Treatment of Relapsed Chronic Subdural Hematoma in Four Young Children with Atorvastatin and Low‐dose Dexamethasone

Huang, Jinhao; Li, Lihong; Zhang, Jingyi; Gao, Chuang; Quan, Wei; Tian, Ye; Sun, Jian; Tian, Qilong; Wang, Dong; Dong, Jing‐fei; Zhang, Jianning; Jiang, Rongcai

doi:10.1002/phar.2276

Cited by 21 publications

(16 citation statements)

References 30 publications

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“…8 Our recent study with four young patients indicated that atorvastatin combined with low-dose dexamethasone treatment completely cured three of the patients and obviously decreased the hematoma size in the remaining patient without any clinical complications. 9 Additionally, with our further proof-of-concept Phase II clinical trial, we showed that atorvastatin combined with low-dose dexamethasone treatment is more effective than atorvastatin alone in reducing the hematoma size and improving neurological function in patients with CSDH. 10 Moreover, the results of our basic research study were the same as those of our clinical study.…”

Section: Introductionmentioning

confidence: 76%

<p>Atorvastatin Combined with Low-Dose Dexamethasone Treatment Protects Endothelial Function Impaired by Chronic Subdural Hematoma via the Transcription Factor KLF-2</p>

Fan¹,

Wang²,

Rao³

et al. 2020

DDDT

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Objective Our previous study showed that the combination therapy with atorvastatin and low-dose dexamethasone protected endothelial cell function in chronic subdural hematoma (CSDH) injury. In this study, we aimed to investigate the mechanism underlying the effects of this combination therapy on CSDH-induced cell dysfunction. Methods Monocytes and endothelial cells were cocultured with CSDH patient hematoma samples to mimic the pathological microenvironment of CSDH. Monocytes (THP-1 cells) and endothelial cells (hCMEC/D3 cells) were cocultured in a transwell system for 24 h before stimulation with hematoma samples diluted in endothelial cell medium (ECM) at a 1:1 ratio. Tight junction markers were detected by Western blotting, PCR and immunofluorescence. hCMEC/D3 cells were collected for Western blot and PCR analyses to detect changes in the expression levels of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and Kruppel-like factor 2 (KLF-2). The IL-6, IL-10 and VEGF levels in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Results KLF-2 expression in endothelial cells was decreased after stimulation with CSDH patient hematoma samples, but combination therapy with atorvastatin and low-dose dexamethasone reversed this trend. KLF-2 protected injured cells by increasing the expression of VE-cadherin and ZO-1; attenuating the expression of VCAM-1, ICAM-1, IL-6 and VEGF; and enhancing the expression of IL-10, all of which play pivotal roles in endothelial inflammation. Moreover, the effect of combination therapy with atorvastatin and low-dose dexamethasone was obviously reduced in endothelial cells with KLF-2 knockdown compared with normal cells. Conclusion Coculture with hematoma samples decreased KLF-2 expression in human cerebral endothelial cells. Combination therapy with atorvastatin and low-dose dexamethasone counteracted hematoma-induced KLF-2 suppression in human cerebral endothelial cells to attenuate robust endothelial inflammation and permeability. KLF-2 plays an important role in drug therapy for CSDH and may become the key factor in treatment and prognosis.

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Section: Introductionmentioning

confidence: 76%

<p>Atorvastatin Combined with Low-Dose Dexamethasone Treatment Protects Endothelial Function Impaired by Chronic Subdural Hematoma via the Transcription Factor KLF-2</p>

Fan¹,

Wang²,

Rao³

et al. 2020

DDDT

Self Cite

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“…Within the context of CSDH, atorvastatin, in particular, was investigated in numerous studies and was repeatedly found to improve the clinical course. The published articles ranged from small case series [ 1 , 5 ] to larger studies [ 6 , 20 , 25 ] and two randomized controlled trials (RCT) [ 7 , 22 ]. Notably, two positive studies were later retracted [ 9 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Do statins reduce the rate of revision surgery after chronic subdural hematoma drain?

et al. 2021

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Background With chronic subdural hematoma (CSDH), surgery is the therapeutic mainstay for large or symptomatic cases. Statins are reported to be effective as the primary therapy of CSDH to obviate the need for surgery. However, the effect of statins on the postoperative course of CSDH is largely unclear. We therefore sought to determine whether statins reduce the rate of repeat surgery after CSDH drain. Methods We performed an analysis of all patients who underwent surgery for CSDH at our institution between 2012 and 2018. The patients were separated into those who received statins as part of their previous medication (statin group) and those who did not (control group). The medical records were reviewed for repeat surgeries and complications. Additionally, patients or their relatives were contacted via phone to obtain missing data and inquire about possible repeat surgeries at other institutions. Results We identified 407 patients who received CSDH evacuation via burr hole craniotomy. In total, 123 patients were treated with statins as part of their daily medication. Repeat surgery was performed in 26 patients in the statin group (21.1%) and 57 patients in the non-statin group (20.1%, p = 0.81). Upon multivariate logistic regression analysis, neither of the variables statins, age, antithrombotic medication, Charlson comorbidity index, or Markwalder grading score yielded a statistically significant effect upon the revision rate. Conclusions We found no evidence for the protective effect of statins in patients who underwent surgery for CSDH. We thus conclude that statin therapy is not warranted for CSDH perioperatively.

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“…Another randomized, placebo-controlled, double-blind phase II clinical trial reported that atorvastatin reduces hematoma, and improves neurological function and quality of life; the effect persisted for a follow-up period of 16 weeks in nonsurgical patients with subdural hematoma (Jiang et al, 2018). In addition, Huang et al found that atorvastatin combined with dexamethasone is a safe and effective option for the treatment of pediatric patients with recurrent subdural hematoma (Huang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Arachnoid Cyst With Spontaneous Hemorrhage With Atorvastatin

Liu

Wang

2019

Front. Pharmacol.

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As one of the common neurological diseases, pediatric middle fossa arachnoid cysts(MFACs) can develop intracystic hemorrhage and subdural hematoma. Risk factors for pediatric arachnoid cyst rupture/hemorrhage is very complicated in mechanism. Although surgery is the first choice for children with MFACs and subdural hematoma, the rate of recurrence of the subdural hematoma is very high after 1 or more surgeries. Atorvastatin has proven to be a bold and safe choice in the management of subdural hematoma with mild symptoms. The present study has described a 7-year-old child with a recurrent rupture of arachnoid cyst develops into a subdural hematoma. We demonstrate that atorvastatin is safe and effective in pediatric patient who has failed surgical treatment of middle fossa arachnoid cyst and subdural hematoma. The patient received atorvastatin monotherapy, once daily for the first week, with an initial dose of 5 mg, followed by 10 mg once daily for 7 weeks. In the third month after the initial treatment, the neurological function recovered, and the hematoma completely resolved. This case report supports the concept that atorvastatin can promote the absorption of subdural hematoma.

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Treatment of Relapsed Chronic Subdural Hematoma in Four Young Children with Atorvastatin and Low‐dose Dexamethasone

Cited by 21 publications

References 30 publications

<p>Atorvastatin Combined with Low-Dose Dexamethasone Treatment Protects Endothelial Function Impaired by Chronic Subdural Hematoma via the Transcription Factor KLF-2</p>

<p>Atorvastatin Combined with Low-Dose Dexamethasone Treatment Protects Endothelial Function Impaired by Chronic Subdural Hematoma via the Transcription Factor KLF-2</p>

Do statins reduce the rate of revision surgery after chronic subdural hematoma drain?

Treatment of Arachnoid Cyst With Spontaneous Hemorrhage With Atorvastatin

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