 102 to the medical-care group. Approximately 27% of patients in each group received alteplase. The percentage of patients with a modified Rankin scale score of 0 to 3 at 90 days was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval [CI], 1.35 to 4.37; P = 0.002). The ordinal shift across the range of modified Rankin scale scores generally favored endovascular therapy. An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (relative risk, 3.51; 95% CI, 1.76 to 7.00), and any intracranial hemorrhage occurred in 58.0% and 31.4%, respectively (P<0.001). CONCLUSIONS: In a trial conducted in Japan, patients with large cerebral infarctions had better functional outcomes with endovascular therapy than with medical care alone but had more intracranial hemorrhages. (Funded by Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy; RESCUE-Japan LIMIT ClinicalTrials.gov number, NCT03702413.).

Ischemia-Induced Multipotent Stem Cells Isolated from Stroke Patients Exhibit Higher Neurogenic Differentiation Potential than Bone Marrow-Derived Mesenchymal Stem Cells.

Perivascular areas of the brain harbor multipotent stem cells. We recently demonstrated that after a stroke, brain pericytes exhibit features of multipotent stem cells. Moreover, these ischemia-induced multipotent stem cells (iSCs) are present within ischemic areas of the brain of patients diagnosed with stroke. Although increasing evidence shows that iSCs have traits similar to those of mesenchymal stem cells (MSCs), the phenotypic similarities and differences between iSCs and MSCs remain unclear. In this study, we used iSCs extracted from stroke patients (h-iSCs) and compared their neurogenic potential with that of human MSCs (h-MSCs) in vitro. Microarray analysis, fluorescence-activated cell sorting, immunohistochemistry, and multielectrode array were performed to compare the characteristics of h-iSCs and h-MSCs. Although h-iSCs and h-MSCs had similar gene expression profiles, the percentage expressing the neural stem/progenitor cell marker nestin was significantly higher in h-iSCs than in h-MSCs. Consistent with these findings, h-iSCs, but not h-MSCs, differentiated into electrophysiologically functional neurons. In contrast, although both h-iSCs and h-MSCs were able to differentiate into several mesodermal lineages, including adipocytes, osteocytes, and chondrocytes, the potential of h-iSCs to differentiate into adipocytes and osteocytes was relatively low. These results suggest that compared with h-MSCs, h-iSCs predominantly exhibit neural rather than mesenchymal lineages. In addition, these results indicate that h-iSCs have the potential to repair the injured brain of patients with stroke by directly differentiating into neuronal lineages.

Neural regeneration by regionally induced stem cells within post-stroke brains: Novel therapy perspectives for stroke patients.

Ischemic stroke is a critical disease which causes serious neurological functional loss such as paresis. Hope for novel therapies is based on the increasing evidence of the presence of stem cell populations in the central nervous system (CNS) and the development of stem-cell-based therapies for stroke patients. Although mesenchymal stem cells (MSCs) represented initially a promising cell source, only a few transplanted MSCs were present near the injured areas of the CNS. Thus, regional stem cells that are present and/or induced in the CNS may be ideal when considering a treatment following ischemic stroke. In this context, we have recently showed that injury/ischemia-induced neural stem/progenitor cells (iNSPCs) and injury/ischemia-induced multipotent stem cells (iSCs) are present within post-stroke human brains and post-stroke mouse brains. This indicates that iNSPCs/iSCs could be developed for clinical applications treating patients with stroke. The present study introduces the traits of mouse and human iNSPCs, with a focus on the future perspective for CNS regenerative therapies using novel iNSPCs/iSCs.

PulseRider-Assisted Coil Embolization for Treatment of Intracranial Bifurcation Aneurysms: A Single-Center Case Series with 24-Month Follow-up.

BACKGROUND: Although endovascular coiling of unruptured aneurysms is widely accepted, the endovascular treatment of wide-neck bifurcation aneurysms remains one of the most challenging morphologies. Our purpose was to describe our experience with 24-month follow-up for the treatment of unruptured intracranial bifurcation aneurysms using the PulseRider (Cerenovus, New Brunswick, NJ). METHODS: This study is a single-center, single-arm registry performed under institutional review board control to evaluate efficacy and safety of the PulseRider. Patients with bifurcation aneurysms were identified and enrolled prospectively. Angiography immediately after treatment and at 6 months, and magnetic resonance imaging and magnetic resonance angiography at 12- and 24-month follow-up were retrospectively analyzed. A modified Rankin score was obtained prior to procedure, at discharge, and at 6-, 12- and 24-month follow-up visits. RESULTS: Eight patients with a mean age of 66 years were treated with the PulseRider. All patients had bifurcation aneurysms (2 anterior communicating, 2 carotid terminus, and 4 basilar apex). The aneurysm diameters ranged from 4.6 to 13.6 mm (mean 7.4 mm) with dome/neck ratio ranging from 1.4 to 2.2 (mean 1.6). In all cases, the PulseRider was successfully deployed. Complete occlusion was demonstrated at 6-month follow-up on 6 of 8 (75%), near complete occlusion in 1 of 8 (12.5%), and residual aneurysm in 1 of 8 (12.5%) patients. There was no change or recurrence on magnetic resonance angiography, nor clinical complication after the procedure through 24-month follow-up. CONCLUSIONS: Our experience with 24-month follow-up demonstrated favorable efficacy in the treatment of intracranial wide-neck bifurcation aneurysms using the PulseRider.

Isolation and Characterization of Cerebellum-Derived Stem Cells in Poststroke Human Brain.

There is compelling evidence that the mature central nervous system (CNS) harbors stem cell populations outside conventional neurogenic regions. We previously demonstrated that brain pericytes (PCs) in both mouse and human exhibit multipotency to differentiate into various neural lineages following cerebral ischemia. PCs are found throughout the CNS, including cerebellum, but it remains unclear whether cerebellar PCs also form ischemia-induced multipotent stem cells (iSCs). In this study, we demonstrate that putative iSCs can be isolated from poststroke human cerebellum (cerebellar iSCs [cl-iSCs]). These cl-iSCs exhibited multipotency and differentiated into electrophysiologically active neurons. Neurogenic potential was also confirmed in single-cell suspensions. DNA microarray analysis revealed highly similar gene expression patterns between PCs and cl-iSCs, suggesting PC origin. Global gene expression comparison with cerebral iSCs revealed general similarity, but cl-iSCs differentially expressed certain cerebellum-specific genes. Thus, putative iSCs are present in poststroke cerebellum and possess region-specific traits, suggesting potential capacity to regenerate functional cerebellar neurons following ischemic stroke.

Intravenous administration of human adipose-derived stem cells ameliorates motor and cognitive function for intracerebral hemorrhage mouse model.

Even today, intracerebral hemorrhage (ICH) is a major cause of death and disabilities. Rehabilitation is preferentially applied for functional recovery although its effect is limited. Recent studies have suggested that intravenous administration of mesenchymal stem cells would improve the post-ICH neurological deficits. Human adipose-derived stem cells (hADSCs) have been established in our laboratory. We aimed to evaluate the therapeutic efficacy of the hADSCs on the post-ICH neurological deficits using a clinical-relevant ICH mouse model. We also evaluated immune responses to clarify the underlying mechanisms. The hADSCs expressed MSC markers at high levels. The hADSCs administration into the ICH-bearing mice improved the neurological deficits during the subacute phases, which was shown by neurobehavioral experiments. Besides, the hADSC administration decreased the number of CD11+CD45+ cells and increased the proportion of CD86+ and Ly6C+ cells in the ICH lesions. In summary, intravenous administration of hADSCs during the acute phase improved ICH-induced neurological deficits during the subacute phase because of the suppression of acute inflammation mediated by CD11+CD45+ subpopulations. Our data suggest that hADSCs can be served as a novel strategy for ICH treatment.

Comparative Characterization of Ischemia-Induced Brain Multipotent Stem Cells with Mesenchymal Stem Cells: Similarities and Differences.

Mesenchymal stem cells (MSCs) are multipotent stem cells localized to the perivascular regions of various organs, including bone marrow (BM). While MSC transplantation represents a promising stem cell-based therapy for ischemic stroke, increasing evidence indicates that exogenously administered MSCs rarely accumulate in the injured central nervous system (CNS). Therefore, compared with MSCs, regionally derived brain multipotent stem cells may be a superior source to elicit regeneration of the CNS following ischemic injury. We previously identified ischemia-induced multipotent stem cells (iSCs) as likely originating from brain pericytes/perivascular cells (PCs) within poststroke regions. However, detailed characteristics of iSCs and their comparison with MSCs remains to be investigated. In the present study, we compared iSCs with BM-derived MSCs, with a focus on the stemness and neuron-generating activity of each cell type. From our results, stem and undifferentiated cell markers, including c-myc and Klf4, were found to be expressed in iSCs and BM-MSCs. In addition, both cell types exhibited the ability to differentiate into mesoderm lineages, including as osteoblasts, adipocytes, and chondrocytes. However, compared with BM-MSCs, high expression of neural stem cell markers, including nestin and Sox2, were found in iSCs. In addition, iSCs, but not BM-MSCs, formed neurosphere-like cell clusters that differentiated into functional neurons. These results demonstrate that iSCs are likely multipotent stem cells with the ability to differentiate into not only mesoderm, but also neural, lineages. Collectively, our novel findings suggest that locally induced iSCs may contribute to CNS repair by producing neuronal cells following ischemic stroke.

Postoperative in-stent protrusion is an important predictor of perioperative ischemic complications after carotid artery stenting.

BACKGROUND AND PURPOSE: Although in-stent protrusion is a potential risk factor for thromboembolism following carotid artery stenting, the correlation between in-stent protrusion and postoperative ipsilateral stroke has not been well examined. MATERIALS AND METHODS: We retrospectively reviewed 342 consecutive carotid artery lesions in 319 patients who underwent carotid artery stenting between April 2008 and April 2015. After excluding cases with carotid artery dissection and acute occlusion, 301 lesions in total of 277 patients were included in the analysis. We examined the association between in-stent protrusion, which was detected by intravascular ultrasound, and postoperative ipsilateral stroke within 30 days. RESULTS: In-stent protrusion was observed in 47 (15.6%) lesions, of which postoperative ipsilateral stroke within 30 days occurred with 4 (8.5%) lesions. All these events occurred within 10 days after treatment. On the other hand, only 1 (0.39%) of the 256 lesions without in-stent protrusion showed this symptom, and the event occurred at 30days after treatment. Thus, lesions with in-stent protrusion had a higher cumulative risk of ipsilateral stroke than those without in-stent protrusion (8.5% vs 0.4% at 30 days, log-rank P < 0.001). In-stent protrusion, which was more often seen in symptomatic lesions, was associated with a vulnerable plaque assessed by MRI. After adjustment for postoperative stroke risks such as symptomatic lesions, plaque vulnerability, age or sex, in-stent protrusion was still significantly associated with postoperative ipsilateral stroke within 30 days (OR = 27.03, P = 0.001). CONCLUSIONS: Postoperative ipsilateral stroke was observed more frequently in patients with demonstrated in-stent protrusion (ISP) following CAS.

Optimal dilution of contrast medium for quantitating parenchymal blood volume using a flat-panel detector.

Objective Similar to perfusion studies after acute ischemic stroke, measuring cerebral blood volume (CBV) via C-arm computed tomography before and after therapeutic interventions may help gauge subsequent revascularization. We tested serial dilutions of intra-arterial injectable contrast medium (CM) to determine the optimal CM concentration for quantifying parenchymal blood volume by flat-panel detector imaging (FD-PBV). Methods CM was diluted via saline power injector, instituting time delays for FD-PBV studies. A red/green/blue (RGB) color scale was employed to quantify/compare FD-PBV and magnetic resonance-derived CBV (MRCBV). Results Contrast values of right and left common carotid arteries did not differ significantly at CM dilutions of ≥20%. RGB analysis of FD-PBV imaging (relative to MR-CVB), showed CM dilution altered the colors (by 16%), increasing red and decreasing blue ratios. Conclusion Diluting CM to 20% resulted in no laterality differential of FD-PBV imaging, with left/right quantitative ratios approaching 1.1 (optimal for clinical use).

[Two Cases of Ruptured Blood Blister-like Aneurysm Treated with X-ray Angiography Perfusion(XAP)Analysis].

Two cases of ruptured blood blister-like internal carotid artery aneurysms for which low flow bypass was sufficient to attain successful treatment of trapping are reported. In the acute stage of rupture, it is troublesome to perform accurate examinations of tolerance to ischemia like balloon occlusion test(BOT)for estimating the required amount of bypass flow. In our cases, X-ray angiography perfusion(XAP)analysis was introduced, which could be performed in a couple dozen seconds without room-to-room transfer of patients, following the ordinary examination of diagnostic digital subtraction angiography. The perfusion index(PI)ratio measured in this analysis is equivalent to the laterality of cerebral blood flow between the right and left hemispheres. The PI ratio of 0.85 approximately corresponds to the mean stump pressure(MSTP)of 40mmHg, on the basis of the correlation diagram between the PI ratio and MSTP(approximate straight line:PI ratio%=0.6×MSTP+60). Even though the PI ratio of the cases was superior to this threshold of tolerance for parent artery occlusion, complementary low flow bypass was added in the acute case for the overwhelming succeeding vasospasm and for securing the flow to peripheral perforators, which resulted in a successful treatment without any ischemic events.

Endovascular parent-artery occlusion of large or giant unruptured internal carotid artery aneurysms. A long-term single-center experience.

The development of stent-like devices has increased treatment options for complex internal carotid artery (ICA) aneurysms, but the optimal treatment remains unclear. The purpose of this study was to evaluate the safety and efficacy of endovascular parent-artery occlusion (PAO) for ICA aneurysms. We retrospectively reviewed 28 patients with unruptured ICA aneurysms ⩾10mm treated with PAO between April 2002 and March 2015 at our institution. Patients who developed neurologic symptoms or with venous-phase delay >2s during balloon test occlusion were not treated by PAO. Patients with venous-phase delays of 1-2s underwent superficial temporal artery to middle cerebral artery (STA-MCA) bypass prior to PAO. The median patient age was 65 (range, 26-84)years. Nineteen aneurysms (68%) were located in the cavernous segment. The median aneurysm size was 25 (range 11-40)mm. Venous-phase delay of 1-2s was observed in five patients. Perioperative ischemic complications (N=9, 32%), which occurred within 30days after treatment, were significantly associated with venous-phase delays of 1-2s (p<0.01) and history of hypertension (p<0.01). Six-month morbidity was observed in one (3.6%) patient. Complete occlusion at final follow-up and delayed (i.e. ⩾31days after treatment) ischemic events were observed in 100% and 0% of patients, respectively, over a median period of 63 (range, 6-147) months. Despite the high frequency of perioperative ischemic episodes, endovascular PAO with selective use of STA-MCA bypass showed excellent long-term outcomes in patients with unruptured ICA aneurysms ⩾10mm.