Development and Validation of an Early Neurological Deterioration Prediction Model for Patients with Cerebral Infarction Caused by Moderate-to-Severe Symptomatic Intracranial Arterial Stenosis

doi:10.3969/j.issn.1673-5765.2025.12.005

Abstract

Abstract: Objective To analyze the risk factors for early neurological deterioration (END) in patients with cerebral infarction caused by moderate-to-severe symptomatic intracranial arterial stenosis, and to develop and validate a prediction model for END based on independent risk factors.
Methods This was a retrospective study that consecutively enrolled patients with cerebral infarction caused by moderate-to-severe symptomatic intracranial arterial stenosis, who were admitted to the Department of Cerebrovascular Disease, Guangdong Provincial Hospital of Chinese Medicine between January 2019 and December 2023. Patients were divided into the END group and the non-END group based on the occurrence of END within 7 days of onset. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for END. A nomogram regression prediction model was subsequently constructed based on these factors, and its validity was verified using the Bootstrap resampling method within the original dataset.
Results A total of 152 patients were included, with 47 in the END group and 105 in the non-END group. The END group consisted of 47 patients aged 65 (57-75) years, including 33 males (70.21%); the non-END group consisted of 105 patients aged 64 (54-75) years, including 72 males (68.57%). Univariate and multivariate logistic regression analyses identified acute cerebral watershed infarction, severe stenosis of the responsible vessel, and a higher age, blood pressure, clinical features, duration of symptoms, diabetes, dual transient ischemic attack, ipsilateral carotid stenosis, infarction on diffusion-weighted-imaging (ABCD3-I) score as independent risk factors for END. A nomogram regression prediction model was constructed based on these three factors, with an AUC of 0.85 (95%CI 0.78-0.92) and an optimal cut-off value of 0.43. The sensitivity and specificity were 0.77 and 0.79, respectively. Internal validation of the model was performed using the Bootstrap resampling method, yielding an AUC of 0.85 (95%CI 0.84-0.89).
Conclusions The END prediction model constructed in this study incorporates acute cerebral watershed infarction, severe stenosis of the responsible vessel, and the ABCD3-I score, demonstrating good predictive performance. Internal validation indicates good model stability.

Key words: Symptomatic intracranial arterial stenosis; Early neurological deterioration; Prediction model

摘要： 目的分析症状性颅内动脉中重度狭窄脑梗死患者早期神经功能恶化（early neurological deterioration，END）的危险因素，基于独立危险因素构建并验证END预测模型。
方法本研究为回顾性研究，连续纳入2019年1月—2023年12月广东省中医院脑血管病科收治的符合纳排标准的症状性颅内动脉中重度狭窄脑梗死患者，根据发病7 d内是否发生END分为END组和非END组。通过单因素及多因素logistic回归分析筛选END的独立危险因素。随后，基于所得独立危险因素构建列线图预测模型，采用Bootstrap重采样法在原始数据集中进行有效性验证。
结果共纳入152例患者，其中END组47例，非END组105例，END组患者年龄为65（57～75）岁，男性33例（70.21%）；非END组患者年龄为64（54～75）岁，男性72例（68.57%）。单因素及多因素logistic回归分析显示，急性分水岭梗死、责任血管重度狭窄及较高的年龄、血压、临床特征、症状持续时间、糖尿病、双重TIA、同侧颈动脉狭窄和DWI梗死灶（age，blood pressure，clinical features，duration of symptoms，diabetes，dual transient ischemic attack，ipsilateral carotid stenosis，infarction on
diffusion-weighted-imaging；ABCD3-I）评分是END的独立危险因素。基于上述危险因素构建列线图预测模型，其AUC为0.85（95%CI 0.78～0.92），最佳截断值为0.43，此时模型的敏感度为0.77，特异度为0.79。采用Bootstrap重采样法对模型进行内部验证，AUC为0.85（95%CI 0.84～0.89）。
结论本研究构建的END预测模型包含急性分水岭梗死、责任血管重度狭窄及ABCD3-I评分，具有良好的预测效能，内部验证表明模型稳定性良好。

关键词: 症状性颅内动脉狭窄; 早期神经功能恶化; 预测模型

CLC Number:

XIONG Zini, PENG Zhuli, WANG Xindi, LIU Haolin, CHEN Xiaolong, BAI Xiaoxin. Development and Validation of an Early Neurological Deterioration Prediction Model for Patients with Cerebral Infarction Caused by Moderate-to-Severe Symptomatic Intracranial Arterial Stenosis[J]. Chinese Journal of Stroke, 2025, 20(12): 1499-1507.

熊紫妮, 彭株丽, 王欣迪, 刘浩林, 陈小龙, 白小欣. 症状性颅内动脉中重度狭窄脑梗死患者早期神经功能恶化预测模型的构建与验证[J]. 中国卒中杂志, 2025, 20(12): 1499-1507.

References

[1] WANG Y J，ZHAO X Q，LIU L P，et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China：the Chinese intracranial atherosclerosis（CICAS）study[J]. Stroke，2014，45（3）：663-669.
[2] 谭泽锋，杨万勇，徐安定. 症状性大脑中动脉、基底动脉狭窄与进展性卒中的相关性[J]. 暨南大学学报（自然科学与医学版），2015，36（3）：251-255.
TAN Z F，YANG W Y，XU A D. Correlation of symptomatic stenosis in middle cerebral artery，and basilar artery to stroke in progression[J]. Journal of Jinan University（Natural Science & Medicine Edition），2015，36（3）：251-255.
[3] CAPLAN L R，GORELICK P B，HIER D B. Race，sex and occlusive cerebrovascular disease：a review[J]. Stroke，1986，17（4）：648-655.
[4] AMARENCO P，LAVALLÉE P C，LABREUCHE J，et al. One-year risk of stroke after transient ischemic attack or minor stroke[J]. N Engl J Med，2016，374（16）：1533-1542.
[5] GHANDEHARI K，AHMADI F，EBRAHIMZADEH S，et al. The ABCD2 score is highly predictive of stroke in minor ischemic stroke patients[J]. Transl Stroke Res，2012，3（2）：273-278.
[6] ZHAO M，WANG S，ZHANG D，et al. Comparison of stroke prediction accuracy of ABCD2 and ABCD3-I in patients with transient ischemic attack：a meta-analysis[J]. J Stroke Cerebrovasc Dis，2017，26（10）：2387-2395.
[7] MERWICK A，ALBERS G W，AMARENCO P，et al. Addition of brain and carotid imaging to the ABCD2 score to identify patients at early risk of stroke after transient ischaemic attack：a multicentre observational study[J]. Lancet Neurol，2010，9（11）：1060-1069.
[8] JOHNSTON S C，ROTHWELL P M，NGUYEN-HUYNH M N，et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack[J]. Lancet，2007，369（9558）：283-292.
[9] ROTHWELL P M，GILES M F，FLOSSMANN E，et al. A simple score（ABCD）to identify individuals at high early risk of stroke after transient ischaemic attack[J]. Lancet，2005，366（9479）：29-36.
[10] 苏立华，隋汝波. 改进的ABCD-I评分对进展性脑卒中的预测价值[J]. 中国老年学杂志，2015，35（9）：2410-2412.
SU L H，SUI R B. The predictive value of the modified ABCD-I score for progressive stroke[J]. Chinese Journal of Gerontology，2015，35（9）：2410-2412.
[11] ADAMS H P，Jr，BENDIXEN B H，KAPPELLE L J，et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment[J]. Stroke，1993，24（1）：35-41.
[12] 董强，黄家星，黄一宁，等. 症状性动脉粥样硬化性颅内动脉狭窄中国专家共识[J]. 中国神经精神疾病杂志，2012，38（3）：129-145.
DONG Q，HUANG J X，HUANG Y N，et al. Chinese expert consensus on symptomatic intracranial atherosclerotic stenosis[J]. Chin J Nerv Ment Dis，2012，38（3）：129-145.
[13] 中国卒中学会，中国卒中学会神经介入分会，中华预防医学会卒中预防与控制专业委员会介入学组. 症状性颅内动脉粥样硬化性狭窄血管内治疗中国专家共识2018[J]. 中国卒中杂志，2018，13（6）：594-604.
Chinese Stroke Association，Chinese Interventional Neuroradiology Society，Intervention Group of Committee of Stroke Prevention and Control of Chinese Preventive Medicine Association. Chinese expert consensus on endovascular treatment for symptomatic intracranial atherosclerotic stenosis 2018[J]. Chin J Stroke，2018，13（6）：594-604.
[14] CHIMOWITZ M I，KOKKINOS J，STRONG J，et al. The warfarin-aspirin symptomatic intracranial disease study[J]. Neurology，1995，45（8）：1488-1493.
[15] KWON H M，LEE Y S，BAE H J，et al. Homocysteine as a predictor of early neurological deterioration in acute ischemic stroke[J]. Stroke，2014，45（3）：871-873.
[16] KANAMARU T，SUDA S，MURAGA K，et al. Albuminuria predicts early neurological deterioration in patients with acute ischemic stroke[J/OL]. J Neurol Sci，2017，372：417-420[2025-06-24]. https://doi.org/10.1016/j.jns.2016.11.007.
[17] RYU W S，HONG K S，JEONG S W，et al. Association of ischemic stroke onset time with presenting severity，acute progression，and long-term outcome：a cohort study[J/OL]. PLoS Med，2022，19（2）：e1003910[2025-06-24]. https://doi.org/10.1371/journal.pmed.1003910.
[18] WERRING D J，OZKAN H，DOUBAL F，et al. Early neurological deterioration in acute lacunar ischemic stroke：systematic review of incidence，mechanisms，and prospects for treatment[J]. Int J Stroke，2025，20（1）：7-20.
[19] WANG J，ZHAO M，QIAO Y，et al. Neurological deterioration after acute ischemic stroke：a common phenomenon with important implications[J]. Cerebrovasc Dis，2025，54（6）：1016-1031.
[20] MIYAMOTO N，TANAKA R，UENO Y，et al. Analysis of the usefulness of the WORSEN score for predicting the deterioration of acute ischemic stroke[J]. J Stroke Cerebrovasc Dis，2017，26（12）：2834-2839.
[21] 中国卒中学会神经介入分会. 症状性颅内动脉粥样硬化性狭窄血管内治疗中国专家共识2022[J]. 中国卒中杂志，2022，17（8）：863-888.
Chinese Stroke Association，Chinese Interventional Neuroradiology Society. Chinese experts consensus on endovascular treatment for symptomatic intracranial atherosclerotic stenosis 2022[J]. Chin J Stroke，2022，17（8）：863-888.
[22] PSYCHOGIOS K，STATHOPOULOS P，TAKIS K，et al. The pathophysiological mechanism is an independent predictor of long-term outcome in stroke patients with large vessel atherosclerosis[J]. J Stroke Cerebrovasc Dis，2015，24（11）：2580-2587.
[23] KIM J T，YOON G J，NAM T S，et al. Internal border zone lesions as a predictor of early neurological deterioration in minor stroke patients with severe arterial steno-occlusion[J]. J Neuroimaging，2011，21（2）：173-176.
[24] KUMARI R，WILLING L B，PATEL S D，et al. Increased cerebral matrix metalloprotease-9 activity is associated with compromised recovery in the diabetic db/db mouse following a stroke[J]. J Neurochem，2011，119（5）：1029-1040.
[25] LAI K，PRITIŠANAC I，LIU Z Q，et al. Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury[J]. Nature，2024，631（8022）：826-834.
[26] XIA Q，QUE M X，ZHAN G F，et al. SENP6-mediated deSUMOylation of Nrf2 exacerbates neuronal oxidative stress following cerebral ischemia and reperfusion injury[J/OL]. Adv Sci（Weinh），2025，12（7）：e2410410[2025-06-24]. https://doi.org/10.1002/advs.202410410.
[27] SU W X，ZHAO Y，WEI Y Q，et al. Exploring the pathogenesis of psoriasis complicated with atherosclerosis via microarray data analysis[J/OL]. Front Immunol，2021，12：667690[2025-06-24]. https://doi.org/10.3389/fimmu.2021.667690.
[28] KLEIN L W. Clinical implications and mechanisms of plaque rupture in the acute coronary syndromes[J]. Am Heart Hosp J，2005，3（4）：249-255.
[29] DZAU V J. Theodore Cooper lecture：tissue angiotensin and pathobiology of vascular disease：a unifying hypothesis[J]. Hypertension，2001，37（4）：1047-1052.
[30] XU Y C，CHEN Y，CHEN R W，et al. External validation of the WORSEN score for prediction the deterioration of acute ischemic stroke in a Chinese population[J/OL]. Front Neurol，2020，11：482[2025-06-24]. https://doi.org/10.3389/fneur.2020.00482.
[31] 肖静怡. 急性缺血性脑卒中早期神经功能恶化预测模型的构建与验证[D]. 广州：广州医科大学，2021.
XIAO J Y. Construction and validation of predictive models of early neurological deterioration in acute ischemic stroke[D]. Guangzhou：Guangzhou Medical University，2021.
[32] BARBER P A，DEMCHUK A M，ZHANG J J，et al. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy[J]. Lancet，2000，355（9216）：1670-1674.