Clinical course, causes of worsening, and outcomes of severe ischemic stroke: A prospective multicenter cohort study

Simiao Wu; Yanan Wang; Ruozhen Yuan; Meng Liu; Xing Hua; Linrui Huang; Fuqiang Guo; Dongdong Yang; Zuoxiao Li; Bihua Wu; Chun Wang; Jingfeng Duan; Tianjin Ling; Hao Zhang; Shihong Zhang; Bo Wu; Cairong Zhu; Craig S Anderson; Ming Liu

doi:10.1097/CM9.0000000000003556

Clinical course, causes of worsening, and outcomes of severe ischemic stroke: A prospective multicenter cohort study

Chin Med J (Engl). 2025 Jul 5;138(13):1578-1586. doi: 10.1097/CM9.0000000000003556. Epub 2025 Mar 17.

Authors

Simiao Wu^{1

2

3}, Yanan Wang^{1

2

3}, Ruozhen Yuan⁴, Meng Liu¹, Xing Hua¹, Linrui Huang¹, Fuqiang Guo⁵, Dongdong Yang⁶, Zuoxiao Li⁷, Bihua Wu⁸, Chun Wang⁹, Jingfeng Duan¹⁰, Tianjin Ling¹¹, Hao Zhang¹², Shihong Zhang¹, Bo Wu¹, Cairong Zhu¹³, Craig S Anderson^{14

15}, Ming Liu^{1

2}

Affiliations

¹ Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
² Center of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
³ Institute of Brain Science and Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
⁴ Department of Neurology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, China.
⁵ Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
⁶ Department of Neurology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.
⁷ Department of Neurology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
⁸ Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 634700, China.
⁹ Department of Neurology, People's Hospital of Deyang City, Deyang, Sichuan 618000, China.
¹⁰ Department of Neurology, Mianyang Central Hospital, Mianyang, Sichuan 621000, China.
¹¹ Department of Neurology, The First People's Hospital of Ziyang, Ziyang, Sichuan 641300, China.
¹² Department of Neurology, Jiangyou People's Hospital, Jiangyou, Sichuan 621000, China.
¹³ Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
¹⁴ The George Institute for Global Health, Sydney, NSW 2050, Australia.
¹⁵ Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 201210, China.

Abstract

Background: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke.

Methods: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes.

Results: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P <0.01).

Conclusions: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes.

Registration: ClinicalTrials.gov , NCT03222024.

Keywords: Brain edema; Clinical course; Clinical worsening; Outcomes; Reperfusion; Severe stroke.

Publication types

Multicenter Study

MeSH terms

Aged
Aged, 80 and over
Brain Ischemia*
Female
Humans
Ischemic Stroke* / mortality
Ischemic Stroke* / pathology
Male
Middle Aged
Prospective Studies
Stroke*

Associated data

ClinicalTrials.gov/NCT03222024