Cerebrospinal Fluid Neopterin, but not Osteopontin, is a Valuable Biomarker for the Treatment Response in Patients with HTLV-I-associated Myelopathy

Abstract

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.