Randomized assessment of rapid endovascular treatment of ischemic stroke.

BACKGROUND: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS: The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). CONCLUSIONS: Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.).

Temporal Changes in Periprocedural Events in the Carotid Revascularization Endarterectomy Versus Stenting Trial.

BACKGROUND AND PURPOSE: Post-hoc, we hypothesized that over the recruitment period of the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), increasing experience and improved patient selection with carotid stenting, and to a lesser extent, carotid endarterectomy would contribute to lower periprocedural event rates. METHODS: Three study periods with approximately the same number of patients were defined to span recruitment. Composite and individual rates of periprocedural stroke, myocardial infarction, and death rate were calculated separately by treatment assignment (carotid stenting/carotid endarterectomy). Temporal changes in unadjusted event rates, and rates after adjustment for temporal changes in patient characteristics, were assessed. RESULTS: For patients randomized to carotid stenting, there was no significant temporal change in the unadjusted composite rates that declined from 6.2% in the first period, to 4.9% in the second, and 4.6% in the third (P=0.28). Adjustment for patient characteristics attenuated the rates to 6.0%, 5.9%, and 5.6% (P=0.85). For carotid endarterectomy-randomized patients, both the composite and the combined stroke and death outcome decreased between periods 1 and 2 and then increased in period 3. CONCLUSIONS: The hypothesized temporal reduction of stroke+death events for carotid stenting-treated patients was not observed. Further adjustment for changes in patient characteristics between periods, including the addition of asymptomatic patients and a >50% decrease in proportion of octogenarians enrolled, resulted in practically identical rates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Stroke after carotid stenting and endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).

BACKGROUND: Stroke occurs more commonly after carotid artery stenting than after carotid endarterectomy. Details regarding stroke type, severity, and characteristics have not been reported previously. We describe the strokes that have occurred in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). METHODS AND RESULTS: CREST is a randomized, open-allocation, controlled trial with blinded end-point adjudication. Stroke was a component of the primary composite outcome. Patients who received their assigned treatment within 30 days of randomization were included. Stroke was adjudicated by a panel of board-certified vascular neurologists with secondary central review of clinically obtained brain images. Stroke type, laterality, timing, and outcome were reported. A periprocedural stroke occurred among 81 of the 2502 patients randomized and among 69 of the 2272 in the present analysis. Strokes were predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4-year mortality after stroke was 21.1% compared with 11.6% for those without stroke. The adjusted risk of death at 4 years was higher after periprocedural stroke (hazard ratio, 2.78; 95% confidence interval, 1.63-4.76). CONCLUSIONS: Stroke, particularly severe stroke, was uncommon after carotid intervention in CREST, but stroke was associated with significant morbidity and was independently associated with a nearly 3-fold increased future mortality. The delayed timing of major and hemorrhagic stroke after revascularization suggests that these strokes may be preventable.

Communicating hydrocephalus after endovascular coiling of unruptured aneurysms: report of 2 cases.

To the authors' knowledge, only 1 case of communicating hydrocephalus after endovascular coiling of unruptured brain aneurysms has been reported previously. Here, they report on 2 such cases of delayed communicating hydrocephalus after treatment with hydrogel-coated coils and offer the first histopathological evidence of foreign material, presumably related to the coils, as the cause of hydrocephalus.

Sphenoid sinus mucocele--rupture causing brainstem inflammation and stroke.

BACKGROUND: Posterior rupture of a sphenoid sinus mucocele is a rare cause of brainstem injury. METHODS: Case report. RESULTS: A healthy young woman with a history of prior surgical excision of nasal polyps presented with a headache and evolving neurologic symptoms. The clinical presentation and imaging studies were consistent with a posterior rupture of a large sphenoid mucocele with subsequent inflammatory changes in the brainstem and evidence of brainstem stroke. Relatively rapid recovery coincided temporally with the resolution of local inflammation. Longer-term recovery continued over months, as expected following stroke. CONCLUSIONS: Posterior rupture of a sphenoid sinus mucocele may cause brainstem injury by multiple mechanisms.

Clinical utility of a screening protocol for blunt cerebrovascular injury using computed tomography angiography.

OBJECTIVE Blunt cerebrovascular injury (BCVI) occurs in approximately 1% of the blunt trauma population and may lead to stroke and death. Early vascular imaging in asymptomatic patients at high risk of having BCVI may lead to earlier diagnosis and possible stroke prevention. The objective of this study was to determine if the implementation of a formalized asymptomatic BCVI screening protocol with CT angiography (CTA) would lead to improved BCVI detection and stroke prevention. METHODS Patients with vascular imaging studies were identified from a prospective trauma registry at a single Level 1 trauma center between 2002 and 2008. Detection of BCVI and stroke rates were compared during the 3-year periods before and after implementation of a consensus-based asymptomatic BCVI screening protocol using CTA in 2005. RESULTS A total of 5480 patients with trauma were identified. The overall BCVI detection rate remained unchanged postprotocol compared with preprotocol (0.8% [24 of 3049 patients] vs 0.9% [23 of 2431 patients]; p = 0.53). However, postprotocol there was a trend toward a decreased risk of stroke secondary to BCVI on a trauma population basis (0.23% [7 of 3049 patients] vs 0.53% [13 of 2431 patients]; p = 0.06). Overall, 75% (35 of 47) of patients with BCVI were treated with antiplatelet agents, but no patient developed new or progressive intracranial hemorrhage despite 70% of these patients having concomitant traumatic brain injury. CONCLUSIONS The results of this study suggest that a CTA screening protocol for BCVI may be of clinical benefit with possible reduction in ischemic complications. The treatment of BCVI with antiplatelet agents appears to be safe.

The Frequency of Subarachnoid Hemorrhage from Very Small Cerebral Aneurysms (< 5 mm): A Population-Based Study.

BACKGROUND:  The prevailing view amongst neurosurgeons is that the larger the aneurysm, the higher the chance of rupture. This implies that very small aneurysms rarely rupture. To investigate this theory, we conducted a cross-sectional hospital-based study of aneurysmal subarachnoid hemorrhage, with an emphasis on aneurysm size at the time of rupture. METHODS:  We retrospectively reviewed hospital records and radiological tests of all patients admitted to Foothills Medical Center, Calgary, Alberta, with a ruptured saccular aneurysm from January 2008 to January 2012. The size of the dome and neck (in millimeters), the aspect ratio (aneurysm depth to aneurysm neck), and location of the aneurysms were determined using preoperative computed tomography angiography and digital subtraction angiography. FINDINGS:  One hundred and twenty-three patients with a ruptured saccular aneurysm were identified. The average size of the dome, neck, and the aspect ratio was 6.6±4.4 mm (range: 1.5-26 mm), 3.1 mm, and 2.6±0.9, respectively. Forty-six patients (37%) had a ruptured aneurysm with dome size < 5 mm (range: 1.5-4.9 mm). For these small aneurysms, the average size of the dome, neck, and the aspect ratio was 3.9+1.1 mm, 1.6 mm, and 2.1+0.6, respectively. The anterior communicating artery was the most common location regardless of size. CONCLUSION:  Small aneurysms (< 5 mm) are a common cause of aneurysmal subarachnoid hemorrhage. When unruptured, looking for other risk factors for rupture is highly recommended before simply leaving them alone.

Comparison of pre- and postcontrast 3D time-of-flight MR angiography for the evaluation of distal intracranial branch occlusions in acute ischemic stroke.

BACKGROUND AND PURPOSE: Three-dimensional time-of-flight (TOF) MR angiography is used routinely in stroke workup to detect arterial occlusions, but a major drawback is its inadequate depiction of vessels with slow or in-plane flow. We hypothesized that the use of contrast-enhanced MR angiography improves delineation of vessels with diminished or absent flow on precontrast MR angiograms. METHODS: Pre- and postcontrast 3D TOF MR angiograms were acquired in 55 consecutive patients with acute stroke. Patency of 480 intracranial vessels was assessed on both the pre- and postcontrast angiograms. Diffusion-weighted (DW) and perfusion-weighted (PW) imaging data were also obtained and results correlated with those of pre- and postcontrast MR angiography. RESULTS: For 50 abnormal vessel segments seen on precontrast MR angiograms, postcontrast MR angiograms resulted in change in the vascular signal intensity in 70% (35 vessel segments); 94% of these changes showed a greater extent of vessel patency. Venous and soft-tissue contrast enhancement had no effect on assessment in 95% of all 480 vessels examined. Interobserver reliability was moderate, with postcontrast interpretation (kappa = 0.48) showing a slight improvement over precontrast interpretation (kappa = 0.41). Good agreement was found between the TOF results and the pooled DW and PW imaging results. CONCLUSIONS: Compared with precontrast 3D TOF MR angiograms, postcontrast 3D TOF angiograms improve assessment of intracranial vessel patency in acutely ischemic vascular territories. In some patients, an improved understanding of acute ischemic stroke was obtained by viewing the pre- and postcontrast images. Postcontrast MR angiography should be included in the MR evaluation of acute stroke.

Combined full-dose IV and endovascular thrombolysis in acute ischaemic stroke.

BACKGROUND: There is an increasing trend to treating proximal vessel occlusions with intravenous-inter-arterial (IV-IA) thrombolysis. The best dose of IV tissue plasminogen activator (tPA) remains undetermined. We compared the combination of full-dose IV recombinant tissue plasminogen activator (rtPA) and IA thrombolytic therapy to IA therapy. METHODS: Between 2002 and 2009, we reviewed our computed tomographic angiography database for patients who received full-dose intravenous rtPA and endovascular therapy or endovascular therapy alone for acute ischaemic stroke treatment. Details of demographics, risk factors, endovascular procedure, and symptomatic intracranial haemorrhage were noted. Modified Rankin Scale ≤2 at three-months was used as good outcome. Recanalization was defined as Thrombolysis in Myocardial Ischaemia 2-3 flow on angiography. RESULTS: Among 157 patients, 104 patients received IV-IA treatment and 53 patients underwent direct IA therapy. There was a higher recanalization rate with IV-IA therapy compared with IA alone (71% vs. 60%, P < 0·21) which was driven by early recanalization after IV rtPA. Mortality and independent outcome were comparable between the two groups. Symptomatic intracranial haemorrhage occurred in 8% of patients (12% in the IA group, 7% in the IV-IA group) but was more frequent as the intensity of intervention increased from device alone to thrombolytic drug alone to device plus thrombolytic drug(s). Recanalization was a strong predictor of reduced mortality risk ratio (RR) 0·48 confidence interval95 0·27-0·84) and favourable outcome (RR 2·14 confidence interval95 1·3-3·5). CONCLUSIONS: Combined IV-IA therapy with full-dose intravenous rtPA was safe and results in good recanalization rates without excess symptomatic intracranial haemorrhage. Testing of full-dose IV tPA followed by endovascular treatment in the IMS3 trial is justified.

Carotid angioplasty and stenting is safe in women.

BACKGROUND: Results of randomized controlled trials have shown that carotid endarterectomy poses greater perioperative risks to women than to men. There are limited studies regarding sex differences in carotid angioplasty and stenting. OBJECTIVES: To compare male and female patients undergoing carotid stenting with regard to their intraprocedural complications and 30-day outcome. METHODS: We reviewed patients who underwent carotid stenting between 1997 and 2007 at our tertiary centre. Distal protection devices were used in all patients after 1999. Demographics, risk factors, intraprocedural complications, and 30-day outcomes were compared between female and male patients. RESULTS: Among 243 patients who underwent 255 procedures, 67 were women (27.6%). The mean (SD) age of the female patients was 72.2 ± 8.4 years and that of the male patients was 72.0 ± 9.6 years (P = .83). The majority of patients had symptomatic carotid artery disease; 11 women (16.4%) and 30 men (16.0%) were asymptomatic. The following intraprocedural complications were noticed in female vs male patients: asymptomatic carotid and/or iliac dissections 7.5% vs 0% (P = .001), minor stroke 0% vs 1.1% (P = 1.00), major stroke 0% vs 0.5% (P = 1.00), and cardiac dysrhythmias 3% vs 2.7% (P = 1.00). At 30 days, the outcomes in women vs men were as follows: mortality 3.0% vs 3.2% (P = 1.00), major stroke 3.0% vs 2.1 % (P = .66), and minor stroke 3.0% vs 3.2% (P = 1.00). CONCLUSION: Although minor asymptomatic intraprocedural dissections were more common in women, we did not find any impact of sex on the 30-day outcome. We concluded that carotid stenting can be performed as safely in women as in men.

Acute ischemic stroke: accuracy of diffusion-weighted MR imaging--effects of b value and cerebrospinal fluid suppression.

PURPOSE: To prospectively determine which diffusion-weighted magnetic resonance (MR) imaging technique (ie, conventional diffusion-weighted MR imaging [b = 1000 or 1500 sec/mm2] or fluid-inversion prepared diffusion [FLIPD] MR imaging [b = 1500 sec/mm2]) is most accurate in depicting acute ischemic stroke at 3 T. MATERIALS AND METHODS: The Health Research Ethics Board approved this study; written informed consent was provided by all participants or their surrogate. Diffusion-weighted MR imaging was performed in 75 consecutive patients (43 men, 32 women; mean age, 64.0 years) with acute ischemic stroke. Two experienced neuroradiologists determined the presence of hyperacute stroke lesions at diffusion-weighted MR imaging by locating areas of hyperintensity that corresponded to regions with a decreased diffusion coefficient. These findings were used as the reference standard. Four raters who were blinded to patient history assessed all images and apparent diffusion coefficient maps for the presence of changes that were consistent with acute ischemic stroke. Accuracy, sensitivity, specificity, negative predictive value, positive predictive value, and inter- and intrarater reliability scores were calculated for each technique. RESULTS: Specificity, positive predictive value, and accuracy were not significantly different among the techniques. FLIPD MR images obtained with a b value of 1500 sec/mm2 had decreased sensitivity for acute ischemic stroke (mean, 61.8%; 95% confidence interval [CI]: 55.4%, 67.9%) compared with conventional diffusion-weighted MR images obtained with a b value of either 1000 sec/mm2 (mean, 82.5%; 95% CI: 77.1%, 87.0%) or 1500 sec/mm2 (mean, 84.5%; 95% CI: 79.3%, 88.9%). FLIPD MR images also had decreased negative predictive value (mean, 96.5%; 95% CI: 95.7%, 97.2%) compared with conventional diffusion-weighted MR images obtained with a b value of either 1000 sec/mm2 (mean, 98.4%; 95% CI: 97.8%, 98.8%) or 1500 sec/mm2 (mean, 98.6%; 95% CI: 98.1%, 99.0%). Intra- and interrater reliability scores were generally excellent for all three techniques. CONCLUSION: FLIPD MR images obtained with a b value of 1500 sec/mm2 are less suitable for the detection of acute ischemic stroke owing to a decreased sensitivity and negative predictive value. The performance of the two conventional diffusion-weighted MR imaging techniques (b = 1000 and 1500 sec/mm2) was equivalent.