title: Preventive effects of cilostazol against the development of shunt-dependent hydrocephalus after subarachnoid hemorrhage.
abstract: OBJECTIVE Chronic hydrocephalus develops in association with the induction of tenascin-C (TNC), a matricellular protein, after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to examine if cilostazol, a selective inhibitor of phosphodiesterase Type III, suppresses the development of chronic hydrocephalus by inhibiting TNC induction in aneurysmal SAH patients. METHODS The authors retrospectively reviewed the factors influencing the development of chronic shunt-dependent hydrocephalus in 87 patients with Fisher Grade 3 SAH using multivariate logistic regression analyses. Cilostazol (50 or 100 mg administered 2 or 3 times per day) was administered from the day following aneurysmal obliteration according to the preference of the attending neurosurgeon. As a separate study, the effects of different dosages of cilostazol on the serum TNC levels were chronologically examined from Days 1 to 12 in 38 SAH patients with Fisher Grade 3 SAH. RESULTS Chronic hydrocephalus occurred in 12 of 36 (33.3%), 5 of 39 (12.8%), and 1 of 12 (8.3%) patients in the 0 mg/day, 100 to 200 mg/day, and 300 mg/day cilostazol groups, respectively. The multivariate analyses showed that older age (OR 1.10, 95% CI 1.13-1.24; p = 0.012), acute hydrocephalus (OR 23.28, 95% CI 1.75-729.83; p = 0.016), and cilostazol (OR 0.23, 95% CI 0.05-0.93; p = 0.038) independently affected the development of chronic hydrocephalus. Higher dosages of cilostazol more effectively suppressed the serum TNC levels through Days 1 to 12 post-SAH. CONCLUSIONS Cilostazol may prevent the development of chronic hydrocephalus and reduce shunt surgery, possibly by the inhibition of TNC induction after SAH.
authors: Departments of 1 Neurosurgery and.
authors: Yoshinari
authors: Y
authors: Nakatsuka
authors: Departments of 1 Neurosurgery and.
authors: Fumihiro
authors: F
authors: Kawakita
authors: Departments of 1 Neurosurgery and.
authors: Ryuta
authors: R
authors: Yasuda
authors: Center for Vessels and Heart, Mie University Hospital, Tsu, Japan.
authors: Yasuyuki
authors: Y
authors: Umeda
authors: Departments of 1 Neurosurgery and.
authors: Naoki
authors: N
authors: Toma
authors: Innovative Neuro-Intervention Radiology, Mie University Graduate School of Medicine; and.
authors: Hiroshi
authors: H
authors: Sakaida
authors: Departments of 1 Neurosurgery and.
authors: Hidenori
authors: H
authors: Suzuki
mesh_terms: D000368:Aged; D002908:Chronic Disease; D000077407:Cilostazol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology* / Q000517:prevention & control* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058987:Phosphodiesterase 3 Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D017287:Ventriculoperitoneal Shunt
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D000077407:Cilostazol
keywords: IL = interleukin; MAPK = mitogen-activated protein kinase; PDGF = platelet-derived growth factor; SAH = subarachnoid hemorrhage; TGF = transforming growth factor; TNC = tenascin-C; TNF = tumor necrosis factor; WFNS = World Federation of Neurosurgical Societies; cAMP = cyclic adenosine monophosphate; cilostazol; hydrocephalus; pSEED = Prospective Registry for Searching Mediators of Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage; subarachnoid hemorrhage; tenascin-C; vascular disorders