Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke. METHODS: We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621. FINDINGS: Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores. INTERPRETATION: Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

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.

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months. METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812. FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups. INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. FUNDING: Fonds NutsOhra.

Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment.

OBJECTIVES: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure. MATERIALS AND METHODS: We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage. RESULTS: Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups. CONCLUSIONS: The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.

Cerebral circulation time on DSA during endovascular treatment in WFNS grade I aneurysmal SAH patients-a predictor of DCI?

PURPOSE: Delayed cerebral ischemia (DCI) remains a contributor to poor outcome following aneurysmal subarachnoid hemorrhage (aSAH). We evaluated cerebral circulation time (CCT) on digital subtraction angiography (DSA) during endovascular treatment (EVT) in WFNS grade I aSAH patients as a predictor of DCI. METHODS: Of 135 consecutive WNFS grade I aSAH patients, 90 were included. Age, gender, time of DSA from ictus (< 72 h or > 72 h), Fisher scale, severe vasospasm, development of DCI, EVD-dependent hydrocephalus, re-bleeding, and procedural complications were recorded. CCT was calculated retrospectively from multiphase DSA. Association with DCI was established through univariate and, subsequently, multivariable logistic regression. An optimal threshold value was identified using ROC curve analysis. Patient groups defined by threshold CCT value, DCI, and, subsequently, time of DSA from ictus were analyzed using χ2 and Fisher's exact test. RESULTS: CCT was the only significant factor in the multivariable logistic regression for the outcome development of DCI (OR/second increase in CCT = 1.46 [95% CI 1.14-1.86, p = .003]). When CCT was dichotomized at 8.5 s, the odds ratio for developing DCI was 7.12 (95% CI 1.93-26.34, p = .003) for CCT > 8.5 s compared with < 8.5 s. There was a significant difference for DCI in all patient groups dichotomized by CCT < 8.5 s and > 8.5 s (all patients, p = .001; patients imaged before and after 72 h of ictus, p = .024 and p = .034, respectively). CONCLUSION: A CCT > 8.5 s on DSA during EVT in WFNS grade I aSAH patients is associated with an increased risk of developing DCI and may aid in the management of high-risk patients.

Thrombectomy for acute ischemic stroke patients with isolated distal internal carotid artery occlusion: a retrospective observational study.

PURPOSE: Acute stroke patients presenting with a distal internal carotid artery occlusion and patent carotid terminus, allowing for collateral flow via the circle of Willis, may have a more favorable natural history. Therefore, benefit of endovascular treatment (EVT) is less evident. We performed an exploratory analysis of EVT results compared to conservative treatment in patients with 'carotid-I' occlusions. METHODS: We report on EVT-treated and non-EVT-treated patients with carotid-I occlusions from the MR CLEAN Registry, MR CLEAN trial, and our comprehensive stroke center. CT-angiography was reviewed on primary collateral patency and choroid plexus enhancement. Perfusion deficits were assessed on CT-perfusion (CTP). Clot migration was assessed by comparing clot location on baseline CTA to its location on periprocedural digital subtraction angiography. Outcomes included 90-day functional independence (mRS 0-2), successful reperfusion and mortality. RESULTS: We included 51 patients. Forty-one patients received EVT, ten patients did not. Intravenous thrombolysis was administered in 32 (78%) EVT-treated patients and 6 (60%) non-EVT-treated patients. CTP, available for 17 patients, showed hypoperfusion on cerebral blood flow maps in 13 (76%) patients. Successful reperfusion after EVT occurred in 23 (56%), and clot migration in 8 patients (20%). Functional independence was achieved in 54% (21/39) of EVT-treated and in 10% (1/10) of non-EVT-treated patients. Mortality was 26% (10/39) and 30% (3/10), respectively. Anterior choroidal artery patency and choroid plexus enhancement were positively associated with functional independence. CONCLUSION: In our population, data suggest improved outcomes after EVT in carotid-I occlusion patients and provide no arguments to withhold EVT in these patients.

Tranexamic acid for chronic subdural hematoma.

BACKGROUND: There is no consensus on optimal treatment for a chronic subdural hematoma (cSDH). In patients with only moderate symptoms treatment with tranexamic acid (TXA) has been suggested. We report off-label use of TXA in seven patients. METHODS: Between August 2016 and May 2018 we identified seven patients for primary conservative treatment with TXA until satisfactory clinical and radiological status was achieved. Primary outcome was surgery for cSDH evacuation. Radiological follow-up was performed at regular intervals for hematoma volume measurements. RESULTS: Five patients experienced complete resolution of symptoms, one patient had a burr-hole craniostomy five days after initiation of TXA treatment due to an increase of left-sided weakness and dysarthria and in one patient symptoms did not improve. Median follow-up was 15 weeks (range 6-25, without the operated patient). The median total volume before start of treatment was 83 mL (range 11-137) for all patients. At the last follow-up, the median total volume in the non-operated patients decreased by 73% to 33 mL (range 0-77). CONCLUSIONS: TXA could be considered as primary medical treatment in patients with a cSDH and mild symptoms. The results of current randomized clinical trials must be awaited.

Endovascular aneurysm closure during out of office hours is not related to complications or outcome.

PURPOSE: A possible disadvantage of endovascular occlusion outside work hours is that complex procedures might expose patients to additional risk when performed in a suboptimal setting. In this prospective cohort study, we evaluated whether treatment during out of office hours is a risk factor for per-procedural complications and clinical outcome. METHODS: We included 471 endovascular-treated, consecutive aneurysmal subarachnoid hemorrhage patients (56.6 ± 13.1, 69% female), from two prospective observational databases which were retrospectively analyzed. Primary outcome was the occurrence of per-procedural complications. Secondary outcomes were good clinical outcome (modified ranking scale ≤ 2) and death at 6-month follow-up. We determined odds ratios (OR) with 95% confidence intervals (CI) by ordered polytomous logistic regression analysis and adjusted odds ratios (aOR) for age, World Federation of Neurosurgical Societies grade, and time to treatment. RESULTS: Most patients were treated during office hours (363/471; 77.1%). Treatment during out of office hours did not result in an increased risk of per-procedural complications (OR 0.85 (95% CI 0.53-1.37; p = 0.51). Patients treated during out of office hours displayed similar odds of good clinical outcome and death after 6 months (OR 1.14, 95% CI 0.68-1.97 and 1.16 95% CI 0.56-2.29, respectively) compared to patients treated during office hours. CONCLUSION: In our study, endovascular coil embolization during out of office hours did not expose patients to an increased risk of procedural complications or affect functional outcome after 6 months.

Thrombus Migration Paradox in Patients With Acute Ischemic Stroke.

Background and Purpose- The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial noninvasive imaging. We studied the incidence of thrombus dynamics, its impact on patient outcomes, and its association with intravenous thrombolytics. Methods- We included patients from the MR CLEAN registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke) with an initial target occlusion on computed tomography angiography located in the intracranial internal carotid artery, M1, or M2. The conventional angiography target occlusion was defined during endovascular treatment. Thrombus dynamics were classified as growth, stability, migration, and resolution. The primary outcome was functional outcome at 90 days (modified Rankin Scale). The secondary outcomes were successful and complete reperfusion (extended treatment in cerebral infarction scores of 2b-3 and 3, respectively). Results- The analysis included 1349 patients. Thrombus migration occurred in 302 (22%) patients, thrombus growth in 87 (6%), and thrombus resolution in 39 (3%). Intravenous treatment with alteplase was associated with more thrombus migration (adjusted odds ratio, 2.01; CI, 1.29-3.11) and thrombus resolution (adjusted odds ratio, 1.85; CI, 1.22-2.80). Thrombus migration was associated with a lower chance of complete reperfusion (adjusted odds ratio, 0.57; CI, 0.42-0.78) and successful reperfusion (adjusted odds ratio, 0.74; CI, 0.55-0.99). In the subgroup of patients with M1 initial target occlusion, thrombus migration was associated with better functional outcome (adjusted common odds ratio, 1.49; CI, 1.02-2.17), and there was a trend towards better functional outcome in patients with thrombus resolution (adjusted common odds ratio, 2.23; CI, 0.93-5.37). Conclusions- In patients with acute ischemic stroke, thrombus location regularly changes between computed tomography angiography and digital subtraction angiography. Administration of intravenous alteplase increases the chance of thrombus migration and resolution. Thrombus migration is associated with better functional outcome but reduces the rate of complete reperfusion.

Radiological scales predicting delayed cerebral ischemia in subarachnoid hemorrhage: systematic review and meta-analysis.

PURPOSE: Delayed cerebral ischemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage (aSAH). The extent of subarachnoid blood is a strong predictor of DCI and is frequently estimated with the Fisher scale, modified Fisher scale, or Hijdra sum score. It is unclear which scale has the strongest association with clinical DCI. To evaluate this, we performed a systematic review of the literature. METHODS: We performed a MEDLINE and EMBASE search from 1980 to 20th of June 2017. Radiological grade and occurrence of clinical DCI were extracted along with odds ratios (ORs) for DCI. When possible, pooled ORs with 95% confidence intervals were calculated per grade increase on the radiological scale. RESULTS: Fifty-three studies were included. The Fisher scale was significantly associated with DCI in 62% of the studies compared to 88-100% for the other scales. In studies using the Fisher scale, Fisher 3 had the strongest association with DCI (pooled OR 3.21 (1.87-5.49)). In studies using the modified Fisher score, DCI occurred most frequently (42%) in modified Fisher 4. No pooled OR could be calculated for the other scales. CONCLUSION: The Fisher scale, modified Fisher scale, and Hijdra sum score are all associated with clinical DCI. The risk of DCI, however, does not increase with increasing Fisher grade as opposed to the modified Fisher scale. Furthermore, the modified Fisher scale was more commonly significantly associated with DCI than the Fisher scale, which may advocate using the modified Fisher in future SAH-related studies.

Vessel wall enhancement of intracranial aneurysms: fact or artifact?

OBJECTIVE: For patients with subarachnoid hemorrhage (SAH) and multiple intracranial aneurysms, it is often challenging to identify the ruptured aneurysm. Some investigators have asserted that vessel wall imaging (VWI) can be used to identify the ruptured aneurysm since wall enhancement after contrast agent injection is presumably related to inflammation in unstable and ruptured aneurysms. The aim of this study was to determine whether additional factors contribute to aneurysm wall enhancement by assessing imaging data in a series of patients. METHODS: Patients with symptoms of SAH who subsequently underwent VWI in the period between January 2017 and September 2018 were eligible for study inclusion. Three-dimensional turbo spin-echo sequences with motion-sensitized driven-equilibrium preparation pulses were acquired using a 3-T MRI scanner to visualize the aneurysm wall. Identification of the ruptured aneurysm was based on aneurysm characteristics and hemorrhage distributions on MRI. Complementary imaging data (CT, DSA, MRI) were used to assess potential underlying enhancement mechanisms. Additionally, aneurysm luminal diameter measurements on MRA were compared with those on contrast-enhanced VWI to assess the intraluminal contribution to aneurysm enhancement. RESULTS: Six patients with 14 aneurysms were included in this series. The mean aneurysm size was 5.8 mm (range 1.1-16.9 mm). A total of 10 aneurysms showed enhancement on VWI; 5 ruptured aneurysms showed enhancement, and 1 unruptured but symptomatic aneurysm showed enhancement on VWI and ruptured 1 day later. Four unruptured aneurysms showed enhancement. In 6 (60%) of the 10 enhanced aneurysms, intraluminal diameters appeared notably smaller (≥ 0.8 mm smaller) on contrast-enhanced VWI compared to their appearance on multiple overlapping thin slab acquisition time of flight (MOTSA-TOF) MRA and/or precontrast VWI, suggesting that enhancement was at least partially in the aneurysm lumen itself. CONCLUSIONS: Several factors other than the hypothesized inflammatory response contribute to aneurysm wall enhancement. In 60% of the cases in this study, enhancement was at least partially caused by slow intraaneurysmal flow, leading to pseudo-enhancement of the aneurysm wall. Notwithstanding, there seems to be clinical value in differentiating ruptured from unruptured aneurysms using VWI, but the hypothesis that we image the inflammatory cell infiltration in the aneurysm wall is not yet confirmed.

Insufficient slow-flow suppression mimicking aneurysm wall enhancement in magnetic resonance vessel wall imaging: a phantom study.

OBJECTIVE: MR vessel wall imaging (VWI) is increasingly performed in clinical settings to support treatment decision-making regarding intracranial aneurysms. Aneurysm wall enhancement after contrast agent injection is expected to be related to aneurysm instability and rupture status. However, the authors hypothesize that slow-flow artifacts mimic aneurysm wall enhancement. Therefore, in this phantom study they assess the effect of slow flow on wall-like enhancement by using different MR VWI techniques. METHODS: The authors developed an MR-compatible aneurysm phantom model, which was connected to a pump to enable pulsatile inflow conditions. For VWI, 3D turbo spin echo sequences-both with and without motion-sensitized driven equilibrium (MSDE) and delay alternating with nutation for tailored excitation (DANTE) preparation pulses-were performed using a 3-T MR scanner. VWI was acquired both before and after Gd contrast agent administration by using two different pulsatile inflow conditions (2.5 ml/sec peak flow at 77 and 48 beats per minute). The intraluminal signal intensity along the aneurysm wall was analyzed to assess the performance of slow-flow suppression. RESULTS: The authors observed wall-like enhancement after contrast agent injection, especially in low pump rate settings. Preparation pulses, in particular the DANTE technique, improved the performance of slow-flow suppression. CONCLUSIONS: Near-wall slow flow mimics wall enhancement in VWI protocols. Therefore, VWI should be carefully interpreted. Preparation pulses improve slow-flow suppression, and therefore the authors encourage further development and clinical implementation of these techniques.

Intracranial aneurysm growth: consistency of morphological changes.

OBJECTIVE: Previous studies have shown a relation between growth and rupture of intracranial aneurysms. Additionally, several morphological characteristics are frequently measured to estimate rupture risk. Little is known about how the rupture risk is associated with morphological characteristic changes during growth. The aim of this study was to provide insights into how morphological characteristics, associated with rupture, change during an aneurysm's growth. METHODS: The authors retrospectively identified patients with longitudinal MRA images of unruptured growing aneurysms. The MRA images had an in-plane resolution of 0.2-0.5 mm and a slice thickness of 0.2-0.75 mm. Therefore, growth was defined as an increase of at least 0.5 mm in two directions or 1 mm in one direction. Using the MRA images, the authors semiautomatically segmented the aneurysm and the perianeurysmal vasculature. Twelve morphological characteristics were automatically measured. These characteristics were related to size (diameter, height, width, neck diameter, volume, surface area, aspect ratio, height-width ratio, and bottleneck factor) and shape (ellipticity index, nonsphericity index, and undulation index) of the aneurysm. Morphological characteristics before and after growth were compared using the Wilcoxon signed-rank test. RESULTS: The authors included 31 patients with 38 growing aneurysms. The aneurysms' growth was detected after a mean of 218 weeks (range 23-567 weeks). A significant increase was seen in all size-related characteristics, and the bottleneck factor also significantly increased (from a median of 1.00 [IQR 0.85-1.04] to 1.03 [IQR 0.93-1.18]), while the ellipticity index decreased (from a median of 0.26 [IQR 0.25-0.28] to 0.25 [IQR 0.24-0.26]). The changes in size ratios and shape indices varied largely among patients. Larger aneurysms more often showed an increase in shape ratios. CONCLUSIONS: Although aneurysm growth, size-related characteristics, bottleneck factor, and ellipticity index changed significantly during growth, most size ratios and shape indices showed inconsistent changes among aneurysms. This suggests that, for an accurate rupture prediction, morphological parameters need to be reassessed after growth.

Impact of superior ophthalmic vein thrombosis: a case series and literature review.

Purpose: To present nine new cases of superior ophthalmic vein thrombosis (SOVT) and compare these with the literature, and to assess the impact of SOVT for the clinician. Methods: Using the data bases of the Department of Ophthalmology of the AMC, we searched for patients with radiologically evidenced SOVT between January 2006 and December 2014. In addition, a PubMed search, using the mesh term 'superior ophthalmic vein thrombosis', was done. Results: We found nine patients with SOVT. In three patients, SOVT was related to dural arteriovenous fistulae. In one patient, it was caused by the acute reversal of warfarin by vitamin K. In two patients, an infectious cause was found. In three patients, the cause of SOVT was not found despite screening for coagulation and other disorders. All patients presented with eyelid swelling, proptosis, and/or motility impairment. We found complete recovery in four patients. Three patients had mild sequelae and two patients had severe visual impairment. In the literature, we found 60 cases reporting on SOVT with various aetiologies. Clinical presentation, treatment modalities, and outcomes were comparable to our findings. Conclusion: Our case series and literature review show that SOVT can occur simultaneously with cavernous sinus thrombosis (CST) but can also be a separate entity. Clinical presentation can mimic orbital cellulitis (OC) or CST and when no signs of OC can be found, an alternative cause for SOVT should be sought. When timely and adequate treatment is conducted, the prognosis is predominantly favourable.

Operator Versus Core Lab Adjudication of Reperfusion After Endovascular Treatment of Acute Ischemic Stroke.

Background and Purpose- The modified Treatment In Cerebral Ischemia (mTICI) score is the standard method to quantify the degree of reperfusion after endovascular treatment in acute ischemic stroke. In clinical practice, it is commonly assessed by local operators after the procedure. In clinical trials and registries, mTICI is evaluated by an imaging core lab. The aim of this study was to compare operator mTICI with core lab mTICI scores in patients included in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. Methods- All patients with an intracranial carotid or middle cerebral artery occlusion with anteroposterior and lateral digital subtraction angiography runs were included. Operators determined the mTICI score immediately after endovascular treatment. Core lab neuroradiologists were blinded to clinical characteristics and assessed mTICI scores based on pre- and postintervention digital subtraction angiography. The agreement between operator and core lab mTICI scores and their value in the prediction of outcome (score on modified Rankin Scale at 90 days) was determined. Results- In total, 1130 patients were included. The proportion of agreement between operator and core lab mTICI score was 56% (95% CI, 54%-59%). In 33% (95% CI, 31%-36%), mTICI was overestimated by operators. Operators reported a higher rate of successful reperfusion than the core lab (77% versus 67%; difference 10% [95% CI, 6%-14%]; P<0.001). In 252 (33%) of 763 patients scored as incomplete reperfusion by the core lab (mTICI <3), the local read was mTICI 3. Multivariable logistic regression models containing either core lab scored or operator scored successful reperfusion predicted outcome on the full (C statistic of both models: 0.76) or dichotomized modified Rankin Scale (modified Rankin Scale, 0-2; C statistic of both models: 0.83) equally well. Conclusions- Operators tend to overestimate the degree of reperfusion compared with the core lab although this does not affect the accuracy of outcome prediction.

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.).

Absence of Cortical Vein Opacification Is Associated with Lack of Intra-arterial Therapy Benefit in Stroke.

Purpose To assess the degree of cortical vein opacification in patients with internal carotid artery or middle cerebral artery (MCA) stroke and to evaluate the relationship with treatment benefit from intra-arterial therapy (IAT). Materials and Methods Written informed consent was obtained from all patients in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands. From the trial's database, all patients (recruited from December 2010 until March 2014) with baseline computed tomographic (CT) angiograms were retrospectively included. Enhancement of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein was graded by one neuroradiologist, as follows: 0, not visible; 1, moderate opacification; and 2, full opacification. The sum for the ipsilateral hemisphere was calculated, resulting in the cortical vein opacification score (COVES) (range, 0-6). Primary outcome was the modified Rankin Scale score at 90 days. Association with treatment according to full cortical vein score and different dichotomized cutoff points was estimated with ordinal logistic regression. Interobserver agreement was assessed by two separate observers who reviewed 100 studies each. Results In total, 397 patients were analyzed. Interaction of the cortical vein score with treatment was significant (P = .044) when dichotomized COVES was 0 versus more than 0. The adjusted odds ratio for shift toward better functional outcome was 1.0 (95% confidence interval [CI]: 0.5, 2.0) for a COVES of 0 (n = 123) and 2.2 (95% CI: 1.6, 4.1) for a COVES greater than 0 (n = 274). The multirater κ value was 0.73. Conclusion In this study, patients with acute middle cerebral artery stroke with absence of cortical vein opacification in the affected hemisphere (COVES = 0) appeared to have no benefit from IAT, whereas patients with venous opacification (COVES >0) were shown to benefit from IAT. © RSNA, 2017 Clinical trial registration nos. NTR(1804) and ISRCTN10888758 Online supplemental material is available for this article.

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.

Spinal cord arteriovenous shunts of the ventral (anterior) sulcus: anatomical, clinical, and therapeutic considerations.

INTRODUCTION: Ventral sulcus spinal cord arteriovenous shunts (SCAVS) are rare vascular lesions that are located outside the spinal cord, are exclusively vascularized by the anterior spinal axis, and drain exclusively through the anterior spinal vein. We report the anatomical, clinical, and neuro-radiological features of SCAVS managed by our team. METHODS: We conducted a retrospective study of patients with SCAVSs evaluated by the senior author of this report (GR) between 1981 and 2014. Data were collected by reviewing clinical notes and by a systematic analysis of spinal angiograms and MRI. RESULTS: Among 358 patients, we identified 8 patients (3 women) with ventral sulcus spinal cord arteriovenous shunts. Mean age was 30.5 years. Six patients presented with progressive neurological symptoms, and two with acute neurological symptoms related to hematomyelia. Three shunts were located in the cervical cord, four in the thoracic cord, and one at the conus medullaris; there were two nidus type A-V shunts (AVMs) and six fistula type A-V shunts (AVFs). Seven patients were treated by endovascular therapy with glue embolization. Embolization led to anatomical cure in 5 cases, and a significant reduction of shunt volume and flow of more than 75% in 2 cases. In none of the cases we observed permanent morbidity. CONCLUSIONS: AVS of the ventral sulcus of the spinal cord are rare. Recognition of these lesions and precise localization of the anatomical space in which they are located, may allow a better understanding of their pathophysiology and clinical manifestations and guide proper therapeutic decisions.

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.