The relationship between inflammatory markers and prognosis in patients with ruptured aneurysms treated by endovascular intervention

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Korean J Cerebrovasc Surg. 2025;.jcen.2025.E2024.12.002

Publication date (electronic) : 2025 April 8

doi : https://doi.org/10.7461/jcen.2025.E2024.12.002

Necati Ucler, Sedat Yasin

Department of Neurosurgery, Gaziantep University, Faculty of Medicine, Gaziantep, Turkiye

Correspondence to Necati Ucler Department of Neurosurgery, Gaziantep University, Sahinbey Education and Research Hospital, 27310, Gaziantep, Turkiye Tel +90 (0342) 360 60 60 Fax +90 (0342) 216 10 15 E-mail necati_ucler@yahoo.com

Received 2024 December 16; Revised 2025 January 19; Accepted 2025 February 23.

Abstract

INTRODUCTION

Endovascular treatment has become a popular method for managing cerebral aneurysms [7,13]. However, the clinical consequences of this method, particularly in the context of aneurysmal subarachnoid hemorrhage (aSAH), are still under investigation. According to growing evidence, inflammation plays a critical role in the pathophysiology of cerebral aneurysms, as well as the development of catastrophic consequences such as vasospasm and delayed cerebral ischemia that can occur after aneurysm rupture.

This leads to a complicated cascade of inflammatory events, including the production of cytokines, chemokines, and other inflammatory mediators.5) These inflammatory indicators have been linked to the development of cerebral vasospasm, a strong vasoconstrictor response that can impair cerebral perfusion and result in delayed cerebral ischemia [9,13].

The breakdown of red blood cells following a hemorrhage can exacerbate the inflammatory reaction, leading to an extended cycle of injury and tissue harm [9]. Several studies have investigated the relevance of inflammatory indicators in predicting outcomes following endovascular treatment for aneurysmal subarachnoid hemorrhage [3,11,14]. High levels of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha have been associated to an increased risk of vasospasm, delayed cerebral ischemia, and poor neurological outcomes [16]. The severity and duration of the inflammatory response are important variables in predicting prognosis, with a more severe and prolonged inflammatory state associated with poorer clinical outcomes [3,4,18,19].

The purpose of this study is to determine the possible role of inflammatory markers in predicting the prognosis of bleeding aneurysms treated using endovascular methods.

MATERIAL AND METHODS

As a result of retrospective evaluation of medical records, 223 consecutive patients who received endovascular subarachnoid hemorrhage (SAH) treatment after anterior communicating (Acom) artery aneurysm rupture between 2019 and 2022 were included in the study (Fig. 1). All patients admitted with aSAH within 24 hours of symptom onset and treated in the intensive care unit, as well as those who had their ruptured aneurysm treated endovascularly within 72 hours of symptom onset, were included.

Fig. 1.

Flow diagram of patient selection with ruptured the Anterior communicating artery aneurysms. SAH, subarachnoid hemorrhage; EVT, endovascular thrombectomy; mRS, modified Rankin Scale

The study included patients with World Federation of Neurological Surgeons (WFNS) scores of 1-3, Fisher scores of 1-3, Huntt-Hess scores of 1-3, and Glasgow coma scale (GCS) scores of 13-15 at the time of admission, as well as those with modified Rankin Scale (mRS) values of 0-2 and 3-6. Patients who did not match the required criteria and scores were excluded from the study.

In this study, the levels of white blood cells (WBC), neutrophils, lymphocytes, C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), and CRP/lymphocyte ratio (CLR) were retrospectively analyzed based on the mRS (Modified Rankin Scale) values of patients classified into groups.

The patients with ruptured Acom artery aneurysms were divided into two groups: Group 1 (57 patients, 71.2%) on a scale of 0-2 according to mRS, and Group 2 (23 patients, 28.8%) on a scale of 3-6 according to mRS. The study included mRS obtained 30 days after the endovascular procedure (Fig. 2).

Fig. 2.

It shows the distribution of the patients’ modified Rankin Scale values during the first month across the two groups: Group 1 and Group 2.

The preoperative NLR and CLR levels were calculated by dividing the absolute neutrophil count and CRP by the absolute lymphocyte count from the same preoperative complete blood count (CBC) sample. A review of the medical records revealed demographic information, comorbidities, interventional data, and follow-up details (Table 1).

Table 1.

The Groups’ characteristics and features

We excluded patients who reported any symptoms considered to be connected to an earlier bleeding more than 24 hours before admission, as well as those who died within 7 days of being admitted and patients with ruptured aneurysms at other locations. Furthermore, individuals who were diagnosed with thromboembolic complications, disseminated intravascular coagulation, sepsis, or another confirmed symptomatic bacterial infection during the admission were removed, leaving 80 patients eligible for the study.

RESULTS

A total of 223 individuals were assessed for the study. After removing patients who underwent microsurgery following endovascular treatment, patients who underwent diagnostic angiography, or patients who required additional surgery, 80 patients (mean age 51.62 years ±13.21, range 31-68 years) were eligible for the study (Table 1). The female-to-male ratio (F/M) was 1.58 (49F–31E). The mean age and gender distribution of the groups were not statistically significant (p=0.1) (Table 1).

WBC: The p-value of 0.006 suggests that Group 2 has a significantly greater amount of WBC than Group 1. This indicates that the difference in WBC counts between the two groups is unlikely to be due to chance (Table 2).

Table 2.

Statistical comparison of biochemical markers between the two Groups

Neutrophils: Group 2 has considerably greater neutrophil counts (p=0.010). This suggests a significant difference in neutrophil counts across the groups, which could indicate a higher inflammatory response or infection in Group 2 (Table 2).

Lymphocytes: A p-value of 0.019 indicates a significant difference in lymphocyte numbers, with Group 2 showing greater counts. This could indicate differences in immunological response or stress levels between the groups (Table 2).

CRP: A p-value of 0.015 indicates that CRP levels are considerably higher in Group 2, indicating increased inflammation or infection (Table 2).

NLR: A p-value of 0.030 indicates a statistically significant difference in NLR, with Group 2 having a greater ratio. This is frequently used as a measure for systemic inflammation and stress (Table 2).

CLR: CLR levels are considerably greater in Group 2 (p-value=0.010), indicating enhanced inflammatory activity (Table 2).

According to the mRS results after one month, the values of WBC, neutrophil, lymphocyte, CRP, NLR, and CLR levels at the first hospital admission were all statistically significant.

The aneurysm diameter was bigger in Group 1, although the difference was not statistically significant (p=0.135) (Table 1). Multiple aneurysms were more likely in Group 1, with a statistically significant difference (p=0.011). There was no significant correlation between narrowneck and wide-neck characteristics (p=0.214).

WFNS, Fisher scores, Huntt-Hess scores, and GCS did not differ significantly between the groups (Table 1). When comorbidities such as drinking, smoking, diabetes, hypertension, and coronary artery disease (CAD) were evaluated, there was no statistically significant difference (Table 3).

Table 3.

Comparison of diseases such as alcohol, smoking, DM, HT, and CAD among the Groups

DISCUSSION

It was determined that patients with high levels of WBC, neutrophil, lymphocyte, CRP, NLR, and CLR at the time of hospital admission had higher risk of developing more severe neurological sequelae in the future, despite getting equal therapy. Other studies have shown that elevated inflammatory markers have a negative impact on treatment outcomes [1,20]. Our study findings may be useful in cases such as subarachnoid hemorrhage, which has a high morbidity and mortality and requires us to take safeguards by forecasting the patient’s advancement.

Patients in our study were chosen retrospectively in a highly selective manner (only ruptured Acom artery aneurysms). The mRS was used to assess functional recovery. The impact of six inflammatory markers (WBC, neutrophil, lymphocyte, CRP, NLR, and CLR) on the functional outcomes of patients with similar WFNS, Fisher scores, Hunt-Hess scores, and GCS scores were demonstrated, with no statistically significant differences. As a result, numerous confounders were excluded, allowing for a more accurate assessment of the impact of inflammatory markers on functional results.

These inflammatories are linked to rebleeding, vasospasm, and bleeding volume, all of which are thought to have a direct impact on the prognosis of SAH [6]. The unruptured aneurysm is monitored using radiological imaging. High-resolution magnetic resonance imaging can detect severe inflammation prior to aneurysm rüptüre [15]. Neutrophils, lymphocytes, as well as other cytokines and inflammatory mediators, have been shown to be beneficial in phenotypic modification of vascular smooth muscle cells [1,17]. When all of these parameters are considered, an increase in the number of severe inflammatory agents may enhance the aneurysm wall’s potential to rebleed following SAH, impacting mortality and morbidity. In this regard, the significance of inflammatory indicators may grow in the follow-up of patients who have not bled.

Clinical examination using digital subtraction angiography and transcranial Doppler is critical in determining cerebral vasospasm following SAH. Unfortunately, no widely accepted objective evaluation of the degree of vasospasm development could be established other than the Fisher scale [6]. Vasospasm may occur in bacterial meningitis, malaria, traumatic brain injury, or SAH. Vasospasm causes narrowed arterial and arteriolar diameters, which impede brain perfusion and worsen the prognosis. In this regard, there may be an association between inflammation and vasospasm. As a result, inflammatory agents have been investigated. However, the conflicting findings of anti-inflammatory, statin, endothelin receptor antagonist, and calcium channel blocker treatments in vasospasm do not substantially support the inflammation-vasospasm relationship [10]. However, the insufficiency of these treatments in vasospasm does not imply the absence of this link, but rather that the treatment used may be insufficient. For years, clinicians have used the Fisher score to assess vasospasm. Blood moving out of the vascular region following SAH is hypothesized to promote vasospasm via inflammatory mediators [12]. Studies reveal that neuro-inflammation markers are associated with brain injury formation and degradation of neural function. Unfortunately, its clinical application has not been established [2]. Following aneurysm bleeding, erythrocyte breakdown products spread to the subarachnoid area, and chemicals that cause brain injury frequently reach all sections of the central nervous system (CNS) via cerebrospinal fluid (CSF) [1]. With its dissemination, the inflammatory initiator-progressive and completing molecules in the blood that cause brain injury begin the process of contacting the CSF, arachnoid, and vascular structures, which can lead to early-mid-long-term effects. Neuroinflammation is caused by microglia, toll-like receptor 4, proinflammatory chemokines and cytokines (e.g. interleukin-6, interleukin-1β) [20], tumor necrosis factor-alpha, nitric oxide NO, cell adhesion molecules, endothelial cell luminal surface, and recruitment of macrophages and neutrophils [2,8,20].

WBC, neutrophils, lymphocytes, CRP, NLR, and CLR are valuable and promising markers for discriminating between aSAH and SAH from other causes [21]. Neuroinflammation may play an important role in vasospasm, rebleeding, and the formation, weakening, and rupture of cerebral aneurysms [8,22]. The concept that the NLR can be employed as an early warning index following an aneurysm rupture warrants further investigation into the biology of aneurysm development and neuroinflammation.

CONCLUSIONS

Our study looked at the impact of WBC, neutrophils, lymphocytes, CRP, NLR, and CLR inflammatory markers on the prognosis of patients with intracerebral aneurysmal hemorrhage who were treated endovascularly. It is critical for treatment planning to assess the association between endovascular treatment and the prognosis of these patients using inflammatory markers, as well as to anticipate the patients’ prognosis from this perspective. Our findings revealed that these parameters coincided in predicting the severity of the neurological picture.

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