title: Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients.
abstract: Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3-5, days 7-9 and days 12-14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3-5 (p=0.002) after SAH, peaked on days 7-9 (p<0.001) and remained elevated until days 12-14 (p<0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7-9 (correlation coefficient=-0.55, p=0.012; 95% confidence interval -0.80 to -0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7-9 predicted a poor clinical outcome at 2year follow-up after SAH (odds ratio=1.722, p=0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, Nanjing, Jiangsu Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Jinling Hospital, Nanjing 210002, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China. Electronic address: hang_neurosurgery@163.com.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D013129:Spinal Puncture; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis / Q000503:physiopathology*; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Asymmetric dimethylarginine; HPLC; Outcome; Subarachnoid hemorrhage; Vasospasm