2021 CMSC Annual Meeting

Cerebrospinal Fluid Protein Is Higher in Males with Multiple Sclerosis: Results from an International Multicenter Cohort


Background: Sex has a differential effect on MS disease severity. Males tend to have a more severe clinical course and a greater tendency towards primary progressive phenotype and neurodegeneration compared to females. While hormonal factors are possible explanations of this variability, little is known about differences in cerebrospinal fluid (CSF) profile.
Objectives: To compare the cellular, chemical, and immunological profile of CSF at the time of diagnosis in MS patients stratified by sex.
Methods: This is a cross-sectional study. We analyzed data from CSF obtained at the time of MS diagnosis in patient cohorts at the Medical College of Wisconsin and Jordan University of Science and Technology. We compared nucleated cells (NCs), protein, IgG index, IgG synthesis rate, and oligoclonal band (OCBs) positivity. We used the student’s t-test to compare continuous variables and chi-square to compare categorical variables; p-value was set at 0.05.
Results: We included 43 male patients and 89 female patients who had complete CSF profiles. Age mean(SD) was 38.4(12.1) for males and 35(13) for females, p=0.59. Males included 23 Caucasians (53.5%), 10 Arabs (23.3%), 8 African Americans (18.60%), 2 Hispanics (4.7%). Female included 50 Caucasians (56.2%), 24 Arabs (27%), 14 African Americans (15.7%), 1 Hispanic (1.1%). Pleocytosis of >5 NCs was observed in 21/43(48.8%) of males and 39(43.8%) of females, p=0.59. The mean(SD) NCs were 5.65(5.84) in males and 5.73(6.94) in females, p=0.36. Protein was greater than 45mg/mL in 19/43(44.2%) of males and 17/87(19.5%) of females, p<0.005. The mean(SD) for CSF protein was 52.60(28.56) in males and 37.56(12.39) in females, p<0.005. Elevated IgG index >0.85 was observed in 10/36(27.8%) of males and 31/67(46.3%) of females, p=0.068. IgG index mean(SD) was 0.83(0.45) in males and 1.09(0.86) for females, p=0.11. IgG synthesis rate was >12 mg/24hrs in 7/30(23.3%) of males and 19/54(35.2%) of females, p=0.26. The mean(SD) of IgG synthesis rate was 9.69(7.49) in males and 12.77(17.73) in females, p=0.37. Unique OCBs of 2 or more were present in 29/43(67.4%) of males and 53/89(59.6%) of females, p=0.38.
Conclusions: In a multi-ethnic cohort of MS patients, males had significantly higher CSF protein than females. This may imply a sex difference in the blood-brain barrier (BBB) function. Future studies are needed to investigate sex differences in biomarkers of BBB permeability in MS and their association with the observed sex differences in clinical parameters.