Nagai Masahiro, Tsujii Tomoaki, Iwaki Hirotaka, Nishikawa Noriko, Nomoto Masahiro
Department of Neurology and Clinical Pharmacology, Ehime University Graduate School of Medicine, Japan.
Intern Med. 2013;52(19):2203-8. doi: 10.2169/internalmedicine.52.0869. Epub 2012 Mar 1.
The concentrations of neopterin and osteopontin in the cerebrospinal fluid (CSF) were measured in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in order to evaluate their utility as biomarkers for the treatment response.
Seven HAM/TSP patients were treated intravenously with high-dose methylprednisolone (1,000 mg/day) for 3 days. CSF samples were collected before and after the treatment. The neopterin and osteopontin concentrations were determined using high-performance liquid chromatography (HPLC) and an enzyme immunoassay, respectively. The clinical symptoms were evaluated using the Osame Motor Disability Score and the Urinary Disturbance Score.
Four out of the seven patients showed an improvement in motor function with the treatment, and were therefore classed as responders. The pre-treatment CSF neopterin concentration exceeded the upper limit of normal in all seven of the patients, and tended to be higher in treatment responders as compared to non-responders. The CSF neopterin concentration was reduced following treatment in all patients. The mean CSF neopterin concentration significantly (p<0.01) decreased following treatment by almost 60% (from 124.1±79.9 nmol/L to 49.2±29.8 nmol/L). The mean CSF osteopontin concentration was significantly (p<0.01) higher in the HAM/TSP patients in comparison to the 18 HTLV-1-seronegative patients who were designated as controls (9.54±4.53 mg/L vs. 3.72±3.04 mg/L). No significant (p=0.47) reduction of the CSF osteopontin concentration was observed following the intravenous administration of high-dose methylprednisolone.
These results indicate that the CSF neopterin concentration, but not the osteopontin concentration, is a potentially valuable biomarker for monitoring the treatment response in HAM/TSP patients. Furthermore, high pre-treatment CSF neopterin concentrations may be a predictive biomarker for a response to intravenous high-dose methylprednisolone therapy.
测定人类嗜T淋巴细胞病毒I型相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者脑脊液（CSF）中新蝶呤和骨桥蛋白的浓度，以评估其作为治疗反应生物标志物的效用。
7例HAM/TSP患者静脉注射大剂量甲泼尼龙（1000mg/天），共3天。在治疗前后采集脑脊液样本。分别使用高效液相色谱法（HPLC）和酶免疫测定法测定新蝶呤和骨桥蛋白的浓度。使用小见运动障碍评分和排尿障碍评分评估临床症状。
7例患者中有4例在治疗后运动功能有所改善，因此被归类为反应者。所有7例患者治疗前脑脊液新蝶呤浓度均超过正常上限，与无反应者相比，反应者的浓度往往更高。所有患者治疗后脑脊液新蝶呤浓度均降低。治疗后脑脊液新蝶呤平均浓度显著降低（p<0.01），几乎降低了60%（从124.1±79.9nmol/L降至49.2±29.8nmol/L）。与18例被指定为对照的HTLV-1血清阴性患者相比，HAM/TSP患者脑脊液骨桥蛋白平均浓度显著更高（9.54±4.53mg/L对3.72±3.04mg/L）。静脉注射大剂量甲泼尼龙后，未观察到脑脊液骨桥蛋白浓度有显著降低（p=0.47）。
这些结果表明，脑脊液新蝶呤浓度而非骨桥蛋白浓度是监测HAM/TSP患者治疗反应的潜在有价值的生物标志物。此外，治疗前脑脊液新蝶呤浓度较高可能是静脉注射大剂量甲泼尼龙治疗反应的预测生物标志物。
