Steroids for chronic subdural hematoma

Since glucocorticoids have been used for treatment of chronic subdural hematoma in 1962 their role is still discussed controversially in lack of evident data. On the basis of the ascertained inflammation cycle in cSDH dexamethasone will be an ideal substance for a short lasting, concomitant treatment protocol.

Berghauser et al. stated in 2013 that the proportion of patients primarily treated with corticosteroids are increasing year by year 1)

Patients with lower grades of CSDH can be treated successfully with steroids. Female patients seem to do better with steroids 2).


In 2020 in the The New England Journal of Medicine among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.) 3).

Surveys

Forty-two percent of surgeons never prescribe steroids and 55% prescribe them to those managed conservatively 4).

In another Canadian survey regarding neurosurgical practice of treatment of CSDH, <15% of neurosurgeons prefer using high-dose corticosteroid 5)

Current evidence implicates a potentially beneficial role of dexamethasone in the management of CSDH. However, it remains unclear whether the rate of crossover to surgery is reduced in patients treated with corticosteroids compared with those managed conservatively. A longer duration of study with detailed analysis of individual cases and appropriately randomized cohorts are necessary to draw more reliable conclusions 6)

Scerrati et al. performed a systematic review according to PRISMA criteria of the studies analyzing the nonsurgical strategies for CSDHs. They collected all papers in the English language published between 1990 and 2019 by searching different medical databases. The chosen keywords were “chronic subdural hematoma,” “conservative treatment/management,” “pharmacological treatment,” “non-surgical,” “tranexamic acid,” “dexamethasone,” “corticosteroid,” “glucocorticoid,” “middle meningeal artery,” “endovascular treatment,” and “embolization.”

The authors ultimately collected 15 articles regarding the pharmacological management of CSDHs matching the criteria, and 14 papers included the endovascular treatment.

The results showed that surgery still represents the mainstay in cases of symptomatic patients with large CSDHs; however, adjuvant and alternative therapies can be effective and safe in a carefully selected population. Their inclusion in new guidelines is advisable 7).


A meta-analysis of Holl et al. from 29019 suggested that the addition of corticosteroids to surgery might be effective in the treatment of CSDH. However, the results must be interpreted with caution in light of the serious risk of bias of the included studies. This study stresses the need for large randomized trials to investigate the use of corticosteroids in the management of CSDH 8)


In 2017 a study of Yao et al. had no enough evidence to support DX use as an effective alternation to surgical therapy. But adjuvant DX use may facilitate the surgical therapy by reducing chronic subdural hematoma recurrence. Further study focusing on adjuvant DX was required 9)

Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.) 10).

see DECSA trial.

see SUCRE trial.

A study is designed as a double-blind randomized placebo-controlled trial 820 patients who are operated for cSDH and from the age of 25 years are included after obtaining informed consent. They are randomized for administration of dexamethasone (16-16-12-12-8-4 mg/d) or placebo (maltodextrin) during the first 48 hours after surgery. The type I error is 5% and the type II error is 20%. The primary endpoint is the reoperation within 12 weeks postoperative.

This study tests whether dexamethasone administered over 6 days is a safe and potent agent in relapse prevention for evacuated cSDH 11).

Mebberson et al. presented an interim analysis of the first registered prospective randomised placebo-controlled trial (PRPCT) of adjuvant DX on RR and outcome after CSDH surgery with post-operative drainage. Participants were randomised to either placebo or a reducing DX regime over 2 weeks, with CSDH evacuation and post-operative drainage. Post-operative mortality (POMT) and RR were determined at 30 days and 6 months; modified Rankin Score (mRS) at discharge and 6 months. Post-operative morbidity (POMB) and adverse events (AEs) were determined at 30 days. Interim analysis at approximately 50% estimated sample size was performed (n = 47). Recurrences were not observed with DX: only with placebo (0/23 [0%] v 5/24 [20.83%], P = 0.049). There was no significant between-group differences in POMT, POMB, LOS, mRS or AEs. CONCLUSIONS: In this first registered PRPCT, interim analysis suggested that adjuvant DX with post-operative drainage is both safe and may significantly decrease recurrences. A 12.5% point between-groups difference may be reasonable to power a final sample size of approximately n = 89. Future studies could consider adjuvant DX for longer than the arbitrarily-chosen 2 weeks 12).


Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented.

Results: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events.

Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications 13).

Sunet al. prospectively studied a group of 30 patients, who were managed non-operatively: 26 patients were treated with dexamethasone (Group 1) and four patients expectantly (Group 4). Nineteen patients (73%) from Group 1 were confused or had focal neurological deficits on admission. The mean maximum thickness of the CSDH was 12 mm. Only one of these cases (4%) required surgical drainage 6 weeks after steroid therapy. One patient died of an unrelated stroke (mortality = 4%). Two patients (8%) were left severely disabled. No significant complication from steroid therapy was documented. Out of the 85 surgically treated patients, 69 patients underwent surgical drainage in addition to steroid therapy (Group 2). Thirteen patients were treated with burr-hole drainage only (Group 3). The mean maximum thickness of the CSDH for these two groups were both 16 mm. Comparing with group 1, the redrainage rate of Group 2 [4% (3/69, p = 1)] and that of Group 3 [15% (2/13, p = 0.253)] were not significantly different. 50% of patients in Group 4 (2/4, p = 0.039) required delayed surgical drainage. The mortality rates of Groups 2, 3 and 4 were 3% (2/69, p = 1), 15% (2/13, p = 0.253) and 50% (2/4, p = 0.039), respectively. Our results suggest that steroid treatment in a selected group of patients is a good option, particularly in patients with co-morbidity 14).


1)

Berghauser Pont LM, Dippel DW, Verweij BH, Dirven CM, Dammers R. Ambivalence among neurologists and neurosurgeons on the treatment of chronic subdural hematoma: a national survey. Acta Neurol Belg. 2013 Mar;113(1):55-9. doi: 10.1007/s13760-012-0130-1. Epub 2012 Sep 14. PMID: 22975837.
2)

Thotakura AK, Marabathina NR. Nonsurgical Treatment of Chronic Subdural Hematoma with Steroids. World Neurosurg. 2015 Dec;84(6):1968-72. doi: 10.1016/j.wneu.2015.08.044. Epub 2015 Sep 2. PMID: 26342776.
3) , 10)

Hutchinson PJ, Edlmann E, Bulters D, Zolnourian A, Holton P, Suttner N, Agyemang K, Thomson S, Anderson IA, Al-Tamimi YZ, Henderson D, Whitfield PC, Gherle M, Brennan PM, Allison A, Thelin EP, Tarantino S, Pantaleo B, Caldwell K, Davis-Wilkie C, Mee H, Warburton EA, Barton G, Chari A, Marcus HJ, King AT, Belli A, Myint PK, Wilkinson I, Santarius T, Turner C, Bond S, Kolias AG; British Neurosurgical Trainee Research Collaborative; Dex-CSDH Trial Collaborators. Trial of Dexamethasone for Chronic Subdural Hematoma. N Engl J Med. 2020 Dec 31;383(27):2616-2627. doi: 10.1056/NEJMoa2020473. Epub 2020 Dec 16. PMID: 33326713.
4)

Santarius T, Lawton R, Kirkpatrick PJ, Hutchinson PJ. The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland. Br J Neurosurg. 2008 Aug;22(4):529-34. doi: 10.1080/02688690802195381. PMID: 18686063.
5)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. doi: 10.1017/s0317167100004510. PMID: 16408582.
6)

Petralia CCT, Manivannan S, Shastin D, Sharouf F, Elalfy O, Zaben M. Effect of Steroid Therapy on Risk of Subsequent Surgery for Neurologically Stable Chronic Subdural Hemorrhage-Retrospective Cohort Study and Literature Review. World Neurosurg. 2020 Jun;138:e35-e41. doi: 10.1016/j.wneu.2020.01.160. Epub 2020 Feb 27. PMID: 32113994.
7)

Scerrati A, Visani J, Ricciardi L, Dones F, Rustemi O, Cavallo MA, De Bonis P. To drill or not to drill, that is the question: nonsurgical treatment of chronic subdural hematoma in the elderly. A systematic review. Neurosurg Focus. 2020 Oct;49(4):E7. doi: 10.3171/2020.7.FOCUS20237. PMID: 33002869.
8)

Holl DC, Volovici V, Dirven CMF, van Kooten F, Miah IP, Jellema K, Peul WC, van der Gaag NA, Kho KH, den Hertog HM, Dammers R, Lingsma HF. Corticosteroid treatment compared with surgery in chronic subdural hematoma: a systematic review and meta-analysis. Acta Neurochir (Wien). 2019 Jun;161(6):1231-1242. doi: 10.1007/s00701-019-03881-w. Epub 2019 Apr 10. PMID: 30972566.
9)

Yao Z, Hu X, Ma L, You C. Dexamethasone for chronic subdural haematoma: a systematic review and meta-analysis. Acta Neurochir (Wien). 2017 Nov;159(11):2037-2044. doi: 10.1007/s00701-017-3309-7. Epub 2017 Sep 1. PMID: 28865006.
11)

Emich S, Richling B, McCoy MR, Al-Schameri RA, Ling F, Sun L, Wang Y, Hitzl W. The efficacy of dexamethasone on reduction in the reoperation rate of chronic subdural hematoma – the DRESH study: straightforward study protocol for a randomized controlled trial. Trials. 2014 Jan 6;15(1):6. doi: 10.1186/1745-6215-15-6. PubMed PMID: 24393328; PubMed Central PMCID: PMC3891985.
12)

Mebberson K, Colditz M, Marshman LAG, Thomas PAW, Mitchell PS, Robertson K. Prospective randomized placebo-controlled double-blind clinical study of adjuvant dexamethasone with surgery for chronic subdural haematoma with post-operative subdural drainage: Interim analysis. J Clin Neurosci. 2020 Jan;71:153-157. doi: 10.1016/j.jocn.2019.08.095. Epub 2019 Sep 3. PMID: 31492485.
13)

Prud’homme M, Mathieu F, Marcotte N, Cottin S. A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma. Can J Neurol Sci. 2016 Mar;43(2):284-90. doi: 10.1017/cjn.2015.393. Epub 2016 Feb 8. PMID: 26853325.
14)

Sun TF, Boet R, Poon WS. Non-surgical primary treatment of chronic subdural haematoma: Preliminary results of using dexamethasone. Br J Neurosurg. 2005 Aug;19(4):327-33. doi: 10.1080/02688690500305332. PMID: 16455539.

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