Risk factors for early neurological deterioration in acute ischemic stroke: a case-control study

Background: Early neurological deterioration (END) represents major complication of acute ischemic stroke (AIS) and is associated with high mortality and disability. In the present study, we aimed to identify potential risk factors for early neurological deterioration in patients with AIS. Methods: This was a retrospective and case-control study conducted at Sun Yat-sen University’s Fifth Affiliated Hospital. Between January 2021 and October 2022, 358 patients with AIS patients were examined and grouped according to whether they developed END or not. END was defined as an increase of >2 points on the National Institutes of Health Stroke Scale (NIHSS) score within the first week of admission. Baseline characteristics, vascular risk factors, laboratory findings, and neuroimaging were then compared between the END and non-END groups of patients. Results: END was observed in 58 of the 358 patients. The END group of patients showed a significantly higher prevalence of unstable carotid plaques (51.7% vs. 15.3%, p < 0.001) and high NIHSS scores at the time of admission (median 4.0 vs. 2.0, p < 0.001). Key biochemical markers were significantly higher in the END group, including fibrinogen, total cholesterol, low density lipoprotein cholesterin (LDL-cholesterol) and glycosylated hemoglobin A1c (HbA1c). Multivariate analysis confirmed that higher NIHSS scores at the time of admission and unstable carotid plaques were independent prognostic factors of END. Conclusions: Higher NIHSS scores upon admission and the presence of unstable carotid plaques were identified as significant risk factors for END in AIS patients. Identifying these factors may facilitate the early diagnosis of END and improve patient outcomes.

Risk factors; Acute ischemic stroke; END; NIHSS; Unstable carotid plaque

[1] 2019 Stroke Collaborators GBDS. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet Neurology. 2021; 20: 795–820.

[2] Sharma A, Pandit AK, Mishra B, Padma Srivastava MV, Srivastava AK, Vishnu VY, et al. Early neurological deterioration in acute ischemic stroke. Irish Journal of Medical Science. 2024; 193: 949–955.

[3] Che F, Wang A, Ju Y, Ding Y, Duan H, Geng X, et al. Early neurological deterioration in acute ischemic stroke patients after intravenous thrombolysis with alteplase predicts poor 3-month functional prognosis—data from the thrombolysis implementation and monitor of acute ischemic stroke in China (TIMS-China). BMC Neurology. 2022; 22: 212.

[4] Amer HA, El-Jaafary SIM, Sadek H, Fouad AM, Mohammed SS. Clinical and paraclinical predictors of early neurological deterioration and poor outcome in spontaneous intracerebral hemorrhage. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2023; 59: 74.

[5] Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke. 2018; 49: e46–e110.

[6] Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Journal of the American College of Cardiology. 2019; 73: 3168–3209.

[7] Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, 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. Stroke. 1993; 24: 35–41.

[8] Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European stroke conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovascular Diseases. 2012; 34: 290–296.

[9] Saini V, Guada L, Yavagal DR. Global epidemiology of stroke and access to acute ischemic stroke interventions. Neurology. 2021; 97: S6–S16.

[10] Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the global burden of disease study 2017. The Lancet. 2019; 394: 1145–1158.

[11] Zhao Y, Zhang X, Chen X, Wei Y. Neuronal injuries in cerebral infarction and ischemic stroke: from mechanisms to treatment (Review). International Journal of Molecular Medicine. 2022; 49: 15.

[12] Sharma A, Pandit AK, Mishra B, Srivastava MVP, Srivastava AK, Vishnu VY, et al. Early neurological deterioration in acute ischemic stroke. Irish Journal of Medical Science. 2024; 193: 949–955.

[13] Zietz A, Gorey S, Kelly PJ, Katan M, McCabe JJ. Targeting inflammation to reduce recurrent stroke. International Journal of Stroke. 2024; 19: 379–387.

[14] Zhang X, Xue J, Yang W, Xu X, Sun H, Hu L, et al. Inflammatory markers as independent predictors for stroke outcomes. Brain and Behavior. 2021; 11: e01922.

[15] Liu H, Liu K, Zhang K, Zong C, Yang H, Li Y, et al. Early neurological deterioration in patients with acute ischemic stroke: a prospective multicenter cohort study. Therapeutic Advances in Neurological Disorders. 2023; 16: 175628642211477.

[16] Arboix A, Jiménez C, Massons J, Parra O, Besses C. Hematological disorders: a commonly unrecognized cause of acute stroke. Expert Review of Hematology. 2016; 9: 891–901.

[17] Kelley R, Bir S. Carotid atherosclerotic disease: a systematic review of pathogenesis and management. Brain Circulation. 2022; 8: 127.

[18] Mistry EA, Yeatts S, de Havenon A, Mehta T, Arora N, De Los Rios La Rosa F, et al. Predicting 90-day outcome after thrombectomy: baseline-adjusted 24-hour NIHSS is more powerful than NIHSS score change. Stroke. 2021; 52: 2547–2553.

[19] Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016; 316: 1289.

[20] Bao Y, Gu D. Glycated hemoglobin as a marker for predicting outcomes of patients with stroke (ischemic and hemorrhagic): a systematic review and meta-analysis. Frontiers in Neurology. 2021; 12: 642899.

[21] Roquer J, Giralt-Steinhauer E, Cerdà G, Rodríguez-Campello A, Cuadrado-Godia E, Jiménez-Conde J, et al. Glycated hemoglobin value combined with initial glucose levels for evaluating mortality risk in patients with ischemic stroke. Cerebrovascular Diseases. 2015; 40: 244–250.

[22] Adams HP, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: a report of the trial of org 10172 in acute stroke treatment (TOAST). Neurology. 1999; 53: 126–131.

[23] Hankey GJ. Secondary stroke prevention. The Lancet Neurology. 2014; 13: 178–194.

[24] Zhou L, Li X, Zhou Z, Chen H. Effect of argatroban combined with dual antiplatelet therapy on early neurological deterioration in acute minor posterior circulation ischemic stroke. Clinical and Applied Thrombosis/Hemostasis. 2020; 26: 107602962090413.

[25] Yi X, Chi W, Wang C, Zhang B, Lin J. Low-molecular-weight heparin or dual antiplatelet therapy is more effective than aspirin alone in preventing early neurological deterioration and improving the 6-month outcome in ischemic stroke patients. Journal of Clinical Neurology. 2015; 11: 57.

[26] Thomas SE, Plumber N, Venkatapathappa P, Gorantla V. A review of risk factors and predictors for hemorrhagic transformation in patients with acute ischemic stroke. International Journal of Vascular Medicine. 2021; 2021: 4244267.

[27] Redgrave JNE, Lovett JK, Gallagher PJ, Rothwell PM. Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study. Circulation. 2006; 113: 2320–2328.

[28] Liu C, Xie J, Sun S, Li H, Li T, Jiang C, et al. Hemorrhagic transformation after tissue plasminogen activator treatment in acute ischemic stroke. Cellular and Molecular Neurobiology. 2022; 42: 621–646.

[29] Mehta V, Prabhakar R, Kumar R, Jyoti D, Sharma CB. Fibrinogen as a predictor of early neurological deterioration and poor outcome in acute ischemic stroke. Journal of the Association of Physicians of India. 2022; 70: 11–12.

[30] Prasad MK, Marandi S, Mishra B, Guria RT, Kumar A, Birua H, et al. Association of fibrinogen with ischemic stroke: a systematic review and meta-analysis. Cureus. 2023; 15: e34335.

[31] Thanvi B, Treadwell S, Robinson T. Early neurological deterioration in acute ischaemic stroke: predictors, mechanisms and management. Postgraduate Medical Journal. 2008; 84: 412–417.

[32] Dong N, Shen X, Wu X, Guo X, Fang Q. Elevated glycated hemoglobin levels are associated with poor outcome in acute ischemic stroke. Frontiers in Aging Neuroscience. 2021; 13: 821336.