Brain edema growth after thrombectomy is associated with comprehensive collateral blood flow.

BACKGROUND: We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy. METHODS: This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes. RESULTS: 538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC- profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC- (ß 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (ß 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence. CONCLUSION: A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy.

Thrombectomy in basilar artery occlusions: impact of number of passes and futile reperfusion.

BACKGROUND: The number of mechanical thrombectomy (MT) passes is strongly associated with angiographic reperfusion as well as clinical outcomes in patients with anterior circulation ischemic stroke. However, these associations have not been analyzed in patients with basilar artery occlusion (BAO). We investigated the influence of the number of MT passes on the degree of reperfusion and clinical outcomes, and compared outcome after ≤3 passes versus >3 passes. METHODS: We used data from the prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry at 18 sites in France. Patients with BAO treated with MT were included. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0-3 at 90 days. We fit mixed multiple regression models, with center as a random effect. RESULTS: We included 275 patients. Successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3) was achieved in 88.4%, and 41.8% had a favorable outcome. The odds ratio for favorable outcome with each pass above 1 was 0.41 (95% CI 0.23 to 0.73) and for recanalization (mTICI 2b-3) it was 0.70 (95% CI 0.57 to 0.87). In patients with ≤3 passes, the rate of favorable outcome in recanalized versus non-recanalized patients was 50.5% versus 10.0% (p=0.001), while in those with >3 passes it was 16.7% versus 15.2% (p=0.901). CONCLUSIONS: We found that BAO patients had a significant relationship between the number of MT passes and both recanalization and favorable functional outcome. We further found that the benefit of recanalization in BAO patients was significant only when recanalization was achieved within three passes, encouraging at least three passes before stopping the procedure.

Influence of prior intravenous thrombolysis in patients treated with mechanical thrombectomy for M2 occlusions: insight from the Endovascular Treatment in Ischemic Stroke (ETIS) registry.

BACKGROUND: Intravenous thrombolysis (IVT) for patients treated with mechanical thrombectomy (MT) for proximal occlusions has recently been questioned through randomized trials. However, few patients with M2 occlusions were included. We investigated the influence of prior IVT for patients presenting M2 occlusions treated with MT in comparison with MT alone. METHODS: We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry, a multicenter observational study. Data from consecutive patients treated with MT for M2 occlusions between January 2015 and January 2022 at 26 comprehensive stroke centers were analyzed. The primary endpoint was 90-day modified Rankin Scale score of 0-2. Outcomes were compared using propensity score approaches. We also performed sensitivity analysis in relevant subgroups of patients. RESULTS: Among 1132 patients with M2 occlusions treated with MT, 570 received prior IVT. The two groups were comparable after propensity analysis. The rate of favorable functional outcome was significantly higher in the IVT+MT group compared with the MT alone group (59.8% vs 44.7%; adjusted OR 1.38, 95% CI 1.10 to 1.75, P=0.008). Hemorrhagic and procedural complications were similar in both groups. In sensitivity analysis excluding patients with anticoagulation treatment, favorable recanalization was more frequent in the IVT+MT group (OR 1.37, 95% CI 1.11 to 1.70, P=0.004). CONCLUSIONS: In cases of M2 occlusions, prior IVT combined with MT resulted in better functional outcome than MT alone, without increasing the rate of hemorrhagic or procedural complications. These results suggest the benefit of IVT in patients undergoing MT for M2 occlusions.

MRI spot sign in acute intracerebral hemorrhage: an independent biomarker of hematoma expansion and poor functional outcome.

BACKGROUND: In acute intracerebral hemorrhage (ICH), the prognostic value of the MRI spot sign on hematoma expansion (HE) and poor functional outcome is poorly known. METHODS: We retrospectively included patients admitted over a 4-year period for an acute ICH in a single institution using MRI as the first-line imaging tool. The presence and number of MRI spot signs on contrast-enhanced T1-weighted imaging was evaluated by one neuroradiologist, blinded from outcomes. The primary outcome was HE, defined as > 6 mL or > 33% ICH volume growth from initial MRI to 24-48 h follow-up imaging; the secondary outcome was poor 3-month modified Rankin score (4-6). RESULTS: Overall, 147 patients were included, and 62% had a spot sign. Among the 130 patients with follow-up imaging, 24% experienced HE. HE occurred in 6%, 21% and 43% patients with 0, 1 and ≥ 2 spots, respectively (P < 0.001). The MRI spot sign was independently associated with HE (adjusted OR 6.15 [95% CI 1.60-23.65]; P = 0.008), with a dose-dependent effect. The negative and positive predictive values of the spot sign for HE were 0.94 and 0.35, respectively. Poor functional outcome occurred in 27%, 32% and 71% patients with 0, 1 and ≥ 2 spots, respectively (P < 0.001). In multivariable analysis, the presence of ≥ 2 spots was independently associated with poor functional outcome (adjusted OR 3.67 [95% CI 1.21-11.10]; P = 0.024). CONCLUSION: The MRI spot sign is an independent biomarker of HE, and the presence of ≥ 2 spots is independently associated with poor 3-month outcome. The lack of spot sign is highly predictive of a favorable evolution.

Intended Bridging Therapy or Intravenous Thrombolysis Alone in Minor Stroke With Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with basilar artery occlusion remains uncertain. METHODS: Multicentric retrospective observational study of consecutive minor stroke patients (National Institutes of Health Stroke Scale score ≤5) with basilar artery occlusion intended for IVT alone or bridging therapy. Propensity-score weighting was used to reduce baseline between-groups differences, and residual imbalance was addressed through adjusted logistic regression, with excellent outcome (3-month modified Rankin Scale score 0-1) as the dependent variable. RESULTS: Fifty-seven patients were included (28 and 29 in the bridging therapy and IVT alone groups, respectively). Following propensity-score weighting, the distribution of baseline clinical and radiological variables was similar across the 2 patient groups, except age, posterior circulation Alberta Stroke Program Early CT Score, history of hypertension and smoking, and onset-to-IVT time. Compared with IVT alone, bridging therapy was associated with excellent outcome (adjusted odds ratio=3.37 [95% CI, 1.13-10.03]; P=0.03). No patient experienced symptomatic intracranial hemorrhage. CONCLUSIONS: Our results suggest that bridging therapy may be superior to IVT alone in minor stroke with basilar artery occlusion.

3D T1-weighted black-blood magnetic resonance imaging for the diagnosis of giant cell arteritis.

OBJECTIVES: Imaging techniques have an increasing place in the diagnosis of giant cell arteritis (GCA). Achieving a confident diagnosis of GCA is often challenging and temporal artery biopsy is still considered as the gold standard despite the delayed results. 3T-MRI with 2D sequences has been evaluated for the detection of mural inflammation in extracranial arteries to support the diagnosis of GCA. METHODS: We evaluated the diagnostic performance of fat-suppressed 3D T1-weighted black-blood MRI (CUBE T1) with 3D TOF coregistration. RESULTS: Thirty-two patients with clinically suspected GCA were included and 10 had a diagnosis of GCA. Sensitivity and specificity of CUBE T1 were 80% and 100% respectively. Therefore, the positive predictive value of post-contrast CUBE T1 was 100% and the negative predictive value was 92%. Intra- and inter-observer agreement for mural enhancement on CUBE T1 was 1 and 0.83, respectively. CONCLUSIONS: We demonstrate that CUBE T1 is accurate for the diagnosis of GCA. The reproducibility and short scan duration of the technique support a wider use of MRI in the diagnosis process.

MT-DRAGON score for outcome prediction in acute ischemic stroke treated by mechanical thrombectomy within 8 hours.

OBJECTIVES: The MRI-DRAGON score includes clinical and MRI parameters and demonstrates a high specificity in predicting 3 month outcome in patients with acute ischemic stroke (AIS) treated with intravenous tissue plasminogen activator (IV tPA). The aim of this study was to adapt this score to mechanical thrombectomy (MT) in a large multicenter cohort. METHODS: Consecutive cases of AIS treated by MT between January 2015 and December 2017 from three stroke centers were reviewed (n=1077). We derived the MT-DRAGON score by keeping all variables of the MRI-DRAGON score (age, initial National Institutes of Health Stroke Scale score, glucose level, pre-stroke modified Rankin Scale (mRS) score, diffusion weighted imaging-Alberta Stroke Program Early CT score ≤5) and considering the following variables: time to groin puncture instead of onset to IV tPA time and occlusion site. Unfavorable 3 month outcome was defined as a mRS score >2. Score performance was evaluated by c statistics and an external validation was performed. RESULTS: Among 679 included patients (derivation and validation cohorts, n=431 and 248, respectively), an unfavorable outcome was similar between the derivation (51.5%) and validation (58.1%, P=0.7) cohorts, and was significantly associated with all MT-DRAGON parameters in the multivariable analysis. The c statistics for unfavorable outcome prediction was 0.83 (95%CI 0.79 to 0.88) in the derivation and 0.8 (95%CI 0.75 to 0.86) in the validation cohort. All patients (n=55) with an MT-DRAGONscore ≥11 had an unfavorable outcome and 60/63 (95%) patients with an MT-DRAGON score ≤2 points had a favorable outcome. CONCLUSION: The MT-DRAGON score is a simple tool, combining admission clinical and radiological parameters that can reliably predict 3 month outcome after MT.

Revisiting 'progressive stroke': incidence, predictors, pathophysiology, and management of unexplained early neurological deterioration following acute ischemic stroke.

Early neurological deterioration (END) following acute ischemic stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 h following stroke onset, apart from straightforward causes such as symptomatic intracranial haemorrhage and malignant edema, the cause of END remains unclear in more than a half of cases. In the latter situation, patients are often referred to as 'progressive stroke', a default clinical category that does not imply underlying mechanisms, precluding informed management. In this review article, we summarize the available evidence on the incidence, predictors, and associated factors of unexplained END, and discuss its underlying pathophysiology. We particularly address the hemodynamic and thrombotic mechanisms that likely play a critical role in unexplained END, and in turn highlight potential new avenues to prevent and manage this ominous event.

Is Unexplained Early Neurological Deterioration After Intravenous Thrombolysis Associated With Thrombus Extension?

BACKGROUND AND PURPOSE: Early neurological deterioration (END) after anterior circulation stroke is strongly associated with poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END occurring after intravenous thrombolysis remains unclear in most instances. We tested the hypothesis that unexplained END is associated with thrombus extension. METHODS: From our database of consecutively thrombolysed patients, we identified anterior circulation stroke patients who had both admission and 24-hour T2* magnetic resonance imaging, visible occlusion on admission magnetic resonance angiography and no recanalization on 24-hour magnetic resonance angiography. END was defined as ≥4 National Institutes of Health Stroke Scale-point deterioration on 24-hour clinical assessment and unexplained END as END without clear cause. The incidence of susceptibility vessel sign extension on T2* imaging, defined as any new occurrence or extension of susceptibility vessel sign from admission to 24-hour follow-up magnetic resonance, was compared between patients with unexplained END and those without END. RESULTS: Of 120 eligible patients for the present study, 22 experienced unexplained END. Susceptibility vessel sign extension was present in 41 (34%) patients and was significantly more frequent in the unexplained END than in the no-END group (59% versus 29%, respectively; adjusted odds ratio=3.96; 95% confidence interval, 1.25-12.53; P=0.02). CONCLUSIONS: In this study, unexplained END occurring after thrombolysis was independently associated with susceptibility vessel sign extension, suggesting in situ thrombus extension or re-embolization. These findings strengthen the need to further investigate early post-thrombolysis administration of antithrombotics to reduce the risk of this ominous clinical event.

Incidence, causes and predictors of neurological deterioration occurring within 24†h following acute ischaemic stroke: a systematic review with pathophysiological implications.

Early neurological deterioration (END) following ischaemic stroke is a serious event with manageable causes in only a fraction of patients. The incidence, causes and predictors of END occurring within 24 h of acute ischaemic stroke (END24) have not been systematically reviewed. We systematically reviewed Medline and Embase from January 1990 to April 2013 for all studies on END24 following acute ischaemic stroke (<8 h from onset). We recorded the incidence and presumed causes of and factors associated with END24. Thirty-six studies were included. Depending on the definition used, the incidence of END24 markedly varied among studies. Using the most widely used change in National Institutes of Health Stroke Scale ≥4 definition, the pooled incidence was 13.8% following thrombolysis, ascribed to intracranial haemorrhage and malignant oedema each in ∼20% of these. As other mechanisms were rarely reported, in the majority no clear cause was identified. Few data on END24 occurring in non-thrombolysed patients were available. Across thrombolysed and non-thrombolysed samples, the strongest and most consistent admission predictors were hyperglycaemia, no prior aspirin use, prior transient ischaemic attacks, proximal arterial occlusion and presence of early CT changes, and the most consistent 24 h follow-up associated factors were no recanalisation/reocclusion, large infarcts and intracranial haemorrhage. Finally, END24 was strongly predictive of poor outcome. The above findings are discussed with emphasis on END without a clear mechanism. Data on incidence and predictors of the latter subtype is scarce, and future studies using systematic imaging protocols should address its underlying pathophysiology. This may in turn lead to rational preventative and therapeutic measures for this ominous event.

Mechanisms of unexplained neurological deterioration after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Unstable clinical course characterizes the first 24 hours after thrombolysis for anterior circulation stroke, including early neurological deterioration (END), a secondary complication consistently predictive of poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END remains unclear in the majority of cases (ENDunexplained). Based on the core/penumbra model, we tested the hypothesis that ENDunexplained is caused by infarct growth beyond the initial penumbra and assessed the associated vascular patterns. METHODS: From our database of consecutive thrombolyzed patients (n=309), we identified 10 ENDunexplained cases who had undergone both admission and 24-hour MRI. Diffusion-weighted imaging lesion growth both within and beyond the acute penumbra (Tmax>6 seconds) was mapped voxelwise. These 10 cases were compared with 30 no-END controls extracted from the database blinded to 24-hour diffusion-weighted imaging to individually match cases (3/case) according to 4 previously identified clinical and imaging variables. RESULTS: As predicted, lesion growth beyond initial penumbra was present in 9 of 10 ENDunexplained patients (substantial in 8) and its volume was significantly larger in cases than controls (2P=0.047). All ENDunexplained cases had proximal arterial occlusion initially, of which only 2 had recanalized at 24 hours. CONCLUSIONS: In this exploratory study, most instances of ENDunexplained were related to diffusion-weighted imaging growth beyond acute penumbra. Consistent presence of proximal occlusion at admission and lack of recanalization at 24 hours in most cases suggest that hemodynamic factors played a key role, via for instance systemic instability/collateral failure or secondary thromboembolic processes. Preventing END after tissue-type plasminogen activator using, eg, early antithrombotics may therefore be feasible.

Unexplained early neurological deterioration after intravenous thrombolysis: incidence, predictors, and associated factors.

BACKGROUND AND PURPOSE: Early neurological deterioration (END) after anterior circulation stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 hours of intravenous recombinant tissue-type plasminogen activator, apart from definite causes such as symptomatic intracranial hemorrhage and malignant edema whose incidence, predictors, and clinical management are well established, little is known about END without clear mechanism (ENDunexplained). METHODS: We analyzed 309 consecutive patients thrombolysed intravenously ≤4.5 hours from onset of anterior circulation stroke. ENDunexplained was defined as a ≥4-point deterioration on 24-hour National Institutes of Health Stroke Scale, without definite mechanism on concomitant imaging. ENDunexplained and no-END patients were compared for pretreatment clinical and imaging (including magnetic resonance diffusion and diffusion/perfusion mismatch volumes) data and 24-hour post-treatment clinical (including blood pressure and glycemic changes) and imaging (24-hour recanalization) data, using univariate logistic regression. Exploratory multivariate analysis was also performed after variable reduction, with bootstrap analysis for internal validation. RESULTS: Among 33 END patients, 23 (7% of whole sample) had ENDunexplained. ENDunexplained was associated with poor 3-month outcome (P<0.01). In univariate analysis, admission predictors of ENDunexplained included no prior use of antiplatelets (P=0.02), lower National Institutes of Health Stroke Scale score (P<0.01), higher glycemia (P=0.03), larger mismatch volume (P=0.03), and proximal occlusion (P=0.01), with consistent results from the multivariate analysis. Among factors recorded during the first 24 hours, only no recanalization was associated with ENDunexplained in multivariate analysis (P=0.02). CONCLUSIONS: ENDunexplained affected 7% of patients and accounted for most cases of END. Several predictors and associated factors were identified, with important implications regarding underlying mechanisms and potential prevention of this ominous event.