Inflammatory biomarkers are correlated with thrombus burden in cerebral venous sinus thrombosis

Abstract

Background Increasing evidence suggests that inflammatory biomarkers play a significant role in cerebral venous sinus thrombosis (CVST). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are related to thrombotic conditions and indicators of systemic inflammation.

Objective To analyze the correlation between inflammatory biomarkers and the extent of thrombus, determined by the CVST-Score.

Methods A total of 40 patients with CVST (24 female subjects; 60%) and 40 age- and sex-matched healthy controls were retrospectively evaluated. Inflammatory biomarkers, including C-reactive protein (CRP), PLR, NLR, MLR, and the CVST-Score, were recorded to assess the relationship between biomarkers and thrombus burden. The patients were grouped according to symptom duration (group 1: 0–3 days; group 2: 4–7 days; and group 3: 8–30 days) to compare biomarker levels.

Results The CRP, NLR, and PLR were significantly higher in the CVST group (p < 0.001; p = 0.003; p = 0.014 respectively). The NLR and PLR presented a significant positive correlation with the CVST-Score (p = 0.003, r = 0.464; p = 0.040, r = 0.326 respectively). The NLR was significantly higher in group 1 compared with groups 2 and 3 (p = 0.016 and p = 0.014 respectively). In group 1, there was a stronger positive correlation between the CVST-Score and the NLR (p = 0.026, r = 0.591) and the PLR (p = 0.012, r = 0.648). The multiple linear regression analysis revealed that the NLR is a key factor in predicting the CVST-Score (p = 0.019).

Conclusion The NLR and PLR are associated with thrombus burden in CVST, especially in patients admitted to the hospital in the early stages. The NLR is an independent factor to predict the thrombus burden in CVST.

Resumo

Antecedentes Há evidências crescentes de que biomarcadores inflamatórios desempenham um papel importante na trombose venosa cerebral (TVC). A razão neutrófilo-linfócito (NLR), a razão plaqueta-linfócito (PLR) e a razão monócito-linfócito (MLR) estão relacionadas a condições trombóticas e são indicadores de inflamação sistêmica.

Objetivo Analisar a correlação entre NLR, PLR, MLR e a extensão do trombo, determinada pelo escore de TVC.

Métodos Avaliamos retrospectivamente 40 pacientes com TVC (24 mulheres; 60%) e 40 controles pareados por idade e sexo. Biomarcadores inflamatórios, incluindo proteína C reativa (PCR), PLR, NLR, MLR e escore de TVC, foram registrados para avaliar a relação entre biomarcadores e carga trombótica. Os pacientes foram agrupados de acordo com a duração dos sintomas (grupo 1: 0–3 dias; grupo 2: 4–7 dias; e grupo 3: 8–30 dias) para a comparação dos níveis de biomarcadores.

Resultados A PCR, a NLR e a PLR foram significativamente maiores no grupo com TVC (p < 0,001; p = 0,003; e p = 0,014, respectivamente). A NLR e a PLR apresentaram correlação positiva significativa com o escore de TVC (p = 0,003, r = 0,464; e p = 0,040, r = 0,326, respectivamente). A NLR foi significativamente maior no grupo 1 em comparação aos grupos 2 e 3 (p = 0,016 e p = 0,014, respectivamente). No grupo 1, houve correlação mais forte entre o escore de TVC e a NLR (p = 0,026, r = 0,591) e a PLR (p = 0,012, r = 0,648). A análise de regressão linear múltipla identificou a NLR como fator-chave na predição do escore de TVC (p = 0,019).

Conclusão A NLR e a PLR estão associadas à carga trombótica na TVC, especialmente em pacientes admitidos precocemente, e a RNL é um fator independente na previsão da carga trombótica.

Keywords

Sinus Thrombosis, Intracranial - Biomarkers - Inflammation

Palavras-chave

Trombose dos Seios Intracranianos - Biomarcadores - Inflamação

Authors' Contributions

AYK, TA: conceptualization and design of the work, writing the manuscript; AVK, VG: data acquisition; AYT: analysis; SB: measurements on the imaging. All authors approved the final version of the manuscript and are responsible for all aspects of the work.

Publikationsverlauf

Eingereicht: 06. September 2023

Angenommen: 04. April 2024

Artikel online veröffentlicht:
29. Mai 2024

• References

• 1 Ding J, Song B, Xie X. et al. Inflammation in Cerebral Venous Thrombosis. Front Immunol 2022; 13: 833490
• 2 Kalita J, Singh VK, Jain N, Misra UK, Kumar S. Cerebral Venous Sinus Thrombosis Score and its Correlation with Clinical and MRI Findings. J Stroke Cerebrovasc Dis 2019; 28 (11) 104324
• 3 Wu Z, Xie Y, Xiong S. et al. The Venous Occlusion Image Score: A Novel Quantitative Scoring Instrument for Cerebral Venous Sinus Thrombosis. J Stroke Cerebrovasc Dis 2021; 30 (07) 105845
• 4 Zhang X, Ding R, Li H. et al. An Association between Inflammation and Cerebral Venous Thrombosis: A Retrospective Study. J Stroke Cerebrovasc Dis 2021; 30 (11) 106084
• 5 Gu J-J, Chen J-B, Zhang J-H, Zhang H, Wang SS. Recombinant human soluble thrombomodulin protects against brain injury in a CVST rat model, via downregulation of the HMGB1-RAGE axis. Mol Med Rep 2016; 14 (06) 5217-5222
• 6 Kimura R, Nakase H, Sakaki T, Taoka T, Tsuji T. Vasogenic edema and VEGF expression in a rat two-vein occlusion model. Acta Neurochir Suppl (Wien) 2003; 86: 213-217
• 7 Dias L, Pinto MJ, Castro P, Carvalho M. Inflammatory Biomarkers Correlate with Time Evolution in Cerebral Venous Thrombosis. J Stroke Cerebrovasc Dis 2021; 30 (07) 105844
• 8 Karahan SZ, Gazioglu S, Dilaver I, Boz C. The Role of Thrombo-inflammatory Biomarkers in the Prognosis of Cerebral Venous Sinus Thrombosis. Curr Neurovasc Res 2021; 18 (02) 237-243
• 9 Tekesin A, Tunç A. Inflammatory markers are beneficial in the early stages of cerebral venous thrombosis. Arq Neuropsiquiatr 2019; 77 (02) 101-105
• 10 Han J-B, Shu Q-H, Zhang Y-F, Yi YX. Predictive Value of Inflammation Biomarkers in Patients with Portal Vein Thrombosis. J Clin Transl Hepatol 2021; 9 (03) 384-391
• 11 Liu D, Zhu Y, Chen W. et al. Relationship between the inflammation/immune indexes and deep venous thrombosis (DVT) incidence rate following tibial plateau fractures. J Orthop Surg Res 2020; 15 (01) 241
• 12 Melinte RM, Arbănași EM, Blesneac A. et al. Inflammatory Biomarkers as Prognostic Factors of Acute Deep Vein Thrombosis Following the Total Knee Arthroplasty. Medicina (Kaunas) 2022; 58 (10) 1502
• 13 Li S, Liu K, Zhang R. et al. Lower lymphocyte to monocyte ratio is a potential predictor of poor outcome in patients with cerebral venous sinus thrombosis. Stroke Vasc Neurol 2018; 4 (03) 148-153
• 14 Glik A, Benkovich E, Kesler A, Ifergan G, Benifla M, Shelef I. Lateral Sinus Thrombosis: The Importance of the Unaffected Sinus. J Neuroimaging 2016; 26 (06) 599-604
• 15 Miranda B, Ferro JM, Canhão P. et al; ISCVT Investigators. Venous thromboembolic events after cerebral vein thrombosis. Stroke 2010; 41 (09) 1901-1906
• 16 Zubkov AY, McBane RD, Brown RD, Rabinstein AA. Brain lesions in cerebral venous sinus thrombosis. Stroke 2009; 40 (04) 1509-1511
• 17 Wang Z, Dandu C, Guo Y. et al. A novel score to estimate thrombus burden and predict intracranial hypertension in cerebral venous sinus thrombosis. J Headache Pain 2023; 24 (01) 29
• 18 Rust R, Hofer A-S, Schwab ME. Stroke Promotes Systemic Endothelial Inflammation and Atherosclerosis. Trends Mol Med 2018; 24 (07) 593-595
• 19 Kleinig TJ, Vink R. Suppression of inflammation in ischemic and hemorrhagic stroke: therapeutic options. Curr Opin Neurol 2009; 22 (03) 294-301
• 20 Levi M, van der Poll T, Büller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109 (22) 2698-2704
• 21 Xu J-H, He X-W, Li Q. et al. Higher Platelet-to-Lymphocyte Ratio Is Associated With Worse Outcomes After Intravenous Thrombolysis in Acute Ischaemic Stroke. Front Neurol 2019; 10: 1192
• 22 Li W, Hou M, Ding Z, Liu X, Shao Y, Li X. Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Stroke: A Systematic Review and Meta-Analysis. Front Neurol 2021; 12: 686983
• 23 Zhang J, Ren Q, Song Y. et al. Prognostic role of neutrophil-lymphocyte ratio in patients with acute ischemic stroke. Medicine (Baltimore) 2017; 96 (45) e8624
• 24 Zhang X-G, Xue J, Yang W-H. et al. Inflammatory markers as independent predictors for stroke outcomes. Brain Behav 2021; 11 (01) e01922
• 25 Juega J, Palacio-Garcia C, Rodriguez M. et al; ITACAT study group. Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology. Transl Stroke Res 2022; 13 (06) 949-958
• 26 Branchford BR, Carpenter SL. The Role of Inflammation in Venous Thromboembolism. Front Pediatr 2018; 6: 142
• 27 von Brühl M-L, Stark K, Steinhart A. et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209 (04) 819-835
• 28 Hu S, Lee H, Zhao H, Ding Y, Duan J. Inflammation and Severe Cerebral Venous Thrombosis. Front Neurol 2022; 13: 873802
• 29 Ferro JM, Bendszus M, Jansen O. et al; RE-SPECT CVT Study Group. Recanalization after cerebral venous thrombosis. A randomized controlled trial of the safety and efficacy of dabigatran etexilate versus dose-adjusted warfarin in patients with cerebral venous and dural sinus thrombosis. Int J Stroke 2022; 17 (02) 189-197
• 30 Altıokka-Uzun G, Tüzün E, Ekizoğlu E. et al. Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension. Cephalalgia 2015; 35 (13) 1153-1161
• 31 Dhungana S, Sharrack B, Woodroofe N. Cytokines and chemokines in idiopathic intracranial hypertension. Headache 2009; 49 (02) 282-285
• 32 Ceylan OM, Yılmaz M, Yilmaz H, Çelikay O, Köylü MT, Turan A. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammation markers in patients with papilledema due to idiopathic intracranial hypertension. Indian J Ophthalmol 2021; 69 (06) 1499-1505
• 33 Lekcharoensombat N, Chanthanaphak E, Boongird A. Urgent mechanical thrombectomy unlocked the devastating acute superior sagittal sinus thrombosis complicated with acute status epilepticus: Case report. Interdiscip Neurosurg 2024; 36: 101926
• 34 Kuplay H, Erdoğan SB, Bastopcu M, Arslanhan G, Baykan DB, Orhan G. The neutrophil-lymphocyte ratio and the platelet-lymphocyte ratio correlate with thrombus burden in deep venous thrombosis. J Vasc Surg Venous Lymphat Disord 2020; 8 (03) 360-364
• 35 Güneş M, Büyükgöl H. Relationship between generalized epileptic seizure and neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and neutrophil mediated inflammation. Int J Neurosci 2020; 130 (11) 1095-1100
• 36 Li H, Yang Y, Hu M. et al. The correlation of temporal changes of neutrophil-lymphocyte ratio with seizure severity and the following seizure tendency in patients with epilepsy. Front Neurol 2022; 13: 964923
• 37 Wang L, Duan J, Bian T. et al. Inflammation is correlated with severity and outcome of cerebral venous thrombosis. J Neuroinflammation 2018; 15 (01) 329