Safety and effectiveness assessment of endovascular recanalization for non-acute middle cerebral artery occlusion.

BACKGROUND: Endovascular treatment for patients with symptomatic nonacute middle cerebral artery occlusion remains clinically challenging, and proof of a beneficial effect on functional outcome is lacking. We aim to evaluate the effectiveness and safety of endovascular recanalization for patients with symptomatic nonacute middle cerebral artery occlusion. METHODS: Ninety-eight patients with symptomatic atherosclerotic nonacute middle cerebral artery occlusion were divided into drug treatment groups (42) and endovascular treatment groups (56). The rate of recanalization, peri-procedural complications, and follow-up results were evaluated. RESULTS: Among the 56 patients who received endovascular treatment, 53 (94.6%) achieved successful recanalization. The rate of peri-procedural complications was 7.1% (4/56), and the death rate was 1.8% (1/56). Any stroke within 90 days was 7.1% (4/56). Among the 42 patients in drug treatment group, any stroke within 90 days was 19.0% (8/42), death rate was 0. CONCLUSION: Among patients with symptomatic nonacute middle cerebral artery occlusion with a short length of occlusion and a moderate-to-good collateral circulation, endovascular treatment seems to be safe. And endovascular treatment could reduce the recurrence rate of stroke.

Dynamic assessment of brain perfusion in a middle cerebral artery occlusion rat model by contrast-enhanced ultrasound imaging: a pilot study.

BACKGROUND: The middle cerebral artery occlusion model (MCAo) is a commonly used animal model for cerebral ischemia studies but lacks accessible imaging techniques for the assessment of hemodynamic changes of the model. PURPOSE: The study aims to explore the value of contrast-enhanced ultrasound (CEUS) in evaluating brain perfusion in the early stages after MCAo surgery. MATERIAL AND METHODS: In total, 18 adult male Sprague-Dawley rats were subjected to right MCAo using an intraluminal filament model, and CEUS was performed at the three following timepoints: before (T0), immediately after (T1), and 6 h after permanent MCAo (T2). Twelve rats successfully completed the study, and their brains were removed and stained using 2, 3, 5-triphenyltetrazolium chloride (TTC). CEUS video images were visualized offline, and the time-intensity curves (TICs) were analyzed. Different cerebrovascular patterns and manifestations of the contrast enhancement in rat ischemic hemispheres were observed. Semi-quantitative parameters of TICs in ischemic areas (ROIi) and the surrounding normal- or hypo-perfused areas (ROIn) were calculated and compared between T0, T1, and T2, and also between ROIi and ROIn. RESULTS: A significant correlation was found between the lesion volume (%) determined by TTC and CEUS parameters (r = -0.691, P = 0.013 for peak intensity; r = -0.742, P = 0.006 for area under the curve) at T2. After the same occlusion, there were differences in contrast perfusion in each group. CONCLUSION: This study suggests that CEUS could be an effective imaging tool for studying cerebral ischemia and perfusion in small animals as long as the transcranial acoustic window allows it.

Harmonization of sensorimotor deficit assessment in a registered multicentre pre-clinical randomized controlled trial using two models of ischemic stroke.

Multicentre preclinical randomized controlled trials (pRCTs) are a valuable tool to improve experimental stroke research, but are challenging and therefore underused. A common challenge regards the standardization of procedures across centres. We here present the harmonization phase for the quantification of sensorimotor deficits by composite neuroscore, which was the primary outcome of two multicentre pRCTs assessing remote ischemic conditioning in rodent models of ischemic stroke. Ischemic stroke was induced by middle cerebral artery occlusion for 30, 45 or 60 min in mice and 50, 75 or 100 min in rats, allowing sufficient variability. Eleven animals per species were video recorded during neurobehavioural tasks and evaluated with neuroscore by eight independent raters, remotely and blindly. We aimed at reaching an intraclass correlation coefficient (ICC) ≥0.60 as satisfactory interrater agreement. After a first remote training we obtained ICC = 0.50 for mice and ICC = 0.49 for rats. Errors were identified in animal handling and test execution. After a second remote training, we reached the target interrater agreement for mice (ICC = 0.64) and rats (ICC = 0.69). In conclusion, a multi-step, online harmonization phase proved to be feasible, easy to implement and highly effective to align each centre's behavioral evaluations before project's interventional phase.

Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial.

The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance. We included the modified intention-to-treat population of the control mouse cohort of the first SPAN trial (n=421) and examined the biological and procedural independent variables and their covariance. We then determined their impact on the dependent variables cerebral blood flow drop during MCAo, time to achieve MCAo, and total anesthesia duration using multivariable analyses. We found heterogeneity in biological and procedural independent variables introduced mainly by the site. Consequently, all dependent variables also showed heterogeneity among the sites. Multivariable analyses with the site as a random effect variable revealed filament choice as an independent predictor of cerebral blood flow drop after MCAo. Comorbidity, sex, use of laser Doppler flow to monitor cerebral blood flow, days after trial onset, and maintaining anesthesia throughout the MCAo emerged as independent predictors of time to MCAo. Total anesthesia duration was predicted by most independent variables. We present with high granularity the heterogeneity introduced by the biological and model selections by the testing sites in the first trial of cerebroprotection in rodent transient filament MCAo by SPAN. Rather than trying to homogenize all variables across all sites, we embraced the heterogeneity to better approximate clinical trials. Awareness of the heterogeneity, its sources, and how it impacts the study performance may further improve the study design and statistical modeling for future multicenter preclinical trials.

Assessment of thrombus using susceptibility-weighted filtered-phase images in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Recognizing the location and length of the thrombus responsible for large vessel occlusion in patients with acute ischemic stroke can facilitate effective endovascular recanalization therapy (ERT). We hypothesized that the aliasing or dipole effect produced by filtered-phase susceptibility-weighted imaging (SWI) would facilitate thrombus delineation. METHODS: Of the patients with middle cerebral artery occlusion who underwent ERT, we screened those who underwent noncontrast CT (NCCT), multiphase CT angiography (mCTA), and SWI before the endovascular procedure. We used an arbitrary index termed measurement of equivalence in thrombus assessed by digital subtraction angiography (METAD) defined as having the same location as the thrombus observed in the digital subtraction angiography (DSA) and length differing by less than 5 mm. For NCCT, mCTA, SWI_m (magnitude), and SWI_p (phase), the length of the thrombus and METAD were assessed. RESULTS: The mean lengths of the thrombi determined using NCCT, mCTA, SWI_m, SWI_p, and DSA were 14.03, 13.47, 13.89, 9.93, and 8.96 mm, respectively. The absolute agreement for thrombus length was excellent for SWI_p and DSA (intraclass correlation coefficient [ICC] = .96), moderate for SWI_m and DSA (ICC = .53), and poor for mCTA and DSA (ICC = .14). The METADs were 26.7%, 40.0%, 33.3%, and 73.3% for NCCT, mCTA, SWI_m, and SWI_p, respectively. The METADs for NCCT and SWI_p were significantly different (p = .045) and those for mCTA and SWI_m were not (p = .537 and .093, respectively). CONCLUSIONS: The SWI_p was best matched with the DSA for the measurement of the lengths and locations of thrombi. The use of pre-thrombectomy SWI_p imaging for acute ischemic stroke may facilitate a successful ERT strategy.

Role of the optic nerve sheath diameter in the assessment of the effectiveness of decompressive surgery after malignant middle cerebral artery infarction.

BACKGROUND: After a case of stroke, intracranial pressure (ICP) must be measured and monitored, and the gold standard method for that is through an invasive technique using an intraventricular or intraparenchymal device. However, The ICP can also be assessed through a non-invasive method, comprised of the measurement of the optic nerve sheath diameter (ONSD) through ultrasound (US). OBJECTIVE: To evaluate the ICP of patients who underwent wide decompressive craniectomy after middle cerebral artery (MCA) infarction via preoperative and postoperative ONSD measurements. METHODS: A total of 17 patients, aged between 34 and 70 years, diagnosed with malignant MCA infarction with radiological edema and mid-line shift, who underwent decompressive surgery, were eligible. From the records, we collected data on age, sex, preoperative and postoperative Glasgow Coma Scale (GCS) scores, National Institutes of Health Stroke Scale (NIHSS) score, the degree of disability in the preoperative period and three months postoperatively through the scores on the Modified Rankin Scale (MRS), and the preoperative and postoperative midline shift measured by computed tomography (CT) scans of the brain. RESULTS: Preoperatively, the mean GCS score was of 8 (range: 7.7-9.2), whereas it was found to be of 12 (range 10-14) on the first postoperative day (p = 0.001). The mean preoperative NIHSS score was of 21.36 ± 2.70 and, on the first postoperative day, it was of 5.30 ± 0.75 (p < 0.001). As for the midline shift, the mean preoperative value was of 1.33 ± 0.75 cm, and, on the first postoperative day, 0.36 ± 0.40 cm (p < 0.001). And, regarding the ONSD, the mean preoperative measurement was of 5.5 ± 0.1 mm, and, on the first postoperative day, it was of 5 ± 0.9 mm (p < 0.001). CONCLUSION: The ocular US measurement of the ONSD for the preoperative and postoperative monitoring of the ICP seems to be a practical and useful method.

ANTECEDENTES: Após um acidente vascular cerebral (AVC), a pressão intracraniana (PIC) deve ser medida e monitorada, e o método padrão-ouro para isso é um procedimento invasivo por meio de um dispositivo intraventricular ou intraparenquimal. No entanto, a PIC também pode ser avaliada por um método não invasivo, composto da medida do diâmetro da bainha do nervo óptico (DBNO) por ultrassom (US). OBJETIVO: Avaliar a PIC de pacientes submetidos a craniectomia descompressiva ampla após infarto da artéria cerebral média (ACM) por meio das medidas do DBNO nos períodos pré e pós-operatório. MéTODOS: Um total de 17 pacientes, com idades entre 34 e 70 anos, diagnosticados com infarto maligno da ACM com edema radiológico e deslocamento da linha média, e que foram submetidos a cirurgia descompressiva, eram elegíveis. A partir dos prontuários, coletamos informações relativas à idade, gênero, pontuações pré e pós-operatória na Escala de Coma de Glasgow (ECG), pontuação na escala de AVC dos National Institutes of Health (NIH), o grau de incapacidade no pré-operatório e após três meses da operação pelas pontuações na Escala de Rankin Modificada (ERM), e o desvio da linha média no pré e pós-operatório medido por tomografia computadorizada (TC) cerebral. RESULTADOS: No pré-operatório, a pontuação média na ECG foi de 8 (variação: 7,7­9,2), e, no primeiro dia do pós-operatório, 12 variação 10­14) (p = 0,001). A pontuação média na escala dos NIH foi de 21,36 ± 2,70 no pré-operatório, e de 5,30 ± 0,75 no primeiro dia de pós-operatório (p < 0,00 1). Quanto ao desvio da linha média, no pré-operatório ele teve uma média de 1,33 ± 0,75 cm, e de 0,36 ± 0,40 cm no primeiro dia de pós-operatório (p < 0,001). E o DBNO apresentou uma média pré-operatória de 5,5 ± 0,1 mm, e de 5 ± 0,9 mm no primeiro dia de pós-operatório (p < 0,001). CONCLUSãO: A mensuração ocular do DBNO por US para o monitoramento da PIC no pré e no pós-operatório parece ser um método prático e útil.

Application of Three-Dimensional Arterial Spin Labeling Technique in the Assessment of Cerebral Blood Perfusion in Patients with Middle Cerebral Artery Occlusion: Analysis of Clinical Implications and Prognostic Factors.

Objective: To explore the value of three-dimensional- (3D-) arterial spin labeling (ASL) technique in evaluating cerebral perfusion in patients with unilateral middle cerebral artery occlusion (MCAO) and to observe the influencing factors of poor prognosis via long-term follow-up of patients who survived the disease. Methods: The clinical data of 60 patients with unilateral middle cerebral artery (MCA) M1 segment occlusion diagnosed by magnetic resonance angiography (MRA) from January 2018 to January 2022 were retrospectively analyzed. All patients were examined by routine MRI, MRA, and 3D-ASL, in which two postlabeling delays (PLDs; 1525 ms and 2525 ms) were used in 3D-ASL. Cerebral blood flow (CBF) in the regions of interest (ROIs) of MCA on the affected side and the mirror side was measured. The clinical data and laboratory indexes of patients were collected and evaluated by clinical scales. With the modified Rankin Score (mRS) as the outcome indicator, patients were assigned to either the poor or the good prognosis group to analyze the factors influencing patient prognosis via univariate and multivariate analyses. Results: Among unilateral MCAO patients, there was a significant difference in the CBF of the affected side between the PLD 1525 ms and 2525 ms groups (P < 0.05), but there was no significant difference in the CBF of the mirror side (P > 0.05). Compared with the mirror side, 43 cases (71.7%) of the affected CBF presented with hypoperfusion, 9 cases (15.0%) with normal perfusion, and 8 cases (13.3%) with hyperperfusion. Age, NIHSS score, collateral circulation, and homocysteine (Hcy) were identified by multivariate Logistic regression analysis as independent risk factors for adverse outcomes. Conclusion: MCAO can lead to cerebral blood perfusion decline, and 3D-ASL technique can evaluate the post-MCAO cerebral blood perfusion level. Old age, high NIHSS scores, poor collateral circulation, and high Hcy levels are associated with poor clinical outcomes.

Feature-based Quality Assessment of Middle Cerebral Artery Occlusion Using 18F-Fluorodeoxyglucose Positron Emission Tomography.

In animal experiments, ischemic stroke is usually induced through middle cerebral artery occlusion (MCAO), and quality assessment of this procedure is crucial. However, an accurate assessment method based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is still lacking. The difficulty lies in the inconsistent preprocessing pipeline, biased intensity normalization, or unclear spatiotemporal uptake of FDG. Here, we propose an image feature-based protocol to assess the quality of the procedure using a 3D scale-invariant feature transform and support vector machine. This feature-based protocol provides a convenient, accurate, and reliable tool to assess the quality of the MCAO procedure in FDG PET studies. Compared with existing approaches, the proposed protocol is fully quantitative, objective, automatic, and bypasses the intensity normalization step. An online interface was constructed to check images and obtain assessment results.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues-such as incomplete mechanistic knowledge and faulty clinical trial design-a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

Functional Assessment of Stroke-Induced Regulation of miR-20a-3p and Its Role as a Neuroprotectant.

MicroRNAs have gained popularity as a potential treatment for many diseases, including stroke. This study identifies and characterizes a specific member of the miR-17-92 cluster, miR-20a-3p, as a possible stroke therapeutic. A comprehensive microRNA screening showed that miR-20a-3p was significantly upregulated in astrocytes of adult female rats, which typically have better stroke outcomes, while it was profoundly downregulated in astrocytes of middle-aged females and adult and middle-aged males, groups that typically have more severe stroke outcomes. Assays using primary human astrocytes and neurons show that miR-20a-3p treatment alters mitochondrial dynamics in both cell types. To assess whether stroke outcomes could be improved by elevating astrocytic miR-20a-3p, we created a tetracycline (Tet)-induced recombinant adeno-associated virus (rAAV) construct where miR-20a-3p was located downstream a glial fibrillary acidic protein promoter. Treatment with doxycycline induced miR-20-3p expression in astrocytes, reducing mortality and modestly improving sensory motor behavior. A second Tet-induced rAAV construct was created in which miR-20a-3p was located downstream of a neuron-specific enolase (NSE) promoter. These experiments demonstrate that neuronal expression of miR-20a-3p is vastly more neuroprotective than astrocytic expression, with animals receiving the miR-20a-3p vector showing reduced infarction and sensory motor improvement. Intravenous injections, which are a therapeutically tractable treatment route, with miR-20a-3p mimic 4 h after middle cerebral artery occlusion (MCAo) significantly improved stroke outcomes including infarct volume and sensory motor performance. Improvement was not observed when miR-20a-3p was given immediately or 24 h after MCAo, identifying a unique delayed therapeutic window. Overall, this study identifies a novel neuroprotective microRNA and characterizes several key pathways by which it can improve stroke outcomes.

A low-cost mouse cage warming system provides improved intra-ischemic and post-ischemic body temperature control - Application for reducing variability in experimental stroke studies.

BACKGROUND: Brain temperature is a strong determinant of ischemic stroke injury. For this reason, tight management of brain or body temperature (Tcore) in experimental rodent stroke models is recommended to improve the rigor and reproducibility of outcomes. However, methods for managing Tcore during and after stroke vary widely in approach and effectiveness. NEW METHOD: We developed a low-cost warm ambient air cage (WAAC) system to provide improved temperature control during the intra-ischemic and post-ischemic recovery periods. The system is incorporated into standard holding cages for maintaining Tcore during the intra-ischemic period as well as for several hours into the recovery period. RESULTS AND COMPARISON WITH EXISTING METHODS: We compared the WAAC system with a commonly used heat support method, consisting of a cage on a heating pad. Both heat support systems were evaluated for the middle cerebral artery occlusion (MCAo) stroke model in mice. The WAAC system provided improved temperature control (more normothermic Tcore and less Tcore variation) during the intra- ischemic period (60 min) and post-ischemic period (3 h). Mean infarct volume was not statistically different by heat support system, however, standard deviation was 54 % lower in the WAAC system group. CONCLUSIONS: Mice and other small rodents are highly vulnerable to heat loss during and after the MCAo procedure. The WAAC system provides more precise and controlled Tcore maintenance compared with frequently used induction heating methods in mice undergoing the MCAo stroke model. The improved temperature control should enhance experimental rigor and reduce the number of experimental animals needed.

Mortality after large artery occlusion acute ischemic stroke.

Despite randomized trials showing a functional outcome benefit in favor of endovascular therapy (EVT), large artery occlusion acute ischemic stroke is associated with high mortality. We performed a retrospective analysis from a prospectively collected code stroke registry and included patients presenting between November 2016 and April 2019 with internal carotid artery and/or proximal middle cerebral artery occlusions. Ninety-day mortality status from registry follow-up was corroborated with the Social Security Death Index. A multivariable logistic regression model was fitted to determine demographic and clinical characteristics associated with 90-day mortality. Among 764 patients, mortality rate was 26%. Increasing age (per 10 years, OR 1.48, 95% CI 1.25-1.76; p < 0.0001), higher presenting NIHSS (per 1 point, OR 1.05, 95% CI 1.01-1.09, p = 0.01), and higher discharge modified Rankin Score (per 1 point, OR 4.27, 95% CI 3.25-5.59, p < 0.0001) were independently associated with higher odds of mortality. Good revascularization therapy, compared to no EVT, was independently associated with a survival benefit (OR 0.61, 95% CI 0.35-1.00, p = 0.048). We identified factors independently associated with mortality in a highly lethal form of stroke which can be used in clinical decision-making, prognostication, and in planning future studies.

Comparative Assessment of the Proteolytic Stability and Impact of Poly-Arginine Peptides R18 and R18D on Infarct Growth and Penumbral Tissue Preservation Following Middle Cerebral Artery Occlusion in the Sprague Dawley Rat.

Poly-arginine peptides R18 and R18D have previously been demonstrated to be neuroprotective in ischaemic stroke models. Here we examined the proteolytic stability and efficacy of R18 and R18D in reducing infarct core growth and preserving the ischaemic penumbra following middle cerebral artery occlusion (MCAO) in the Sprague Dawley rat. R18 (300 or 1000 nmol/kg), R18D (300 nmol/kg) or saline were administered intravenously 10 min after MCAO induced using a filament. Serial perfusion and diffusion-weighted MRI imaging was performed to measure changes in the infarct core and penumbra from time points between 45- and 225-min post-occlusion. Repeated measures analyses of infarct growth and penumbral tissue size were evaluated using generalised linear mixed models (GLMMs). R18D (300 nmol/kg) was most effective in slowing infarct core growth (46.8 mm3 reduction; p < 0.001) and preserving penumbral tissue (21.6% increase; p < 0.001), followed by R18 at the 300 nmol/kg dose (core: 29.5 mm3 reduction; p < 0.001, penumbra: 12.5% increase; p < 0.001). R18 at the 1000 nmol/kg dose had a significant impact in slowing core growth (19.5 mm3 reduction; p = 0.026), but only a modest impact on penumbral preservation (6.9% increase; p = 0.062). The in vitro anti-excitotoxic neuroprotective efficacy of R18D was also demonstrated to be unaffected when preincubated for 1-3 h or overnight, in a cell lysate prepared from dying neurons or with the proteolytic enzyme, plasmin, whereas the neuroprotective efficacy of R18 was significantly reduced after a 2-h incubation. These findings highlight the capacity of poly-arginine peptides to reduce infarct growth and preserve the ischaemic penumbra, and confirm the superior efficacy and proteolytic stability of R18D, which indicates that this peptide is likely to retain its neuroprotective properties when co-administered with alteplase during thrombolysis for acute ischaemic stroke.

Ischemic Lesion Location Based on the ASPECT Score for Risk Assessment of Neurogenic Dysphagia.

Dysphagia is common in patients with middle cerebral artery (MCA) infarctions and associated with malnutrition, pneumonia, and mortality. Besides bedside screening tools, brain imaging findings may help to timely identify patients with swallowing disorders. We investigated whether the Alberta stroke program early CT score (ASPECTS) allows for the correlation of distinct ischemic lesion patterns with dysphagia. We prospectively examined 113 consecutive patients with acute MCA infarctions. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed within 24 h after admission for validation of dysphagia. Brain imaging (CT or MRI) was rated for ischemic changes according to the ASPECT score. 62 patients (54.9%) had FEES-proven dysphagia. In left hemispheric strokes, the strongest associations between the ASPECTS sectors and dysphagia were found for the lentiform nucleus (odds ratio 0.113 [CI 0.028-0.433; p = 0.001), the insula (0.275 [0.102-0.742]; p = 0.011), and the frontal operculum (0.280 [CI 0.094-0.834]; p = 0.022). A combination of two or even all three of these sectors together increased relative dysphagia frequency up to 100%. For right hemispheric strokes, only non-significant associations were found which were strongest for the insula region. The distribution of early ischemic changes in the MCA territory according to ASPECTS may be used as risk indicator of neurogenic dysphagia in MCA infarction, particularly when the left hemisphere is affected. However, due to the exploratory nature of this research, external validation studies of these findings are warranted in future.

Mobile Interventional Stroke Team Model Improves Early Outcomes in Large Vessel Occlusion Stroke: The NYC MIST Trial.

BACKGROUND AND PURPOSE: Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models. METHODS: This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary stroke center or TSC to comprehensive stroke center, MIST with patient presentation to TSC and MIST transfer, or a combination of DS with patient transfer from primary stroke center to TSC and MIST. The prespecified primary end point was initial door-to-recanalization time and secondary end points measured additional time intervals and clinical outcomes at discharge and 3 months. RESULTS: MIST had a faster mean initial door-to-recanalization time than DS by 83 minutes (P<0.01). MIST and mothership had similar median door-to-recanalization times of 192 minutes and 179 minutes, respectively (P=0.83). A greater proportion had a complete recovery (National Institutes of Health Stroke Scale of 0 or 1) at discharge in MIST compared with DS (37.9% versus 16.7%; P<0.01). MIST had 52.8% of patients with modified Rankin Scale of ≤2 at 3 months compared with 38.9% in DS (P=0.10). CONCLUSIONS: MIST led to significantly faster initial door-to-recanalization times compared with DS, which was comparable to mothership. This decrease in time has translated into improved short-term outcomes and a trend towards improved long-term outcomes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03048292.

[Contrast-enhanced Ultrasonography and Color Doppler Ultrasonography for Dynamic Assessment of Intracranial Changes in Early MCAO Rats Models].

OBJECTIVE: To assess the value of contrast-enhanced ultrasound (CEUS) and color Doppler ultrasound (DUS) on hemodynamic changes and cerebral perfusion quantitative analyses in Sprague-Dawley (SD) rats with focal permanent ischemic stroke. METHODS: Sixteen SD rats with thin skulls were subjected to establish middle cerebral artery occlusion (MCAO) model. CEUS images were performed before modeling (T 0), immediately after modeling (5-15 min after modeling, T 1), 3 h after modeling (T 2), followed by the measurement of bilateral middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA) using DUS. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and mean velocity (MV) of these arteries were obtained. The brain time-intensity curve was taken as interest region of the whole right brain, and the quantitative parameters of CEUS were obtained, including peak intensity (PI), area under the curve ( AUC), wash in slope (WIS), time to peak (TTP), rise time (RT) and time from peak to one half (TPH). The modified neurological deficit score (mNSS) of the rats was performed 3 h after the modeling, and the data of the rats with a score of 9-11 were statistically analyzed. RESULTS: A total of 12 rats were successfully modeled and completed with mNSS score 9-11. No blood flow signals were observed on the right MCA and ACA in the 12 rats at T 1 and T 2. From T 0 to T 1, PI, AUC and WIS of the right hemisphere decreased sharply with TTP and RT significantly prolonged, and the differences were statistically significant. However, there was no significant difference in hemodynamic parameters at that period of time. From T 1 to T 2, there were no significant changes in CEUS quantitative parameters (except AUCand TPH), while PSV, EDV, MV of LMCA and bilateral PCA showed significant acceleration, and the differences were statistically significant. CONCLUSION: CEUS and DUS can reveal the intracranial hemodynamics and brain tissue perfusion trends of MCAO rats, which could be new methods in assessment of ischemic stroke model at multiple time points.

Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients.

INTRODUCTION: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. PATIENTS AND METHODS: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. RESULTS: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = -0.47, P < .001 for 3-month modified Rankin Scale; rho = -0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. CONCLUSIONS: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

Transcranial Doppler sonography for detecting stenosis or occlusion of intracranial arteries in people with acute ischaemic stroke.

BACKGROUND: An occlusion or stenosis of intracranial large arteries can be detected in the acute phase of ischaemic stroke in about 42% of patients. The approved therapies for acute ischaemic stroke are thrombolysis with intravenous recombinant tissue plasminogen activator (rt-PA), and mechanical thrombectomy; both aim to recanalise an occluded intracranial artery. The reference standard for the diagnosis of intracranial stenosis and occlusion is intra-arterial angiography (IA) and, recently, computed tomography angiography (CTA) and magnetic resonance angiography (MRA), or contrast-enhanced MRA. Transcranial Doppler (TCD) and transcranial colour Doppler (TCCD) are useful, rapid, noninvasive tools for the assessment of intracranial large arteries pathology. Due to the current lack of consensus regarding the use of TCD and TCCD in clinical practice, we systematically reviewed the literature for studies assessing the diagnostic accuracy of these techniques compared with intra-arterial IA, CTA, and MRA for the detection of intracranial stenosis and occlusion in people presenting with symptoms of ischaemic stroke. OBJECTIVES: To assess the diagnostic accuracy of TCD and TCCD for detecting stenosis and occlusion of intracranial large arteries in people with acute ischaemic stroke. SEARCH METHODS: We limited our searches from January 1982 onwards as the transcranial Doppler technique was only introduced into clinical practice in the 1980s. We searched MEDLINE (Ovid) (from 1982 to 2018); Embase (Ovid) (from 1982 to 2018); Database of Abstracts of Reviews of Effects (DARE); and Health Technology Assessment Database (HTA) (from 1982 to 2018). Moreover, we perused the reference lists of all retrieved articles and of previously published relevant review articles, handsearched relevant conference proceedings, searched relevant websites, and contacted experts in the field. SELECTION CRITERIA: We included all studies comparing TCD or TCCD (index tests) with IA, CTA, MRA, or contrast-enhanced MRA (reference standards) in people with acute ischaemic stroke, where all participants underwent both the index test and the reference standard within 24 hours of symptom onset. We included prospective cohort studies and randomised studies of test comparisons. We also considered retrospective studies eligible for inclusion where the original population sample was recruited prospectively but the results were analysed retrospectively. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened the titles and abstracts identified by the search strategies, applied the inclusion criteria, extracted data, assessed methodological quality (using QUADAS-2), and investigated heterogeneity. We contacted study authors for missing data. MAIN RESULTS: A comprehensive search of major relevant electronic databases (MEDLINE and Embase) from 1982 to 13 March 2018 yielded 13,534 articles, of which nine were deemed eligible for inclusion. The studies included a total of 493 participants. The mean age of included participants was 64.2 years (range 55.8 to 69.9 years). The proportion of men and women was similar across studies. Six studies recruited participants in Europe, one in south America, one in China, and one in Egypt. Risk of bias was high for participant selection but low for flow, timing, index and reference standard. The summary sensitivity and specificity estimates for TCD and TCCD were 95% (95% CI = 0.83 to 0.99) and 95% (95% CI = 0.90 to 0.98), respectively. Considering a prevalence of stenosis or occlusion of 42% (as reported in the literature), for every 1000 people who receive a TCD or TCCD test, stenosis or occlusion will be missed in 21 people (95% CI = 4 to 71) and 29 (95% CI = 12 to 58) will be wrongly diagnosed as harbouring an intracranial occlusion. However, there was substantial heterogeneity between studies, which was no longer evident when only occlusion of the MCA was considered, or when the analysis was limited to participants investigated within six hours. The performance of either TCD or TCCD in ruling in and ruling out a MCA occlusion was good. Limitations of this review were the small number of identified studies and the lack of data on the use of ultrasound contrast medium. AUTHORS' CONCLUSIONS: This review provides evidence that TCD or TCCD, administered by professionals with adequate experience and skills, can provide useful diagnostic information for detecting stenosis or occlusion of intracranial vessels in people with acute ischaemic stroke, or guide the request for more invasive vascular neuroimaging, especially where CT or MR-based vascular imaging are not immediately available. More studies are needed to confirm or refute the results of this review in a larger sample of stroke patients, to verify the role of contrast medium and to evaluate the clinical advantage of the use of ultrasound.

Novel Technique for Detection of Actual Position of Clot During Endovascular Clot Retrieval: Assessment of Microcatheter Withdrawing Angiography.

BACKGROUND: When endovascular clot retrievals are performed using a stent retriever and/or an aspiration catheter, identifying the accurate position of a clot is extremely important for a successful immediate recanalization. Herein, we report a new technique called microcatheter withdrawing angiography, which facilitates the identification of the precise position of a clot. The negative shadow appearance of the clot on angiography was referred to as the actual crab claw sign. METHODS: When a 0.027-inch microcatheter penetrated the clot after inserting a 0.014-inch microwire, selective angiography was conducted using the microcatheter. Simultaneously, the microcatheter was slowly withdrawn with continuous contrast media injection, while the microwire was kept in the distal vessel. The precise position of the clot was found, which was referred to as the actual crab claw sign. Next, we conducted in vitro and in vivo analyses. RESULTS: The actual crab claw sign could be identified in the vascular model and in actual clinical settings. Therefore the sweet spot of the stent retriever could be set over the clot, and an accurate contact aspiration could be performed using an aspirator. CONCLUSIONS: Microcatheter withdrawing angiography can help identify the actual crab claw sign. This technique has a higher success rate and faster recanalization than conventional strategy, particularly in challenging cases of unsuccessful recanalization during the first attempt.