Liqun Jiao

Correlation Between Carotid Intraplaque Hemorrhage and Clinical Symptoms Systematic Review of Observational Studies

Background and Purpose— We sought to investigate the association between carotid intraplaque hemorrhage (IPH) and ipsilateral symptoms of cerebral ischemia. Methods— A search was performed for clinical observational studies comparing the incidence of IPH between symptomatic and asymptomatic patients. Odds ratios (ORs) for IPH as a factor in the pathogenesis of neurologic events were calculated and combined by a meta-analysis. Interstudy heterogeneity, estimated effects, and methodologic quality of the studies were assessed. Results— Thirty-one studies were included for analysis. The reported ORs varied widely. Overall, the incidence of IPH in the symptomatic groups was significantly higher than in the asymptomatic group. However, there was an apparent trend for heterogeneity (P<0.00001) between studies. The random-effects summary estimator of ORs was 2.25 (95% CI, 1.57 to 3.22; P<0.00001). To identify potential sources of heterogeneity, subgroup analyses were performed. The pooled ORs varied greatly by stratification. Major heterogeneity was found among studies with low quality, microscopic methods of examination, significant effects, small sizes, early publication, and unequal severity of carotid stenosis in both groups. Large, recent, macroscopic, or high-quality studies, as well as studies with equal degrees of stenosis, tended to yield insignificant associations. The methods in defining and evaluating hemorrhage were very heterogeneous. Characterizations of the age, size, number, and location of hemorrhages were poorly reported and highly variable. In addition, a lack of control of confounders and selection bias were frequently identified among studies. Conclusions— Statistical inferences have suggested a plausible role in the production of cerebral ischemia; however, reliable interpretation was strongly undermined by poor methodologic quality, substantial heterogeneity, and suspicious publication bias. To preciously estimate the underlying correlation, a well-designed study with uniformity in definition and evaluation for IPH might be warranted.

Endovascular Hypothermia in Acute Ischemic Stroke Pilot Study of Selective Intra-Arterial Cold Saline Infusion

Background and Purpose— We conducted a pilot feasibility and safety study of selective brain cooling with intra-arterial infusion of cold saline combined with endovascular reperfusion for acute ischemic stroke. Methods— Patients with large-vessel occlusion within 8 hours after symptom onset were enrolled. All patients received intra-arterial recanalization combined with infusion of cold isotonic saline (4°C) in the ischemic territory through the angiographic catheter. Results— Twenty-six patients underwent the procedure, which was technically successful in all. The temperature of ischemic cerebral tissue was decreased by at least 2°C during infusion of the cold solution, and systemic temperature was mildly reduced (maximum 0.3°C). No obvious complications related to intra-arterial hypothermia were observed. Conclusions— Selective brain cooling by intra-arterial infusion of cold saline combined with endovascular recanalization therapy in acute ischemic stroke seems feasible and safe.

China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A new, prospective, multicenter, randomized controlled trial in China

Background Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding natural history nor treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective, randomized, multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. Methods The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial is an ongoing, government-funded, prospective, multicenter, randomized trial. It recruits patients with recent TIA or stroke caused by 70%–99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. The CASSISS trial will be conducted in eight sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 participants (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by December 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. Conclusion In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The present manuscript outlines the rationale and design of the study. We estimate that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high-volume centers.

Randomized controlled trial of symptomatic middle cerebral artery stenosis: endovascular versus medical therapy in a Chinese population.

Background and Purpose— To investigate the efficacy and safety of percutaneous transluminal angioplasty and stenting (PTAS) for symptomatic middle cerebral artery stenosis compared with standard medical treatment in a low-risk Chinese population. Methods— A prospective, randomized, controlled, single-center clinical trial was conducted comparing PTAS with medical treatment for symptomatic middle cerebral artery stenosis (≥70%). Patients were enrolled according to 1:1 enroll ratio (PTAS: medical). The PTAS group received stenting or balloon angioplasty, whereas the medical treatment group received standard medical treatment (aspirin 100mg plus clopidogrel 75mg/d), and all the patients were under strict control of the risk factors. The end point events were any kind of ipsilateral stroke or transient ischemic attack, or death from any origin during 1-year follow-up. Results— The enrollment was stopped after 70 patients were enrolled from August 2007 to December 2010, with a 30-day rate of end point events of 8.3% versus 5.9% (P=0.69) for PTAS and medical group, respectively, and 1-year rate of end point events of 19.4% versus 17.6% (P=0.85), respectively. There was no significant difference in baseline characteristics between the 2 groups. The mean follow-up time, which was ongoing, was 9.9 ± 3.9 and 9.7 ± 4.4 months, respectively. Among the risk factors, hypertension was the independent related to the outcome (P=0.015). Conclusions— This study showed that endovascular treatment is as safe but not better than medical treatment for symptomatic middle cerebral artery stenosis in a low-risk Chinese population. History of hypertension increases the risk of recurrent ischemic events.

Safety and Efficacy of Remote Ischemic Preconditioning in Patients with Severe Carotid Artery Stenosis Prior to Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial

Background: Remote ischemic preconditioning (RIPC) can inhibit recurrent ischemic events effectively in patients with acute or chronic cerebral ischemia. However, it is still unclear whether RIPC can impede ischemic injury after carotid artery stenting (CAS) in patients with severe carotid artery stenosis. Methods: Subjects with severe carotid artery stenosis were recruited in this randomized controlled study, and assigned to RIPC, sham, and no intervention (control) groups. All subjects received standard medical therapy. Subjects in the RIPC and sham groups underwent RIPC and sham RIPC twice daily, respectively, for 2 weeks before CAS. Plasma neuron-specific enolase and S-100B were used to evaluate safety, hypersensitive C-reactive protein, and new ischemic diffusion-weighted imaging lesions were used to determine treatment efficacy. The primary outcomes were the presence of ≥1 newly ischemic brain lesions on diffusion-weighted imaging within 48 hours after stenting and clinical events within 6 months after stenting. Results: We randomly assigned 189 subjects in this study (63 subjects in each group). Both RIPC and sham RIPC procedures were well tolerated and completed with high compliance (98.41% and 95.24%, respectively). Neither plasma neuron-specific enolase levels nor S-100B levels changed significantly before and after treatment. No severe adverse event was attributed to RIPC and sham RIPC procedures. The incidence of new diffusion-weighted imaging lesions in the RIPC group (15.87%) was significantly lower than in the sham group (36.51%; relative risk, 0.44; 96% confidence interval, 0.20–0.91; P<0.01) and the control group (41.27%; relative risk, 0.39; 96% confidence interval, 0.21–0.82; P<0.01). The volumes of lesions were smaller in the RIPC group than in the control and sham groups (P<0.01 each). Ischemic events that occurred after CAS were 1 transient ischemic attack in the RIPC group, 2 strokes in the control group, and 2 strokes and 1 transient ischemic attack in the sham group, but these results were not significantly different among the 3 groups (P=0.597). Conclusions: RIPC is safe in patients undergoing CAS, which may be able to decrease ischemic brain injury secondary to CAS. However, the mechanisms and effects of RIPC on clinical outcomes in this cohort of patients need further investigation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654666

Multicenter Prospective Trial of Stent Placement in Patients with Symptomatic High-Grade Intracranial Stenosis

BACKGROUND AND PURPOSE: On the basis of the high 1-month stroke and/or death (14.7%) rates associated with stent placement in the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial, modifications in patient selection and procedural aspects for intracranial stent placement have been recommended. We performed a multicenter prospective single-arm trial to determine whether such modifications would result in lower rates of periprocedural stroke and/or death. MATERIALS AND METHODS: The study enrolled patients with recent transient ischemic attack or ischemic stroke (excluding perforator ischemic events) related to high-grade (70%–99% in severity) stenosis of a major intracranial artery. Patients were treated by using angioplasty and self-expanding stents 3 weeks after the index ischemic event at 1 of the 10 high-volume centers in China. An independent neurologist ascertained the occurrence of any stroke and/or death within 1 month after the procedure. RESULTS: A total of 100 consecutive patients were recruited. The target lesions were located in the middle cerebral artery (M1) (n = 38, 38%), intracranial internal carotid artery (n = 17, 17%), intradural vertebral artery (n = 18, 18%), and basilar artery (n = 27, 27%). The technical success rate of stent deployment with residual stenosis of <50% was 100%. The overall 1-month stroke and/or death rate was 2% (95% confidence interval, 0.2%–7.0%). Two ischemic strokes occurred in the pontine region (perforator distribution) in patients following angioplasty and stent placement for basilar artery stenosis. CONCLUSIONS: The results of this prospective multicenter study demonstrated that modifications in patient selection and procedural aspects can substantially reduce the 1-month stroke and/or death rate following intracranial stent placement.

Intra-arterial thrombolysis for acute central retinal artery occlusion.

Abstract Objective: In this study, we aimed at exploring the effect and safety of local intra-arterial thrombolysis on acute central retinal artery occlusion. Methods: Retrospective data analysis of 49 consecutive acute central retinal occlusion patients was performed. All the patients were treated with urokinase perfusion through the ophthalmology artery within the first 6 hours after central retinal artery occlusion attack. Conventional treatments including intra-ocular pressure decreasing, microcirculation improvement, neuroprotection and antiplatelet aggregation were conducted. The visual acuity (with International Snellen Chart) and field of vision were detected after thrombolysis. The complications and adverse events were observed. Results: Recanalization was found in 71% of patients. The visual acuity improvement was greater in the recanalization group (n=35) than in the non-recanalization group (n=14). The averaged visual acuity was 0.15±0.02, 0.25±0.03 and 0.4±0.05 after 2, 28 days and 6 months, respectively. Of the patients, 24.5% regained >0.6 of visual acuity, and the visual field deficit was less than 30% in 34.7% of patients after 28 days. Six months later, 36.7% patients regained visual acuity of >0.6, and the field deficit was less than 30% in 44.9% of patients. The difference between visual acuity in recanalization (0.6±0.04) and non-recanalization (0.002±0.0012) patients after 6 months after thrombolysis was significant (p>0.05). Conclusions: Intra-arterial thrombolysis could obviously improve the short- and long-term visual function for patients with acute central retinal artery occlusion within 6 hours of symptom onset.

The Carotid and Middle cerebral artery Occlusion Surgery Study (CMOSS): a study protocol for a randomised controlled trial

BackgroundPatients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion with haemodynamic insufficiency are at high risk for recurrent stroke when treated medically.MethodsThe Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS) trial is an ongoing, government-funded, prospective, multicentre, randomised controlled trial. The CMOSS will recruit 330 patients with symptomatic ICA or MCA occlusion (parallel design, 1:1 allocation ratio) and haemodynamic insufficiency. Participants will be allocated to best medical treatment alone or best medicine plus extracranial-intracranial (EC-IC) bypass surgery. The primary outcome events are all strokes or deaths occurring between randomisation and 30xa0days post operation or post randomisation and ipsilateral ischaemic stroke within 2xa0years. Recruitment will be finished by December 2016. All the patients will be followed for at least 2xa0years. The trial is scheduled to complete in 2019.DiscussionThe CMOSS will test the hypothesis that EC-IC bypass surgery plus best medical therapy reduces subsequent ipsilateral ischaemic stroke in patients with symptomatic ICA or MCA occlusion and haemodynamic cerebral ischaemia. This manuscript outlines the rationale and the design of the study. CMOSS will allow for more critical reappraisal of the EC-IC bypass for selected patients in China.Trial registrationNCT01758614 with ClinicalTrials.gov. Registered on 24 December 2012.

Superficial Temporal Artery–Middle Cerebral Artery Bypass Surgery for Refractory Symptomatic Intracranial Atherosclerotic Stenosis

OBJECTIVEnTo evaluate blood flow changes after bypass surgery for refractory symptomatic intracranial atherosclerotic stenosis (ICAS).nnnMETHODSnWe examined a cohort of consecutive patients with symptomatic ICAS. Superficial temporal artery-middle cerebral artery (MCA) bypass was performed in refractory patients with poor perfusion. Angiograms were graded systematically for antegrade, collateral, and bypass flow, and clinical variables were collected preoperatively, at 7 days postoperatively, and 3, 6, and 12 months postoperatively.nnnRESULTSnAmong 185 consecutive cases with ICAS, 15 patients who were unsuitable for or did not respond to the best medical therapy or stenting underwent bypass surgery. No patients had new ischemic deficits within 7 days postoperatively. The mean follow-up period was 30.2 ± 12.3 months. Within this period, all anastomoses were patent by methods of ultrasound or computed tomography angiography. In 2 patients, stenotic lesions exhibited early postoperative occlusion conversion at 7 days on digital subtraction angiography. In 2 patients, stenotic lesions showed progression of occlusion at 6 and 8 months. The 2 lesions with early occlusion were both located in the MCA. The extent of retrograde blood flow via bypass anastomosis was correlated with early occlusion conversion.nnnCONCLUSIONSnFor refractory ICAS in patients with compromised hemodynamics, direct bypass might induce early occlusion of a stenotic area. MCA lesions may have a greater tendency toward early occlusion conversion.

The Comparison of Monitoring of Cerebral Blood Flow by c-FLOW and Transcranial Doppler in Carotid Endarterectomy

OBJECTIVEnTo prospectively compare the use of the cerebral blood flow monitor (c-FLOW) and transcranial Doppler (TCD) as 2 techniques for assessing brain perfusion during carotid endarterectomy.nnnMETHODSnThis was a prospective, single-center, observational study. All patients were monitored using c-FLOW and TCD during the operation. Changes from baseline values of cerebral blood flow index and blood flow velocity of middle cerebral artery (V-MCA) were recorded following carotid artery clamping and unclamping. The correlation analysis was conducted for c-FLOW and TCD monitoring values.nnnRESULTSnSeventy-three consecutive patients were enrolled from August 2015 to March 2016. No death or stroke occurred during the postoperative hospitalization. Fresh infarction was identified on magnetic resonance imaging in 17 patients. Ten patients showed a significant decrease of V-MCA following carotid clamping. A shunt was placed for only 4. The Pearson correlation index between CFI and V-MCA was 0.647 (P < 0.001). A cut-off of 21% decrease of CFI was proposed as optimal to detect intraoperative hypoperfusion. Seven patients were diagnosed as having hyperperfusion by TCD monitoring. The Pearson correlation index between CFI and V-MCA was 0.286 (Pxa0= 0.014). A cut-off of 15% increase of CFI following carotid unclamping was suggested as optimal to detect the postoperative hyperperfusion.nnnCONCLUSIONSnc-FLOW could continuously and noninvasively monitor the cerebral blood flow in real-time during carotid endarterectomy and effectively detect the intraoperative hypoperfusion and postoperative hyperperfusion as defined by TCD so that it may serve as a favorable modality in future intraoperative monitoring.