Endovascular sono-lysis using EKOS system in acute stroke patients with a main cerebral artery occlusion – A pilot study

Abstract Background Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes. Methods Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient’s serum, at the acute phase of stroke, to determine if they could predict PSCI 3 months later. Results We found long-term spatial memory was impaired in diabetic mice 6 weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients. Conclusions we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients.

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Abstract 2925: DWI-ASPECTS As A Predictor Of Neurological Recovery In Acute Stroke Patients With The Middle Cerebral Artery Occlusion Treated With IV t-PA.

Stroke ◽

10.1161/str.43.suppl_1.a2925 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Junya Aoki ◽

Kazumi Kimura ◽

Yasuyuki Iguchi ◽

Kensaku Shibazaki ◽

Noriko Matsumoto ◽

...

Keyword(s):

Acute Stroke ◽

Middle Cerebral Artery ◽

Artery Occlusion ◽

Neurological Recovery ◽

Stroke Patients ◽

Short Term ◽

Nihss Score ◽

Point Reduction ◽

Cerebral Artery Occlusion ◽

Iv Tpa

Background and Purpose: Diffusion-weighted imaging-Alberta Stroke Programme Early CT Score (DWI-ASPECTS) has been associated with short-term and long-term neurological recovery and outcome in acute stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). However, previous reports did not analyze the DW-ASPECTS based on the presence of major arterial occlusion. We investigated whether initial DWI-ASPECTS can predict the short-term neurological recovery in acute stroke patients with the middle cerebral artery occlusion (MCAO) treated with IV t-PA. Methods: Consecutive acute stroke patients with MCAO treated with IV t-PA within 3 hours of onset were enrolled from 2005 October to 2011 May. All patients were examined using DWI and magnetic resonance angiography on admission. Only patients with horizontal MCAO were included. Neurological deficits were assessed using National Institutes of Health Stroke Scale (NIHSS) score on admission and day 7. On day 7, dramatic recovery (DR) was defined as a ≥10 point reduction or a total NIHSS score of 0 or 1. Good recovery (GR) was a ≥4 point reduction, excluding DR. Worsening was a ≥4 point increase. Results: Seventy-one patients (median age [quartiles]; 77 [70-83], male; 44 [62%]) were enrolled into the study. The median NIHSS score was 18 (12-22). The median DWI-ASPECTS was 4 (6-9). Median DWI-ASPECTS was 7 (6-9) in 27 patients with DR group, 5 (4-9) in 13 with GR group, and 3 (2-6) in 17 with worsening (p<0.001). Median DWI-ASPECTS was 4 (3-6) in 4 (6%) patients with type2-parencymal hematoma within 7 days. Using ROC curve, the optimal cut-off DWI-ASPECTS to differentiate DR group from others was >5 (sensitivity of 85% and specificity of 57%, area under curve [AUC] 0.692, p=0.007), and that for worsening group was <4 (sensitivity of 96% and specificity of 59%, AUC 0.785, p<0.001). Multivariate regression analysis demonstrated that initial DWI-ASPECTS of >5 was significantly associated with DR (OR 9.75, 95%CI 1.41-67.67, p=0.021), and <4 with worsening (OR 15.94, 95%CI 4.01-63.25, p<0.001). Conclusion: DWI-ASPECTS can predict the short-term outcome in acute stroke patients with MCAO treated with IV-tPA.

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Imaging of Brain Hypoxia in Permanent and Temporary Middle Cerebral Artery Occlusion in the Rat using 18F-Fluoromisonidazole and Positron Emission Tomography: A Pilot Study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9600405 ◽

2006 ◽

Vol 27 (4) ◽

pp. 679-689 ◽

Cited By ~ 49

Author(s):

Masashi Takasawa ◽

John S Beech ◽

Tim D Fryer ◽

Young T Hong ◽

Jessica L Hughes ◽

...

Keyword(s):

Positron Emission Tomography ◽

Pilot Study ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Artery Occlusion ◽

Emission Tomography ◽

Brain Hypoxia ◽

Positron Emission ◽

Cerebral Artery Occlusion

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THE RELATIONSHIP BETWEEN TIMING OF RECANALIZATION AND CLINICAL OUTCOME OF ISCHEMIC STROKE DUE TO ACUTE MIDDLE CEREBRAL ARTERY OCCLUSION AFTER ULTRASOUND-ENHANCED THROMBOLYSIS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2017.2.6 ◽

2017 ◽

pp. 38-43

Author(s):

Quang Thang Tran ◽

Dat Anh Nguyen ◽

Van Chi Nguyen ◽

Duy Ton Mai ◽

Van Thinh Le

Keyword(s):

Ischemic Stroke ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Recombinant Tissue Plasminogen Activator ◽

Artery Occlusion ◽

Stroke Patients ◽

Tissue Plasminogen ◽

Cerebral Artery Occlusion ◽

The Relationship

Purpose: The relationship between arterial recanalization after use of intravenous recombinant tissue plasminogen activator (rtPA) and outcome is still uncertain. The aim of our study was to evaluate the association between the timing and impact of recanalization on functional outcomes in ischemic stroke patients due to acute middle cerebral artery occlusion. Subjects and methods: Nonrandomized 40 stroke patients with proximal middle arterial occlusion on a prebolus TCD receiving intravenously 0.6 mg/kg rtPA within 4.5 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5. Results: 40 patients (mean age 67±14 years, NIH Stroke Scale [NIHSS] 16.15±8.6 points) were treated at 180±80 minutes from symptom onset. TCD was monitored continously for 120 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 13 patients (32.5%). In this group, NIHSS decreased quickly at 2 hours and 24 hours. Modified Rankins 0-1point was seen in 92.3% of patients with complete recanalization compared to 37.0% of patients with uncomplete recanalization at 90 days. Non-symptomatic intracranial hemorrhage was seen in 1 patient in the group of complete recanalization. Conclusions: Complete recanalization of middle cerebral arteries within 2 hours after IV rtPA treatment plays a role in predicting the good functional and clinical outcomes after ultrasound-enhanced thrombolysis in acute ischemic stroke patients due to acute middle cerebral artery occlusion. Key words: stroke, recombinant tissue plasminogen activator, transcranial Doppler sonography

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Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even After Lethal Ischemia with Mature Neural Cell Death

Cells ◽

10.3390/cells9061374 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1374 ◽

Cited By ~ 2

Author(s):

Yasue Tanaka ◽

Nami Nakagomi ◽

Nobutaka Doe ◽

Akiko Nakano-Doi ◽

Toshinori Sawano ◽

...

Keyword(s):

Ischemic Stroke ◽

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Artery Occlusion ◽

Neural Cells ◽

Stroke Patients ◽

Early Reperfusion ◽

Beneficial Effects ◽

Cerebral Artery Occlusion

Ischemic stroke is a critical disease caused by cerebral artery occlusion in the central nervous system (CNS). Recent therapeutic advances, such as neuroendovascular intervention and thrombolytic therapy, have allowed recanalization of occluded brain arteries in an increasing number of stroke patients. Although previous studies have focused on rescuing neural cells that still survive despite decreased blood flow, expanding the therapeutic time window may allow more patients to undergo reperfusion in the near future, even after lethal ischemia, which is characterized by death of mature neural cells, such as neurons and glia. However, it remains unclear whether early reperfusion following lethal ischemia results in positive outcomes. The present study used two ischemic mouse models—90-min transient middle cerebral artery occlusion (t-MCAO) paired with reperfusion to induce lethal ischemia and permanent middle cerebral artery occlusion (p-MCAO)—to investigate the effect of early reperfusion up to 8 w following MCAO. Although early reperfusion following 90-min t-MCAO did not rescue mature neural cells, it preserved the vascular cells within the ischemic areas at 1 d following 90-min t-MCAO compared to that following p-MCAO. In addition, early reperfusion facilitated the healing processes, including not only vascular but also neural repair, during acute and chronic periods and improved recovery. Furthermore, compared with p-MCAO, early reperfusion after t-MCAO prevented behavioral symptoms of neurological deficits without increasing negative complications, including hemorrhagic transformation and mortality. These results indicate that early reperfusion provides beneficial effects presumably via cytoprotective and regenerative mechanisms in the CNS, suggesting that it may be useful for stroke patients that experienced lethal ischemia.

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