. Analyzing the serum biochemical factors that influence early neurological deterioration in ischemic stroke patients and developing a nomogram prediction model

serum biochemical factors that influence early neurological deterioration

  • Xiaoni Zhan Department of Neurology, Dongyang Peoples Hospital, Wenzhou Medical University, Zhejiang, 322100, China
  • Yunyun Xu Department of Neurology, Dongyang Peoples Hospital, Wenzhou Medical University, Zhejiang, 322100, China
  • Rongrong Ma Department of Neurology, Dongyang Peoples Hospital, Wenzhou Medical University, Zhejiang, 322100, China
Keywords: serum biochemical factors; Early neurological deterioration; Nomogram prediction model

Abstract


Objective: To investigate the risk factors associated with early neurological deterioration (END) in ischemic stroke (IS) patients and develop a predictive nomogram model. Methods: General clinical data from 220 IS patients treated between December 2022 and November 2023 were collected for observation. Based on the National Institutes of Health Stroke Scale (NIHSS) in the United States, patients were categorized into two groups: END (n = 69) and non-END (n = 151). Basic demographics, medical history, and biochemical test results of both groups were compared. Influencing factors were identified using the least absolute shrinkage and selection operator (LASSO) method, and these variables were included in a multivariate logistic regression analysis to construct a nomogram for predicting END in IS patients. Model performance was evaluated using internal validation with the Bootstrap method, assessing discrimination, calibration, and clinical validity. Results: Factors such as history of diabetes, fasting plasma glucose (FBG), triglyceride (TG), homocysteine (Hcy), and C-reactive protein (CRP) were identified as single factors for early functional deterioration in IS patients (P<0.05). A logistic regression model was established with END as the dependent variable and significant single factors (P<0.05) as independent variables. The results indicated that diabetes history (OR = 1.398, P = 0.301), TG (OR = 6.149, P<0.05), ASPECT score (OR = 7.641, P<0.05), FBG (OR = 2.172, P<0.05), CRP (OR = 1.706, P<0.05), NIHSS score 7 days post-admission (OR = 1.336, P<0.05), and Hcy (OR=1.425, P<0.05) were independent risk factors for END in IS patients (P<0.05). ROC analysis showed an ASPECT area under the curve of 0.910 (95% CI:0.864 to 0.944), with 84.06% sensitivity and 86.09% specificity. Hcy had an area under the curve of 0.808 (95% CI:0.750 to 0.858), with 79.71% sensitivity and 70.20% specificity. FBG had an area under the curve of 0.847 (95% CI:0.793 to 0.892), with 69.57% sensitivity and 95.36% specificity. TG had an area under the curve of 0.937 (95% CI: 0.896 - 0.965), with 91.30% sensitivity and 82.78% specificity. NIHSS had an area under the curve of 0.857 (95% CI: 0.803-0.900), with 89.86% sensitivity and 70.20% specificity. A nomogram model for END risk prediction was constructed based on the logistic regression analysis results, assigning preliminary scores for each of the 9 predictive factors. The total score, ranging from 0-100 points, was used to predict END risk in patients (0-100%).The constructed nomogram model showed that ASPECT was 59.2, Hcy was 84.0, FBG was 61.4, TG≧7.0 mmol/L was 39.4 and NIHSS was 98.1 with a total score of 345.7 which predicted the risk of END at 68.9%. Conclusion: ASPECT, Hcy, FBG, TG and NIHSS are independent influencing factors of END after IS. On this basis, a visual predictive nomogram model is constructed to accurately predict the risk of END in patients.

References

References
Akella A, Bhattarai S, Dharap A. Long Noncoding RNAs in the Pathophysiology of Ischemic Stroke. Neuromolecular Med. 2019,21(4):474-483. doi: 10.1007/s12017-019-08542-w.
An H, Zhou B, Ji X. Mitochondrial quality control in acute ischemic stroke. J Cereb Blood Flow Metab. 2021,41(12):3157-3170. doi: 10.1177/0271678X211046992. Epub 2021 Sep 22.
Carandina A, Lazzeri G, Villa D, Di Fonzo A, Bonato S, Montano N, Tobaldini E. Targeting the Autonomic Nervous System for Risk Stratification, Outcome Prediction and Neuromodulation in Ischemic Stroke. Int J Mol Sci. 2021,22(5):2357. doi: 10.3390/ijms22052357.
Chojnowski K, Opielka M, Nazar W, Kowianski P, Smolenski RT. Neuroprotective Effects of Guanosine in Ischemic Stroke-Small Steps towards Effective Therapy. Int J Mol Sci. 2021,22(13):6898. doi: 10.3390/ijms22136898.
Currò CT, Cotroneo M, Ciacciarelli A, Dell'Aera C, Grillo F, La Spina P, Fazio MC, Laganà A, De Caro J, Trimarchi G, Toscano A, Musolino RF, Casella C. Ischemic Stroke and Asymptomatic Pulmonary Opacities. J Stroke Cerebrovasc Dis. 2022,31(2):106230. doi: 10.1016/j.jstrokecerebrovasdis.2021.106230.
De Oliveira EP, Fiebach JB, Vagal A, Schaefer PW, Aviv RI. Controversies in Imaging of Patients With Acute Ischemic Stroke: AJR Expert Panel Narrative Review. AJR Am J Roentgenol. 2021,217(5):1027-1037. doi: 10.2214/AJR.21.25846.
DeLong JH, Ohashi SN, O'Connor KC, Sansing LH. Inflammatory Responses After Ischemic Stroke. Semin Immunopathol. 2022,44(5):625-648. doi: 10.1007/s00281-022-00943-7.
Ebinger M, Siegerink B, Kunz A, Wendt M, Weber JE, Schwabauer E, Geisler F, Freitag E, Lange J, Behrens J, Erdur H, Ganeshan R, Liman T, Scheitz JF, Schlemm L, Harmel P, Zieschang K, Lorenz-Meyer I, Napierkowski I, Waldschmidt C, Nolte CH, Grittner U, Wiener E, Bohner G, Nabavi DG, Schmehl I, Ekkernkamp A, Jungehulsing GJ, Mackert BM, Hartmann A, Rohmann JL, Endres M, Audebert HJ; Berlin_PRehospital Or Usual Delivery in stroke care (B_PROUD) study group. Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin. JAMA. 2021,325(5):454-466. doi: 10.1001/jama.2020.26345. Erratum in: JAMA. 2021 Apr 6;325(13):1335.
Ekkert A, Šliachtenko A, Grigaitė J, Burnytė B, Utkus A, Jatužis D. Ischemic Stroke Genetics: What Is New and How to Apply It in Clinical Practice? Genes (Basel). 2021,13(1):48. doi: 10.3390/genes13010048.
Farina M, Vieira LE, Buttari B, Profumo E, Saso L. The Nrf2 Pathway in Ischemic Stroke: A Review. Molecules. 2021,26(16):5001. doi: 10.3390/molecules26165001.
Feske SK. Ischemic Stroke. Am J Med. 2021,134(12):1457-1464. doi: 10.1016/j.amjmed.2021.07.027.
Garcia-Cazares R, Merlos-Benitez M, Marquez-Romero JM. Role of the physical examination in the determination of etiology of ischemic stroke. Neurol India. 2020,68(2):282-287. doi: 10.4103/0028-3886.284386.
Grassl N, Baumann S, Kruska M, Fatar M, Akin I, Platten M, Borggrefe M, Alonso A, Szabo K, Fastner C. Akuter ischämischer Schlaganfall und Troponinerhöhung: Diagnostische Abklärung und therapeutische Konsequenzen [Acute ischemic stroke and elevated troponin: Diagnostic work-up and therapeutic consequences]. Dtsch Med Wochenschr. 2021,146(8):534-541. German. doi: 10.1055/a-1308-7490.
Green TL, McNair ND, Hinkle JL, Middleton S, Miller ET, Perrin S, Power M, Southerland AM, Summers DV; American Heart Association Stroke Nursing Committee of the Council on Cardiovascular and Stroke Nursing and the Stroke Council. Care of the Patient With Acute Ischemic Stroke (Posthyperacute and Prehospital Discharge): Update to 2009 Comprehensive Nursing Care Scientific Statement: A Scientific Statement From the American Heart Association. Stroke. 2021,52(5):e179-e197. doi: 10.1161/STR.0000000000000357.
Greenberg K, Bykowski J. Modern Neuroimaging Techniques in Diagnosing Transient Ischemic Attack and Acute Ischemic Stroke. Emerg Med Clin North Am. 2021,39(1):29-46. doi: 10.1016/j.emc.2020.09.002.
Gruenbaum SE, Gruenbaum BF, Bertasi RAO, Bertasi TGO, Zlotnik A. Intraoperative management of thrombectomy for acute ischemic stroke: Do we need general anesthesia? Best Pract Res Clin Anaesthesiol. 2021,35(2):171-179. doi: 10.1016/j.bpa.2020.10.003.
Herpich F, Rincon F. Management of Acute Ischemic Stroke. Crit Care Med. 2020,48(11):1654-1663. doi: 10.1097/CCM.0000000000004597.
Heydari E, Alishahi M, Ghaedrahmati F, Winlow W, Khoshnam SE, Anbiyaiee A. The role of non-coding RNAs in neuroprotection and angiogenesis following ischemic stroke. Metab Brain Dis. 2020,35(1):31-43. doi: 10.1007/s11011-019-00485-2.
Jolugbo P, Ariëns RAS. Thrombus Composition and Efficacy of Thrombolysis and Thrombectomy in Acute Ischemic Stroke. Stroke. 2021,52(3):1131-1142. doi: 10.1161/STROKEAHA.120.032810.
Kamal FZ, Lefter R, Jaber H, Balmus IM, Ciobica A, Iordache AC. The Role of Potential Oxidative Biomarkers in the Prognosis of Acute Ischemic Stroke and the Exploration of Antioxidants as Possible Preventive and Treatment Options. Int J Mol Sci. 2023,24(7):6389. doi: 10.3390/ijms24076389.
Karaszewski B, Jabłoński B, Żukowicz W. The salvageable brain in acute ischemic stroke. The concept of a reverse mismatch: a mini-review. Metab Brain Dis. 2020,35(2):237-240. doi: 10.1007/s11011-019-00517-x.
Ladak AA, Sandhu S, Itrat A. Use of Intravenous Thrombolysis in Acute Ischemic Stroke Management in Patients with Active Malignancies: A Topical Review. J Stroke Cerebrovasc Dis. 2021,30(6):105728. doi: 10.1016/j.jstrokecerebrovasdis.2021.105728.
Lapergue B, Blanc R, Costalat V, Desal H, Saleme S, Spelle L, Marnat G, Shotar E, Eugene F, Mazighi M, Houdart E, Consoli A, Rodesch G, Bourcier R, Bracard S, Duhamel A, Ben Maacha M, Lopez D, Renaud N, Labreuche J, Gory B, Piotin M; ASTER2 Trial Investigators. Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER2 Randomized Clinical Trial. JAMA. 2021,326(12):1158-1169. doi: 10.1001/jama.2021.13827.
Matsuzono K, Mashiko T, Ozawa T, Miura K, Suzuki M, Furuya K, Ozawa M, Anan Y, Shimazaki H, Koide R, Tanaka R, Kameda T, Fujimoto S. Characteristics of aged ischemic stroke patients indicative of cardioembolism. J Thromb Thrombolysis. 2021,51(2):522-529. doi: 10.1007/s11239-020-02198-1.
Miao Z, Schultzberg M, Wang X, Zhao Y. Role of polyunsaturated fatty acids in ischemic stroke - A perspective of specialized pro-resolving mediators. Clin Nutr. 2021,40(5):2974-2987. doi: 10.1016/j.clnu.2020.12.037.
Montellano FA, Ungethüm K, Ramiro L, Nacu A, Hellwig S, Fluri F, Whiteley WN, Bustamante A, Montaner J, Heuschmann PU. Role of Blood-Based Biomarkers in Ischemic Stroke Prognosis: A Systematic Review. Stroke. 2021,52(2):543-551. doi: 10.1161/STROKEAHA.120.029232.
Ohara T, Farhoudi M, Bang OY, Koga M, Demchuk AM. The emerging value of serum D-dimer measurement in the work-up and management of ischemic stroke. Int J Stroke. 2020,15(2):122-131. doi: 10.1177/1747493019876538.
Onose G, Anghelescu A, Blendea D, Ciobanu V, Daia C, Firan FC, Oprea M, Spinu A, Popescu C, Ionescu A, Busnatu Ș, Munteanu C. Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke. Int J Mol Sci. 2022,23(2):907. doi: 10.3390/ijms23020907.
Pan J, Wang Z, Huang X, Xue J, Zhang S, Guo X, Zhou S. Bacteria-Derived Outer-Membrane Vesicles Hitchhike Neutrophils to Enhance Ischemic Stroke Therapy. Adv Mater. 2023,35(38):e2301779. doi: 10.1002/adma.202301779.
Parvez S, Kaushik M, Ali M, Alam MM, Ali J, Tabassum H, Kaushik P. Dodging blood brain barrier with "nano" warriors: Novel strategy against ischemic stroke. Theranostics. 2022,12(2):689-719. doi: 10.7150/thno.64806.
Patabendige A, Singh A, Jenkins S, Sen J, Chen R. Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke. Int J Mol Sci. 2021,22(8):4280. doi: 10.3390/ijms22084280.
Putaala J. Ischemic Stroke in Young Adults. Continuum (Minneap Minn). 2020,26(2):386-414. doi: 10.1212/CON.0000000000000833.
Rabinstein AA. Update on Treatment of Acute Ischemic Stroke. Continuum (Minneap Minn). 2020,26(2):268-286. doi: 10.1212/CON.0000000000000840.
Sato T, Sakai K, Nakada R, ShirIShi T, Tanabe M, Komatsu T, Sakuta K, Terasawa Y, Umehara T, Omoto S, Mitsumura H, Murakami H, Matsushima M, Iguchi Y. Employment Status Prior to Ischemic Stroke and Weekly Variation of Stroke Onset. J Stroke Cerebrovasc Dis. 2021,30(8):105873. doi: 10.1016/j.jstrokecerebrovasdis.2021.105873.
Schnabel RB, Camen S, Knebel F, Hagendorff A, Bavendiek U, Böhm M, Doehner W, Endres M, Gröschel K, Goette A, Huttner HB, Jensen C, Kirchhof P, Korosoglou G, Laufs U, Liman J, Morbach C, Nabavi DG, Neumann-Haefelin T, Pfeilschifter W, Poli S, Rizos T, Rolf A, Röther J, Schäbitz WR, Steiner T, Thomalla G, Wachter R, Haeusler KG. Expert opinion paper on cardiac imaging after ischemic stroke. Clin Res Cardiol. 2021,110(7):938-958. doi: 10.1007/s00392-021-01834-x. Epub 2021 Jun 18.
Shi GS, Qin QL, Huang C, Li ZR, Wang ZH, Wang YY, He XY, Zhao XM. The Pathological Mechanism of Neuronal Autophagy-Lysosome Dysfunction After Ischemic Stroke. Cell Mol Neurobiol. 2023,43(7):3251-3263. doi: 10.1007/s10571-023-01382-0.
Singer DE, Ziegler PD, Koehler JL, Sarkar S, Passman RS. Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke. JAMA Cardiol. 2021,6(12):1364-1369. doi: 10.1001/jamacardio.2021.3702.
Steliga A, Kowiański P, Czuba E, Waśkow M, Moryś J, Lietzau G. Neurovascular Unit as a Source of Ischemic Stroke Biomarkers-Limitations of Experimental Studies and Perspectives for Clinical Application. Transl Stroke Res. 2020,11(4):553-579. doi: 10.1007/s12975-019-00744-5. Epub 2019 Nov 7.
Sun LR, Lynch JK. Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke. Neurotherapeutics. 2023,20(3):633-654. doi: 10.1007/s13311-023-01373-5.
Szczuko M, Kozioł I, Kotlęga D, Brodowski J, Drozd A. The Role of Thromboxane in the Course and Treatment of Ischemic Stroke: Review. Int J Mol Sci. 2021,22(21):11644. doi: 10.3390/ijms222111644.
Václavík D, Volný O, Cimflová P, Švub K, Dvorníková K, Bar M. The importance of CT perfusion for diagnosis and treatment of ischemic stroke in anterior circulation. J Integr Neurosci. 2022,21(3):92. doi: 10.31083/j.jin2103092.
Vasudeva K, Dutta A, Munshi A. Role of lncRNAs in the Development of Ischemic Stroke and Their Therapeutic Potential. Mol Neurobiol. 2021,58(8):3712-3728. doi: 10.1007/s12035-021-02359-0.
Xu G, Liu G, Wang Z, Li Y, Fang W. Circular RNAs: Promising Treatment Targets and Biomarkers of Ischemic Stroke. Int J Mol Sci. 2023,25(1):178. doi: 10.3390/ijms25010178.
Yi Y, Liu Z, Wang M, Sun M, Jiang X, Ma C, Xie F, Ma X. Penumbra in Acute Ischemic Stroke. Curr Neurovasc Res. 2021;18(5):572-585. doi: 10.2174/1567202619666211231094046.
Yu JM, Chen WM, Shia BC, Wu SY. Protective Effects of Different Classes, Intensity, Cumulative Dose-Dependent of Statins Against Primary Ischemic Stroke in Patients with Type 2 Diabetes Mellitus. Curr Atheroscler Rep. 2023,25(9):619-628. doi: 10.1007/s11883-023-01135-w.
Zhao J, Wang Q, Zhu R, Yang J. Circulating Non-coding RNAs as Potential Biomarkers for Ischemic Stroke: A Systematic Review. J Mol Neurosci. 2022,72(8):1572-1585. doi: 10.1007/s12031-022-01991-2.
Zheng K, Lin L, Jiang W, Chen L, Zhang X, Zhang Q, Ren Y, Hao J. Single-cell RNA-seq reveals the transcriptional landscape in ischemic stroke. J Cereb Blood Flow Metab. 2022,42(1):56-73. doi: 10.1177/0271678X211026770. Epub 2021 Sep 9.
Published
2024/10/03
Section
Original paper