Letter to the Editor, Regarding “Corticosteroid Suppression of Vascular Endothelial Growth Factor and Recurrence of Chronic Subdural Hematoma”

We read with interest the article by Berghauser et al1 in which the authors described that in surgical treatment of chronic subdural hematoma (CSDH) with burr hole craniostomy, a longer period of preoperative dexamethasone administration is associated with a lower recurrence rate of CSDH and that dexamethasone administration seems to be unrelated to the higher incidence of complications and treatment-related deaths compared with the current literature. However, the authors mentioned that the mechanism of action of dexamethasone in CSDH has not been fully clarified. We wish to provide further comments on the issue of the effect of preoperative dexamethasone administration on CSDH recurrence.

The involvement of vascular endothelial growth factor (VEGF), a potent inducer of angiogenesis and vascular permeability, in the pathogenesis of CSDH and the mechanism of recurrent CSDH has been reported.2-4 Weigel et al2 reported that 5% (4 of 81) of the patients with angiotensin-converting enzyme (ACE) inhibition experienced recurrence as opposed to 18% (42 of 229) of patients without ACE inhibition (P = .00345) and that VEGF content was significantly lower in the hematomas of patients with ACE inhibition than in those without. Greenberger et al5 reported that systemic treatment with dexamethasone led to dose-dependent inhibition of vasculogenesis in an in vivo model of infantile hemangioma and that dexamethasone suppressed VEGF production in hemangioma-derived stem cells in vitro. On the basis of these reports, we consider that the effect of preoperative dexamethasone administration on the recurrence of CSDH might be dependent on the corticosteroid suppression of VEGF.

Additionally, Funai et al3 recently reported that phosphatidylinositol 3-kinase/Akt signaling is activated in CSDH outer membranes and that the phosphatidylinositol 3-kinase/Akt pathway might be activated by VEGF in outer membranes. A previous study by Nanko et al4 also revealed that VEGF expression in the outer membrane of 30 patients with CSDH was significantly correlated with VEGF concentration in the hematoma (r[s] = .654, P = .0013) and that VEGF concentration in layered hematomas, which have an intrahematoma membranous structure, was significantly higher than in nonlayered hematomas (P < .01), suggesting that the high concentration of VEGF in the hematoma can originate from the hematoma membrane. We previously reported recurrence rates in 64 consecutive patients after CSDH evacuation.6 Recurrence was noted in 7 of the 64 patients (10.9%) after burr-hole craniostomy with drainage, and layered hematoma was seen in 3 of the 7 recurrent cases (42.9%). Therefore, we consider that preoperative dexamethasone administration might be effective in the prevention of recurrent CSDH, especially in the case of layered-type CSDH. Further investigations on the relationship between preoperative dexamethasone administration and VEGF concentration in the hematoma and the correlation of preoperative dexamethasone administration and preoperative radiological findings of hematomas with CSDH recurrence will provide additional insights into the recurrence of CSDH after preoperative dexamethasone administration.

Nagatani, Kimihiro; Wada, Kojiro; Takeuchi, Satoru; Nawashiro, Hiroshi
Saitama, Japan

1. Berghauser Pont LM, Dammers R, Schouten JW, Lingsma HF, Dirven CM. Clinical factors associated with outcome in chronic subdural hematoma: a retrospective cohort study of patients on pre-operative corticosteroid therapy. Neurosurgery. 2011 Sep 20 [Epub ahead of print].
2. Weigel R, Hohenstein A, Schlickum L, Weiss C, Schilling L. Angiotensin converting enzyme inhibition for arterial hypertension reduces the risk of recurrence in patients with chronic subdural hematoma possibly by an antiangiogenic mechanism. Neurosurgery. 2007;61(4):788–792.
3. Funai M, Osuka K, Usuda N, et al.. Activation of PI3 kinase/Akt signaling in chronic subdural hematoma outer membranes. J Neurotrauma. 2011;28(6):1127–1131.
4. Nanko N, Tanikawa M, Mase M, et al.. Involvement of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in the mechanism of development of chronic subdural hematoma. Neurol Med Chir (Tokyo). 2009;49(9):379–385.
5. Greenberger S, Boscolo E, Adini I, Mulliken JB, Bischoff J. Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells. N Engl J Med. 2010;362(11):1005–1013.
6. Sakakibara F, Tsuzuki N, Uozumi Y, Nawashiro H, Shima K. [Chronic subdural hematoma—recurrence and prevention]. Brain Nerve. 2011;63(1):69–74.