Time correlation between mononucleosis and initial symptoms of MS

Area of Science:

• Neurology
• Epidemiology
• Immunology

Background:

• Epstein-Barr virus (EBV) infection, often manifesting as infectious mononucleosis (IM), is a known risk factor for multiple sclerosis (MS).
• The precise temporal relationship between EBV infection and MS onset, particularly considering demographic and immunological factors, remains an area of active investigation.

Purpose of the Study:

• To investigate the average age of MS onset in relation to the age of prior Epstein-Barr infection.
• To stratify this relationship by sex and levels of Epstein-Barr nuclear antigen 1 (EBNA1) antibody titers.

Main Methods:

• Utilized data from the Swedish epidemiologic investigation of MS, identifying 259 adult infectious mononucleosis/multiple sclerosis (IM/MS) cases.
• Augmented data to include childhood infection periods, enabling determination of average MS onset age stratified by IM age, sex, and EBNA1 titer.

Main Results:

• A positive time correlation was observed between IM and MS onset across all ages (approximately 5-30 years), with the delay decreasing as age at IM increased.
• Males and individuals with high EBNA1 titers exhibited a stronger positive correlation, indicating faster MS development post-IM.
• Females and those with low EBNA1 titers showed a negative correlation (longer delay) in early childhood, with a shift to positive correlation after puberty.

Conclusions:

• The observed time correlations suggest a causal link between IM and MS, particularly if IM occurs randomly in time.
• Childhood EBV infection in females or those with low EBNA1 titers is associated with a slower MS development.
• Males and individuals with high EBNA1 titers experience more rapid MS development following IM at any age.
• Post-pubescent EBV infection appears critical for initiating and rapidly progressing MS in all individuals.