Statistical Analysis Plan for the INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4).

INTRODUCTION: Recruitment is complete in the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a multicenter, prospective, randomized, open-label, blinded endpoint assessed trial of pre-hospital blood pressure (BP) lowering initiated in the ambulance for patients with a suspected acute stroke and elevated BP in China. According to the registered and published trial protocol and developed by the blinded trial Steering Committee and Operations team, this manuscript outlines a detailed statistical analysis plan for the trial prior to database lock. METHODS: Patients were randomized (1:1) to intensive (target systolic BP [SBP] 130-140 mmHg within 30 minutes) or guideline-recommended BP management (BP lowering only considered if SBP >220 mmHg) group. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale at 90 days. A modified sample size of 2320 was estimated to provide 90% power to detect a 22% reduction in the odds (common odds ratio of 0.78) of a worse functional outcome using ordinal logistic regression, on the assumption of 5% patients with missing outcome and 6% patients with a stroke mimic. CONCLUSION: The statistical analysis plan for the trial has been developed to ensure transparent, verifiable, and prespecified analysis, and to avoid potential bias in the evaluation of the trial intervention.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Association between fibrinogen-to-albumin ratio and functional prognosis of 3 months in patients with acute ischemic stroke after intravenous thrombolysis.

BACKGROUND: The presence of high fibrinogen and low albumin levels in serum is associated with a negative prognosis in acute ischemic stroke (AIS). Fibrinogen-to-albumin ratio (FAR), a new inflammatory biomarker, may provide better prognostic insights in patients with AIS than separate evaluation of fibrinogen or albumin. The objective of this investigation is to examine the correlation between FAR and 3-month functional prognosis after intravenous thrombolysis (IVT) in AIS patients. METHODS: The retrospective study recruited AIS patients who received IVT from June 2014 to December 2021. The 3-month functional prognosis was assessed using the Modified Rankin Scale (mRS). A mRS score of ≤2 indicated a good outcome, whereas a mRS score of >2 suggested a poor outcome. RESULTS: A total of 591 AIS patients who underwent IVT were included and 147 patients (24.9 %) had a poor outcome. Among the 102 pairs of patients after propensity score matching, there was a significant association between FAR and 3-month prognosis (adjusted OR, 1.19; 95% CI, 1.03-1.38; p = .020). The optimal FAR cutoff value was found to be 7.57, and even after stratifying patients based on this value, we still observed a significant correlation between high FAR level and poor outcome (adjusted OR, 2.08; 95% CI, 1.28-3.40; p = .003). CONCLUSIONS: FAR may serve as a prospective biomarker of predicting 3-month prognosis in AIS patients after IVT.

Update on the INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): progress and baseline features in 2053 participants.

BACKGROUND AND AIMS: Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date. METHODS: INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP] <140mmHg within 30 min) or guideline-recommended BP management. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale scores at 90 days. RESULTS: Between March 2020 and April 2023, 2053 patients (mean age 70 years, female 39%) were recruited with a mean BP 178/98 mmHg in whom 45% have a diagnosis of primary intracerebral hemorrhage upon arrival at hospital. At the time of presentation to hospital, the mean SBP was 160 and 170mmHg in the intensive and control groups (Δ10 mmHg), respectively. The independent data and safety monitoring board has not identified any safety concerns and recommended continuation of the trial. The sample size was reduced from 3116 to 2320 after meetings in August 2022 as the stroke mimic rate was persistently lower than initially estimated (6% vs 30%). The study is expected to be completed in late 2023 and the results announced in May 2024. CONCLUSIONS: INTERACT4 is on track to provide reliable evidence of the effectiveness of ambulance-delivered intensive BP lowering in patients with suspected acute stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03790800 ; registered on 2 January 2019. Chinese Trial Registry ChCTR1900020534 , registered on 7 January 2019.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Bridging Thrombolysis Before Endovascular Therapy in Stroke Patients With Faster Core Growth.

BACKGROUND AND OBJECTIVES: It is still uncertain that going direct to endovascular thrombectomy (EVT) leads to equivalent outcomes as bridging IV thrombolysis (IVT) in acute ischemic patients. This study aimed to explore whether the rate of ischemic core growth influenced the patient outcomes after bridging IVT vs direct EVT. METHODS: This was a retrospective cohort study based on the International Stroke Perfusion Imaging Registry (INSPIRE). It selected acute ischemic stroke patients receiving perfusion CT within 4.5 hours of stroke onset. Patients who went direct to EVT were compared with those who received bridging treatment of IVT before EVT. Ischemic core growth rate was estimated by the acute ischemic core volume on perfusion CT divided by the time from stroke onset to perfusion CT, based on the assumption of a linear growth pattern of ischemic core. Core growth rate was stratified into fast (>15 mL/h) and slow (≤15 mL/h), based on its interaction with bridging IVT in predicting the primary outcome. The primary outcome was modified Rankin scale of 0-2 at 3 months. The secondary outcomes included successful thrombectomy reperfusion defined by modified Thrombolysis in Cerebral Infarction score of 2b-3 and time from groin puncture to reperfusion. RESULTS: Of the 1,221 EVT patients in the INSPIRE, 323 patients were selected, of which 82 patients received direct EVT and 241 patients received bridging IVT. Bridging IVT was associated with a higher rate of good clinical outcome among patients with fast core growth (39% vs 7% for direct EVT, odds ratio [OR] 8.75 [1.96-39.1], p = 0.005), but the difference was not notable for patients with slow core growth (55% vs 55% for direct EVT, OR 1.00 [0.53-1.87], p = 0.989). In patients with fast core growth, the bridging and direct EVT patients showed no difference in the reperfusion rate (80% vs 76%, p = 0.616). However, patients who received bridging IVT were more likely to achieve reperfusion earlier (the median groin to reperfusion time of 63.0 vs 94.0 minutes, p = 0.005). DISCUSSION: Patients with fast core growth were more likely to benefit from bridging IVT. This is likely because prior IVT facilitates clot removal and thus reduces time to reperfusion.

Diagnostic value of whole-brain computed tomographic perfusion imaging for suspected large artery occlusion stroke patients in emergency department.

PURPOSE: To evaluate the diagnostic value of whole-brain computed tomographic perfusion (WB-CTP) in emergency department for suspected large artery occlusion stroke. METHODS: Suspected large artery occlusion (LAO) stroke patients had initial WB-CTP in the neurological emergency department from August 2016 to August 2018 were retrospectively reviewed for analysis. The sensitivity and specificity of non-contrast computed tomographic scan (NCCT) or WB-CTP for diagnosis of cerebral infarction was compared between the anterior circulation and posterior circulation. The imaging characteristics of WB-CTP in patients with stroke-mimics were described. RESULTS: Among the 300 included patients, 259 patients (86.3%) were finally diagnosed as cerebral infarction, 16 (5.3%) were transient ischemic attack, 10 (3.3%) were epileptic seizure and 3 (1%) were cerebral venous sinus thrombosis (CVST). For patients with final diagnosis of cerebral infarction, WB-CTP found abnormality in 206 cases (79.5%). NCCT had poor sensitivity (4.6%) but high specificity (100%) for cerebral infarction. The CTP imaging had a sensitivity of 81.2% in anterior circulation and 59.6% in posterior circulation stroke, both with good specificity (57.1% and 92.6%, respectively). 60% (6/10) of epileptic patients showed abnormal perfusion in CTP maps, which was inconsistent with cerebral arterial supply territories. Hypoperfusion manifestations were discovered in areas adjacent to occlusion sinus of all 3 CVST cases. CONCLUSION: This retrospective study indicates WB-CTP can be useful in identifying acute ischemic stroke in emergency department, especially for patients with acute LAO stroke. Moreover, WB-CTP may have a value in differentiating stroke mimics such as epilepsy and CVST.

INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): study protocol for a randomized controlled trial.

BACKGROUND: Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4). METHODS: A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China. Patients are randomized through a mobile phone digital system to intensive BP lowering to a target systolic BP of < 140 mmHg within 30 min, or guideline-recommended BP management according to local protocols. After the collection of in-hospital clinical and management data and 7-day outcomes, trained blinded assessors conduct telephone or face-to-face assessments of physical function and health-related quality of life in participants at 90 days. The primary outcome is the physical function on the modified Rankin scale at 90 days, analyzed as an ordinal outcome with 7 categories. The sample size was estimated to provide 90% power (α = 0.05) to detect a 22% reduction in the odds of a worse functional outcome using ordinal logistic regression. DISCUSSION: INTERACT4 is a pragmatic clinical trial to provide reliable evidence on the effectiveness and safety of ambulance-delivered hyperacute BP lowering in patients with suspected acute stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03790800. Registered on 2 January 2019; Chinese Trial Registry ChiCTR1900020534. Registered on 7 January 2019. All items can be found in this protocol paper.

Mechanical Thrombectomy for Acute Stroke Due to Large-Vessel Occlusion Presenting With Mild Symptoms.

Purpose: To evaluate the safety and efficacy of mechanical thrombectomy (MT) for acute stroke due to large vessel occlusion (LVO), presenting with mild symptoms. Methods: A prospective cohort study of patients with mild ischemic stroke and LVO was conducted. Patients were divided into two groups: MT group or best medical management (MM) group. Propensity score matching (PSM) was conducted to reduce the confounding bias between the groups. The primary outcome was functional independence at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Univariate and multivariate logistic regression analyses were used to identify the independent factors associated with outcomes. Results: Among the 105 included patients, 43 were in the MT group and 62 in the MM group. Forty-three pairs of patients were generated after PSM. There were no significant differences in sICH rates between two groups (p = 1.000). The MT group had a higher proportion of independent outcomes (83.7% MT vs. 67.4% MM; OR 2.483; 95% CI 0.886-6.959; p = 0.079) and excellent outcomes (76.7% MT vs. 51.2% MM; OR 3.150; 95% CI 1.247-7.954; p = 0.013) compared to the MM group, especially in patients with stroke of the anterior circulation (p < 0.05). Multivariate logistic regression analysis showed that small infarct core volume (p = 0.015) and MT treatment (p = 0.013) were independently associated with excellent outcomes. Conclusions: Our results suggest that MT in stroke patients, presenting with mild symptoms, due to acute LVO in the anterior circulation may be associated with satisfactory clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04526756.

Lenticulostriate arteries appearance before thrombectomy predicts good outcome in acute middle cerebral artery occlusion.

BACKGROUND: Endovascular therapy is widely used in acute large vessel occlusion. This study investigated whether imaging of lateral lenticulostriate arteries (LSAs) before thrombectomy would potentially be helpful for predicting prognosis of patients with acute M1 segment of middle cerebral artery occlusion (MCAO). METHODS: 59 consecutive patients with acute M1 segment of MCAO treated with mechanical thrombectomy at two comprehensive stroke centers were analyzed. Patients were categorized into LSA+ (appearing of lateral LSAs) and LSA- (sparing of lateral LSAs) group according to preprocedural digital substraction angiography (DSA). Baseline data and clinical outcomes were compared. A good clinical outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The association between clinical and imaging parameters and functional outcome was evaluated with logistic regression analysis. RESULTS: LSA+ was shown in 36 patients (61%). LSA+ group had a significantly higher proportion of good outcome (72.2% vs. 8.7%, OR 27.3,95% CI 5.38-138.4, P < 0.001), lower risk of symptomatic intracranial haemorrhages (sICH) (8.3% vs. 47.8%,OR 0.10,95% CI 0.02-0.42, P = 0.001) and lower mortality in hospital (5.6% vs. 34.8%, OR 0.11,95% CI 0.02-0.58, P < 0.004) compared with LSA- group. Patients in LSA+ group had lower baseline NIHSS score(P < 0.01) and NIHSS score at 14 days(P < 0.01) and smaller infarct core volume (P = 0.016) on computed tomography perfusion imaging (CTP) compared to the LSA- group. Multivariate logistic regression analysis showed that a small infarct core volume (OR 6.74,95% CI 1.148-39.569, P = 0.035) and LSA+(OR 22.114,95% CI 3.339-146.470, P = 0.001) were associated with a good clinical outcome. CONCLUSIONS: Our data suggest that appearance of lateral LSAs before mechanical thrombectomy would be potentially helpful for predicting favorable prognosis of patients with acute M1 segment of MCAO.

Clinical and laboratory factors related to acute isolated vertigo or dizziness and cerebral infarction.

OBJECTIVE: To clarify the relationship of clinical factors with isolated vertigo or dizziness of cerebrovascular origin. METHODS: Clinical data of patients admitted in East Hospital from Jan. 2015 to Apr. 2016, whose complaint were acute vertigo or dizziness were retrospectively collected. All patients arrived at the emergency department within 24 hr of symptom onset, had no acute ischemic lesion first CT and NIHSS score of 0. Patients were divided into cerebral infarction group and noncerebral infarction group according to subsequent cerebral imaging results and clinical and laboratory factors related to cerebral infarction were analyzed. RESULT: 51.6% of patients were female (n = 141). 46 patients (16.8%) were diagnosed with acute cerebral infarction. Baseline demographic data of the two groups was not significantly different. Univariate analysis found that history of smoking (p = 0.009), headache (p = 0.028), unsteadiness (p = 0.009), neuron specific enolase (p = 0.001), and vertebral artery abnormalities found on imaging (p = 0.009) were the significant difference between two groups. Increased neuron specific enolase (p = 0.005) and an abnormal vertebral artery (p = 0.044) were significant on multivariate analysis. CONCLUSIONS: 16.8% of acute isolated vertigo or dizziness presentations were diagnosed with acute cerebral infarction. Increased serum neuron specific enolase and vertebral artery abnormalities were the strongest indicators of acute cerebral infarction.

An Adaptive Transmitting Scheme for Interrupted Sampling Repeater Jamming Suppression.

The interrupted sampling repeater jamming (ISRJ) based on a digital radio frequency memory (DRFM) device is a new type of coherent jamming. This kind of jamming usually occurs as main-lobe jamming and has the advantages of low power requirements and easy parameter adjustment, posing a serious threat to the modern radar systems. In order to suppress the ISRJ, this paper proposes an adaptive transmitting scheme based on a phase-coded signal. The scheme firstly performs jamming perception to estimate the jamming parameters, then, on this basis, optimizes the waveform with genetic algorithm. With the optimized waveform, the jamming signal is orthogonal to the target echo, thus it can be easily suppressed with pulse compression. Simulation experiments are performed to verify the effectiveness of the scheme and the results suggest that the peak-to-side-lobe ratio (PSR) and integrated side-lobe level (ISL) of the pulse compression can be improved by about 16 dB and 15 dB, respectively, for the case where the jamming-to-signal ratio (JSR) is 13 dB.

Relationship of Early Spontaneous Type V Blood Pressure Fluctuation after Thrombolysis in Acute Cerebral Infarction Patients and the Prognosis.

We examined the relationship between an early spontaneous type V blood pressure fluctuation and the post-thrombolysis prognosis of patients with acute cerebral infarction. Patients were admitted consecutively. All patients were categorized into the type V blood pressure fluctuation group or non-type V blood pressure group. Their blood pressure was monitored before thrombolysis and until 6 h after thrombolysis. Baseline data and clinical outcomes were compared. Of 170 patients, 43 (25.2%) had an early type V blood pressure fluctuation. The National Institute of Health Stroke Scale (NIHSS) score before thrombolysis and 24 h after thrombolysis, and the modified Rankin scale score at 90 days differed significantly between the two groups (P < 0.05). Multiple logistic regression analysis showed that an unfavorable prognosis at 3 months was associated with the NIHSS score before thrombolysis (P = 0.000) but probably not with this blood pressure fluctuation (P = 0.058). An early spontaneous type V blood pressure fluctuation is common in patients with acute cerebral infarction who received venous thrombolysis, especially if they have a higher NIHSS score before thrombolysis. The type V blood pressure fluctuation may not influence patients' prognosis; however, this needs to be confirmed in future trials.

Acute phase homocysteine related to severity and outcome of atherothrombotic stroke.

BACKGROUND: Homocysteine (HCY) is associated with risk of stroke, but whether HCY affects stroke severity and prognosis remains controversial. We hypothesized HCY has an impact on atherothrombosis and this prospective study was aimed to explore the association between acute phase HCY with stroke severity and outcome in patients with atherothrombosis. METHODS: Patients <72 h after symptom onset were categorized by the modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and those typed as atherothrombosis were included. Neurologic function was assessed with National Institute of Health Stroke Score (NIHSS) <72 h after symptom onset and Modified Rankin Scale (mRS) and Barthel Index (BI) 6-month, 12-month and 18-month poststroke respectively. HCY was recorded <72 h after symptom onset. Participants were divided into hHCY (HCY>15 µmol/l) and nhHCY (HCY≤15 µmol/l). The correlation between HCY and mRS was analyzed. RESULTS: 125 of 130 participants without HCY interventional therapy completed the 18-month follow-up. There was no difference in demographics, histories of hypertension, diabetes mellitus, coronary heart disease, previous cerebral vascular event, and plasma low-density lipoprotein between hHCY and nhHCY. NIHSS, mRS were significantly higher and BI was significantly lower in hHCY than in nhHCY. The 18-month recurrence rate in hHCY (21.0%) was significantly higher than that in nhHCY (6.8%). Spearman correlation analysis revealed correlation between HCY and mRS (p=0.000). By ordinal logistic regression, HCY was an independent predictor of 18-month mRS (odds ratio 1.08, 95% confidence interval 1.04-1.13, p=0.000). CONCLUSIONS: Acute phase elevated HCY correlated with severity and prognosis in patients with atherothrombotic stroke.