Longitudinal prediction of progression in MS: The PrograMS Cohort

Multiple sclerosis (MS) is the most important cause of acquired disability in
young adults with a significant impact on the lives of patients and their
relatives and forms a major economic burden to society. Both internal (e.g.
genetic) and external (e.g. environmental) factors are thought to play a role
in the initiation and the evolution of the disease process. That being said,
our understanding of the mechanisms involved in disease progression remains
limited. This scarcity of knowledge on the mechanism and predictors of disease
progression can lead to under- and overtreatment which can both negatively
affect patient wellbeing and societal costs.
A growing body of predominantly cross-sectional evidence has shown that both
conventional and advanced imaging and blood (bio)markers contain unique
(predictive) information on the clinical status and outcomes of patients with
MS. In the past decade, a number of studies have investigated the role of
conventional MRI (i.e. lesions) in disease progression and have indicated that
there is much to be gained in this field of research. The latest advancements
in the field explore the relationship between disease progression and advanced
imaging markers that are more sensitive to damage in the grey and white matter,
as well as serum-based biomarkers of inflammation and degeneration such as
Neurofilament Light (NfL). In addition, relative newcomers to the field with
high potential are changes in brain functioning and brain networks, as well as
neuro-ophthalmology.

The main objective of this project is to build a comprehensive model for a
better predictio n of progression in MS, as a first step to move towards
personalized prediction. Secondary objectives aim to study specific aspects of
underlying mechanisms of progression in MS. By investigating the evolution of
grey and white matter damage (lesions, atrophy, microstructural myelin damage),
changes is brain function and connectivity, and the relation of such measures
with ophthalmologic measurements (OCT and eye movements) and blood biomarkers
we aim to significantly improve our understanding of MS, its progression, and
its clinical course.

The proposed study is a single center, observational, follow-up cohort study
for which we aim to include all people with MS and all healthy controls (HC)
who have previously participated in the Presto, GeneOCT, and LTD studies
(collectively now known as *PrograMS*) and have not provided objection to be
contacted for follow-up study. The inclusion of the previously followed HC
groups associated with the three subcohorts is necessary as a reference to
understand the longitudinal changes in patients i.e. to distinguish
pathological change from normal variations over time and healthy aging .
Because of the large amount of persons to be included (around 240 patients and
60 controls) the total inclusion period and thereby duration of the acquisition
of data for this cohort visit is estimated at 1,5 years. All included persons
will be invited at the VUmc for a 1 day program in which all data will be
collected, which is comparable to earlier visits of these subjects.
All subjects in this study will visit the Amsterdam University Medical Center,
location VUmc. For patients the visit will consist of a neurological
examination, a neuropsychological examination, blood sampling (8 vials of 42
ml), MR imaging (~60 minutes, without contrast), a magnetoencephalography (MEG)
scan (~45 minutes) and retinal optical coherence tomography (OCT) and eye
movement examination. Healthy control subjects will undergo a similar protocol,
except for the neurological examination and blood sampling. All subjects will
fill out questionnaires on anxiety and depression, fatigue, sleep disturbances,
and subjective cognitive functioning. The entire protocol has been administered
before to all subjects in the study.

For patients, duration of the study will be a visit of approximately 6 hours
(including a 30-minute break halfway through the visit, and including 30
minutes of questionnaires which can optionally be completed at home). For
controls, the visit will last approximately 4 hours and 30 minutes (due to
exclusion of neurological examination and blood sampling). From previous
studies, the protocol is known to be well tolerated by patients.