Collateral status and recanalization after endovascular treatment for acute ischemic stroke.

BACKGROUND: Successful recanalization and good collateral status are associated with good clinical outcomes after endovascular treatment (EVT) for acute ischemic stroke, but the relationships among them are unclear. OBJECTIVE: To assess if collateral status is associated with recanalization after EVT and if collateral status modifies the association between successful recanalization and functional outcome. METHODS: We retrospectively analyzed data from the MR CLEAN Registry, a multicenter prospective cohort study of patients with a proximal anterior occlusion who underwent EVT in the Netherlands. We determined collateral status with a previously validated four-point visual grading scale and defined successful recanalization as an extended Thrombolysis in Cerebral Infarction score ≥2B. Functional outcome was determined using the modified Rankin Scale score at 90 days. We assessed, with multivariable logistic regression models, the associations between (1) collateral status and successful recanalization, (2) successful recanalization and functional outcome, (3) collateral status and functional outcome. An interaction of collateral status and successful recanalization was assessed. Subgroup analyses were performed for patients treated with intravenous thrombolysis. RESULTS: We included 2717 patients, of whom 1898 (70%) had successful recanalization. There was no relationship between collateral status and successful recanalization (adjusted common OR (95% CI) of grades 1, 2, and 3 vs 0: 1.19 (0.82 to 1.72), 1.20 (0.83 to 1.75), and 1.10 (0.74 to 1.63), respectively). Successful recanalization (acOR (95% CI): 2.15 (1.84 to 2.52)) and better collateral grades (acOR (95% CI) of grades 1, 2, and 3 vs 0: 2.12 (1.47 to 3.05), 3.46 (2.43 to 4.92), and 4.16 (2.89 to 5.99), respectively) were both associated with a shift towards better functional outcome, without an interaction between collateral status and successful recanalization. Results were similar for the subgroup of thrombolysed patients. CONCLUSIONS: Collateral status is not associated with the probability of successful recanalization after EVT and does not modify the association between successful recanalization and functional outcome.

Improvements in Endovascular Treatment for Acute Ischemic Stroke: A Longitudinal Study in the MR CLEAN Registry.

BACKGROUND: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. METHODS: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). RESULTS: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P<0.001 and 236 versus 270 minutes; P<0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P<0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile. CONCLUSIONS: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Intracranial carotid artery calcification subtype and collaterals in patients undergoing endovascular thrombectomy.

BACKGROUND AND AIMS: Distinct subtypes of intracranial carotid artery calcification (ICAC) have been found (i.e., medial and intimal), which may differentially be associated with the formation of collaterals. We investigated the association of ICAC subtype with collateral status in patients undergoing endovascular thrombectomy (EVT) for ischemic stroke. We further investigated whether ICAC subtype modified the association between collateral status and functional outcome. METHODS: We used data from 2701 patients with ischemic stroke undergoing EVT. Presence and subtype of ICAC were assessed on baseline non-contrast CT. Collateral status was assessed on baseline CT angiography using a visual scale from 0 (absent) to 3 (good). We investigated the association of ICAC subtype with collateral status using ordinal and binary logistic regression. Next, we assessed whether ICAC subtype modified the association between collateral status and functional outcome (modified Rankin Scale, 0-6). RESULTS: Compared to patients without ICAC, we found no association of intimal or medial ICAC with collateral status (ordinal variable). When collateral grades were dichotomized (3 versus 0-2), we found that intimal ICAC was significantly associated with good collaterals in comparison to patients without ICAC (aOR, 1.41 [95%CI:1.06-1.89]) or with medial ICAC (aOR, 1.50 [95%CI:1.14-1.97]). The association between higher collateral grade and better functional outcome was significantly modified by ICAC subtype (p for interaction = 0.01). CONCLUSIONS: Patients with intimal ICAC are more likely to have good collaterals and benefit more from an extensive collateral circulation in terms of functional outcome after EVT.

7T versus 3T MR Angiography to Assess Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Aneurysm size and neck measurements are important for treatment decisions. The introduction of 7T magnetic resonance angiography (MRA) led to new possibilities assessing aneurysm morphology and flow due to the higher signal-to-noise ratio. However, it is unknown if the size measurements on 7T MRA are similar to those on the standard 3T MRA. This study aimed to compare aneurysm size measurements between 7T and 3T MRA. METHODS: We included 18 patients with 22 aneurysms who underwent both 3T and 7T MRA. Three acquisition protocols were compared: 3T time of flight (TOF), 7T TOF, and 7T contrast-enhanced MRA. Each aneurysm on each protocol was measured by at least two experienced neuroradiologists. Subsequently, the differences were evaluated using scatterplots and the intraclass correlation coefficients (ICC) of agreement. RESULTS: There was a good agreement among the neuroradiologists for the height and width measurements (mean ICC: .78-.93); the neck measurements showed a moderate agreement with a mean ICC of .57-.72. Between the MR acquisition protocols, there was a high agreement for all measurements with a mean ICC of .81-.96. Measurement differences between acquisition protocols (0-2.9 mm) were in the range of the differences between the neuroradiologists (0-3.6 mm). CONCLUSION: Our study showed that 7T MRA, both nonenhanced and contrast-enhanced, has a high agreement in aneurysm size measurements compared to 3T. This suggests that 7T is useful for reliable aneurysm size assessment.

Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry.

Background and Purpose- Collateral circulation status at baseline is associated with functional outcome after ischemic stroke and effect of endovascular treatment. We aimed to identify clinical and imaging determinants that are associated with collateral grade on baseline computed tomography angiography in patients with acute ischemic stroke due to an anterior circulation large vessel occlusion. Methods- Patients included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n=500) and MR CLEAN Registry (n=1488) were studied. Collateral status on baseline computed tomography angiography was scored from 0 (absent) to 3 (good). Multivariable ordinal logistic regression analyses were used to test the association of selected determinants with collateral status. Results- In total, 1988 patients were analyzed. Distribution of the collateral status was as follows: absent (7%, n=123), poor (32%, n=596), moderate (39%, n=735), and good (23%, n=422). Associations for a poor collateral status in a multivariable model existed for age (adjusted common odds ratio, 0.92 per 10 years [95% CI, 0.886-0.98]), male (adjusted common odds ratio, 0.64 [95% CI, 0.53-0.76]), blood glucose level (adjusted common odds ratio, 0.97 [95% CI, 0.95-1.00]), and occlusion of the intracranial segment of the internal carotid artery with occlusion of the terminus (adjusted common odds ratio 0.50 [95% CI, 0.41-0.61]). In contrast to previous studies, we did not find an association between cardiovascular risk factors and collateral status. Conclusions- Older age, male sex, high glucose levels, and intracranial internal carotid artery with occlusion of the terminus occlusions are associated with poor computed tomography angiography collateral grades in patients with acute ischemic stroke eligible for endovascular treatment.

[Cranial computed tomography, lumbar puncture and clinical deterioration in bacterial meningitis: a nationwide cohort study]. / CT-hersenen, lumbaalpunctie en klinische achteruitgang bij bacteriële meningitis.

BACKGROUND: Investigate how often cerebral herniation occurs following lumbar puncture (LP) in patients with bacterial meningitis, and whether cranial computed tomography (CT) can be used to identify patients at a higher risk of cerebral herniation. STUDY DESIGN: Prospective, nationwide cohort study covering the period March 2006 - November 2014. METHOD: We identified patients with community-acquired bacterial meningitis who showed signs of clinical deterioration, possibly caused by LP. For systematic evaluation of contraindications for LP on cranial CT, the included patients were matched to bacterial meningitis patients without deterioration. Four experts, blinded for patient outcome, scored cranial CT scan imaging for the cases as well as control patients in relation to contraindications for LP. Inter-assessor reliability was determined with Fleiss' generalized κ. RESULTS: Of the 1533 bacterial meningitis patients included, 47 (3.1%) exhibited clinical deterioration possibly caused by LP. Two patients deteriorated within 1 hour after LP (0.1%). In 43 of 47 patients that showed signs of clinical deterioration, cranial CT was performed prior to LP. The inter-rater reliability of assessment of contraindications for LP on cranial CT was moderate (Fleiss' generalized κ = 0.47). A contraindication for LP was reported by all four raters in 6 patients with clinical deterioration (14%) and in 5 patients without clinical deterioration (11%). CONCLUSION: LP can be performed safely in the large majority of patients with bacterial meningitis, as it only very rarely results in cerebral herniation. Cranial CT can be considered a screening method to identify patients who are at a higher risk of cerebral herniation, but the inter-rater reliability of the CT scan assessment for contraindications of LP is moderate.

Impact of single phase CT angiography collateral status on functional outcome over time: results from the MR CLEAN Registry.

BACKGROUND: Collateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent. METHODS: We included consecutive patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry (March 2014-June 2016) with an anterior circulation large vessel occlusion undergoing EVT. Functional outcome was measured on the modified Rankin Scale (mRS) at 90 days. We investigated the association between collaterals and mRS in the MR CLEAN Registry with ordinal logistic regression and if this association was time dependent with an interaction term. Additionally, we determined modification of EVT effect by collaterals compared with MR CLEAN controls, and also investigated if this was time dependent with multiplicative interaction terms. RESULTS: 1412 patients were analyzed. Functional independence (mRS score of 0-2) was achieved in 13% of patients with grade 0 collaterals, in 27% with grade 1, in 46% with grade 2, and in 53% with grade 3. Collaterals were significantly associated with mRS (adjusted common OR 1.5 (95% CI 1.4 to 1.7)) and significantly modified EVT benefit (P=0.04). None of the effects were time dependent. Better collaterals corresponded to lower mortality (P<0.001), but not to lower rates of symptomatic intracranial hemorrhage (P=0.14). CONCLUSION: In routine clinical practice, better collateral status is associated with better functional outcome and greater treatment benefit in EVT treated acute ischemic stroke patients, independent of time to treatment. Within the 6 hour time window, a substantial proportion of patients with absent and poor collaterals can still achieve functional independence.

Association of Time From Stroke Onset to Groin Puncture With Quality of Reperfusion After Mechanical Thrombectomy: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials.

Importance: Reperfusion is a key factor for clinical outcome in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) for large-vessel intracranial occlusion. However, data are scarce on the association between the time from onset and reperfusion results. Objective: To analyze the rate of reperfusion after EVT started at different intervals after symptom onset in patients with AIS. Design, Setting, and Participants: We conducted a meta-analysis of individual patient data from 7 randomized trials of the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) group. This is a multicenter cohort study of the intervention arm of randomized clinical trials included in the HERMES group. Patients with anterior circulation AIS who underwent EVT for M1/M2 or intracranial carotid artery occlusion were included. Each trial enrolled patients according to its specific inclusion and exclusion criteria. Data on patients eligible but not enrolled (eg, refusals or exclusions) were not available. All analyses were performed by the HERMES biostatistical core laboratory using the pooled database. Data were analyzed between December 2010 and April 2015. Main Outcomes and Measures: Successful reperfusion was defined as a modified thrombolysis in cerebral infarction score of 2b/3 at the end of the EVT procedure adjusted for age, occlusion location, pretreatment intravenous thrombolysis, and clot burden score and was analyzed in relation to different intervals (onset, emergency department arrival, imaging, and puncture) using mixed-methods logistic regression. Results: Among the 728 included patients, with a mean (SD) age of 65.4 (13.5) years and of whom 345 were female (47.4%), decreases in rates of successful reperfusion defined as a thrombolysis in cerebral infarction score of 2b/3 were observed with increasing time from admission or first imaging to groin puncture. The magnitude of effect was a 22% relative reduction (odds ratio, 0.78; 95% CI, 0.64-0.95) per additional hour between admission and puncture and a 26% relative reduction (odds ratio, 0.74; 95% CI, 0.59-0.93) per additional hour between imaging and puncture. Conclusions and Relevance: Because the probability of reperfusion declined significantly with time between hospital arrival and groin puncture, we provide additional arguments for minimizing the intervals after symptom onset in anterior circulation acute ischemic stroke.

Do older patients with acute or subacute subdural hematoma benefit from surgery?

PURPOSE: According to the international guidelines, acute subdural hematomas (aSDH) with a thickness of >10 mm, or causing a midline shift of >5 mm, should be surgically evacuated. However, high mortality rates in older patients resulted in ongoing controversy whether elderly patients benefit from surgery. We identified predictors of outcome in a single-centre cohort of elderly patients undergoing surgical evacuation of aSDH or subacute subdural hematoma (saSDH). MATERIALS AND METHODS: This retrospective study included all patients aged ≥65 years undergoing surgical evacuation of aSDH/saSDH from 2000 to 2015. One-year outcome was dichotomized into favourable (Glasgow Outcome Scale (GOS) 4-5) and unfavourable (GOS 1-3). Predictors of outcome were identified by analysing patient characteristics. RESULTS: Eighty-four patients aged ≥65 years underwent craniotomy for aSDH/saSDH during the 16 year time period. Twenty-five percent regained functional independence, 11% survived severely disabled, and 64% died. Most patients died of respiratory failure following withdrawal of artificial respiration or following restriction of treatment. Age of the SDH or Glasgow Coma Scores ≤8/intubation did not predict unfavourable outcome. All patients with bilaterally absent pupillary light reflexes died, also those who still exhibited one normal-sized pupil. CONCLUSION: The low number of operated patients per year probably suggests that this cohort represents a selection of patients who were judged to have good chances of favouring from surgery. Functional independence at one-year follow-up was reached in 25% of patients, 64% died. Patients with bilaterally absent pupillary light reflexes did not benefit from surgery. The tendency to restrict treatment because of presumed poor prognosis may have acted as a self-fulfilling prophecy.

Unfavorable Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage WFNS Grade I.

BACKGROUND: Patients with an aneurysmal subarachnoid hemorrhage (aSAH) and World Federation of Neurosurgical Societies (WFNS) grade I on admission are generally considered to have a good clinical outcome. OBJECTIVE: The objective of this study was to assess the actual clinical outcome of WFNS grade I aSAH patients, and to determine which factors are associated with unfavourable outcome. METHODS: For this prospective cohort study, 132 consecutive patients (age 18 years or older) with a WFNS grade I aSAH admitted to our hospital between December 2011 and January 2016 were eligible. Clinical outcome was measured using the modified Rankin Scale (mRS) at 6-month follow-up. Unfavorable outcome was defined as an mRS score of 3-6. Univariable analyses were performed using logistic regression models. RESULTS: Of 116 patients, only 5 patients (4%) had an mRS score of 0 and most (65%) had an mRS score of 2. Twenty-five patients (22%) had an unfavorable outcome. Nine (8%) patients died, of whom 4 died during admission. Factors associated with unfavorable outcome were age (per increasing decade: odds ratio [OR]. 1.78; 95% confidence interval [CI], 1.16-2.72), delayed cerebral ischemia (OR, 4.32; 95% CI, 1.63-11.44), pneumonia (OR, 10.75; 95% CI, 1.94-59.46) and meningitis (OR, 28.47; 95% CI, 1.42-571.15). CONCLUSIONS: Despite their neurologically optimal clinical condition on admission, 1 in 5 patients with WFNS grade I aSAH has an unfavorable clinical outcome or is dead at 6-month follow-up. Additional multivariable analysis in larger patient cohorts is necessary to identify the extent to which preventable complications contribute to unfavorable outcomes in these patients.

Cranial Computed Tomography, Lumbar Puncture, and Clinical Deterioration in Bacterial Meningitis: A Nationwide Cohort Study.

Background: It is unclear how often lumbar puncture (LP) is complicated by cerebral herniation in patients with bacterial meningitis and whether cranial computed tomography (CT) can be used to identify patients at risk for herniation. Methods: We performed a nationwide prospective cohort study of patients with community-acquired bacterial meningitis from 2006 to 2014 and identified patients with clinical deterioration possibly caused by LP. For systematic evaluation of contraindications for LP on cranial CT, these patients were matched to patients in the cohort without deterioration. Four experts, blinded for outcome, scored cranial CT results for contraindications for LP. A Fleiss' generalized κ for this assessment was determined. Results: Of 1533 episodes, 47 (3.1%) had deterioration possibly caused by LP. Two patients deteriorated within 1 hour after LP (0.1%). In 43 of 47 patients with deterioration, cranial CT was performed prior to LP, so CT results were matched with 43 patients without deterioration. The interrater reliability of assessment of contraindications for LP on cranial CT was moderate (Fleiss' generalized κ = 0.47). A contraindication for LP was reported by all 4 raters in 6 patients with deterioration (14%) and in 5 without deterioration (11%). Conclusions: LP can be performed safely in the large majority of patients with bacterial meningitis, as it is only very rarely complicated by cerebral herniation. Cranial CT can be considered a screening method for contraindications for LP, but the interrater reliability of this assessment is moderate.

Decompressive craniectomy in aneurysmal subarachnoid haemorrhage for hematoma or oedema versus secondary infarction.

PURPOSE: Decompressive craniectomy (DC) has been proposed as lifesaving treatment in aneurysmal subarachnoid haemorrhage (aSAH) patients with elevated intracranial pressure (ICP). However, data is sparse and controversy exists whether the underlying cause of elevated ICP influences neurological outcome. The purpose of this study is to clarify the role of the underlying cause of elevated ICP on outcome after DC. MATERIALS AND METHODS: We retrospectively studied the one-year neurological outcome in a single-centre cohort to identify predictors of favourable (Glasgow Outcome Scale (GOS) 4-5) and unfavourable (GOS 1-3) outcome. Additionally, available individual patient data in the literature was reviewed with a special emphasis on the underlying reason for DC. RESULTS: From 2006-2015, 53 consecutive aSAH patients underwent DC. Nine (17%) achieved favourable, 44 (83%) unfavourable outcome (31 patients died). One fourth of the patients undergoing DC for hematoma or (hematoma-related) oedema survived favourably (increasing to 46% for patients aged <51 years), versus none of the patients undergoing DC for secondary infarction. Analysis of individual data of 105 literature patients showed a similar trend, although overall outcome was much better: half of the patients undergoing DC for hematoma/oedema regained independence, versus less than one-fourth of patients undergoing DC for secondary infarction. CONCLUSIONS: DC in aSAH patients is associated with high rates of unfavourable outcome and mortality, but hematoma or oedema as underlying reason for DC is associated with better outcome profiles compared to secondary infarction. Future observational cohort studies are needed to further explore the different outcome profiles among subpopulations of aSAH patients requiring DC.

Clot Burden Score on Baseline Computerized Tomographic Angiography and Intra-Arterial Treatment Effect in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. METHODS: For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the χ2 test to assess treatment effect modification by CBS. RESULTS: Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04-1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12-2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. CONCLUSIONS: A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR1804. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758.

Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra-arterial treatment: a subgroup analysis of a randomised phase 3 trial (MR CLEAN).

BACKGROUND: Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). METHODS: MR CLEAN was a randomised, controlled, open-label, phase 3 trial of intra-arterial treatment in patients (aged ≥18 years from the Netherlands) with proximal arterial occlusion of the anterior circulation, given intra-arterial treatment within 6 h of stroke onset. The primary outcome was 90 day modified Rankin Scale (mRS) score. We estimated the intra-arterial treatment effect for all patients in MR CLEAN who had ASPECTS graded by using multivariable ordinal logistic regression analysis (a proportional odds model) to calculate the adjusted common odds ratio for a shift towards a better functional outcome according to the mRS for intra-arterial treatment and usual care than for usual care alone. We entered an interaction term into the model to test for interaction with prespecified ASPECTS subgroups: 0-4 (large infarct) versus 5-7 (moderate infarct) versus 8-10 (small infarct). MR CLEAN is registered with the Netherlands Trial Registry, number NTR1804, and the ISRCTN Registry, number ISRCTN10888758. FINDINGS: 496 patients-232 (47%) in the intra-arterial treatment and usual care group and 264 (53%) in the usual care alone group-were included in the analysis. We noted no significant difference in intra-arterial treatment effect between the ASPECTS subgroups according to 90 day ordinal mRS (adjusted common odds ratio interaction term relative to ASPECTS 8-10: ASPECTS 0-4: 0·79 [95% CI 0·20-3·19], p=0·740; and ASPECTS 5-7: 1·02 [0·44-2·35], p=0·966). Intra-arterial treatment did not cause a significant increase in the proportion of patients with at least one serious adverse event in any of the ASPECTS subgroups (ASPECTS 0-4: eight [73%] of 11 patients in treatment and usual care group vs 11 [58%] of 19 in usual care alone group, p=0·42; ASPECTS 5-7: 32 [59%] of 54 vs 19 [49%] of 39, p=0·31; ASPECTS 8-10: 70 [42%] of 167 vs 82 [40%] of 206; p=0·68). For death within 7 days or within 30 days and hemicraniectomy, the differences between the intra-arterial treatment and usual care versus usual care alone groups were not significant by ASPECTS subgroups. A significantly higher proportion of patients had recurrent ischaemic stroke in the intra-arterial treatment plus usual care group than in the usual care alone group in the ASPECTS 8-10 subgroup (eight [5%] vs one [<1%]; p=0·007). INTERPRETATION: Contrary to findings from previous studies suggesting that only patients with non-contrast CT ASPECTS of more than 7 benefit from intra-arterial treatment, data from this study suggest that patients with ASPECTS 5-7 should be treated. Further evidence is needed for patients with ASPECTS 0-4, for whom treatment might yield only marginal absolute benefit. FUNDING: Dutch Heart Foundation, AngioCare, Medtronic/Covidien/EV3, Medac/Lamepro, Penumbra, Stryker, and Top Medical.

Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients With Proximal Anterior Circulation Stroke.

BACKGROUND AND PURPOSE: Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). METHODS: MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. RESULTS: We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7-6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0-2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7-2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1-8.7] for patients with absent collaterals (grade 0). CONCLUSIONS: In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial.

IMPORTANCE: Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE: To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS: The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES: Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS: Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE: For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1804.

Treatment of dissecting aneurysms of the PICA: anatomical considerations and clinical outcome.

BACKGROUND AND PURPOSE: Posterior inferior cerebellar artery (PICA) dissecting aneurysms require rapid and aggressive treatment by sacrificing the parent vessel of the aneurysm-bearing dissected vessel. We assessed the clinical consequences of PICA occlusion in view of the local vascular anatomy. MATERIALS AND METHODS: We performed a retrospective search of our neurovascular database in the period 2007-2012. Patient characteristics, including clinical presentation, WFNS (World Federation of Neurosurgical Societies) grading and Glasgow Outcome Scale (GOS), were recorded. CT and CT angiographic findings as well as the detailed vascular anatomy including collateral circulation were assessed. RESULTS: We identified 10 patients (5 male; mean age 50 years). Eight patients presented with WFNS grade I and II, one with grade IV and one with grade V. All patients were treated with parent vessel occlusion (PVO). An extradural PICA origin was seen in three patients. Collateral circulation was visible before PVO in two and after PVO in seven additional patients. Despite the presence of collaterals, mild cerebellar ischemia occurred in three patients, without development of a Wallenberg syndrome. Outcome was favorable in 9 patients (8 patients GOS 5, one patient GOS 4). One patient died due to the mass effect of the initial cerebellar hematoma. CONCLUSION: PVO to treat PICA dissecting aneurysms was well tolerated with a 90% favorable outcome. Regional collateral circulation and vascular variations permitted relative safe vessel occlusion with only minor cerebellar symptoms in this small group of patients.

A randomized trial of intraarterial treatment for acute ischemic stroke.

BACKGROUND: In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS: We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS: We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

Angiogenesis in steno-occlusive vasculopathies as a common pathway for intracranial haemorrhage. A report of six cases.

Vasculopathies, including vasculitis of the central nervous system, can lead to stenosed, cicatrized vessels and the development of arterio-arteriolar collateral vessels. Bleeding due to these vascular changes, although rare, does occur. We describe six patients (all female, age range, 21-52 years; mean age, 42 years) with steno-occlusive lesions of intracranial vessels who presented with an acute intracranial haemorrhage. All had arterial steno-occlusive changes in conjunction with extensive leptomeningeal and arterio-arteriolar collaterals. Within the collaterals, focal dilatations could be identified, which were in close spatial relationship with the intracranial haemorrhage. Cause of bleeding was depicted on CT angiography in four out of six patients. One patient presented in childhood with acute stroke, one patient was diagnosed with Buerger's disease and one with sickle cell disease; the other three patients had no relevant history and the exact cause remained unclear. Outcome was favourable in all patients. Despite focal vascular weaknesses, no recurrent haemorrhage was seen during follow-up, supporting, at least in this small patient group, a conservative wait-and-see policy.

First-in-man intracoronary use of the Trevo® Pro 4 mechanical thrombectomy device for the retrieval of large intracoronary thrombus in patients with acute coronary syndromes.

AIMS: Large intracoronary thrombus in patients with acute coronary syndromes remains a challenge in percutaneous coronary intervention, despite technical advances of manual aspiration catheters and mechanical thrombectomy devices. The Trevo® Pro 4 is a novel self-expanding mechanical thrombus retrieval device, designed for removal of occlusive thrombi in the setting of acute ischaemic stroke. We describe the first use of this novel mechanical thrombus retrieval device in the setting of coronary intervention. METHODS AND RESULTS: In close collaboration with the interventional radiology department, two patients presenting with an acute coronary syndrome, complicated by refractory large intracoronary thrombus, were treated using the Trevo Pro 4. Both patients were treated successfully, resulting in complete removal of refractory thrombus without the occurrence of adverse events. CONCLUSIONS: The Trevo Pro 4 can be successfully used in the setting of coronary intervention. It is simple to use, does not require complex preparations, and the handling is straightforward. A larger study to assess the safety and efficacy of this device in the setting of coronary interventions is warranted.