Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis

Houwei Du; Sangru Wu; Hanhan Lei; Gareth Ambler; David J Werring; Hangfeng Li; Yangui Chen; Dongping Chen; Qilin Yuan; Shuangfang Fang; Ronghua Chen; Yixian Zhang; Jin Wei; Guangliang Chen; Jianhua Chen; Nan Liu

doi:10.3389/fnagi.2022.790262

Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis

Front Aging Neurosci. 2022 Apr 11:14:790262. doi: 10.3389/fnagi.2022.790262. eCollection 2022.

Authors

Houwei Du^{1

2}, Sangru Wu^{1

3}, Hanhan Lei^{1

2}, Gareth Ambler⁴, David J Werring⁵, Hangfeng Li⁶, Yangui Chen⁶, Dongping Chen⁶, Qilin Yuan^{1

2}, Shuangfang Fang^{1

2}, Ronghua Chen^{1

2}, Yixian Zhang⁷, Jin Wei⁸, Guangliang Chen⁸, Jianhua Chen⁸, Nan Liu^{1

7}

Affiliations

¹ Department of Neurology, Stroke Research Center, Fujian Medical University Union Hospital, Fuzhou, China.
² Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China.
³ Department of Neurology, Fujian Provincial Governmental Hospital, Fuzhou, China.
⁴ Department of Statistical Science, University College London, London, United Kingdom.
⁵ Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology, London, United Kingdom.
⁶ Department of Neurology, Longyan First Hospital of Fujian Medical University, Longyan, China.
⁷ Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, China.
⁸ Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China.

Abstract

Objective: The aim of this study was to investigate the association of total cerebral small vessel disease (cSVD) score with the risk of intracerebral hemorrhage (ICH) in patients with acute ischemic stroke who received intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA).

Methods: We retrospectively reviewed clinical data from two stroke registries of patients with acute ischemic stroke treated with IVT. We assessed the baseline magnetic resonance (MR) visible cSVD markers and total cSVD score (ranging from 0 to 4) between patients with and without ICH after IVT. Logistic regression analysis was used to determine the association of total cSVD score with the risk of ICH after IVT, adjusted for cofounders selected by least absolute shrinkage and selection operator (LASSO). We additionally performed an E-value analysis to fully explain away a specific exposure-outcome association. Receiver operating characteristic (ROC) curve analysis was used to quantify the predictive potential of the total cSVD score for any ICH after IVT.

Results: Among 271 eligible patients, 55 (20.3%) patients experienced any ICH, 16 (5.9%) patients experienced a symptomatic ICH (sICH), and 5 (1.85%) patients had remote intracranial parenchymal hemorrhage (rPH). Logistic regression analysis showed that the risk of any ICH increased with increasing cSVD score [per unit increase, adjusted odds ratio (OR) 2.03, 95% CI 1.22-3.41, P = 0.007]. Sensitivity analyses using E-value revealed that it would need moderately robust unobserved confounding to render the exposure-outcome (cSVD-any ICH) association null. ROC analysis showed that compared with the National Institutes of Health Stroke Scale (NIHSS) score alone, a combination of cSVD and NIHSS score had a larger area under the curve for any ICH (0.811, 95% CI 0.756-0.866 vs. 0.784, 95% CI 0.723-0.846, P = 0.0004).

Conclusion: The total cSVD score is associated with an increased risk of any ICH after IVT and improves prediction for any ICH compared with NIHSS alone.

Keywords: cerebral bleeding risk; cerebral small vessel disease; intracerebral hemorrhage; ischemic stroke; thrombolysis.