Proximal Middle Cerebral Artery Occlusion Research Articles

Preliminary experience with 088 large bore intracranial catheters during stroke thrombectomy.

Thromboaspiration technology continues to evolve at an accelerated pace with increasing availability of larger and more navigable devices. Herein, we provide our initial experience with the intracranial navigation of a large-bore (.088" inner diameter) catheters during mechanical thrombectomy (MT). Retrospective review of consecutive large vessel occlusion stroke patients in whom a TracStar™ or Zoom 88™ (Imperative Care, Campbell, CA) large-bore catheters were utilized in MT. The primary outcome was successful reperfusion (eTICI2b-3) at the end of the procedure. Safety measures included procedural complications and rates of symptomatic intracranial hemorrhage. Five patients (age,∼50-85 years; baseline NIHSS,17-23) were treated. The .088" catheters were used as the primary tool for contact aspiration in two patients (distal basilar artery and proximal MCA occlusions) with complete thrombus ingestion (eTICI3) during the first pass. In two patients, the .088" catheter was used for flow control where it was placed in the distal M1-segment of a patient with M2 occlusion treated with a combination of stent-retriever and .070" aspiration catheter and in the proximal M1 in a patient with distal M1 occlusion treated with .071" aspiration catheter resulting in eTICI3 reperfusion in both cases. In the fifth patient, the .088" catheter was navigated into the cavernous ICA to support .071" aspiration catheter treatment of an M2 occlusion resulting in eTCI2b67 reperfusion. Procedural duration ranged between 14 and 33 minutes. There were no adverse events. Intracranial navigation of .088" large-bore catheters in MT appears technically feasible and safe. Larger prospective studies are warranted.

FLAIR vascular hyperintensity with DWI for regional collateral flow and tissue fate in recanalized acute middle cerebral artery occlusion

PurposeFluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) extent or FVH-DWI mismatch as a primary influencing factor of clinical outcome in acute ischemic stroke is controversial. This study elucidated the regional pathophysiology and tissue fate in four types of cortical territories classified by the initial FVH and DWI findings in patients with acute proximal middle cerebral artery (M1) occlusion successfully recanalized using mechanical thrombectomy. MethodsWe retrospectively evaluated 35 patients successfully recanalized within 24 h of acute M1 occlusion onset between 2016 and 2019. Each Alberta stroke program early CT score area of M1–M6 were categorized as group A (DWI-, FVH-), B (DWI-, FVH+), C (DWI+, FVH+), or D (DWI+, FVH-). Territorial collateral status was graded on a 4-point scale by initial angiogram. Follow-up head computed tomography (CT) findings on days 2–9 were assessed for the territorial outcome. ResultsOverall, 210 cortical territories were identified; of these, 88 (41.9 %) were categorized into group A; 72 (34.3 %), group B; 37 (17.6 %), group C; and 13 (6.2 %), group D. The rate of territories with good collaterals (grade 2 or 3) significantly decreased in the order of groups as 78.3 %, 62.7 %, 27.6 %, and 0%, respectively (Ptrend <.001). Conversely, the rate of territories with any hypo- or hyper-density on follow-up CT significantly increased in the order of groups as 13.4 %, 23.1 %, 88.5 %, and 85.7 %, respectively (Ptrend <.001). ConclusionCategorization of cortical areas based on the FVH and DWI findings can stratify territorial collateral status and tissue fate.

The impact of FLAIR vascular hyperintensity on clinical severity and outcome : A retrospective study in stroke patients with proximal middle cerebral artery stenosis or occlusion.

The clinical significance of fluid-attenuated inversion recovery vascular hyperintensity (FVH) has not been clarified. The aim of this study was to clarify the effects of FVH on the clinical severity and long-term prognosis of patients with proximal middle cerebral artery (MCA) occlusion or severe stenosis. Because their clinical and imaging data is not accessible, we excluded the patients being treated with IV thrombolysis or mechanical thrombectomy. Clinical and imaging characteristics were documented in 282 consecutive AIS patients with proximal MCA occlusion or severe stenosis. We assessed clinical severity using the National Institutes of Health Stroke Scale (NIHSS) score and clinical outcomes using mRS scores. The average time interval between symptom onset and imaging was 16-18h. The FVH score according to FVH-ASPECTS ranged from 0 to 7, based on the numbers of territories where FVH is positive. FVH was observed in 235 (83.33%) of the AIS patients. The FVH(+) group tended to have more alcoholics (65 [27.66%] vs 6 [12.77%], P = 0.032), a higher NIHSS score on the 7th day (3 [1-6] vs 2 [1-3], P = 0.039), more instances of early neurological deterioration (END) (27 [11.4%] vs 1 [2.12%], P = 0.05), and more patients with MCA occlusion (94 [40.00%] vs 3 [6.38%]). Among the patients with positive FVH, a high FVH score represented severe clinical impairment (higher NIHSS score on admission [P = 0.009] and 7th day since admission [P = 0.02]) and poor clinical outcomes. Spearman's rank correlations showed that FVH scores were positively correlated with NIHSS scores on admission and NIHSS scores on the 7th day (P = 0.039; P = 0.017, respectively). In patients with proximal middle cerebral artery (MCA) occlusion or stenosis ≥ 70%, a high FVH score represented severe clinical impairment and poor clinical outcomes. In acute ischemic stroke (AIS) patients with proximal MCA occlusion, a high FVH score represented favorable clinical outcomes.

Value of computed tomography angiographic collateral status in prediction of malignant middle cerebral artery infarction

Background: Cerebral collateral circulation is necessary to maintain cerebral blood flow and penumbra when arterial insufficiency occurred. Only a few studies about collateral status on development of malignant middle cerebral artery infarction (mMCAi) have been documented.&#x0D; Objective: To determine whether collateral status evaluated by single phase computed tomographic angiography (CTA) help prediction of mMCAi in patients with large arterial occlusion whom not received endovascular treatment.&#x0D; Material and Methods: We retrospectively reviewed patients with acute ischemic stroke in anterior circulation in our institute during January 2015 to December 2015. We analyzed clinical data, baseline National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early CT Score (ASPECTS) on baseline nonenhanced computed tomography of the brain (NECT brain), and CTA collateral status. Malignant MCA infarction was defined according to clinical criteria.&#x0D; Results: Thirty-five patients were included. Mean age was 68.8±15.56 years. Mean baseline NIHSS and baseline ASPECTS were 17(±5) and 6(±3), respectively. All patients received intravenous thrombolysis. CTA collateral status and baseline NECT ASPECTS significantly correlated with development of mMCAi (P-value = 0.007 and 0.001). Only baseline NECT ASPECTS was an independent predictive factor for mMCAi (OR 0.63, 95%CI 0.46-0.86, P-value =0.004). Patients with baseline NECT ASPECTS ? 7 were more likely develop mMCAi (OR 14.29 95%CI 1.57-129.94, P-value 0.018).&#x0D; Conclusion: In acute stroke patients with proximal MCA or ICA occlusion received intravenous thrombolysis alone, baseline NECT ASPECTS and CTA collateral status were significantly correlate with development of mMCAi. However, only baseline ASPECTS ? 7 was an independent predictor for mMCAi.

Value of computed tomography angiographic collateral status in prediction of malignant middle cerebral artery infarction

Background: Cerebral collateral circulation is necessary to maintain cerebral blood flow and penumbra when arterial insufficiency occurred. Only a few studies about collateral status on development of malignant middle cerebral artery infarction (mMCAi) have been documented. Objective: To determine whether collateral status evaluated by single phase computed tomographic angiography (CTA) help prediction of mMCAi in patients with large arterial occlusion whom not received endovascular treatment. Material and Methods: We retrospectively reviewed patients with acute ischemic stroke in anterior circulation in our institute during January 2015 to December 2015. We analyzed clinical data, baseline National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early CT Score (ASPECTS) on baseline nonenhanced computed tomography of the brain (NECT brain), and CTA collateral status. Malignant MCA infarction was defined according to clinical criteria. Results: Thirty-five patients were included. Mean age was 68.8±15.56 years. Mean baseline NIHSS and baseline ASPECTS were 17(±5) and 6(±3), respectively. All patients received intravenous thrombolysis. CTA collateral status and baseline NECT ASPECTS significantly correlated with development of mMCAi (P-value = 0.007 and 0.001). Only baseline NECT ASPECTS was an independent predictive factor for mMCAi (OR 0.63, 95%CI 0.46-0.86, P-value =0.004). Patients with baseline NECT ASPECTS ≤ 7 were more likely develop mMCAi (OR 14.29 95%CI 1.57-129.94, P-value 0.018). Conclusion: In acute stroke patients with proximal MCA or ICA occlusion received intravenous thrombolysis alone, baseline NECT ASPECTS and CTA collateral status were significantly correlate with development of mMCAi. However, only baseline ASPECTS ≤ 7 was an independent predictor for mMCAi.

Identifying Severe Stroke Patients Likely to Benefit From Thrombectomy Despite Delays of up to a Day

Selected patients with large vessel occlusions (LVO) can benefit from thrombectomy up to 24 hours after onset. Identifying patients who might benefit from late intervention after transfer from community hospitals to thrombectomy-capable centers would be valuable. We searched for presentation biomarkers to identify such patients. Frequent MR imaging over 2 days of 38 untreated LVO patients revealed logarithmic growth of the ischemic infarct core. In 24 patients with terminal internal carotid artery or the proximal middle cerebral artery occlusions we found that an infarct core growth rate (IGR) <4.1 ml/hr and initial infarct core volumes (ICV) <19.9 ml had accuracies >89% for identifying patients who would still have a core of <50 ml 24 hours after stroke onset, a core size that should predict favorable outcomes with thrombectomy. Published reports indicate that up to half of all LVO stroke patients have an IGR <4.1 ml/hr. Other potentially useful biomarkers include the NIHSS and the perfusion measurements MTT and Tmax. We conclude that many LVO patients have a stroke physiology that is favorable for late intervention, and that there are biomarkers that can accurately identify them at early time points as suitable for transfer for intervention.

Abstract TP282: Increased Resiliency of Astrocytic Mitochondria After Focal Ischemic Stroke in Juvenile Mice

Introduction: Astrocytes provide bioenergetic support to neurons, mediate neurovascular coupling, buffer extracellular ions, and limit excitotoxicity. They undergo many rapid changes following ischemic brain injury, which may shape the extent of damage. The role of astrocytic mitochondria in astroglial functioning and response to brain injury remain underexplored. We investigated age dependent changes to astrocytic mitochondria following focal ischemic stroke in vivo using a clot-based mouse model of middle cerebral artery (MCA) occlusion. Methods: Male and female wildtype C57BL/6N neonatal mice underwent retro-orbital injections of AAV2/5 viral vectors containing mitochondrial targeted enhanced green fluorescent protein under the control of the astrocyte-specific glial fibrillary acidic protein promoter. Mice were allowed to age to 21-35 days (juvenile group) or 10-20 weeks (adult group). Proximal right MCA occlusion was provoked via photothrombosis using Rose Bengal dye and a targeted 532 nm laser beam. Control mice underwent sham procedures. Mice were perfused at 1, 3 or 24 hours post-stroke onset. Brains were processed and sectioned for mitochondrial analysis ( n = 3 animals/30 cells per time point per age group). Quantitative analyses were performed using a novel mitochondrial morphology scoring system. Results: Penumbral astrocytic mitochondria are markedly reduced in density, demonstrate decreased network complexity and adopt punctate spherical morphology compared to contralateral non-stroke hemisphere and sham animals. These changes are present within 1 hour of stroke onset. Preliminary data indicate at least 50% change in adult mice. These changes are attenuated in juvenile mice, with increased recovery seen at 24 hours post-stroke ictus. Conclusions: Astrocytic mitochondria within the penumbra undergo rapid loss and morphologic changes suggestive of dysfunction following proximal MCA occlusion. These changes are less severe in young mice indicating age-dependent resiliency of astrocytic mitochondria to ischemic injury. Further investigation into the mechanisms underlying astrocytic mitochondrial resiliency in the developing brain may reveal new strategies to limit stroke injury and improve outcomes.

Abstract 56: Neuroimaging in Ischemic Stroke is Different Between Men and Women in the Defuse 3 Cohort

Introduction: Clinical deficits from ischemic stroke are more severe in women but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes were assessed in this sub-study of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE)-3 clinical trial. Methods: DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6-16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on CT or MRI. Using univariate and adjusted regression models, the effect of sex was assessed on pre-randomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results: All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline NIHSS, baseline modified Rankin score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (IQR) volumes for core were 8.0 mL (1.9-18.4) in women vs 12.6 mL (2.7-29.6) in men, for T max &gt;6 seconds 89.0 mL (63.8-131.7) vs 133.9 mL (87.0-175.4), and for mismatch 82.1 (53.8-112.8) vs 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) vs. 0.39 (0.26-0.57), p = 0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (p = 0.003). Conclusions: In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions.

Abstract WP134: 3K3A-APC Protects Pericyte-deficient Mice From Ischemic Brain Injury

Pericytes play a key role in maintaining the blood-brain barrier (BBB) integrity. BBB disruption occurs during early stages after ischemic stroke. However, the role of pericytes in the pathogenesis of ischemic stroke remains still understudied. 3K3A-APC, a recombinant variant of activated protein C, has shown benefits in preclinical models of ischemic stroke and has favorable safety profile and reduces hemorrhage in Phase 2 study in ischemic stroke patients (RHAPSODY). In the present study, we used PDGFRβ heterozygous knockout (PDGFRβ+/-) mice to investigate the effects of pericyte deficiency on ischemic brain injury using transient proximal middle cerebral artery occlusion (tMCAO). Additionally, we investigated the effects of 3K3A-APC therapy (0.2mg/kg i.v. 4h after stroke) in this model. Compared to controls, pericyte deficiency in PDGFRβ+/- mice resulted in ~35% increase in the infarct and edema volumes, reduction in pericyte coverage from 58% to 25%, and increased IgG and fibrin deposition suggesting accelerated BBB breakdown 24h after stroke. Additionally, PDGFRβ+/- mice showed by 36% more degenerating Fluoro-Jade+ neurons and exhibited accelerated neurobehavioral abnormalities. 3K3A-APC improved neuropathological changes and functional deficits. Our results suggest that pericyte deficiency worsens brain damage and functional outcome after ischemic stroke in mice suggesting that pericytes may play an important role in protecting brain from post-ischemic. We also suggests that 3K3A-APC protects pericyte function in stroked mice which could contribute to its overall neuroprotective effects.

Abstract TP116: Effect of Voluntary Physical Activity on Circulating LG3 and Its Impact on Ischemic Stroke

Physical activity (PA) is neuroprotective. However, the mechanism for the benefit of PA prior to ischemic stroke is not well understood. Circulating LG3 levels, a 25-kDa protein fragment of brain extracellular matrix proteoglycan (perlecan), increases with PA in humans. We showed that LG3 significantly reduces infarct volume following ischemic stroke. The aim of this study is to assess whether LG3 concentration increases with voluntary physical activity in mice and to determine how circulating LG3 concentration, prior to ischemic stroke, influences outcomes. Male mice (C57BL/6J, 8-9 weeks old, 21–24 g) were randomized into sedentary control group (individually housed in motorized running wheel cages with applied brakes) and an exercise group with access to running wheels. Blood draws were collected via submental method on day 1, 7, 14 and 20 of wheel activity prior to middle cerebral artery occlusion (MCAO), to evaluate LG3 concentration in serum. Following three weeks of voluntary PA or sedentary condition, 25 mice (sedentary n=13, exercise n=12) underwent transient distal MCAO for 60 min and were recovered for three days. In another study, 29 mice (sedentary n=15, exercise n=14) underwent transient proximal MCAO for 60 min. Calf muscles (soleus and gastrocnemius) and brain samples were collected for histology, protein analysis, and infarct volume assessment. We show that voluntary PA significantly reduces ischemic lesion volume compared to sedentary controls, following distal MCAO (15.2±8 vs 5.3±2 mm 3 ; P&lt;0.0001, Figure 1). The analysis of LG3 concentration, neurofunction, as well as brain and muscle samples are currently ongoing. We expect that the findings will link LG3 concentration to the volume of exercise as well as the neuroprotection it confers in the setting of ischemic stroke.

Predictors for the extent of pial collateral recruitment in acute ischemic stroke.

Pial arterioles can provide a variable degree of collateral flow to ischemic vascular territories during acute ischemic stroke. This study sought to identify predictive factors of the degree of pial collateral recruitment in acute ischemic stroke. Clinical information and arteriograms from 62 consecutive patients with stroke due to either middle cerebral artery (MCA) M1 segment or internal carotid artery (ICA) terminus occlusion within 6 h following symptom onset were retrospectively reviewed. Pial collaterals were defined based on the extent of reconstitution of the MCA territory. Patients with slow antegrade flow distal to the occlusion site were excluded and no anesthetics were used prior or during angiography. Results were analyzed using multivariate nominal logistic regression. Better pial collateral recruitment was associated with proximal MCA versus ICA terminus occlusion (p = 0.005; odds ratio (OR) = 9.3; 95% confidence interval (CI), 2.16-53.3), lower presenting National Institutes of Health Stroke Scale Score (NIHSSS) (p = 0.023; OR = 6.51; 95% CI, 1.49-41.7), and lower diastolic blood pressure (p = 0.0411; OR = 5.05; 95% CI, 1.20-29.2). Age, gender, symptom duration, diabetes, laterality, systolic blood pressure, glucose level, hematocrit, platelet level, and white blood cell count at presentation were not found to have a statistically significant association with pial collateral recruitment. Extent of pial collateral recruitment is strongly associated with the occlusion site (MCA M1 segment versus ICA terminus) and less strongly associated with presenting NIHSSS and diastolic blood pressure.

Cuprizone-induced demyelination under physiological and post-stroke condition leads to decreased neurogenesis response in adult mouse brain

Due to the limitation in treatment window of the rtPA (recombinant tissue plasminogen activator), the development of delayed treatment for stroke is needed. We previously reported that there is a difference in neurogenesis and neuroblast migration patterns in different mouse stroke models (proximal and distal middle cerebral artery occlusion models, pMCAo or dMCAo). Specifically, compared to robust neurogenesis and substantial migration of newly born neuroblasts in pMCAo model, dMCAo only illicit limited neurogenesis and migration of neuroblasts towards ischemic area. One potential reason for this difference is the relative location of ischemic area to white matter and the neurogenic niche (subventricular zone, SVZ). Specifically, white matter could serve as a physical barrier or inhibitory factor to neurogenesis and migration in the dMCAo model. Given that a major difference in human and rodent brains is the content of white matter in the brain, in this study, we further characterize these two models and test the important hypothesis that white matter is an important contributing inhibitory factor for the limited neurogenesis in the dMCAo model. We utilized a genetically inducible NSC-specific reporter mouse line (nestin-CreERT2-R26R-YFP) to label and track NSC proliferation, survival and differentiation in ischemic brain. To test whether myelin is inhibitory to neurogenesis in dMCAo model, we demyelinated mouse brains using cuprizone treatment after stroke and examined whether there is enhanced neurogenesis or migration of neuroblasts cells in stroke mice treated with cuprizone. Our data suggests that demyelination of the brain does not result in enhanced neurogenesis or migration of neuroblasts, supporting that myelin is not a major inhibitory factor for stroke-induced neurogenesis. In addition, our results suggest that in non-stroke mice, demyelination causes decreased neurogenesis in adult brain, indicating a potential positive role of myelin in maintenance of adult neural stem cell niche.

Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort.

Background and Purpose- Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). Methods- DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results- All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9-18.4) in women versus 12.6 mL (2.7-29.6) in men, for Tmax>6 seconds 89.0 mL (63.8-131.7) versus 133.9 mL (87.0-175.4), and for mismatch 82.1mL (53.8-112.8) versus 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) versus 0.39 (0.26-0.57), P=0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (P=0.003). Conclusions- In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

The Effect of Clot Volume and Permeability on Response to Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke

Background and AimsThe characteristics of clot causing acute ischemic stroke, such as size, content, and location, are among the main determinants of response to intravenous tissue plasminogen activator [IV tPA]. Clot heterogeneity and permeability are under-recognized features that might provide additional information in predicting the efficacy of IV tPA. Methods and PatientsPatients with proximal middle cerebral artery occlusion treated with “IV tPA alone” were included. The mean Hounsfield's unit (HU) value, as objective measure of clot attenuation, and its standard deviation (SD), as proposed measure of clot heterogeneity, were obtained. The difference in HU values between CT Angiography and CT was defined as “clot permeability”, or “perviousness’. The size (length and volume-mm3) of pre-clot pouch and occluding clot along with ASPECT score and Maas’ silvian and leptomeningeal collateral score were measured. ResultsThe study included 84 cases (44 women, age: 68 ± 14 years, pretPA NIHSS: 16 ± 5). Patients with excellent response to tPA (31%) had lower thrombus volume (37.54 ± 32.37 versus 63.49 ± 37.36, P = .009) and heterogeneity (4.05 ± 1.49 versus 5.35 ± 2.34, P = .011), along with higher clot permeability (48 ± 35.48 to 31.32 ± 18.62, P = .006). However, significance of permeability did not survived in the regression analysis with adjustment for NIHSS (β:−.296, P = .003); clot volume (β:−.240, P = .014) and collateral status (β:.346, P < .001). In patients with good prognosis, clot volume was significantly lower (37.76 ± 30.08 versus 67.57 ± 37.83, P < .001), whereas permeability was significantly higher (43.97 ± 32.33 versus 31.13 ± 19.01, P = .026). However, this effect did not persist in the regression analysis after adjustment for NIHSS (β:−.399, P < .001), collateral status (β: .343, P < .001) and clot volume (β:−.297, P = .001). Clot permeability was significantly higher (45.78 ± 36.34 versus 33 ± 20.2, P = .045) and heterogeneity was lower (4.1 ± 1.55 to 5.27 ± 2.32, P = .028) in patients with dramatic response to tPA (27%). In patients responding positively to IV tPA (48%), clot permeability was numerically higher (39.85 ± 31.79 to 33.47 ± 19.28, P = .268), while clot volume (48.15 ± 34.5 to 62.07 ± 39.62, P = .093) was lower. Clot volume, permeability and heterogeneity did not show a significant difference in any (38.1%) or symptomatic (8.3%) bleeders after IV tPA. The chance of IV tPA to be beneficial increased in patients with clot volume lower than 45 mm3, with an increased likelihood of this benefit to be observed within the first day after IV tPA. Our detailed explorative ROC analysis was not able to detect a volume threshold above which the positive effect of IV tPA disappeared. ConclusionClot volume is critical for the effectiveness of IV tPA in acute ischemic stroke. Clot permeability and heterogeneity may modify its effect. CT technologies, which are readily available when evaluating a stroke patient in an emergency setting, provide us with useful parameters regarding the size, permeability and heterogeneity of the clot.

Early versus Delayed Extracranial-Intracranial Bypass Surgery in Symptomatic Atherosclerotic Occlusion.

Clinical trials of extracranial-intracranial (EC-IC) bypass surgery studied patients in subacute and chronic stage after ischemic event. To investigate the short-term outcomes of EC-IC bypass in progressive acute ischemic stroke or recent transient ischemic attacks. The study was a retrospective review at a single tertiary referral center from 2008 to 2015. Inclusion criteria consisted of EC-IC bypass within 1 yr of last ischemic symptoms ipsilateral to atherosclerotic occlusion of internal carotid or middle cerebral artery. Early bypass group who underwent surgery within 7 d of last ischemic symptoms were compared to late bypass group who underwent surgery >7 d from last ischemic symptom. The primary endpoint was perioperative ischemic or hemorrhagic stroke or intracranial hemorrhage within 7 d of surgery. Of 126 patients who underwent EC-IC bypass during the period, 81 patients met inclusion criteria, 69 (85%) persons had carotid artery occlusion, 7 (9%) had proximal MCA occlusion, and 5 (6%) had both. Early surgery had a 31% (9/29) perioperative stroke rate compared to 11.5% (6/52) of patients undergoing late bypass (P=.04). Of patients with acute stroke within 7 d of surgery, 41% (7/17) had perioperative stroke within 7 d (P=.07). Six of nine patients (67%) with blood pressure dependent fluctuation of neurologic symptoms had perioperative stroke (P=.049). EC-IC bypass in setting of acute symptomatic stroke within 1 wk may confer higher risk of perioperative stroke. Patients undergoing expedited or urgent bypass for unstable or fluctuating stroke symptoms might be at highest risk for perioperative stroke.

Retrievable stent thrombectomy in acute ischemic stroke: Is it beneficial in the elderly?

Mechanical thrombectomy in acute stroke is used in case of systemic thrombolysis failure or contraindication. Stent retrievers have proved to be safe and efficient. However, this therapy is still under debate in the elderly. Patients ineligible for systemic thrombolysis, treated with stent retrievers’ thrombectomy only were studied. We aimed to analyze the outcome (rate of recanalization and functional independence) and the safety (intracranial hemorrhage and mortality) of elderly (≥75years) in a series of patients with ischemic stroke due to acute proximal MCA occlusion treated with stent-based thrombectomy. In 65 consecutive acute ischemic stroke patients ineligible for systemic thrombolysis, outcomes of elderly patients (16/32 women; 12/33 men) were compared to those of younger (<75years) patients (17/32 women; 20/33 men). Admission NIHSS was not significantly different between younger and elderly patients. Recanalization was completely achieved in 49 cases (72%) and didn't differ between younger and older patients (Fisher’s exact p>0.05). NIHSS improvement before and after stent retriever recanalization was highly significant in younger (p<0.0001) and in older patients (p<0.0001). However, the size of improvements did not differ significantly between younger and older patients (p=0.17). Good functional outcome (mRS 0–2) was significantly worse in the elderly (Fisher’s exact p>0.0006), but there were no gender differences (Fisher’s exact p>0.05). Hemorrhagic transformation did not differ significantly. These results suggest that stent-based thrombectomy in selected patients for acute MCA occlusion is safe, very effective, associated with improved neurological outcome and should be considered in elderly patients without gender consideration.

Appropriateness of pediatric CT utilization in clinical practice

Background: Cerebral collateral circulation is necessary to maintain cerebral blood flow and penumbra when arterial insufficiency occurred. Only a few studies about collateral status on development of malignant middle cerebral artery infarction (mMCAi) have been documented. Objective: To determine whether collateral status evaluated by single phase computed tomographic angiography (CTA) help prediction of mMCAi in patients with large arterial occlusion whom not received endovascular treatment. Material and Methods: We retrospectively reviewed patients with acute ischemic stroke in anterior circulation in our institute during January 2015 to December 2015. We analyzed clinical data, baseline National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early CT Score (ASPECTS) on baseline nonenhanced computed tomography of the brain (NECT brain), and CTA collateral status. Malignant MCA infarction was defined according to clinical criteria. Results: Thirty-five patients were included. Mean age was 68.8±15.56 years. Mean baseline NIHSS and baseline ASPECTS were 17(±5) and 6(±3), respectively. All patients received intravenous thrombolysis. CTA collateral status and baseline NECT ASPECTS significantly correlated with development of mMCAi (P-value = 0.007 and 0.001). Only baseline NECT ASPECTS was an independent predictive factor for mMCAi (OR 0.63, 95%CI 0.46-0.86, P-value =0.004). Patients with baseline NECT ASPECTS ≤ 7 were more likely develop mMCAi (OR 14.29 95%CI 1.57-129.94, P-value 0.018). Conclusion: In acute stroke patients with proximal MCA or ICA occlusion received intravenous thrombolysis alone, baseline NECT ASPECTS and CTA collateral status were significantly correlate with development of mMCAi. However, only baseline ASPECTS ≤ 7 was an independent predictor for mMCAi.

Simultaneous cardio-cerebral embolization associated with atrial fibrillation: a case report

BackgroundSimultaneous cerebral and myocardial infarction is called cardiocerebral infarction (CCI), and is rarely encountered. Because of the narrow time window and complex pathophysiology, CCI is challenging to immediately diagnose and treat.Case presentationA 73-year-old woman suddenly developed right hemiplegia and severe aphasia. Twelve-lead electrocardiography showed tachycardic atrial fibrillation without any significant ST-T change. Magnetic resonance imaging revealed a proximal middle cerebral artery occlusion. She was immediately treated with alteplase at the dosage approved for ischemic stroke followed by mechanical thrombectomy as bridging therapy, and complete recanalization was achieved. Aphasia improved and she began to complain of chest pain, and reported that she had experienced chest discomfort just prior to right limb weakness. Coronary angiography showed a partial filling defect in the right coronary artery with rapid and adequate distal flow, for which percutaneous coronary intervention was not required. Alteplase was suggested to have effectively resolved the coronary emboli. The occlusions of the cerebral and coronary arteries were assumed to have occurred nearly simultaneously and cardiogenic embolism due to atrial fibrillation was considered as the most likely etiology.ConclusionsAs seen in the present case, CCI may benefit from immediate treatment with intravenous tissue plasminogen activator (IV-tPA). Although which of percutaneous coronary intervention or cerebral thrombectomy should be performed first remains unclear, we must decide whether to rescue the brain or heart first in each patient within a limited window of time. This dilemma has recently become evident in this era with mechanical thrombectomy strongly established as an effective intervention for acute ischemic stroke. Close cooperation between stroke physicians and cardiologists is becoming more important.

Prominent FLAIR Vascular Hyperintensity Is a Predictor of Unfavorable Outcomes in Non-thrombolysed Ischemic Stroke Patients With Mild Symptoms and Large Artery Occlusion.

Background and objective: The aim was to evaluate the clinical significance of prominent fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) on the prognosis of mild acute ischemic stroke with middle cerebral artery (MCA) occlusion.Methods: We recruited consecutive stroke patients with initial National Institutes of Health Stroke Scale (NIHSS) scores ≤5 and MCA occlusion on magnetic resonance angiography within 24 h of stroke onset. Prominent distal FVH was defined as an extension to more than one-third of the MCA territory. We compared clinical outcomes between prominent and non-prominent FVH groups in patients who had and had not received reperfusion therapy.Results: Of 112 participants [43 women; median age, 67 years [Interquartile range, 54–79]], prominent FVH was identified in 80 (71.4%). For 75 patients who had not received reperfusion therapy, the prominent FVH group had a more unfavorable outcome (modified Rankin Scale score >1) at 3 months than the non-prominent FVH group (44.4 vs. 15.0%, P = 0.029). In multivariate analysis, a higher NIHSS score [odd ratio [OR] = 1.67; 95% confidence interval [CI], 1.16–2.41; P = 0.006], proximal MCA occlusion [OR = 7.31; 95% CI, 1.68–31.9; P = 0.008], and prominent FVH [OR = 5.49; 95% CI, 1.29–23.4; P = 0.021], were independently associated with an unfavorable outcome. There was no association between prominent FVH and the clinical outcome in the reperfusion therapy group.Conclusions: For acute stroke patients with mild symptoms and MCA occlusion who do not receive reperfusion therapy, prominent FVH and proximal MCA occlusion may be independent predictors of an unfavorable outcome.

Distal versus Proximal Middle Cerebral Artery Occlusion: Different Mechanisms

Background: Clinical and radiological characteristics of middle cerebral artery (MCA) infarction may differ according to the location of occlusion. Objectives: We investigated the difference between proximal and distal symptomatic MCA occlusion (MCAO) in patients with ischemic stroke. The factors associated with the imaging characteristics were also analyzed. Methods: Patients with ischemic stroke due to MCAO were consecutively enrolled. The location of MCAO was determined by the ratio of the length of the ipsilesional MCA to that of the contralateral MCA and dichotomized to proximal and distal MCAO. Clinical and radiological characteristics were compared between patients with proximal and distal MCAO. Factors associated with the basal ganglia (BG) involvement, hemorrhagic transformation (HT), and neurological change during admission were investigated. Results: Among 181 included patients, MCAO location showed a bimodal peak (at the proximal [n = 99] and distal MCA [n = 82]). Proximal MCAO was more frequently associated with hyperlipidemia and large artery atherosclerosis, whereas distal MCAO was more frequently associated with hypertension, atrial fibrillation, and cardioembolic stroke. BG involvement was similar between the 2 groups (48 vs. 39%; p = 0.21), whereas HT was more frequent in distal MCAO (10 vs. 23%; p = 0.02). Among patients with proximal MCAO, hyperintense vessel sign was less frequently observed in those with a BG involvement than those without (38 vs. 60%; p = 0.03). Among those without BG involvement, the presence of HT was very low and similar between patients with proximal and distal MCAOs (1.9 vs. 2.0%). However, in patients with BG involvement, HT was more frequently observed in those with distal MCAO than in those with proximal MCAO (54.8 vs. 15.7%; p < 0.001). The presence of hyperintense vessel sign (OR 0.172, 95% CI 0.051–0.586; p = 0.005) and distal MCAO (OR 0.200, 95% CI 0.059–0.683; p = 0.011) was independently associated with improvement during admission. Conclusion: Proximal MCAO is more frequently associated with atherosclerosis, whereas distal MCAO is more frequently associated with cardioembolism. In proximal MCAO, the status of collateral flow presented by hyperintense vessel sign may affect the involvement of BG. In distal MCAO, distal migration of the embolus, which first impacted at the proximal MCA causing BG ischemia, may explain the high rate of HT by reperfusion injury. Hyperintense vessel sign and distal MCAO were independently associated with neurological improvement during admission.