Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

Abstract

Background: Reports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).

Objective: To assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.

Methods: CSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Q_alb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.

Results: Of 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Q_alb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.

Conclusions: CSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.

Keywords: albumin quotient; cerebrospinal fluid; cytology; diagnosis; immunoglobulin synthesis; multiple sclerosis; total protein; white blood cells.

Figure 1

Flowchart of patients included in the study. CIS, clinically isolated syndrome; FU, follow-up; PPMS, primary progressive MS; RBC, red blood cell; RRMS, relapsing remitting MS; SPMS, secondary progressive MS.

Figure 2

Routine CSF parameters in different MS disease courses. (A) Frequency of elevated WBC count (≥5/μl) is higher in relapsing than progressive MS. (B) Median WBC count is higher in relapsing than progressive MS. (C) Intrathecal IgG fraction is higher in secondary progressive than relapsing MS. (D) Frequency of intrathecal IgA and IgM synthesis is lower according to Auer & Hegen than Reiber formula. (E, F) Frequency of CSF-restricted OCB is highest in definite MS. Group comparisons were performed by Mann-Whitney-U test or Pearson Chi-squared test. P values (marked as p*) were corrected for multiple comparisons after Bonferroni. CIS, clinically isolated syndrome; CSF, cerebrospinal fluid; DIS, dissemination in space; dissemination in time; IF, intrathecal fraction; Ig, immunoglobulin; MRI, magnetic resonance imaging; MS, multiple sclerosis; OCB, oligoclonal bands; PPMS, primary progressive multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.