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Cerebrospinal Fluid Concentrations of Nitric Oxide Metabolites in Spinal Cord Injury

Kimura, Shinji, MD, PhD*; Hosaka, Noboru, MD, PhD; Yuge, Itaru, MD, PhD; Yamazaki, Akiyoshi, MD, PhD§; Suda, Kohta, MD, PhD; Taneichi, Hiroshi, MD, PhD; Denda, Hiroshi, MD**; Endo, Naoto, MD, PhD**§

doi: 10.1097/BRS.0b013e3181abda1d
Clinical Case Series

Study Design. Multiple center study to evaluate cerebrospinal fluid (CSF) concentrations of nitric oxide metabolites [NOx] in relation to neurologic severity and prognosis in spinal cord injury (SCI).

Objective. To examine whether CSF [NOx] correlates with neurologic severity and recovery in SCI.

Summary of Background Data. Inducible nitric oxide synthase is expressed in rat spinal cord immediately after SCI. Excessive nitric oxide production is cytotoxic, causing neuronal apoptosis with subsequent neurodysfunction in the spinal cord. We previously reported a significant correlation between initial [NOx] after incomplete cervical cord injury (CCI) and neurologic recovery at the final follow-up in 25 cases.

Methods. Ninty-six cases (SCI group), including 76 patients with CCI and 20 patients with thoracic cord injury were examined. Mean follow-up period was 11 months. The control group comprised 40 cases (3 healthy volunteers and 37 patients with neither pain nor neurologic disorders). CSF [NOx] were measured using the Griess method. Severity of neurologic impairment was assessed using Frankel's classification and the American Spinal Injury Association motor score (ASIA MS). Degree of neurologic recovery was assessed using Frankel's classification and the ASIA motor recovery percentage.

Results. CSF [NOx] did not differ significantly among the control, CCI, and thoracic cord injury groups at the initial examination. In the CCI group, [NOx] in the Frankel A and B classes were significantly higher than [NOx] in the control group at 5 to 14 days, in the Frankel A and B classes at 0 to 4 days, and in the Frankel C and D classes at 5 to 14 days. Also, in the CCI group at 5 to 14 days, [NOx] correlated significantly with ASIA MS and motor recovery percentage.

Conclusion. There was a significant correlation between CSF [NOx] at the pathologic early subacute stage (approximately 5–14 days) and neurologic severity and recovery in SCI.

This study evaluated the correlation between nitric oxide metabolite concentrations in cerebrospinal fluid and neurologic recovery after treatment in spinal cord injury. Cerebrospinal fluid nitric oxide metabolite at 5 to 14 days after trauma significantly correlated with the neurologic recovery rate in spinal cord injury.

From the *Rehabilitation Center, Niigata University Medical and Dental Hospital, Niigata-shi, Niigata, Japan; †Department of Orthopedic Surgery, Niigata Rosai Hospital, Joetsu-shi, Niigata, Japan; ‡Department of Orthopaedic Surgery, Japan Labour Health and Welfare Organization, Spinal Injuries Center, Fukuoka, Japan; §Department of Orthopaedic Surgery, Spine Center, Niigata Central Hospital, Niigata, Japan; ¶Department of Orthopedic Surgery, Spinal Cord Injury Center, Hokkaido Chuo Rosai Hospital, Bibai-shi, Bibai, Japan; ∥Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, Mibu, Japan; and **Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata-shi, Niigata, Japan.

Acknowledgment date: October 14, 2008. Acceptance date: February 26, 2008.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Foundation funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Supported in part by a medical research grant on traffic accidents from The General Insurance Association of Japan. This study was approved by the Ethics Committee of Niigata University.

Noboru Hosaka, MD, PhD, equally contributed as a first author.

Address correspondence and reprint requests to Shinji Kimura, MD, PhD, Rehabilitation Center, Niigata University Medical and Dental Hospital, Asahimachi-dori 1-754, Niigata-shi, 951-8520, Japan; E-mail:

© 2009 Lippincott Williams & Wilkins, Inc.