LAUSR

OBJECTIVE The objective of this study was to evaluate total protein (TP) in the cerebrospinal fluid (CSF) and immunoglobulins in the serum and CSF in patients with sporadic amyotrophic lateral sclerosis (sALS). We also assessed the correlations of these variables with sALS progression and severity and estimated their roles in predicting prognosis. METHODS We retrospectively collected data on CSF TP and immunoglobulins in the CSF and serum, including immunoglobulin G, immunoglobulin A and immunoglobulin M, from 326 sALS patients. The relationships between these variables and clinical features, including sex, age, disease duration, site of onset, respiratory function and survival time, were analysed by Wilcoxon's nonparametric tests. Kaplan-Meier and Cox proportional hazards models were used to explore whether levels of TP and immunoglobulins in the CSF were independently correlated with the survival time of patients with ALS. RESULTS The CSF TP was elevated in 55% of the patients. The median CSF TP was 417.7 (349.4-539.5) mg/L, and 6 patients (2%) had a CSF TP level greater than 1000 mg/L. The CSF TP levels were significantly higher in male patients than in female patients (p<.001). In females, the CSF TP had positive associations with onset age (rho =0.196, p = .021) and disease progression rate (DPR) (rho =0.230, p = .035) but negative associations with disease duration (rho = -0.204, p = .016) and revised ALS functional rating scale (ALSFRS-R) (rho = -0.288, p = .008). The ALSFRS-R scores of male patients were negatively correlated with the s-IgM levels (rho = -0.562, p = .005). Onset age was negatively associated with the s-IgM levels (rho = -0.534, p = .005) in females. Kaplan-Meier survival analyses showed that no correlations were found between survival time and the levels of TP and immunoglobulins in the CSF. CONCLUSION Elevated levels of TP and immunoglobulins in the CSF suggest impaired blood-brain barrier (BBB) function and immune responses in the CNS of ALS patients. Higher CSF TP levels were associated with later onset age, a shorter disease duration and worse disease severity in females. The changes in the levels of CSF TP and s-IgM might indicate the severity of the disease in some ALS patients.