Predictive value of intracranial high-density areas in neurological function

Abstract

BACKGROUND

Intracranial high-density areas (HDAs) have attracted considerable attention for predicting clinical outcomes; however, whether HDAs predict worse neurological function and mental health remains controversial and unclear, which requires further investigation.

AIM

To investigate the predictive value of intracranial HDAs for neurological function and mental health after endovascular treatment.

METHODS

In this prospective study, 96 patients with acute ischemic stroke (AIS) who accepted endovascular mechanical thrombectomy (EMT) were included. The enrolled patients underwent cranial computed tomography (CT) examination within 24 hours after EMT. Clinical data in terms of National Institutes of Health Stroke Scale (NIHSS), the 3-month modified Rankin Scale (mRS), self-rating depression scale (SDS), and self-rating anxiety scale (SAS) scores were collected and compared between patients with HDAs and non-HDAs and between patients with good and poor clinical prognosis.

RESULTS

Compared to patients without HDAs, patients with HDAs presented severe neurological deficits (admission NIHSS score: 18 ± 3 vs 19 ± 4), were more likely to have post-stroke disabilities (mRS < 3: 35% vs 62%), and suffered more severe depression (SDS score: 58 ± 16 vs 64 ± 13) and anxiety disorder (SAS score: 52 ± 8 vs 59 ± 10). Compared to patients with a good prognosis, patients with a poor prognosis presented severe neurological deficits (admission NIHSS score: 17 ± 4 vs 20 ± 3), were more likely to have HDAs on CT images (64% vs 33%), and suffered more severe depression (SDS score: 55 ± 19 vs 65 ± 11) and anxiety (SAS score: 50 ± 8 vs 58 ± 12). Multivariate analysis revealed that HDAs were independent negative prognostic factors.

CONCLUSION

In conclusion, HDAs on CT images predicted poor prognosis and severe depressive and anxiety symptoms in patients with AIS who underwent EMT.

Key Words: Acute ischemic stroke; Endovascular mechanical thrombectomy; High-density areas; Depressive disorder; Anxiety disorder

Core Tip: High-density areas (HDAs) have great potential in predicting clinical outcomes in patients with acute ischemic stroke (AIS). This prospective study focused on the association of intracranial HDAs with neurological function and mental health after endovascular mechanical thrombectomy for AIS. Through comprehensive evaluation of National Institutes of Health Stroke Scale, the 3-month modified Rankin Scale, self-rating depression scale, and self-rating anxiety scale scores, our study demonstrated that intracranial HDAs on computed tomography images predict poor prognosis and severe depressive and anxiety symptoms.

INTRODUCTION

Acute ischemic stroke (AIS), with high morbidity, disability, and mortality rates, has become one of the most common causes of death in China in recent years. The lifetime risk of stroke in China is estimated to be 39.3%, ranking first in the world[1]. Moreover, the highest risk is 41.1% in males and 36.7% in females[1]. Intracranial large-artery occlusion in AIS, especially in the anterior circulation, occurs with a high disability rate and severe complications such as stroke-related pneumonia, bedsores, and even death, ultimately leading to a heavy economic burden on households. Over the past three decades, the age-standardized morbidity and mortality rates of stroke have decreased in China, but the stroke burden remains substantial[2].

Early revascularization is key to the treatment of AIS. Endovascular mechanical thrombectomy (EMT) is a safe and effective method for treating AIS resulting from large-artery occlusions[3]. In clinical practice, intracranial high-density areas (HDAs) are observed in patients who undergo initial (within 24 hours) computed tomography (CT) after EMT, with an incidence of 31.2%-60%[4]. Most HDAs are caused by contrast leakage, and a few are caused by intracerebral hemorrhage or a combination of both[4]. Recent studies have suggested that intracranial HDAs after vascular recanalization may indicate a poor prognosis[5-7]. However, one study showed that the occurrence of HDAs was not related to prognosis[4]. The reasons for the association between HDAs and ineffective recanalization are unknown, but the presence of HDAs may indicate blood–brain barrier injury and dysfunction after reperfusion[8].

Although the occluded artery is recanalized, and blood flow is restored after EMT, not all patients with arterial recanalization have good clinical outcomes. This study aimed to investigate the relationship between the occurrence of intracranial HDAs on CT images and clinical outcomes after EMT in anterior circulation cerebral infarctions.

MATERIALS AND METHODS

Patient selection

A total of 96 patients with acute anterior circulation ischemic stroke who underwent EMT at the Ganzhou People’s Hospital, China, between January 2022 and December 2023 were included. The inclusion criteria were as follows: (1) Patients admitted to the intensive care unit for ≥ 3 days; (2) patients with AIS in the anterior circulation within 24 hours of onset who underwent endovascular intervention; and (3) patients who provided informed consent for participation in the study. The exclusion criteria were as follows: (1) Cerebral infarction caused by other causes, such as vasculitis; (2) age < 14 years; (3) pregnant or lactating females; (4) concurrent multi-site cerebral infarction; (5) patients with intracranial space-occupying lesions; (6) patients with incomplete data collection due to various factors; and (7) patients in other clinical trials or studies.

Procedures and assessments

This prospective cohort study included patients with AIS who required endovascular thrombectomy due to occlusion or stenosis of large arteries in the anterior circulation. All patients underwent cranial CT (Philips Healthcare, Best, The Netherlands/Artis zee ceiling, Siemens Healthcare, Erlangen, Germany) examination within 24 hours after EMT and were subsequently divided into HDA and non-HDA groups. Baseline data, including age, sex, risk factors, and routine stroke scales, including the National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS), were compared between the two groups. The mRS was used to assess clinical prognosis at 3 months, with a good prognosis defined as an mRS score < 3. The self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to assess the severity of depressive and anxiety disorders, respectively, and were compared between the non-HDA and HDA groups. According to the mRS score, patients were divided into the good prognosis group (mRS score 0-3) and the poor prognosis group (mRS score 4-6) at 3 months. The HDA, SDS, and SAS scores were compared between the two groups to determine the role of HDAs in clinical outcomes.

Statistical analysis

This prospective cohort study was a triple-blind study. Continuous variables are presented as mean ± SD. Categorical variables are presented as frequencies and percentages, n (%). Differences in the continuous variables and the categorical variables were examined with student’s t-test and the chi-square or Fisher exact test, respectively. The Wilcoxon rank-sum test was used to compare multiple samples of categorical variables and McNemar’s test was used to compare two paired samples of continuous variables. Multivariate logistic regression analysis was used to determine the correlation between variables and clinical outcomes. Statistical significance was set at P < 0.05. All data were collected using Epidata 3.0, and statistically analyzed using SPSS software (version 13.0).

RESULTS

Patients with or without HDAs on CT images post-EMT

In this study, a triple-blind design was adopted. All patients with acute anterior circulation ischemic stroke underwent cranial CT within 24 hours after EMT. They were divided into non-HDA and HDA groups according to CT image outcomes. Among the 96 patients included in this study, 46 (48%) had non-HDAs (Figure 1A) and 50 (52%) had HDAs on CT images (Figure 1B-D).

Figure 1 Computed tomography images of non-intracranial high-density areas and high-density areas. A: Computed tomography (CT) image post-endovascular mechanical thrombectomy (EMT) shows no high-density areas (HDAs) in a patient with an admission National Institutes of Health Stroke Scale (NIHSS) of 15 and 3 month modified Rankin Scale (mRS) of 0; B: CT image post-EMT shows right basilar ganglia HDA in a patient with an admission NIHSS of 16 and 3 month mRS of 0; C: CT image post-EMT shows right basilar ganglia and cortical HDAs in a patient with an admission NIHSS of 24 and 3 month mRS of 6; D: CT image post-EMT shows left basilar ganglia HDA in a patient with an admission NIHSS of 25 and 3 month mRS of 6.

Patient prognosis in the presence or absence of HDAs

The clinical characteristics of patients in the non-HDA and HDA groups are shown in Table 1. The mRS was used to assess patient prognosis at 3 months. No significant differences were observed in the baseline data between the two groups (P > 0.05). Compared to patients with non-HDAs, those with HDAs presented a higher admission NIHSS score (P = 0.047). Among the 46 patients with non-HDAs, 16 had a poor prognosis, while 31 of 50 patients with HDAs had a poor prognosis (mRS < 3: 35% vs 62%, P = 0.001).

Table 1 Clinical characteristics of patients in the non-high-density areas and high-density areas groups, n (%).

	non-HDAs (n = 46)	HDAs (n = 50)	P value
Age (years, mean)	63 ± 10	67 ± 14	0.683
Gender (male)	25 (54)	26 (52)	0.869
Hypertension	20 (43)	23 (46)	0.453
Hyperlipidemia	5 (11)	7 (14)	0.879
Diabetes mellitus	8 (17)	10 (20)	0.648
Heart disease	24 (52)	27 (54)	0.872
Admission NIHSS score (mean)	18 ± 3	19 ± 4	0.047
mRS score < 3	16(35)	31 (62)	0.001

mRS: Modified Rankin Scale; HDAs: High-density areas; NIHSS: National Institutes of Health Stroke Scale.

HDAs in patients with good or poor prognosis

Based on the clinical outcomes at 3 months, patients were divided into good and poor prognosis groups. The clinical characteristics of the patients in the two groups are shown in Table 2. No significant differences were observed in the baseline data between the two groups (P > 0.05). Poor prognosis was observed in 47 (49%) of the 96 patients in the study. Compared to patients with a good prognosis, those with a poor prognosis presented a higher admission NIHSS score (P = 0.007) and were more likely to have HDAs on CT images (64% vs 33%, P = 0.0.004). Based on the results of multivariate logistic regression analysis, HDAs on CT (OR = 0.326; 95%CI: 0.253-0.323, P = 0.002) were independently associated with a poor prognosis.

Table 2 Clinical characteristics of patients in the good prognosis and poor prognosis groups, n (%).

	Good prognosis (n = 49)	Poor prognosis (n = 47)	P value
Age (years, mean)	65 ± 11	67 ± 16	0.878
Gender (male)	26 (53)	25 (53)	0.889
Hypertension	22 (45)	21 (45)	0.552
Hyperlipidemia	6 (12)	6 (13)	0.879
Diabetes mellitus	7 (14)	11 (23)	0.068
Heart disease	26 (53)	25 (53)	0.872
Admission NIHSS score (mean)	17 ± 4	20 ± 3	0.007
HDAs presence	16 (33)	30 (64)	0.004

HDAs: High-density areas; NIHSS: National Institutes of Health Stroke Scale.

Depressive and anxiety disorders among patients after EMT

SDS and SAS were used to assess the severity of depressive and anxiety disorders, respectively, in patients with and without HDAs and in patients with good or poor prognosis who accepted EMT. Compared to patients with non-HDAs, patients with HDAs were likely to have more severe depression (P = 0.015) and anxiety (P = 0.032) (Table 3). Moreover, compared to patients with a good prognosis, those with a poor prognosis had more severe depressive (SDS score: 55 ± 19 vs 65 ± 11, P = 0.021) and anxiety (SAS score: 50 ± 8 vs 58 ± 12, P = 0.044) disorders (Table 3).

Table 3 Self-rating depression scale and self-rating anxiety scale scores of patients in the non-high-density areas and high-density areas groups.

	non-HDAs (n = 46)	HDAs (n = 50)	P value
SDS score	58 ± 16	64 ± 13	0.015
SAS score	52 ± 8	59 ± 10	0.032
	Good prognosis (n = 49)	Poor prognosis (n = 47)
SDS score	55 ± 19	65 ± 11	0.021
SAS score	50 ± 8	58 ± 12	0.044

HDAs: High-density areas; SDS: Self-rating depression scale; SAS: Self-rating anxiety scale.

DISCUSSION

This study aimed to investigate the predictive value of HDAs on CT images for neurological function and mental health after EMT in patients with AIS. These findings suggest that the presence of HDAs predicts severe clinical prognosis and depressive and anxiety symptoms.

AIS is a common cerebrovascular disease with high disability and mortality rates and a low cure rate. To treat AIS, it is essential to restore perfusion to the ischemic brain tissue and protect the function of brain cells. EMT is a safe and effective method for treating AIS with large-artery occlusion. However, numerous studies have demonstrated that although endovascular therapy improves recanalization rates (defined as an mRS score < 3 at 3 months), only approximately 50% of patients have a good prognosis[9-13]. Approximately 50% of patients have poor outcomes, which can be explained by ineffective recanalization after EMT (mRS score > 3 at 3 months), despite recanalization of blood vessels with a blood flow grade after thrombolytic therapy for cerebral infarction > grade 2b[14]. Intracranial HDAs are observed on follow-up CT of patients after EMT with an incidence of 31.2%-60%[4]. Chen et al[7] retrospectively analyzed the clinical treatment of 82 patients with AIS due to anterior circulation large-artery occlusion and showed that the presence of HDAs on C-arm CT scans immediately after EMT resulted in ineffective recanalization, suggesting a poor prognosis. However, An et al[15] reported that the presence or absence of HDAs on dual-energy CT scans within 12-24 hours of EMT was not related to clinical outcomes. Whether HDAs predict poor prognosis remains controversial and more extensive research is needed.

In this study, we explored the association between HDAs and neurological function, as well as mental health in patients with AIS after EMT. Based on the CT images, patients were divided into groups with and without HDAs. There were no significant differences in the baseline data including age, sex, and risk factors, whereas the routine stroke scales including admission NIHSS and 3 month-mRS were significantly different between the two groups. Compared to patients without HDAs, those with HDAs presented a higher admission NIHSS score, suggesting severe neurological deficits. Three months after EMT, patients with HDAs were more likely to have post-stroke disabilities, with an mRS score < 3. The SDS and SAS scores at 3 months were significantly higher in patients with HDAs than in those without HDAs, indicating that the presence of HDAs suggests depression and anxiety severity. Moreover, according to the definition of good prognosis with an mRS score < 3 at 3 months, patients were divided into good and poor prognosis groups. The results indicated that patients with a poor prognosis presented with severe neurological deficits, were more likely to have HDAs on CT images, and had more severe depressive and anxiety disorders than patients with a good prognosis. Multivariate analysis showed that the presence of HDAs was an independent negative prognostic factor in patients with AIS. The potential mechanism of the relationship between HDAs and poor prognosis may be related to failed recanalization. HDAs were observed in approximately 25% of patients with AIS following EMT[5]. Previous studies reported that HDAs are related to an increased risk of symptomatic intracerebral hemorrhage and to unfavorable clinical outcomes[5,6,16-18]. Poor outcomes may be attributed to unsuccessful reperfusion hemorrhage[6,19,20]. To the best of our knowledge, this is the first study on the association between HDAs and the mental health of patients with AIS who received EMT. The underlying mechanism remains unclear and further studies are required to clarify this mechanism.

Although our findings suggest that the presence of HDAs predict a severe clinical prognosis and depressive and anxiety symptoms, this study had two limitations. First, thrombectomy devices, procedural techniques, timing of postoperative CT re-examination, and definition of HDAs varied across studies, which probably led to different results in different studies. Second, the present study included a small sample size and was performed at a single center. Therefore, the current findings cannot be generalized to all patients with acute anterior circulation ischemic stroke who received intravascular reperfusion therapy, which needs to be confirmed in large-scale and multicenter clinical studies.

CONCLUSION

In summary, the presence of HDAs on CT images predicts poor prognosis despite successful EMT. Moreover, the presence of HDAs indicates severe depressive and anxiety symptoms. These findings may serve as a reference for clinicians during the treatment of AIS.