Prognostic Value of Routine CSF Biomarkers in MS
Baseline characteristics are in Table 1. The mean age at MS onset was 33.0 ± 11.1 years. The median time between MS onset and CSF testing was 4.6 years [1.0–7.0]. Among registered patients, those included and not included in the study did not differ in age at onset (p = 0.41) and gender (p = 0.31) but did differ in the initial form of MS (p = 0.01) and incomplete recovery at first relapse (p = 0.02).
During the initial course of MS, 349 patients had RR disease at disease onset and 58 PP disease (Table 1). In all, 142 patients had reached EDSS 4. The median time from MS onset to assignment of irreversible EDSS4 by the Kaplan-Meier method was 4.5 years [2.2–7.2]. In total, 188 (46.2%) had elevated CSF IgG index and 354 (87%) CSF OCGBs. The mean IgG index was 0.6 ± 0.7 and mean CSF total protein level 345.5 ± 219.7 mg/L. The proportion of CSF OCGBs was the same whatever the MS course, namely 87.1% and 86.2% of CSF OCGBs positives in RR and PP patients, respectively.
Table 2 gives the results of bivariate analyses of variables associated with median time from MS onset to EDSS4. Among biological variables, CSF total protein level < 500 mg/L was associated with EDSS 4 (HR 0.66, 95% CI 0.46–0.95). Older age at MS onset (≥29 years) was associated with poor prognosis; for age between 29 and 38 years, the HR was 2.56 (95% CI 1.29–5.07) and between 39 and 49 years, 2.58 (1.27–5.25). Univariate analysis showed no significant association of Barkhof criteria (HR 0.8, 95% CI 0.48–1.4; p = 0.4). Other variables associated with good prognosis were the RR form of MS (HR 0.15, 95% CI 0.10–0.21), female sex (HR 0.45, 95% CI 0.32–0.62) and undergoing a treatment (HR 0.20, 95% CI 0.14–0.28).
The time to assignment of irreversible EDSS 4 did not differ for patients without and with OCGBs (5.4 vs. 4.9 years, p = 0.52) and for patients with and without IgG index < 0.60 (4.9 vs. 5.2 years, p = 0.65). This did not differ when varying the IgG index threshold to < 0,65 (p = 0,73) or to < 0,7 (p = 0,81).
Table 3 presents the results of multivariate analysis with extended Cox regression models and reveals no significant impact of routine CSF biological markers on assignment of EDSS 4. Even when adjusting for major covariates at onset (age) and at diagnosis (sex, initial course of MS, Barkhof's criteria, treatment), older age at onset (≥50) (HR 2.48, 95% CI 1.11–5.55) and initial PP course (HR 3.12, 95% CI 2.03–4.79) were associated with poor prognosis, while OCGBs (HR 0.76, 95% CI 0.45–1.30) and IgG index (HR 1.36, 95% CI 0.92–2.02) were not.
Results
Baseline characteristics are in Table 1. The mean age at MS onset was 33.0 ± 11.1 years. The median time between MS onset and CSF testing was 4.6 years [1.0–7.0]. Among registered patients, those included and not included in the study did not differ in age at onset (p = 0.41) and gender (p = 0.31) but did differ in the initial form of MS (p = 0.01) and incomplete recovery at first relapse (p = 0.02).
During the initial course of MS, 349 patients had RR disease at disease onset and 58 PP disease (Table 1). In all, 142 patients had reached EDSS 4. The median time from MS onset to assignment of irreversible EDSS4 by the Kaplan-Meier method was 4.5 years [2.2–7.2]. In total, 188 (46.2%) had elevated CSF IgG index and 354 (87%) CSF OCGBs. The mean IgG index was 0.6 ± 0.7 and mean CSF total protein level 345.5 ± 219.7 mg/L. The proportion of CSF OCGBs was the same whatever the MS course, namely 87.1% and 86.2% of CSF OCGBs positives in RR and PP patients, respectively.
Table 2 gives the results of bivariate analyses of variables associated with median time from MS onset to EDSS4. Among biological variables, CSF total protein level < 500 mg/L was associated with EDSS 4 (HR 0.66, 95% CI 0.46–0.95). Older age at MS onset (≥29 years) was associated with poor prognosis; for age between 29 and 38 years, the HR was 2.56 (95% CI 1.29–5.07) and between 39 and 49 years, 2.58 (1.27–5.25). Univariate analysis showed no significant association of Barkhof criteria (HR 0.8, 95% CI 0.48–1.4; p = 0.4). Other variables associated with good prognosis were the RR form of MS (HR 0.15, 95% CI 0.10–0.21), female sex (HR 0.45, 95% CI 0.32–0.62) and undergoing a treatment (HR 0.20, 95% CI 0.14–0.28).
The time to assignment of irreversible EDSS 4 did not differ for patients without and with OCGBs (5.4 vs. 4.9 years, p = 0.52) and for patients with and without IgG index < 0.60 (4.9 vs. 5.2 years, p = 0.65). This did not differ when varying the IgG index threshold to < 0,65 (p = 0,73) or to < 0,7 (p = 0,81).
Table 3 presents the results of multivariate analysis with extended Cox regression models and reveals no significant impact of routine CSF biological markers on assignment of EDSS 4. Even when adjusting for major covariates at onset (age) and at diagnosis (sex, initial course of MS, Barkhof's criteria, treatment), older age at onset (≥50) (HR 2.48, 95% CI 1.11–5.55) and initial PP course (HR 3.12, 95% CI 2.03–4.79) were associated with poor prognosis, while OCGBs (HR 0.76, 95% CI 0.45–1.30) and IgG index (HR 1.36, 95% CI 0.92–2.02) were not.
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