Research Report: Predictive Role of Cerebrospinal Fluid Routine Parameters in the Disease Process of Multiple Sclerosis

Background

Multiple Sclerosis (MS) is characterized by a highly variable and unpredictable disease course. In the diagnosis of MS, cerebrospinal fluid (CSF) analysis is often a standard procedure. However, there has been ongoing debate in the academic community about whether CSF parameters can serve as indicators for predicting disease progression. With the continuous development and widespread use of disease-modifying therapies (DMTs), especially as their efficacy and safety differences become increasingly evident, finding reliable biomarkers to identify high-risk patients has become particularly important.

Although the diagnostic value of routine CSF analysis for MS is undisputed, its role in prognosis remains unclear. The presence of oligoclonal bands (OCBs) in CSF is independently associated with the conversion of MS from a clinically isolated syndrome to clinically definite MS. However, whether CSF parameters can predict disease activity and disability accumulation is yet to be determined.

Source of the Paper

This article was written by Cathérine Dekeyser et al., with authors from several international leading neurology research units, including the Department of Neurology at Ghent University Hospital in Belgium and Saint-Jan Bruges Hospital. The study was published in the Journal of Neurology, Neurosurgery & Psychiatry and has been accepted (March 22, 2024). The paper is included in the MSBase database, an international MS registry platform containing data from over 97,000 patients.

Research Process

This study is a large-scale cohort study aimed at exploring the association between routine CSF biomarkers and future MS disease progression. The study data comes from the MSBase database.

Subjects

The study included 11,245 MS patients, of which 93.7% (10,533 people) were relapsing-remitting MS (RRMS), and the remainder were primary progressive MS (PPMS). All patients met the following criteria: age ≥ 18 years, diagnosed with RRMS or PPMS according to the McDonald criteria, and underwent CSF analysis either before or within one year of diagnosis. The minimum data requirements included diagnosis date, birth date, disease onset date, gender, MS course, at least three Expanded Disability Status Scale (EDSS) scores after diagnosis, and at least one CSF measurement of interest (OCB status and/or IgG index and/or white cell count).

Process and Methods

Data was extracted on November 2, 2022, and all participants provided informed consent according to local regulations. The primary outcome measure was the time to confirmed attainment of EDSS 4, 6, and 7. Secondary outcome measures included the annualized relapse rate in the two years following diagnosis (ARR2) and the differences in CSF components between RRMS and PPMS.

The study used Cox regression analysis and multivariate linear regression analysis to assess the relationship between CSF parameters and the aforementioned outcomes. All analyses were performed using IBM SPSS statistical software.

Data Collection and Analysis

The time-to-event outcomes were analyzed using Cox proportional hazards models, and multivariate linear regression analysis (generalized linear models) was used to assess ARR2. In RRMS patients, the presence of OCBs was significantly associated with shorter disability milestones (EDSS 4, EDSS 6, and EDSS 7). Multivariate analysis indicated that in OCB-positive patients, the risk of reaching EDSS 4, 6, and 7 increased by 27.2%, 31.4%, and 68.6%, respectively. Additionally, elevated CSF cell count (≥5 cells/μl) was associated with a prolonged time to moderate disability (EDSS 4). On the other hand, in PPMS patients, CSF parameters were not significantly associated with the time to disability milestones.

Research Results

Primary Results

• In RRMS patients, the presence of OCBs was significantly associated with rapid progression to disability milestones (EDSS 4, 6, 7), while elevated CSF cell count may be a protective factor.
• In RRMS patients, elevated CSF cell count (≥5 cells/μl) was significantly associated with short-term inflammatory disease activity within the first two years.

Secondary Results

• In PPMS patients, CSF parameters were not significantly associated with disability accumulation.
• The differences in CSF components between RRMS and PPMS were reflected in the higher proportion of OCB-positive individuals among PPMS patients (88.8% vs. 84.4%).
• Age affected CSF white cell count, with the proportion of elevated CSF cells decreasing with age.

Significance of the Study

This study reveals that routine CSF analysis not only has diagnostic value but also provides prognostic information, especially for RRMS patients. CSF analysis can provide useful early-stage prognostic information, aiding in patient consultation, clinical decision-making, and treatment guidance.

Conclusion and Outlook

The study demonstrates the adverse prognostic role of CSF OCBs in RRMS, whereas elevated CSF cell count may be a protective factor. Although these findings were not validated in PPMS, they still provide valuable information for the clinical management of MS. Future research should further explore the impact of early application of highly effective therapies on CSF parameters and disease progression, and continue to seek more sensitive and quantitative biomarkers to optimize the diagnosis and prognosis of MS.

Research Highlights

• The large sample size and long-term follow-up make the conclusions more convincing.
• Confirms the significant association between CSF OCBs and accelerated disability in RRMS patients.
• Clarifies the impact of CSF white cell count on short-term inflammatory activity.
• Provides strong evidence for early prognosis, aiding decision-making in clinical practice.

The study proves the dual value of routine CSF analysis in both diagnosing and prognosing MS, particularly for RRMS patients. Future research should further investigate the application value of CSF parameters in effective treatment strategies to optimize treatment outcomes for MS patients.