Periprocedural heparin use in acute ischemic stroke endovascular therapy: the TREVO 2 trial.

BACKGROUND: The use of periprocedural heparin has previously been reported to be safe and potentially beneficial during thrombectomy with older generation devices. We aimed to evaluate the safety and clinical outcomes of heparin use in the stent retriever era. METHODS: A post hoc analysis of the TREVO 2 trial was performed comparing baseline characteristics and clinical outcomes between patients who received (HEP+) and those who did not receive periprocedural heparin (HEP-) while undergoing MERCI or TREVO clot retrieval. RESULTS: Of 173 patients, 58 (34%) received periprocedural heparin including 40 who received one preprocedural bolus (median 3000 units). Baseline characteristics among HEP+ and HEP- patients were similar except HEP+ patients had a lower NIH Stroke Scale (NIHSS) score (17 vs 19; p=0.04), lower IV tissue plasminogen activator use (38% vs 64%; p<0.01), and a higher median ASPECTS score (8.0 vs 7.0; p=0.02). HEP+ patients were more likely to have vertebrobasilar and middle cerebral artery (MCA)-M1 occlusions but less likely to have internal carotid artery and MCA-M2 occlusions (p=0.04). Time from symptom onset to puncture was similar in the two groups while procedure duration was longer in HEP+ patients (99 vs 83 min; p<0.01). Thrombolysis In Cerebral Infarction (TICI) 2b-3 reperfusion rates, embolization to unaffected territories, access site complications, and intracranial hemorrhages were similar between the groups. In multivariable logistic regression, a good outcome (90-day modified Rankin Scale score 0-2) was independently associated with heparin bolus use (OR 5.30; 95% CI 1.70 to 16.48), TICI 2b-3 reperfusion (OR 6.56; 95% CI 2.29 to 18.83), stent retriever use (OR 3.54; 95% CI 1.38 to 9.03) and inversely associated with intubation (OR 0.10; 95% CI 0.03 to 0.33), diabetes (OR 0.11; 95% CI 0.03 to 0.39), NIHSS (OR 0.84; 95% CI 0.75 to 0.93), time from symptom onset to puncture (OR 0.64; 95% CI 0.45 to 0.89), and heart failure (OR 0.23; 95% CI 0.06 to 0.83). CONCLUSIONS: The use of periprocedural heparin in stent retriever thrombectomy is associated with a good clinical outcome at 90 days and similar rates of symptomatic intracranial hemorrhage. Further studies are warranted. CLINICAL TRIAL REGISTRATION: URL:http://www.clinicaltrials.gov. Unique identifier: NCT01270867;Post-results.

Management of Symptomatic Intracranial Stenosis.

Intracranial atherosclerotic disease is a common cause of stroke worldwide, causing approximately 10 % of strokes in the USA and up to 50 % in Asian populations. Recurrent stroke risks are particularly high in those with a stenosis of 70 % or more and a recent transient ischemic attack or stroke. Warfarin has been associated with higher major hemorrhage rates and no reduction of recurrent stroke compared to aspirin in patients with symptomatic intracranial stenosis. After early trials showed the feasibility of stenting, two randomized trials compared stenting plus medical management to medical management alone in symptomatic intracranial stenosis. Stenting was linked with increased risk and showed no benefit in any subpopulation of patients. Aggressive medical management in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial was associated with half the risk of stroke compared to that in similar patients in a previous symptomatic intracranial stenosis trial after adjustment of confounding characteristics. Aggressive medical management comprises risk factor control, including a target systolic blood pressure <140 mmHg, a low density lipoprotein <70 mg/dL, hemoglobin A1C <7.0 %, and lifestyle management that incorporates exercise, smoking cessation and weight management, and the use of antithrombotics.

Early arrival at the emergency department is associated with better collaterals, smaller established infarcts and better clinical outcomes with endovascular stroke therapy: SWIFT study.

BACKGROUND AND PURPOSE: Increasing time from symptom onset to emergency department arrival may incur greater ischemic injury and decreased likelihood of good outcomes after acute stroke therapy. The impact of time may be assessed bythe extent of acute CT changes, status of collateral vessels, and clinical outcomes. METHODS: The SOLITAIRE FR With the Intention For Thrombectomy (SWIFT) trial comparing two neurothrombectomy treatments was analyzed by time, Alberta Stroke Program Early CT Scores (ASPECTS), angiographic collaterals, and 90-day modified Rankin Scale outcomes. We determined the interaction of time with ASPECTS, collateral grade, reperfusion, and clinical outcomes, with established determinants of angiographic and clinical outcomes as covariates. RESULTS: 137 patients (52% female) of mean age 67±12 years and median pretreatment NIH Stroke Scale score 18 (range 8-28) were enrolled. Median onset to door (OTD) time was 180 min (IQR 95-250). Presentation within 3 h of last known well was associated with absence of any prestroke disability and presence of atrial fibrillation but was unrelated to age, sex, other vascular risk factors, deficit severity, glucose level, or blood pressure. Worse collaterals were noted with longer OTD intervals: collateral grade 0-1 (n=32): mean 232±84 min; grade 2 (n=48): 164±99 min; grade 3 (n=35): 155±104 min; grade 4 (n=4): 54±16 min (p<0.001). Later presentation was associated with more extensive early infarct imaging changes (median ASPECTS 8 (IQR 7-9) >3 h vs 9 (IQR 8-10) <3 h, p=0.015). Multivariable analyses identified time >3 h as the only predictor of extensive infarct on imaging (ASPECTS ≤7), p=0.003. Earlier presentation was strongly associated with better 90-day modified Rankin Scale outcomes (p<0.001). CONCLUSIONS: Time was a critical factor in successful clinical outcomes for neurothrombectomy in the SWIFT trial. Shorter times to presentation were associated with better collaterals, smaller established infarcts, and better clinical outcome after revascularization.

Stroke recurrence rates among patients with symptomatic intracranial vertebrobasilar stenoses: systematic review and meta-analysis.

BACKGROUND: A recent randomized trial of patients with primarily anterior circulation intracranial artery stenosis showed that intensive medical therapy was superior to intracranial stenting in preventing recurrent stroke. The rate of stroke recurrence or death in symptomatic intracranial vertebrobasilar stenosis with medical therapy alone may be especially high, and rates compared with endovascular therapy need further study. METHODS: We conducted a systematic review and meta-analysis of studies reporting the rates of stroke recurrence or death (the primary outcome) in symptomatic intracranial vertebrobasilar stenosis with medical or endovascular treatment over a minimum follow-up period of 6 months. We included all studies in any language indexed in MEDLINE or EMBASE, supplemented by bibliography searches and by contacting the authors. The secondary endpoints were stroke recurrence, and basilar artery and vertebral artery stroke recurrence rates. RESULTS: 23 studies (592 medical treatment patients and 480 endovascular treatment patients) were included. The risk of combined stroke recurrence or death was 14.8 per 100 person-years (95% CI 9.5 to 20.1) in the medical group compared with 8.9 per 100 person-years (95% CI 6.9 to 11.0) in the endovascular group. The incidence rate ratio was 1.3 (95% CI 1.0 to 1.7). The stroke recurrence rate was 9.6 per 100 person-years (95% CI 5.1 to 14.1) in the medical group compared with 7.2 per 100 person-years (95% CI 5.5 to 9.0) in the endovascular group. CONCLUSIONS: Our results showed that the risk of stroke recurrence or death or the risk of stroke recurrence alone was comparable between the medical and endovascular therapy groups. A small preventive effect of endovascular therapy may exist, particularly if the 30 day postprocedural risk is reduced.

Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis?

BACKGROUND AND PURPOSE: Although the Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial showed that medical therapy alone was superior to stenting plus medical therapy for preventing recurrent strokes in patients with symptomatic intracranial stenosis, we determined whether SAMMPRIS supported the use of stenting in any subpopulations of patients with symptomatic intracranial arterial stenosis. METHODS: The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy versus aggressive medical therapy alone. Baseline factors included sex, age, race, diabetes mellitus, hypertension, lipid disorder, smoking status, type of qualifying event, qualifying event hypoperfusion symptoms, use of antithrombotic or proton pump inhibitor at baseline, days to enrollment, old infarcts in the same territory, percent stenosis, other artery stenosis, and location of the symptomatic artery. RESULTS: A total of 451 patients were enrolled, 227 randomized to aggressive medical therapy and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with aggressive medical therapy in the vast majority and the interaction with treatment was not statistically significant for any of the factors. CONCLUSIONS: The SAMMPRIS results do not provide evidence to support the use of PTAS using the Wingspan stent system compared with medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with qualifying event hypoperfusion symptoms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. METHODS: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42). INTERPRETATION: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

Meta-analysis of randomized intra-arterial thrombolytic trials for the treatment of acute stroke due to middle cerebral artery occlusion.

BACKGROUND: Randomized clinical trials supporting the use of intra-arterial administration of thrombolytics (IAT) for the treatment of stroke due to middle cerebral artery (MCA) occlusion have been positive on some, but not all, endpoints. A meta-analysis was performed to estimate with more precision the effect of IAT on several key clinical endpoints. METHODS: All randomized trials of IAT in the treatment of MCA stroke were identified by PUBMED search and by hand search of potentially relevant references. Trial methodologies were assessed for compatibility in study protocols and statistical analysis. A meta-analysis was performed evaluating the effect of IAT on functional outcome at 90 days and symptomatic intracranial hemorrhage (SICH) within 24 h. RESULTS: Three trials met the criteria for the meta-analysis. IAT treated patients were significantly more likely to have a modified Rankin scale (mRS) ≤ 1 (31% vs 20%, OR 2.0, 95% CI 1.2 to 3.4, p=0.01); mRS ≤ 2 (43% vs 31%, OR 1.9, 95% CI 1.2 to 3.0, p=0.01); and NIH Stroke Scale score 0 or 1 (23% vs 12%, OR 2.4, 95% CI 1.3 to 4.4, p=0.007) at the 90 day follow-up. There was no effect on mortality at 90 days (20% vs 19%, OR 0.84, 95% CI 0.5 to 1.5). The risk of SICH was significantly increased in the active treatment arms (11% vs 2%, OR 4.6, 95% CI 1.3 to 16, p=0.02). CONCLUSIONS: Our meta-analysis demonstrates that all standard functional endpoints for stroke trials were substantially improved in the active treatment arms. Despite an increased risk of SICH, there was no effect on mortality. These results support endovascular treatment of acute ischemic stroke due to MCA occlusion with intra-arterial thrombolytics.

Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists.

This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient ischemic attacks. Formal evidence review included a structured literature search of Medline from 1990 to June 2007 and data synthesis employing evidence tables, meta-analyses, and pooled analysis of individual patient-level data. The review supported endorsement of the following, tissue-based definition of transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Patients with TIAs are at high risk of early stroke, and their risk may be stratified by clinical scale, vessel imaging, and diffusion magnetic resonance imaging. Diagnostic recommendations include: TIA patients should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences; noninvasive imaging of the cervical vessels should be performed and noninvasive imaging of intracranial vessels is reasonable; electrocardiography should occur as soon as possible after TIA and prolonged cardiac monitoring and echocardiography are reasonable in patients in whom the vascular etiology is not yet identified; routine blood tests are reasonable; and it is reasonable to hospitalize patients with TIA if they present within 72 hours and have an ABCD(2) score >or=3, indicating high risk of early recurrence, or the evaluation cannot be rapidly completed on an outpatient basis.

Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study.

OBJECTIVE: Functional magnetic resonance imaging and transcranial magnetic stimulation studies suggest that human cortex shows evidence of neuroplasticity. Preclinical studies in rats and monkeys suggest that motor cortical stimulation can enhance plasticity and improve recovery after stroke. This study assesses the safety and preliminary efficacy of targeted subthreshold epidural cortical stimulation delivered concurrently with intensive rehabilitation therapy while using an investigational device in patients with chronic hemiparetic stroke. METHODS: This is a prospective, multicenter, and nonblinded trial randomizing patients to rehabilitation with or without cortical stimulation. Patients aged 20 to 75 years who had had an ischemic stroke at least 4 months previously causing persistent moderate weakness of the arm were included. Functional magnetic resonance imaging localized hand motor function before surgery to place an epidural cortical electrode. Both groups then underwent rehabilitation for 3 weeks after which the electrode was removed. Outcome measures were obtained at baseline, during therapy, and at 1, 4, 8, and 12 weeks postprocedure. RESULTS: Ten patients were randomized; six patients to surgery, four to the control group. No patient deaths, neurological deterioration, or seizures occurred. There were two infections from nonprotocol-related causes. Of the eight patients completing the treatment, the stimulation plus rehabilitation group improved significantly better than controls in the Upper Extremity Fugl-Meyer (P = 0.003 overall) and the hand function score of the Stroke Impact Scale (P =0.001 overall). CONCLUSION: The technique of cortical stimulation to enhance stroke recovery is well tolerated and safe.

Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study.

OBJECTIVE: Functional magnetic resonance imaging and transcranial magnetic stimulation studies suggest that human cortex shows evidence of neuroplasticity. Preclinical studies in rats and monkeys suggest that motor cortical stimulation can enhance plasticity and improve recovery after stroke. This study assesses the safety and preliminary efficacy of targeted subthreshold epidural cortical stimulation delivered concurrently with intensive rehabilitation therapy while using an investigational device in patients with chronic hemiparetic stroke. METHODS: This is a prospective, multicenter, and nonblinded trial randomizing patients to rehabilitation with or without cortical stimulation. Patients aged 20 to 75 years who had had an ischemic stroke at least 4 months previously causing persistent moderate weakness of the arm were included. Functional magnetic resonance imaging localized hand motor function before surgery to place an epidural cortical electrode. Both groups then underwent rehabilitation for 3 weeks after which the electrode was removed. Outcome measures were obtained at baseline, during therapy, and at 1, 4, 8, and 12 weeks postprocedure. RESULTS: Ten patients were randomized; six patients to surgery, four to the control group. No patient deaths, neurological deterioration, or seizures occurred. There were two infections from nonprotocol-related causes. Of the eight patients completing the treatment, the stimulation plus rehabilitation group improved significantly better than controls in the Upper Extremity Fugl-Meyer (P = 0.003 overall) and the hand function score of the Stroke Impact Scale (P = 0.001 overall). CONCLUSION: The technique of cortical stimulation to enhance stroke recovery is well tolerated and safe.