Absence of Collaterals is Associated with Larger Infarct Volume and Worse Outcome in Patients with Large Vessel Occlusion and Mild Symptoms.

BACKGROUND: Mechanical thrombectomy is the standard of care for patients with large vessel occlusion (LVO) presenting with severe symptoms; however, little is known about the best treatment for patients with LVO and mild symptoms. The absence of good collaterals has been associated with a worse outcome in patients with LVO. In this study, we aim to assess the use of collateral score to identify patients with LVO and mild symptoms that might benefit from mechanical thrombectomy (MT). METHODS: A retrospective review of prospectively collected data on patients presenting with mild ischemic stroke (National Institute of Health Stroke Scale [NIHSS] <6) and anterior circulation LVO between September 2015 and July 2017 was performed. Collected data included baseline demographics, NIHSS on admission, Alberta Stroke Program Early CT Score (ASPECTS), location of occlusion, collateral score using Tan scoring system, final infarct volume, and 90-day modified Rankin Scale (mRS). Patients who underwent MT were excluded from this analysis. Two multivariable models were used to assess outcomes. A gamma distributed generalized linear regression model with a log link was used to examine the impact on final infarct volume. To predict the odds of a positive 90-day outcome we estimated a logistic regression. RESULTS: Forty-one patients were identified. Mean age was 67.7-years with 56.1% males. Median NIHSS on admission was 3. The most common vessels involved were the middle cerebral artery (26), internal carotid artery (14), and anterior cerebral artery (1). Twelve patients received intravenous alteplase. Median ASPECTS score was 9, median collateral score was 2.3. Median infarct volume was 10.7 mL. A good functional outcome (mRS 0-2) at 90 days was achieved in 86.4% of patients. There was a negative relationship between collateral score and final infarct volume (-.3134, P = .046). Multivariable regression results showed that with a one-point increase in NIHSS on admission there was a 25% increase in final infarct volume. Higher infarct volume was associated with lower odds of achieving good functional outcome (mRS 0-2) (odds ratio .96, P = .049 [95% confidence interval .918-.999). CONCLUSIONS: Most patients with anterior circulation LVO and low NIHSS achieve good long-term functional outcome, however, approximately 15% had significant disability. The absence of collaterals correlates with a larger final infarct volume and a worse long-term functional outcome. Collateral score might be a useful tool in identifying patients with LVO and low NIHSS who might benefit from MT.

Dissection of Cervical and Cerebral Arteries.

PURPOSE OF REVIEW: We aimed to summarize recent findings in cervical (CeAD) and intracranial artery dissection (IAD) research. RECENT FINDINGS: Considered a disease of the young- and middle-aged, an analysis on the largest CeAD-population to date (n = 2391) revealed that about 1 of 14 CeAD-patients was aged ≥60 years. Distinct genetic variants were associated with CeAD. However, in clinical practice, genetic investigations are not helpful due to the small effect size. Despite the paucity of data from randomized-controlled trials in CeAD-stroke patients, both intravenous thrombolysis and endovascular treatment should be considered as acute treatment in such patients. Future research is needed to clarify which patients benefit most from each treatment modality. Whether to use antiplatelets or anticoagulants in stroke prevention in CeAD-patients is still a matter of debate. One randomized-controlled feasibility trial has been published, and another trial designed to show non-inferiority of aspirin to vitamin-K-antagonists is underway and will be terminated in late 2018. Non-vitamin-K-oral anticoagulants should not be used in CeAD outside a properly designed trial, as experience with these drugs in CeAD-patients is limited. With many IAD patients developing intracranial hemorrhage, antithrombotic therapy should be used with caution. Knowledge about CeAD and IAD has advanced substantially. Nevertheless, further research is mandatory, in particular regarding pathophysiology, acute treatment, and stroke-preventive therapy, as well as long-term outcome and prognosis.

High-Resolution Vessel Wall Magnetic Resonance Imaging in Varicella-Zoster Virus Vasculitis.

Varicella-zoster virus vasculopathy is a rare but potentially treatable condition. Diagnosis has been based on angiography, brain magnetic resonance imaging (MRI), and cerebrospinal fluid analysis. High-resolution vessel wall MRI may aid to the diagnosis by differentiating inflammation from other vessel wall pathologies. We present the characteristic MRI findings of this condition in a young patient presenting with ischemic stroke.

Prolonged low-dose thrombolysis in posterior circulation stroke.

BACKGROUND: We aimed to investigate the feasibility, preliminary safety, and efficacy of prolonged low-dose intravenous thrombolysis in posterior circulation stroke patients with a thrombus lodged in the basilar artery who were ineligible for standard rtPA administration. METHODS: We retrospectively analyzed consecutively collected patients in our stroke database who suffered from a basilar artery thrombosis and were treated with prolonged (>1 h), intravenous, low-dose (≤20 mg) rtPA between 01/2005 and 11/2012. RESULTS: Patients included in this study (n = 14) were 68.5 years (IQR 55.5; 72.75) of age and presented with a median NIHSS of 2 (1; 5.25). Median time from symptom onset to treatment was 63 h (33; 141). A median dose of 5.21 µg/kg h (4.46; 6.25) rtPA was administered over 24 h (min 10; max 48). No patient experienced symptomatic intracerebral hemorrhage, one patient developed a spinal epidural hematoma, and two elderly patients were switched to comfort care and died. In eight patients (57%) a decrease in thrombus size or no thrombus at all was detected on control imaging. Nine patients (64%) had a favorable outcome (mRS 0-2) at day 90. CONCLUSIONS: Prolonged low-dose thrombolysis with rtPA may be considered as individual treatment option in selected high-risk patients with basilar artery thrombosis. Presented data may lay the groundwork to further investigate safety and efficacy in a prospective trial.

Ankle-brachial index and neurologic deterioration in acute ischemic stroke.

BACKGROUND: Few studies have examined the relationship between abnormal ankle-brachial index (ABI) and short-term outcome in patients with acute ischemic stroke (AIS). METHODS: We included 209 consecutive patients with AIS admitted to our hospital and divided them into abnormal ABI (≤.9) and normal ABI (>.9) groups. We defined neurologic deterioration (ND) as an increase of 1 or more points in the National Institutes of Health Stroke Scale score within 7 days of stroke onset. Clinical characteristics were compared between the 2 groups. Then, we performed a multiple logistic regression analysis to identify independent predictors of ND. In the multivariate analysis, the ABI values were used separately as binary variables in different cutoff thresholds (.9, 1.0, and 1.1). RESULTS: Of the 209 patients, 24 (11.5%) had an abnormal ABI. The patients in abnormal and normal ABI groups showed significant differences in carotid arterial stenosis (37.5% versus 18.9%; P = .040), intracranial artery stenosis (54.2% versus 18.9%; P < .001), and previous use of antiplatelet drugs (58.3% versus 29.2%; P = .004). According to the multivariate analysis, ABIs of .9 or less and 1.0 or less were positively associated with ND (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.03-2.89; P = .034 and OR, 1.63; 95% CI, 1.05-2.54; P = .027, respectively), whereas an ABI value of 1.1 or less was not an independent predictor of ND (OR, 1.17; 95% CI, 0.79-1.74; P = .43). CONCLUSIONS: Not only an ABI of .9 or less but also an ABI of 1.0 or less can be a predictor of ND in patients with AIS.

Low-molecular-weight heparin versus aspirin for acute ischemic stroke with large artery occlusive disease: subgroup analyses from the Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study.

BACKGROUND AND PURPOSE: The Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study showed no superiority of low-molecular-weight heparin (LMWH) over aspirin for the primary end point (Barthel Index) in acute ischemic stroke due to large artery occlusive disease. This study aims to evaluate the efficacy of LMWH and aspirin in selected subgroups so as to generate hypotheses for further studies. METHODS: The FISS-tris study was a multicenter, randomized trial to investigate the efficacy and safety of LMWH (nadroparin calcium 3800 antifactor Xa IU/0.4 mL subcutaneously twice daily) or aspirin (160 mg once daily) for the treatment of patients with acute ischemic stroke and large artery occlusive disease. The primary outcome was the Barthel Index score dichotomized at 85 6 months poststroke. Exploratory subgroup analysis was performed using different levels of baseline characteristics and the distribution of symptomatic arteries. RESULTS: Compared with aspirin, LMWH improved outcome among older patients >68 years (P=0.043; OR, 1.86; 95% CI, 1.02-3.41) without ongoing antiplatelet treatment on admission (P=0.029; OR, 1.85; 95% CI, 1.06-3.21) and with symptomatic posterior circulation arterial disease (P=0.001; OR, 5.76; 95% CI, 2.00-16.56). CONCLUSIONS: Our findings suggest that LMWH may be of benefit in certain subgroups of patients with acute cerebral infarct and large artery occlusive disease. Hence, further investigation of LMWH may be justified in subgroups such as the elderly, nonusers of antiplatelet agents, and patients with posterior circulation stenosis. CLINICAL TRIAL REGISTRATION: URL: www.strokecenter.org/trials. Unique identifier: registration no. 493.

Safety of low-dose heparin for intracranial stent-assisted angioplasty: a randomized controlled pilot study.

PURPOSE: To access the safety of low-dose heparin in comparison to a high-dose regimen in patients undergoing intracranial stent-assisted angioplasty. METHODS: Sixty-four consecutive patients (53 men; mean age 54 years) undergoing stent-assisted angioplasty of 70 intracranial arterial stenoses were randomized to receive either low-dose (2000-U bolus+500 U/h) or high-dose (3000-U bolus+800 U/h) intravenous heparin during the procedure. The activated clotting time (ACT) was measured. The groups were compared for the following primary endpoints until hospital discharge: target lesion acute thrombosis, intracranial hemorrhage (ICH), and death. RESULTS: The overall angioplasty success rate was 93% (65/70 lesions). Stents were placed in 94.7% (36/38) and 90.6% (29/32) of patients in the low-dose and high-dose groups, respectively (p = 0.65). The primary endpoint occurred in 6% (2/33) of patients in the low-dose group versus 16% (5/31) of patients in the high-dose group (p = 0.25). Two patients, 1 patient in each group, experienced acute target lesion thrombosis during the procedure (p = NS); ICH occurred in 5 patients: 1 in the low-dose group and 4 in high-dose group (3.0% versus 12.9%, p = 0.19). CONCLUSION: The use of a low-dose heparin regimen did not increase the incidence of target lesion thrombosis or ICH in this small pilot trial. Intraoperative low-dose heparin seems to be safe for patients undergoing intracranial stent-assisted angioplasty, but these data should be confirmed in a larger trial.

High-sensitive C-reactive protein and dual antiplatelet in intracranial arterial stenosis.

OBJECTIVE: To determine the relationship of high-sensitive C-reactive protein (hsCRP) and the efficacy and safety of dual antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. METHODS: A subgroup of 807 patients with both magnetic resonance angiography images and hsCRP measurement was analyzed. Cox proportional hazards models were used to assess the interaction of hsCRP levels with the effects of dual and single antiplatelet therapy. RESULTS: A total of 358 (44.4%) patients had ICAS and 449 (55.6%) did not. The proportion of patients with elevated hsCRP levels was higher in the ICAS group than in the non-ICAS group (40.2% vs 30.1%, p = 0.003). There was significant interaction between hsCRP and the 2 antiplatelet therapy groups in their effects on recurrent stroke after adjustment for confounding factors in the patients with ICAS (p = 0.012), but not in those without (p = 0.256). Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the risk of recurrent stroke only in the patients with ICAS and nonelevated hsCRP levels (adjusted hazard ratio 0.27; 95% confidence interval 0.11 to 0.69; p = 0.006). Similar results were observed for composite vascular events. No significant difference in bleeding was found. CONCLUSIONS: Presence of both ICAS and nonelevated hsCRP levels may predict better response to dual antiplatelet therapy in reducing new stroke and composite vascular events in minor stroke or high-risk TIA patients. Further large-scale randomized and controlled clinical trials are needed to confirm this finding.

Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis.

BACKGROUND: Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy. METHODS AND RESULTS: WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke in the territory of the stenotic artery was highest with severe stenosis > or =70% (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P=0.0025) and in patients enrolled early (< or =17 days) after the qualifying event (hazard ratio 1.69; 95% confidence interval 1.06 to 2.72; P=0.028). Women were also at increased risk, although this was of borderline significance (hazard ratio 1.59; 95% confidence interval 1.00 to 2.55; P=0.051). Location of stenosis, type of qualifying event, and prior use of antithrombotic medications were not associated with increased risk. CONCLUSIONS: Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis > or =70%, after recent symptoms, and in women.

Gender differences in outcomes among patients with symptomatic intracranial arterial stenosis.

BACKGROUND AND PURPOSE: There are limited and conflicting data on gender differences in clinical outcomes among patients with symptomatic intracranial arterial stenosis. This study examined gender differences in patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study. METHODS: Participants were 569 men and women with symptomatic intracranial arterial stenosis. They were followed-up for the occurrence of ischemic stroke and the combined end point of stroke or vascular death from February 1999 through July 2003 (mean follow-up, 1.8 years). RESULTS: Two-year rates of the primary end point were 28.4% and 16.6% for women and men, respectively. Cumulative probabilities of the outcomes over time were estimated by the Kaplan-Meier product-limit method and were compared between men and women with the use of the log-rank test. Cox proportional hazards regression analyses were used to estimate the hazard ratio of gender (women to men) for ischemic stroke and for the primary end point. The probabilities of ischemic stroke (P=0.005) and of the combined end point of stroke or vascular death (P=0.017) over time were significantly higher in women than men. Women had a greater multivariate-adjusted risk for ischemic stroke (HR, 1.85; 95% CI, 1.14 to 3.01; P=0.013) and for the combined end point of stroke or vascular death (HR, 1.58; 95% CI, 1.01 to 2.48; P=0.045). CONCLUSIONS: Women with symptomatic intracranial arterial stenosis are at significantly greater risk for ischemic stroke and for the combined end point of stroke or vascular death. These findings suggest the need for vigorous screening of risk factors and for aggressive management of risk factors and stroke in women. They also suggest the need to ensure adequate numbers of women in clinical trials designed to explore new and promising therapies for intracranial arterial stenosis.

Echocardiography in patients with symptomatic intracranial stenosis.

BACKGROUND: Echocardiography is often performed in patients with stroke, even when alternative stroke causes are identified. We evaluated the use of echocardiography in patients with transient ischemic attack (TIA) or stroke caused by stenosis of a major intracranial artery. METHODS: The Warfarin Versus Aspirin for Symptomatic Intracranial Disease (WASID) trial was a National Institutes of Health-funded, randomized, double-blind, multicenter clinical trial in which 569 patients with TIA or ischemic stroke attributed to angiographically proven 50% to 99% stenosis of a major intracranial artery were randomly assigned to warfarin or aspirin. Patients with unequivocal cardiac sources of embolism were excluded. The risk of ischemic stroke, myocardial infarction, and vascular death was compared among patients who had or did not have echocardiography performed before enrollment, and Cox proportional hazards models were used to determine whether echocardiographic abnormalities present in greater than 5% of patients were associated with these outcomes. RESULTS: In all, 264 of 569 patients in WASID had echocardiograms; 37% were transesophageal. Of these 264 patients, 69 had subsequent ischemic stroke, myocardial infarction, or vascular death. Patients who underwent echocardiography had similar event rates to those who did not (P = .18). Common abnormalities identified on echocardiography were not associated with subsequent risk in this population. CONCLUSIONS: Among patients with TIA or stroke caused by intracranial arterial stenosis, echocardiography appears to offer limited diagnostic and prognostic value.

The effectiveness and safety of dual antiplatelet therapy in ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis in Chinese patients: A randomized and controlled trail.

BACKGROUND: There are limited data on the effect of dual antiplatelet treatment with clopidogrel plus aspirin in patients with ischemic cerebrovascular disease and intracranial and extracranial arteriostenosis. The aim of our study was to evaluate the efficacy and safety of aspirin plus clopidogrel in the treatment of ischemic cerebrovascular disease with intracranial and extracranial arteriostenosis. METHODS: Patients with clinically evident acute cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis (greater than 50%) who were unsuitable or reluctance to perform stent implantation were enrolled in this study. We randomly assigned these patients to receive clopidogrel (75 or 50 mg) plus aspirin (100 mg) or aspirin (100 mg) once daily through 90 days, and followed them for 90 days. We examined the main endpoints including the recurrence of stroke, death from cardiovascular causes, and bleeding events. RESULTS: In all, 200 patients were recruited and followed for 90 days. Ischemic stroke occurred in 6 patients (9.1%) treated with 50 mg clopidogrel and aspirin, 6 patients (9.1%) receiving 75 mg clopidogrel and aspirin, whereas 19 patients (27.9%) in the aspirin group (aspirin alone vs copidogrel 50 mg plus aspirin; 95% confidence intervals 1.704-23.779, P < 0.05; aspirin alone vs copidogrel 75 mg plus aspirin; 95% confidence intervals 1.190-13.240, P < 0.05). There were more hemorrhagic events among recipients (3 patients [2.3%]) in the copidogrel plus aspirin group than aspirin recipients (0 patient [0%]), including 1 subcutaneous hemorrhage in the group of 50 mg clopidogrel and aspirin, doubling the number of nasal and gum bleeding in the group of 75 mg clopidogrel and aspirin (P > 0.05). No intracranial hemorrhage and gastro-intestinal hemorrhage occurred in these 3 groups. CONCLUSION: Accordingly, 50 mg clopidogrel plus aspirin, and 75 mg clopidogrel plus aspirin were all superior to aspirin alone as stroke prevention in patients with cerebral infarction or transient ischemic attack combined with intracranial and extracranial arteriostenosis. The effect of secondary stroke prevention was similar between 50 mg clopidogrel plus aspirin and 75 mg clopidogrel plus aspirin. The therapy of 75 mg clopidogrel plus aspirin resulted in a worrisome tread in bleeding events.

A case of intracranial arterial dolichoectasia with 4 repeated cerebral infarctions in 6 months and enlargement of basilar artery.

A 78-year-old man was admitted to our hospital because of sudden right hemiparesis and dysarthria. His cranial MRI showed an area of hyperintensity in left pons on DWI and MRA revealed dilated, elongated and tortuous intracranial artery. We diagnosed as acute phase ischemic stroke and intracranial arterial dolichoectasia (IADE). Intravenous infusion of rt-PA was performed 157 minutes after the onset of symptoms, and his hemiparesis improved. However, he subsequently suffered from cerebral infarction 4 times in 6 months, and we treated him twice with thrombolytic therapy. Although thrombolytic therapy was effective in the short term and antithrombotic therapy was continued, he had bilateral hemiplegia and severe dysphagia because of repeated cerebral infarctions. Hence basilar artery was dilated with intramural hemorrhage over 6 months, and we discontinued antithrombolytic therapy. It is possible that antithrombolytic therapy affects enlargement of IADE. Antithrombolytic therapy for IADE should be done carefully.

Dual antiplatelet therapy in stroke and ICAS: Subgroup analysis of CHANCE.

UNLABELLED: AB OBJECTIVE: We aimed to investigate whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone were consistent between patients with and without intracranial arterial stenosis (ICAS), in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. METHODS: We assessed the interaction of the treatment effects of the 2 antiplatelet therapies among patients with and without ICAS, identified by magnetic resonance angiography (MRA) in CHANCE (ClinicalTrials.gov identifier NCT00979589). RESULTS: Overall, 1,089 patients with MRA images available in CHANCE were included in this subanalysis, 608 patients (55.8%) with ICAS and 481 (44.2%) without. Patients with ICAS had higher rates of recurrent stroke (12.5% vs 5.4%; p<0.0001) at 90 days than those without. But there was no statistically significant treatment by presence of ICAS interaction on either the primary outcome of any stroke (hazard ratio for clopidogrel plus aspirin vs aspirin alone: 0.79 [0.47-1.32] vs 1.12 [0.56-2.25]; interaction p=0.522) or the safety outcome of any bleeding event (interaction p=0.277). CONCLUSIONS: The results indicated higher rate of recurrent stroke in minor stroke or high-risk TIA patients with ICAS than in those without. However, there was no significant difference in the response to the 2 antiplatelet therapies between patients with and without ICAS in the CHANCE trial. Classification of evidence: This study provides Class II evidence that for patients with acute minor stroke or TIA with and without ICAS identified by MRA, clopidogrel plus aspirin is not significantly different than aspirin alone in preventing recurrent stroke.

Intracranial clot dissolution is associated with embolic signals on transcranial Doppler.

Reperfusion of intracranial arteries can be detected by transcranial Doppler (TCD). The authors report microembolic signals (MES) on TCD as a sign of clot dissolution and recanalization. Microembolic signals were detected during routine diagnostic TCD examination performed in the emergency room in patients eligible for thrombolytic therapy. Microembolic signals were found at the site of M1 middle cerebral artery (MCA) high-grade stenosis or near-occlusion. Transcranial Doppler was performed before, during, and after thrombolytic therapy. Of 16 consecutive patients, 3 (19%) had MES on TCD. All three patients had a severe MCA syndrome at 2 hours after stroke onset scored using the National Institutes of Health Stroke Scale (NIHSS). In patient #1 (NIHSS 12), clusters of MES were detected distal to a high-grade M1 MCA stenosis preceding spontaneous clinical recovery by 2 minutes. Because of subsequent fluctuating clinical deficit, intraarterial thrombolysis was given with complete recovery. In patient #2 (NIHSS 20), TCD detected an M1 MCA near-occlusion. At 1.5 hours after intravenous tissue plasminogen activator, TCD showed minimal MCA flow signals followed by MES, increased velocities, and normal flow signals in just 2 minutes. She gradually recovered up to NIHSS 8 in 5 days. In patient #3 with NIHSS 22 and an M1 MCA near-occlusion, TCD detected MES 15 minutes after TPA bolus followed by MCA flow velocity improvement from 15 cm/sec to 30 cm/sec. The patient recovered completely by the end of tissue plasminogen activator infusion. The authors conclude that embolic signals detected by TCD at the site of arterial obstruction can indicate clot dissolution. Intracranial recanalization on TCD can be associated with MES and changes in flow waveform, pulsatility, and velocity if insonation is performed at the site of arterial obstruction.