Chapter 1, the introduction, summarizes current knowledge regarding two
special and different situations in multiple sclerosis (MS): Childhood
onset MS and MS during pregnancy.
Chapter 2 describes the clinical (chapter 2.1-2.3) and biological
studies (chapter 2.4-2.6) on pregnancy and MS. In chapter 2.1 we studied
the clinical course of multiple sclerosis before, during and after
pregnancy. We found that the relapse rate increased in the first three
months after delivery, yet normalized within one year after delivery.
Health-related quality of life (QoL) was improved during pregnancy, most
appreciated in the MOS 36 item short form health survey questionnaire
(SF-36) domains vitality and general health. Nine months or more after
delivery we found no adverse effects on MS disease activity at group
level, measured by the expanded disability status scale (EDSS), multiple
sclerosis impact scale 29 (MSIS-29), and the Guy’s neurological
disabilitity scale (GNDS). Nine months or more after delivery QoL,
measured by the SF-36, was not unfavorably altered when compared with
QoL during pregnancy. This indicates that, although the number of
relapses is increased in the short term after delivery, there are no
adverse effects of pregnancy on disease course in the mid-long term
after delivery. Until now the only known predictors of a postpartum
relapse are: number of relapses in the year preceding pregnancy, number
of relapses during pregnancy and duration of disease. We were not able
to reproduce these findings. In chapter 2.2 we describe data on
breastfeeding and disease activity that does not support the recent
claim that breastfeeding protects against postpartum relapse. In chapter
2.3 we found that high serum levels of the chemokine interleukin-8
(IL-8) during the first trimester were associated with postpartum
relapse. The low positive predictive value will likely limit clinical
use of IL-8 as a predictor of postpartum relapse. In chapter 2.4 we
performed a genome wide approach on alterations of the transcriptome of
monocytes of MS patients before and during the third trimester of
pregnancy. We found that during pregnancy expression of the Fc receptor
CD64 was increased. Our results therefore support the hypothesis that
the innate arm of the immune system is more activated during pregnancy.
In chapter 2.5 we investigated the numbers of circulating regulatory T
cells (Treg) and T helper (Th)17 cells. Unexpectedly, we found that the
numbers of circulating Treg were decreased, during the first and third
trimester of pregnancy in both MS patients and healthy controls. We
found no differences in the frequencies of circulating Th17 cells during
pregnancy in MS patients and healthy controls. We concluded that our
results did not support our hypothesis that peripheral blood Th17 and
Treg cells are directly involved in MS disease course alteration during
pregnancy. In chapter 2.6 we studied serum levels of leptin before,
during and after pregnancy in MS patients and healthy controls. We
observed a significant increase in serum levels of leptin in women with
MS during the third trimester, compared to baseline and first trimester
samples. Serum levels of leptin during pregnancy were not associated
with a postpartum relapse. Therefore, serum levels of leptin during
pregnancy cannot be used as a biomarker for postpartum relapse. We found
that women with MS with the largest relative decrease in serum leptin
levels after delivery more often had a postpartum relapse.
Chapter 3 describes the studies on childhood onset in MS. We performed a
retrospective nationwide study in all large neuro-pediatric centres in
The Netherlands, described in chapter 3.1. We included the full spectrum
of acquired demyelinating syndromes (ADS) of the central nervous
system. 44% of the children with a monofocal attack developed MS,
whereas 21% of the children with a polyfocal attack developed MS. Both
the Barkhof MRI-criteria and the KIDMUS MRI-criteria were able to
predict a future diagnosis of MS after a first demyelinating event. In
the very young, aged under ten, we found that the sensitivity of
especially the KIDMUS criteria was very low (18%). Cerebrospinal fluid
(CSF) analysis showed that an increased IgG index and presence of
oligoclonal banding both were able to predict MS. Strikingly, children
with and without encephalopathy both display MRI abnormalities as seen
in typical acute disseminated encephalomyelitis (ADEM) cases (large
lesions and basal ganglia/thalamic lesions). In chapter 3.2 we found
that children with MS, with MRI features consistent with three or four
out of the four Barkhof criteria for dissemination in space, were more
likely to have a relapse soon after their second, MS defining, attack.
We could not reproduce the predictive value of the childhood-onset MS
potential index for early severity. In chapter 3.3 we investigated the
capacity of all known diagnostic MRI criteria for children to
differentiate MS from acute disseminated encephalomyelitis (ADEM). We
found that the Callen criteria for discriminating MS from ADEM had the
best test properties.
In chapter 4, the discussion, the observations from the studies in
chapter 2 and 3 are summarized and discussed in relation to current
literature. Recommendations for further research are described.http://repub.eur.nl/res/pub/32110/120412_Neuteboom%2C%20Rinze.Frederik.pdf
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