Bulletin Spring 2018

Read more at:
mswa.org.au/researchupdate
From the Barts Blog.
EBV in the brain
Epstein Barr Virus (EBV) is a herpes virus spread by saliva and
infects around 95% of us during our lifetimes. In many people
EBV infection does not cause prominent symptoms – it may
cause a ‘flu-like’ illness which gets better on its own, or it
may go completely unnoticed.
Some people infected with EBV experience the more severe
illness – glandular fever or infectious mononucleosis – with
fatigue, sore throat, enlarged lymph nodes, fevers, and a mild
hepatitis (liver inflammation).
There is lots of evidence to suggest a link between EBV
infection and the risk of developing MS:
• PwMS have high levels of antibodies, suggesting a specific
immune response against EBV
• Slightly higher rates of EBV infection in pwMS; 100% of
pwMS are infected vs 95% of the general population
• Increased risk of developing MS after glandular fever; 2.5x
more likely
• The detection of EBV infection in the brains of pwMS
The hypothesis that EBV infection is an important step
in developing MS makes sense. We know EBV evades the
immune system by infecting B cells, driving them towards
dormancy, and then promoting their long-term survival.
EBV has an ingenious arsenal of tricks to promote its own
survival by fashioning a long-term niche for itself inside B
cells. This dormant period is termed ‘latent EBV infection.’
A minority of EBV-infected cells will enter the ‘lytic phase’ of
infection, in which the virus rapidly replicates, kills the host
cells, and is shed to infect other cells. Recent data suggests
that B cells are key drivers of the disease, any factor which
promotes survival of B cells and hijacks the normal pathways
of B cell maturation could conceivably predispose people to
developing the disease.
Whether EBV is present in the brains of people with MS has
been slightly controversial – some people have said yes, and
others have been unable to replicate those results.
A study used a combination of biopsy and post-mortem brain
tissue samples to see whether EBV-infected B cells could be
detected in the brain; samples came from 17 pwMS and nine
controls without neurological diseases.
Latent EBV infection was detected using a marker called
Latent Membrane Protein 1 (LMP1), and lytic infection was
detected using a marker called BZLF1. LMP1 was detected
in chronic lesions both with and without active inflammation.
Importantly, LMP1 was also present in the brains of healthy
individuals. BZLF1 was present in both control brains and
brains from pwMS. Interestingly, BZLF1 was not present in
chronic active lesions – this is surprising and implies that
lytic infection is present in healthy brains, in chronic inactive
lesions, but not in lesions with acute inflammation.
The blog comments that this paper does not answer the
question it set out to answer and they are unsure how to
interpret these results. EBV-infected B cells appear to be
present in both control and ‘MS’ brains, and may be slightly
more common in MS.
The best evidence to date does suggest that EBV is present
in both MS and control brains, but is more common in pwMS
(90% vs 24%).
Clearly, the presence of EBV-infected B cells in the brain is
not sufficient to drive disease activity. Further work needs to
be done to understand why some people are perfectly healthy
despite having EBV in their brain, whereas others go on to
develop MS. Deeper understanding of how EBV is linked to MS
is an essential first step towards developing safe treatments
(and vaccines) which target EBV. EBV-targeted treatments are
in early stages of development.
Spinal cord volume loss: A marker of disease progression
in multiple sclerosis.
Tsagkas C, Magon S, Gaetano L, Pezold S, Naegelin Y,
Amann M, Stippich C, Cattin P, Wuerfel J, Bieri O, Sprenger
T, Kappos L, Parmar K.Neurology. 2018 Jun 27. pii: 10.1212/
WNL.0000000000005853.
Cross-sectional studies show that spinal cord volume (SCV)
loss is related to disease severity in MS. However, long-term
data is lacking. This study aimed to evaluate SCV loss as a
biomarker of disease progression in comparison to other MRI
measurements in a large cohort of patients with relapseonset
MS with a six -year follow-up.
The upper cervical SCV, total brain volume, and the brain T2
lesion volume were measured annually in 231 patients with
MS (180 RRMS and 51 SPMS) over six years using three
-dimensional, T1-weighted, MRI images. Expanded Disability
Status Scale (EDSS) score and relapses were recorded at
every follow-up.
8 | MSWA BULLETIN SPRING 2018