Olga Maisterra

Bridging Intravenous–Intra-Arterial Rescue Strategy Increases Recanalization and the Likelihood of a Good Outcome in Nonresponder Intravenous Tissue Plasminogen Activator-Treated Patients A Case–Control Study

Background and Purpose— Safety and efficacy of the “bridging therapy” (intra-arterial [IA] reperfusion rescue for nonresponder intravenous [IV] tissue plasminogen activator [tPA]-treated patients) is a matter of debate. Our aim was to compare IV and IV–IA thrombolysis using a case–control approach. Methods— Consecutive patients with proximal intracranial occlusion who received IA reperfusion procedures after unsuccessful IV tPA (lack of clinical improvement and arterial recanalization 1 hour after tPA bolus) were studied (IV–IA group). They were compared with occluded vessel, clot location, stroke severity, and time to treatment-matched 1 to 2 historical patients from our prospective IV tPA database with persistent occlusion 1 hour after IV tPA (IV-NR group). Arterial occlusion and recanalization were assessed with transcranial Doppler. Clinical evaluation was assessed by National Institutes of Health Stroke Scale at baseline, 24 hours, and at discharge. Symptomatic intracranial hemorrhage was defined according to the National Institute of Neurological Disorders and Stroke trial. Functional evaluation was determined by modified Rankin Scale, being functional independency defined by modified Rankin Scale score ≤2. Results— Forty-two IV–IA patients were compared with 84 matched IV-NR. Mean age was 71.5±2.9 years, 58 (46%) were women, and baseline median National Institutes of Health Stroke Scale score was 20 (interquartile range, 5). Mean time from symptoms to IV tPA was 176.9±113 minutes. On transcranial Doppler, complete recanalization was significantly higher in IV–IA than control subjects (12 hours: 45.2% versus 18.1%, P=0.002; 24 hours: 46.3% versus 25.3%, P=0.016) with nonsignificant better clinical evolution at 24 hours (40.5% versus 30.1%, P=0.169) and discharge (52.5% versus 39.5%, P=0.123). Symptomatic intracranial hemorrhage was similar (IV–IA 11.9% versus IV-NR 6%, P=0.205). Mortality at 3 months was 50% in the IV–IA group and 35.8% in the IV-NR (P=0.154). Forty percent of IV–IA patients were functionally independent at 3 months and only 14.9% IV-NR (P=0.012). Conclusions— Bridging IV–IA treatment may improve recanalization and clinical outcome in nonresponder IV tPA-treated patients.

PROGNOSTIC SIGNIFICANCE OF BLOOD PRESSURE VARIABILITY AFTER THROMBOLYSIS IN ACUTE STROKE

Objective: To evaluate the impact of early blood pressure (BP) changes on diffusion-weighted imaging (DWI) lesion evolution and clinical outcome in patients with stroke treated with IV tissue plasminogen activator (tPA). Methods: We prospectively evaluated 80 patients with stroke with a documented middle cerebral artery occlusion treated with IV tPA. Multiple repeated systolic (SBP) and diastolic (DBP) BP measurements were obtained during 24 hours after admission. All patients underwent DWI, perfusion-weighted imaging, and magnetic resonance angiography before and 36–48 hours after thrombolysis. Recanalization was assessed on transcranial Doppler at 6 hours of stroke onset. NIH Stroke Scale scores were recorded at baseline and 24 hours. Modified Rankin Scale was used to assess 3-month outcome. Results: Recanalization occurred in 44 (55%) patients. BP variability, estimated as the SD of the mean, was associated with DWI lesion growth (r = 0.46, p = 0.0003 for SBP and r = 0.26, p = 0.02 for DBP), early clinical course (p = 0.06 for SBP and p = 0.01 for DBP), and 3-month outcome (p = 0.002 for SBP and 0.07 for DBP). However, the prognostic significance of BP changes differed depending on the presence of recanalization. SBP variability emerged as an independent predictor of DWI lesion growth (β: 6.9; 95% CI, 3.2 to 10.7, p = 0.003) and worse stroke outcome (OR: 11; 95% CI: 2.2 to 56.1; p = 0.004) in patients without recanalization, but not in recanalized patients. Conclusion: Blood pressure variability is associated with greater diffusion-weighted imaging lesion growth and worse clinical course in patients with stroke treated with IV tissue plasminogen activator. However, its impact varies depending on the occurrence of early recanalization after thrombolysis.

Extending the time window for endovascular procedures according to collateral pial circulation.

Background and Purpose— Good collateral pial circulation (CPC) predicts a favorable outcome in patients undergoing intra-arterial procedures. We aimed to determine if CPC status may be used to decide about pursuing recanalization efforts. Methods— Pial collateral score (0–5) was determined on initial angiogram. We considered good CPC when pial collateral score <3, defined total time of ischemia (TTI) as onset-to-recanalization time, and clinical improvement >4-point decline in admission–discharge National Institutes of Health Stroke Scale. Results— We studied CPC in 61 patients (31 middle cerebral artery, 30 internal carotid artery). Good CPC patients (n=21 [34%]) had lower discharge National Institutes of Health Stroke Scale score (7 versus 21; P=0.02) and smaller infarcts (56 mL versus 238 mL; P<0.001). In poor CPC patients, a receiver operating characteristic curve defined a TTI cutoff point <300 minutes (sensitivity 67%, specificity 75%) that better predicted clinical improvement (TTI <300: 66.7% versus TTI >300: 25%; P=0.05). For good CPC patients, no temporal cutoff point could be defined. Although clinical improvement was similar for patients recanalizing within 300 minutes (poor CPC: 60% versus good CPC: 85.7%; P=0.35), the likelihood of clinical improvement was 3-fold higher after 300 minutes only in good CPC patients (23.1% versus 90.1%; P=0.01). Similarly, infarct volume was reduced 7-fold in good as compared with poor CPC patients only when TTI >300 minutes (TTI <300: poor CPC: 145 mL versus good CPC: 93 mL; P=0.56 and TTI >300: poor CPC: 217 mL versus good CPC: 33 mL; P<0.01). After adjusting for age and baseline National Institutes of Health Stroke Scale score, TTI <300 emerged as an independent predictor of clinical improvement in poor CPC patients (OR, 6.6; 95% CI, 1.01–44.3; P=0.05) but not in good CPC patients. In a logistic regression, good CPC independently predicted clinical improvement after adjusting for TTI, admission National Institutes of Health Stroke Scale score, and age (OR, 12.5; 95% CI, 1.6–74.8; P=0.016). Conclusions— Good CPC predicts better clinical response to intra-arterial treatment beyond 5 hours from onset. In patients with stroke receiving endovascular treatment, identification of good CPC may help physicians when considering pursuing recanalization efforts in late time windows.

Speed of tPA-Induced Clot Lysis Predicts DWI Lesion Evolution in Acute Stroke

Background and Purpose— We sought to evaluate the impact of the speed of recanalization on the evolution of diffusion- weighted imaging (DWI) lesions and outcome in stroke patients treated with tissue-type plasminogen activator (tPA). Methods— We evaluated 113 consecutive stroke patients with a middle cerebral artery occlusion who were treated with intravenous tPA. All patients underwent multiparametric magnetic resonance imaging studies, including DWI and perfusion-weighted imaging before and 36 to 48 hours after administration of a tPA bolus. Patients were continuously monitored with transcranial Doppler during the first 2 hours after tPA administration. The pattern of recanalization on transcranial Doppler was defined as sudden (<1 minute), stepwise (1 to 29 minutes), or slow (>30 minutes). Results— During transcranial Doppler monitoring, 13 (12.3%) patients recanalized suddenly, 32 (30.2%) recanalized in a stepwise manner, and 18 (17%) recanalized slowly. Baseline clinical and imaging parameters were similar among recanalization subgroups. At 36 to 48 hours, DWI lesion growth was significantly (P=0.001) smaller after sudden (3.23±10.5 cm3) compared with stepwise (24.9±37 cm3), slow (46.3±38 cm3), and no (51.7±34 cm3) recanalization. The slow pattern was associated with greater DWI growth (P=0.003), lesser degree of clinical improvement (P=0.021), worse 3-month outcome (P=0.032), and higher mortality (P=0.003). Conclusions— The speed of tPA-induced clot lysis predicts DWI lesion evolution and clinical outcome. Unlike sudden and stepwise patterns, slow recanalization is associated with greater DWI lesion growth and poorer short- and long-term outcomes.

MMP-2/MMP-9 plasma level and brain expression in cerebral amyloid angiopathy-associated hemorrhagic stroke.

Cerebral amyloid angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly. Matrix metalloproteinases (MMPs) have been implicated in blood–brain barrier disruption and ICH pathogenesis. In this study, we determined the levels MMP‐2 and MMP‐9 in plasma and their brain expression in CAA‐associated hemorrhagic stroke. Although MMP‐2 and MMP‐9 plasma levels did not differ among patients and controls, their brain expression was increased in perihematoma areas of CAA‐related hemorrhagic strokes compared with contralateral areas and nonhemorrhagic brains. In addition, MMP‐2 reactivity was found in β‐amyloid (Aβ)‐damaged vessels located far from the acute ICH and in chronic microbleeds. MMP‐2 expression was associated to endothelial cells, histiocytes and reactive astrocytes, whereas MMP‐9 expression was restricted to inflammatory cells. In summary, MMP‐2 expression within and around Aβ‐compromised vessels might contribute to the vasculature fatal fate, triggering an eventual bleeding.

The gender gap in stroke: a meta-analysis

Giralt D, Domingues‐Montanari S, Mendioroz M, Ortega L, Maisterra O, Perea‐Gainza M, Delgado P, Rosell A, Montaner J. The gender gap in stroke: a meta‐analysis. 
Acta Neurol Scand: 2012: 125: 83–90. 
© 2011 John Wiley & Sons A/S.

Is it Time to Reassess the SITS-MOST Criteria for Thrombolysis? A Comparison of Patients With and Without SITS-MOST Exclusion Criteria

Background and Purpose— The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) established guidelines to increase safety in acute stroke thrombolysis, but precluding treatment in an important proportion of patients. We aimed to assess safety/efficacy of thrombolysis in patients with SITS-MOST exclusion criteria. Methods— 369 nonlacunar tPA-treated patients were studied. Patients were classified as SITS-MOST (SM) or non–SITS-MOST (NSM) according to SITS-MOST–criteria fulfilling. Clinical evaluation was assessed by NIHSS and functional outcome by mRS at 3 months (functional independency=mRS ≤2). Results— Baseline NIHSS was 17. 169 (45.8%) patients were SM and 200 (54.1%) NSM. Recanalization (47.6%/50.3%, P=0.36), 24-hour-improvement (55.6%/49.5%, P=0.114), and SICH were similar (4.8%/5.1%, P=0.554). At discharge, clinical improvement in SM-group was higher (66.7%/55.7%, P=0.024). NSM tended to higher mortality (10.5%/16.1%, P=0.084) and lower functional independence (48.7%/39.6%, P=0.082). Conclusion— Thrombolysis may be safe in patients not fulfilling SITS-MOST criteria. Testing thrombolysis in patients outside SITS-MOST could be considered in the future.

Association Between Time to Reperfusion and Outcome Is Primarily Driven by the Time From Imaging to Reperfusion

Background and Purpose— A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear. Methods— We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0–2) was described via adjusted odds ratios (ORs) for every 30-minute delay. Results— Median admission National Institutes of Health Stroke Scale was 17.0 (14.0–20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59–0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67–1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54–0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35–0.9) but not in ASPECTS≥8 (OR, 0.99; 95% CI, 0.68–1.44). Conclusions— Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

Do bubble characteristics affect recanalization in stroke patients treated with microbubble-enhanced sonothrombolysis?

Administration of microbubbles (MB) may augment the effect of ultrasound-enhanced systemic thrombolysis in acute stroke. Bubble structural characteristics may influence the effect of MB on sonothrombolysis. We aimed to compare the effects of galactose-based air-filled MB (Levovist) and sulphur hexafluoride-filled MB (Sonovue) on recanalization and clinical outcome. One hundred thirty-eight i.v. recombinant tissue plasminogen activator-(tPA-) treated patients with middle cerebral artery (MCA) occlusion were studied. Presence and location of arterial occlusion and recanalization (RE) were assessed using the thrombolysis in brain ischemia (TIBI) flow grading system. Patients underwent 2 h of continuous transcranial Doppler (TCD) monitoring and received three bolus of MB after 2, 20 and 40 min of tPA bolus. Ninety-one patients received Levovist (LV) and 47 received Sonovue (SV). NIHSS scores were obtained at baseline and after 24 h. Modified Rankin Scale (mRS) score was used to assess outcome at 3 mo. Median admission NIHSS was 17. On TCD, 96 (69.6%) patients had a proximal and 42 (30.4%) a distal MCA occlusion. Age, baseline NIHSS, clot location, stroke subtypes and time to treatment were similar between LV and SV groups. Recanalization rates after 1 h (32.2%/35.6%), 2 h (50.0%/46.7%) and 6 h (63.8%/54.5%) were similar in LV/SV groups (p > 0.3). Clinical improvement (NIHSS decrease >or= 4 points) at 24 h was similar in both groups (54.9%/51.1%, p = 0.400), as well as symptomatic intracranial haemorrhage rate (3.3%/2.1%, p = 0.580) and in-hospital mortality (8.1%/9.3%, p = 0.531). Similarly, the type of MB administered did not affect long-term outcome after sonothrombolysis. Forty-four percent of patients in the LV group and 48.5% in the SV group achieved functional independence (mRS <or= 2) at 3 mo (p = 0.440). MB administration during sonothrombolysis is associated with a high RE rate. However, RE rates, clinical course and long-term outcome are comparable when administering galactose-based air-filled MB (Levovist) or sulphur hexafluoride-filled MB (Sonovue).

Serum Low-Density Lipoprotein Cholesterol Level Predicts Hematoma Growth and Clinical Outcome After Acute Intracerebral Hemorrhage

Background and Purpose— Lower serum low-density lipoprotein cholesterol (LDL-C) levels have been associated with increased risk of death after intracerebral hemorrhage (ICH). Nevertheless, their link with hematoma growth (HG) is unknown. Therefore, we aimed to investigate the relationship between LDL-C levels, HG, and clinical outcome in patients with acute ICH. Methods— We prospectively studied 108 consecutive patients with primary supratentorial ICH presenting within 6 hours from symptoms onset. National Institutes of Health Stroke Scale score and ICH volume on computed tomography scan were recorded at baseline and at 24 hours. Lipid profile was obtained during the first 24 hours. Significant HG was defined as hematoma enlargement >33% or >6 mL at 24 hours. Early neurological deterioration as well as mortality and poor long-term outcome (modified Rankin Scale score >2) at 3 months were recorded. Results— Although LDL-C levels were not correlated with ICH volume (r=−0.18; P=0.078) or National Institutes of Health Stroke Scale score (r=−0.17; P=0.091) at baseline, lower LDL-C levels were associated with HG (98.1±33.7 mg/dL versus 117.3±25.8 mg/dL; P=0.003), early neurological deterioration (89.2±31.8 mg/dL versus 112.4±29.8 mg/dL; P=0.012), and 3-month mortality (94.9±37.4 mg/dL versus 112.5±28.5 mg/dL; P=0.029), but not with poor long-term outcome (109.5±31.3 mg/dL versus 108.3±30.5 mg/dL; P=0.875). Moreover, LDL-C levels were inversely related to the amount of hematoma enlargement at 24 hours (r=−0.31; P=0.004). In multivariate logistic regression analysis, LDL-C level <95 mg/dL emerged as an independent predictor of HG (OR, 4.24; 95% CI, 1.26–14.24; P=0.020), early neurological deterioration (OR, 8.27; 95% CI, 1.66–41.16; P=0.010), and 3-month mortality (OR, 6.34; 95% CI, 1.29–31.3; P=0.023). Conclusions— Lower serum LDL-C level independently predicts HG, early neurological deterioration, and 3-month mortality after acute ICH.