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. 2023 Sep 29;102(39):e35379. doi: 10.1097/MD.0000000000035379

Efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma

Wuhuan Xu a, Xielin Tang b, Shenghua Liu b, Qianke Li b, Feilong Yang b,*
PMCID: PMC10545255  PMID: 37773816

Abstract

To explore the clinical efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma. We conducted a retrospective study to analyze the clinical data of patients with chronic subdural hematoma. Patients receiving atorvastatin treatment after surgery were divided into the study group while others were divided into the control group. As the primary outcome, we compared the hematoma recurrence rate. The secondary outcomes were the remaining volume of hematoma and the activities of daily living (Barthel index) score at 3 months after discharge. A total of 53 patients were included in the study: 30 patients in the study group (n = 30) and 23 patients in the control group (n = 23). The baseline clinical data were similar in the 2 groups (P > .05). Four patients had recurrence of hematoma in the study group, while 5 patients had recurrence of hematoma in the control group [4/30 (13.3%) versus 5/23 (21.7%), P = .661] at 3 months after discharge. The mean remaining volume of hematoma was 12.10 ± 8.80 mL in the study group and 17.30 ± 9.50 mL in the control group at 3 months after discharge, respectively. The remaining volume of hematoma in the study group was less than that in the control group (P = .045).The activities of daily living score in the study group were higher than those in the control group (97.83 ± 4.48 vs 94.78 ± 5.73, P = .034) at 3 months after discharge. Atorvastatin administration after surgery barely reduce the recurrence rate of chronic subdural hematoma, however, reduced the remaining volume of hematoma and improved neurological function.

Keywords: after surgery, atorvastatin, chronic subdural hematoma, neurological function, recurrence

1. Introduction

Chronic subdural hematoma (CSDH) is characterized by abnormal blood collection in the subdural space and slow progression.[1]It forms over a period of 3 weeks or more weeks. The annual incidence is 1.72-20.6/100000 people, and the prevalence rate of elderly people is higher.[2,3] With aging, the proportion of patients using antithrombic or anticoagulative drugs is increasing; furthermore, anticoagulation medication may increase rebleeding risk,[4]leading to poor prognosis in elderly people. Patients with CSDH suffer higher mortality. The average survival time of patients with CSDH is <1.6 years than that of people without CSDH.[5] The process of CSDH formation and progression remains unclear. There are several hypotheses, including minimal traumatic brain injury,[6] inflammatory responses,[7] hyperfibrinolysis,[8] angiogenic stimuli,[9] and transformation of acute subdural hematoma.[10] The inflammatory response seems to play a role in pathophysiological mechanisms and is mainly recognized,[9] as well as the direction of drug treatment research.

Most patients present with nonspecific symptoms, for example, headache, gait impairment, or dementia.[11] CSDH is often diagnosed based on computed tomography or magnetic resonance imaging. Typical imaging characteristics are crescent iso-density, hypo-density or mixed-density layers of fluid between the brain surface and dura mater.[12]CSDH can also lead to midline shift or lateral ventricle compression in some cases. Patients with symptoms or intracranial mass effect need surgical treatment.

Surgical procedures are current the main treatment for CSDH, including burr-hole drainage or craniotomy. These procedures have been proven effective.[13,14] However, approximately 10% to 20% of cases experience hematoma recurrence after surgery.[15–17]Middle meningeal artery embolization is effective for reducing hematoma recurrence,[18]however, it is not a common treatment in most hospitals. Atorvastatin originally developed to reduce low-density lipoprotein cholesterol levels, has also been shown to reduce inflammation in the vessel wall and promote vascular repair. Atorvastatin shows efficacy in reducing the hematoma volume of CSDHs.[19–21]However, the efficacy of atorvastatin administration after surgery for reducing hematoma recurrence is inconsistent.[22–24] In Sun research,[24] 4 of 21 patients (19.0%) with atorvastatin administration and 5 of 28 patients (17.9%) without atorvastatin administration after surgery were reported as having recurrence (P = .915). However, a retrospective study showed that perioperative atorvastatin administration was significantly related to recurrence risk (odds ratio 0.336; P = .039).[22] In this study, we analyzed patients with CSDH to determine the efficacy of atorvastatin administration after surgery.

2. Materials and method

2.1. Study design and patient selection

This study was a retrospective cohort analysis to determine whether postoperative atorvastatin administration reduced the recurrence of chronic subdural hematoma. We selected patients who were admitted to the hospital affiliated with North Sichuan Medical College from May 2020 to May 2022. Our inclusion criteria were as follows: The first diagnosis was chronic subdural hematoma; received surgical treatment; and aged 18 to 90 years. Exclusion criteria used were: not received burr-hole drainage; clinical date incompleted; readmission during following up for other disease; history of chronic subdural hematoma; longer history of atorvastatin or dexamethasone administration; abnormal coagulation, hepatitis, cancer, or severe cardiopulmonary insufficiency; if atorvastatin administered, duration of atorvastatin administered less 8 weeks; and duration of following up less 3 months. Relevant information, including patient age, sex, symptoms, comorbidities, image characteristics, and the markwalder grading scale/Glasgow Coma Scale, were collected in detail. Eligible patients were assigned to the study group if they received atorvastatin after surgery, while others were assigned to the control group. All patients were informed and signed the informed consent form before participating in our trial. Our study was approved by the ethics committee of the hospital affiliated to North Sichuan Medical college.

2.2. Treatment of chronic subdural hematoma

Surgical indications: symptoms relevant to increased intracranial pressure; hematoma thickness >10 mm and midline shift >10 mm; and obvious compression of the ipsilateral ventricle. Patients who met the indication received burr-hole drainage. After surgery, patients who consented to additional atorvastatin administration received a dose of 20 mg atorvastatin daily for 8 weeks.[25]

2.3. Outcomes

The primary outcome was the recurrence rate at 3 months after surgery. The criterion for recurrent hematoma was defined as subdural hematoma of the ipsilateral region requiring resurgery.[26] The secondary outcomes were the remaining hematoma and activities of daily living (ADL) at 3 months after surgery. The hematoma volume was calculated by 3D slicer software (version 5.1.0). The ADL scale was assessed by 2 neurosurgeons and the mean scores were recorded.

2.4. Statistical analysis

All data were analyzed using the statistical software SPSS (version 26, IMB corporation). The Kolmogorov–Smirnov test was applied to determine whether the quantitative data met normality. Quantitative data following a normal distribution are described as the mean ± standard deviation (SD), and the differences between 2 groups were compared using an independent sample t test. Quantitative data not following a normal distribution are described as the median or range. Quantitative or ordinal data were compared between 2 groups using the Wilcoxon rank sum test. Qualitative data were described as numbers (percentages) and compared using the chi-quarter test or Fisher exact test. A P value (2-sided) <0.05 was considered statistically significant.

3. Result

3.1. Baseline characteristics

There were 102 patients diagnosed with chronic subdural hematoma from May 2020 to May 2022. A total of 76 patients received burr-hole drainage surgery. Among them, a total of 53 patients met the study criteria (inclusion and exclusion). They were divided into the study group (n = 30) and the control group (n = 21). The mean age of the patients was 71.45 years, and 84.9% were male. The most common symptom was headache, followed by gait impairment and memory loss. A total of 22 patients (41.5%), 16 patients (30.2%) and 20 patients (20%) had a history of hypertension, diabetes mellitus and hyperlipidemia, respectively. A total of 30 patients (50.6%) and 16 patients (30.2%) had a history of brain injury and cerebral infarction, respectively. Unilateral hematomas were observed in 47 of 53 patients(88.7%).The mean volume of hematomas was 71.68 mL, and the ADL scale score was 80.38. The baseline characteristics of the study and control groups were similar and are presented in Table 1.

Table 1.

Baseline of characteristics of the study and the control group.

Total (n = 53) Study group (n = 30) Control group (n = 23) P value
Gender, n (%)
 Male 45 (84.9) 24 (80) 21 (91.3) .452
 Female 8 (15.1) 6 (20) 2 (8.7)
Age, yr 71.45 ± 6.44 72.27 ± 6.53 70.39 ± 6.30 .298
Symptoms, n (%)
 Headache 40 (75.5) 21 (70) 19 (82.6) .290
 Vomiting 9 (17) 6 (20) 3 (13) .765
 Memory loss 11 (20.8) 8 (26.7) 3 (13) .384
 Speech arrest 6 (11.3) 4 (13.3) 2 (8.7) .928
 Gait impairment 11 (20.8) 7 (23.3) 4 (17.4) .852
Comorbidities, n (%)
 Hypertension 22 (41.5) 14 (46.7) 8 (34.8) .384
 Diabetes mellitus 16 (30.2) 9 (30) 7 (33.3) .710
 Hyperlipidemia 20 (37.7) 11 (36.7) 9 (39.1) .556
History of BI, n (%) 30 (50.6) 17 (56.7) 13 (56.5) .992
History of CI, n (%) 16 (30.2) 9 (30) 7 (30.4) .973
Aspirin administration,
N (%)		 13 (24.5) 8 (26.7) 5 (21.7) .679
Taking alcohol, n (%) 10 (18.9) 7 (23.3) 3 (13) .552
CT characteristic of Hematoma, n (%)
 Hypodensity 13 (24.5) 8 (26.7) 5 (21.7) .970
 Isodensity 13 (24.5) 7 (23.3) 6 (26.1)
 Hyperdensity 7 (13.2) 3 (10) 4 (17.4)
 Mixed density 20 (37.7) 12 (40) 8 (34.8)
Location, n (%)
 Unilateral 47 (88.7) 26 (86.7) 21 (91.3) .687
 Bilateral 6 (11.3) 4 (13.3) 2 (8.7)
Hematoma volume at admission (mL) 71.68 ± 13.68 71.42 ± 13.39 72.01 ± 14.34 .877
Midline shift (>5mm),
n (%)		 37 (69.8) 22 (73.3) 15 (65.2) .524
MGC/GCS scale, n (%)
 0 0 (0) 0 (0) 0 (0) .195
 1 10 (18.9) 8 (26.7) 2 (8.7)
 2 25 (47.2) 13 (43.3) 12 (52.2)
 3 18 (34) 9 (30) 9 (39.1)
 4 0 (0) 0 (0) 0 (0)
ADL scale at admission 80.38 ± 5.92 80.17 ± 6.63 80.65 ± 5.07 .772
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ADL = activities of daily living, BI = brain injury, CI = cerebral infarction.

3.2. The efficacy of atorvastatin administration after surgery

After the procedure, the residual volumes of hematoma were 18.46 ± 7.49 mL in the study group and 17.17 ± 6.69 mL in the control group (P = .887). At 3 months after discharge, 4 out of 30 patients (13.3%) were reported to have recurrence of chronic subdural hematoma in the study group, while 5 out of 23 patients (21.7%) were reported in the control group (P = .661). The overall hematoma evacuation rate was 74.9% in the study group and 72.7% in the control group at discharge (P = .245). Hematoma evacuation percentages of 59% or less, 60% to 79%, and more than 80% in the study group were similar to those in the control group (P = .777), as shown in Table 2. At 3 months after discharge, the remaining volume of hematoma in the study group was less than that in the control group (12.10 ± 8.80 mL vs 17.30 ± 9.50 mL, P = .045). According to Figure 1, the ADL scores of the study group were higher than those of the control group (P < .05) at 3 months after discharge. The ADL scores of the study group were similar to those in the control group at admission and at discharge (P > .05). The trend of hematoma is shown in Figure 2.

Table 2.

Hematoma recurrence, hematoma volume and hematoma evacuation rate.

Study group (n = 30) Control group (n = 23) P value
Recurrence, n (%) 4 (13.3) 5 (21.7) .661
HER at discharge, n (%)
 Overall (74.9) (72.7) .245
 0%–59% 1 (3.3) 1 (4.3)
 60%–79% 23 (76.7) 18 (78.3) .777
 80%–100% 6 (20) 4 (17.4)
Hematoma volume after evacuation, mL 18.46 ± 7.49 17.17 ± 6.69 .887
Hematoma volume at discharge, mL 17.28 ± 4.40 19.10 ± 4.18 .134
Hematoma volume at 3 mo, mL 12.10 ± 8.80 17.30 ± 9.50 .045
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HER = hematoma evacuation rate, HER = (Va - Vd)/ Va*100%. Va, volume of hematoma at admission, Vd = volume of hematoma at discharge.

Figure 1.

Figure 1.

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The Barthel index score of the study group and the control group at admission, discharge and 3 mo after discharge.

Figure 2.

Figure 2.

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The hematoma volume of the study group and the control group at admission, discharge and 3 mo after discharge.

4. Discussion

This is a retrospective study to determine the efficacy of atorvastatin administration after surgery. We found that patients with atorvastatin administration after surgery had a similar recurrence rate to patients without atorvastatin administration; however, the hematoma volumes of patients with atorvastatin administration after surgery at 3 months after discharge were less than those of patients without atorvastatin administration. In addition, the Barthel index scores were higher in the study group than in the control group. As a result, our study showed that atorvastatin administration after surgery barely reduces the recurrence rate of hematoma. However, atorvastatin can reduce the hematoma volume and increase the ADL.

In our study, we found 4 out of 30 patients (13.3%) reported recurrence of hematoma in the study group, while 5 out of 23 patients (21.7%) reported recurrence in the control group (P = .661). In line with a study conducted by Sun et al,[24] we did not find atorvastatin administration after surgery may reduce recurrence. Similar conclusions were also reported in another study.[23,27] Inconsistent with our conclusion, Tang et al[22] analyzed 245 patients with CSDH and suggested that atorvastatin perioperative administration may reduce the risk of CSDH recurrence. There are many factors attributed to a high risk of recurrence, for example, senior age (>75 years),[28] preoperative hematoma thickness,[29] hematoma density,[17] hematoma volume,[30] postoperative subdural air,[31] and duration of subdural drainage postsurgery.[32] Elderly patients often have more comorbidities, increasing the risk of recurrence,[33] and a considerable proportion of them take anticoagulation or antiplatelet drugs in general, which may increase rebleeding.[4] Furthermore, with aging, brain atrophy gradually leads to an enlargement of the cavity between the brain and dura mater. As a result, the hematoma volume of elderly patients is larger than that of relatively younger patients. The cerebral re-expansion ratio was defined as (preoperative volume of hematoma–postoperative volume of hematoma)/preoperative volume of hematoma*100%.[34] Based on this definition, the cerebral re-expansion ratio was 76.11% in patients under 80 years and 68.75% in patients over 80 years in our research (P < .05). Furthermore, we found the same trend in the study group (Fig. 3). There were only 3 patients over 80 years in the control group, perhaps for this, there was no similar trend in the control group (Fig. 3). In addition, brain re-expansion is also poor after surgery due to poor brain compliance with age.[24] Cerebral atrophy is related to poor cerebral re-expansion and the occurrence of CSDH[35] Our included patients with a mean age of 71.45 years were older than those aged 62.2 years in the study by Tang et al.[22] Moreover, in theirs,[22] the duration of atorvastatin administration after surgery and follow-up were longer than ours. These factors may be possible explanations for why our study did not find that atorvastatin can reduce the hematoma recurrence rate after surgery. Another possible explanation is that 52% of patients received atorvastatin before surgery in Tang study[22]; however, no patient received atorvastatin before surgery in our study. A previous study showed that fewer patients with atorvastatin administration were switched to surgery than patients without atorvastatin administration, indicating that atorvastatin may lower the risk of requiring surgery.[20] Considering this, we speculate that atorvastatin administration before surgery may, more or less, impact recurrence after surgery.

Figure 3.

Figure 3.

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Cerebral re-expansion after surgery.

The process of CSDH formation and progression involves complex inflammation and angiogenesis. Initially, the formation of a collagen neo-membrane around the blood clot is the first step. Then, vascular endothelial growth factor, interleukin-6 (IL-6), interleukin-8 (IL-8), TNF-α, matrix metalloproteinases (MMPs) and more proinflammatory factors promote the formation of neovessel characterized by fragility, widening of gap junctions, and leaky blood vessels, leading to chronic microbleeding.[36] IL-6 and IL-8 correlate with recurrence and layering CSDH.[37] MMP8 and MMP9 also play important roles in the pathogenesis of CSDH.[7] There is increasing evidence to suggest that atorvastatin promotes angiogenesis and anti-inflammation.[38] In this view, atorvastatin may be used to treat CSDH. In fact, there is increasing evidence to have proven the efficacy of atorvastatin in treating CSDH in recent years.[19,20,22,24,39,40] Atorvastatin can increase circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs), promote vessel repair and improve neural function.[41,42] In animal models,[9,41–43] atorvastatin reduces hematoma primarily by suppressing local inflammation, can lower TNF-α and IL-6 levels and can decrease the expression of the VEGF gene.[43] In our study, we found that the hematoma volumes of patients with atorvastatin were less than those of patients without atorvastatin; moreover, the Barthel index scores of patients with atorvastatin were higher than those of patients without atorvastatin at 3 months after discharge. In line with our findings, several studies have drawn similar conclusions.[20,44] The mechanism by which atorvastatin reduces hematoma and improves neural function may involve the pathophysiological factors described above.

There are some limitations that should be noted. This is a retrospective study; therefore, the reliance on medical records may have potential bias if unmeasured. Second, the population of each group was relatively small and was drawn from a single geographic area. Third, the follow-up was only 3 months, so long-term efficacy is still unclear. Further research is required to determine why atorvastatin can reduce volume of hematoma and lower the rate of atorvastatin administration switching to surgery; however, atorvastatin administration barely reduces the recurrence of hematoma.

In summary, our research suggested that atorvastatin administration after surgery can reduce hematoma volume and improve neurological function; however, atorvastatin barely reduces the recurrence rate of hematoma.

Author contributions

Conceptualization: Feilong Yang.

Data curation: Shenghua Liu.

Formal analysis: Xielin Tang, Shenghua Liu.

Investigation: Xielin Tang, Shenghua Liu.

Methodology: Feilong Yang.

Project administration: Feilong Yang.

Resources: Xielin Tang.

Supervision: Qianke Li, Feilong Yang.

Validation: Feilong Yang.

Writing – original draft: Wuhuan Xu.

Abbreviations:

ADL
activities of daily living
CSDH
chronic subdural hematoma

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

The authors have no funding and conflicts of interest to disclose.

How to cite this article: Xu W, Tang X, Liu S, Li Q, Yang F. Efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma. Medicine 2023;102:39(e35379).

Contributor Information

Wuhuan Xu, Email: 491735643@qq.com.

Xielin Tang, Email: 48279230@qq.com.

Shenghua Liu, Email: 854777976@qq.com.

Qianke Li, Email: 357176761@qq.com.

References

  • [1].Toi H, Kinoshita K, Hirai S, et al. Present epidemiology of chronic subdural hematoma in Japan: analysis of 63,358 cases recorded in a national administrative database. J Neurosurg. 2018;128:222–8. [DOI] [PubMed] [Google Scholar]
  • [2].Feghali J, Yang W, Huang J. Updates in chronic subdural hematoma: epidemiology, etiology, pathogenesis, treatment, and outcome. World Neurosurg. 2020;141:339–45. [DOI] [PubMed] [Google Scholar]
  • [3].Yang W, Huang J. Chronic subdural hematoma: epidemiology and natural history. Neurosurg Clin N Am. 2017;28:205–10. [DOI] [PubMed] [Google Scholar]
  • [4].Nathan S, Goodarzi Z, Jette N, et al. Anticoagulant and antiplatelet use in seniors with chronic subdural hematoma: systematic review. Neurology. 2017;88:1889–93. [DOI] [PubMed] [Google Scholar]
  • [5].Hamou HA, Clusmann H, Schulz JB, et al. Chronic subdural hematoma. Dtsch Arztebl Int. 2022;119:208–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Iliescu IA, Constantinescu AI. Clinical evolutional aspects of chronic subdural hematomas - literature review. J Med Life. 2015;8 Spec Issue:26–33. [PMC free article] [PubMed] [Google Scholar]
  • [7].Su G-J, Gao J, Wu C-W, et al. Serum levels of MMP-8 and MMP-9 as markers in chronic subdural hematoma. J Clin Med. 2022;11:902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Kageyama H, Toyooka T, Tsuzuki N, et al. Nonsurgical treatment of chronic subdural hematoma with tranexamic acid. J Neurosurg. 2013;119:332–7. [DOI] [PubMed] [Google Scholar]
  • [9].Edlmann E, Giorgi-Coll S, Whitfield PC, et al. Pathophysiology of chronic subdural hematoma: inflammation, angiogenesis and implications for pharmacotherapy. J Neuroinflammation. 2017;14:108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Lee KS. Natural history of chronic subdural hematoma. Brain Inj. 2004;18:351–8. [DOI] [PubMed] [Google Scholar]
  • [11].Sahyouni R, Goshtasbi K, Mahmoodi A, et al. Chronic subdural hematoma: a historical and clinical perspective. World Neurosurg. 2017;108:948–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Mehta V, Harward SC, Sankey EW, et al. Evidence-based diagnosis and management of chronic subdural hematoma: a review of the literature. J Clin Neurosci. 2018;50:7–15. [DOI] [PubMed] [Google Scholar]
  • [13].Yuan Y, Wang Q-P, Cao Y-L, et al. Burr hole drainage and burr hole drainage with irrigation to treat chronic subdural hematoma: a systematic review and meta-analysis. Medicine (Baltim). 2018;97:e11827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Ozevren H, Cetin A, Hattapoglu S, et al. Burr hole and craniotomy in the treatment of subdural hematoma: a comparative study. Niger J Clin Pract. 2022;25:1056–60. [DOI] [PubMed] [Google Scholar]
  • [15].Andersen-Ranberg NC, Debrabant B, Poulsen FR, et al. The Danish chronic subdural hematoma study-predicting recurrence of chronic subdural hematoma. Acta Neurochir. 2019;161:885–94. [DOI] [PubMed] [Google Scholar]
  • [16].Erdogan B, Is M, Tural Emon S, et al. Retrospective analysis of 195 surgically treated cases of chronic subdural hematoma. Int J Clin Pract. 2021;75:e15014. [DOI] [PubMed] [Google Scholar]
  • [17].Liu LX, Cao XD, Ren YM, et al. Risk factors for recurrence of chronic subdural hematoma: a single center experience. World Neurosurg. 2019;132:e506–13. [DOI] [PubMed] [Google Scholar]
  • [18].Ban SP, Hwang G, Byoun HS, et al. Middle meningeal artery embolization for chronic subdural hematoma. Radiology. 2018;286:992–9. [DOI] [PubMed] [Google Scholar]
  • [19].Wang D, Li T, Tian Y, et al. Effects of atorvastatin on chronic subdural hematoma: a preliminary report from three medical centers. J Neurol Sci. 2014;336:237–42. [DOI] [PubMed] [Google Scholar]
  • [20].Jiang R, Zhao S, Wang R, et al. Safety and efficacy of atorvastatin for chronic subdural hematoma in Chinese patients: a randomized clinicaltrial. JAMA Neurol. 2018;75:1338–46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Yang L, Li N, Yang L, et al. Atorvastatin-induced absorption of chronic subdural hematoma is partially attributed to the polarization of macrophages. J Mol Neurosci. 2022;72:565–73. [DOI] [PubMed] [Google Scholar]
  • [22].Tang R, Shi J, Li X, et al. Effects of atorvastatin on surgical treatments of chronic subdural hematoma. World Neurosurg. 2018;117:e425–9. [DOI] [PubMed] [Google Scholar]
  • [23].Wang D, Wang H, Xu M, et al. The effect of atorvastatin on recurrence of chronic subdural hematoma after novel YL-1 puncture needle surgery. Clin Neurol Neurosurg. 2021;202:106548. [DOI] [PubMed] [Google Scholar]
  • [24].Sun T, Yuan YK, Wu K, et al. Effects of postoperative atorvastatin use in elderly patients with chronic subdural hematoma. Eur Rev Med Pharmacol Sci. 2021;25:7211–7. [DOI] [PubMed] [Google Scholar]
  • [25].Zhang J. Expert consensus on drug treatment of chronic subdural hematoma. Natl Med J China. 2020;100:566–72. [Google Scholar]
  • [26].Hutchinson PJ, Edlmann E, Bulters D, et al. Trial of dexamethasone for chronic subdural hematoma. N Engl J Med. 2020;383:2616–27. [DOI] [PubMed] [Google Scholar]
  • [27].Xu M, Tan W, Wang W, et al. Minimally invasive surgery in chronic subdural hematoma: prognosis and recurrence factors of 516 cases in a single center. J Clin Med. 2022;11:1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Han M-H, Ryu JI, Kim CH, et al. Predictive factors for recurrence and clinical outcomes in patients with chronic subdural hematoma. J Neurosurg. 2017;127:1117–25. [DOI] [PubMed] [Google Scholar]
  • [29].Altaf I, Shams S, Vohra AH. Radiolological predictors of recurrence of chronic subdural hematoma. Pak J Med Sci. 2018;34:194–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Shen J, Yuan L, Ge R, et al. Clinical and radiological factors predicting recurrence of chronic subdural hematoma: a retrospective cohort study. Injury. 2019;50:1634–40. [DOI] [PubMed] [Google Scholar]
  • [31].Ito S, Higuchi K. Subdural air increases postoperative recurrence of chronic subdural hematoma after initial burr-hole surgery only in the very elderly: a pilot study. World Neurosurg. 2021;156:e25–9. [DOI] [PubMed] [Google Scholar]
  • [32].You W, Zhu Y, Wang Y, et al. Prevalence of and risk factors for recurrence of chronic subdural hematoma. Acta Neurochir. 2018;160:893–9. [DOI] [PubMed] [Google Scholar]
  • [33].Martinez-Perez R, Tsimpas A, Rayo N, et al. Role of the patient comorbidity in the recurrence of chronic subdural hematomas. Neurosurg Rev. 2021;44:971–6. [DOI] [PubMed] [Google Scholar]
  • [34].Han S, Feng Y, Xu C, et al. Brain re-expansion predict the recurrence of unilateral CSDH: a clinical grading system. Front Neurol. 2022;13:908151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Ju M-W, Kim S-H, Kwon H-J, et al. Comparision between brain atrophy and subdural volume to predict chronic subdural hematoma: volumetric CT imaging analysis. Korean J Neurotrauma. 2015;11:87–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Bounajem MT, Campbell RA, Denorme F, et al. Paradigms in chronic subdural hematoma pathophysiology: current treatments and new directions. J Trauma Acute Care Surg. 2021;91:e134–41. [DOI] [PubMed] [Google Scholar]
  • [37].Frati A, Salvati M, Mainiero F, et al. Inflammation markers and risk factors for recurrence in 35 patients with a posttraumatic chronic subdural hematoma: a prospective study. J Neurosurg. 2004;100:24–32. [DOI] [PubMed] [Google Scholar]
  • [38].Huang J, Gao C, Dong J, et al. Drug treatment of chronic subdural hematoma. Expert Opin Pharmacother. 2020;21:435–44. [DOI] [PubMed] [Google Scholar]
  • [39].Fan Y, Wang D, Rao C, et al. Atorvastatin combined with low-dose dexamethasone treatment protects endothelial function impaired by chronic subdural hematoma via the transcription factor KLF-2. Drug Des Devel Ther. 2020;14:3291–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].Gong Z, Zhan D, Nie M, et al. Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages. J Neuroinflammation. 2021;18:203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [41].Wang B, Sun L, Tian Y, et al. Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in traumatic brain injury in rats. J Neurol Sci. 2012;319:117–23. [DOI] [PubMed] [Google Scholar]
  • [42].Quan W, Zhang Z, Li P, et al. Role of regulatory T cells in atorvastatin induced absorption of chronic subdural hematoma in rats. Aging Dis. 2019;10:992–1002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [43].Li T, Wang D, Tian Y, et al. Effects of atorvastatin on the inflammation regulation and elimination of subdural hematoma in rats. J Neurol Sci. 2014;341:88–96. [DOI] [PubMed] [Google Scholar]
  • [44].Chan DYC, Chan DTM, Sun TFD, et al. The use of atorvastatin for chronic subdural hematoma: a retrospective cohort comparison study. Br J Neurosurg. 2017;31:72–7. [DOI] [PubMed] [Google Scholar]

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