Background

Historically, disease activity diminished during pregnancy in women with relapsing-remitting MS. Today, women with high disease activity are more likely to attempt pregnancy due to the disease control that new therapies offer. But disease activity during pregnancy in the modern day remains understudied.

Objectives

Describe disease activity in a modern pregnancy cohort, grouped by preconception disease-modifying therapy (DMT) class; determine the predictors of relapse during pregnancy.

Methods

Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 were included. DMT were classed by low, moderate and high-efficacy. Annualized relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of relapse during pregnancy were determined using clustered logistic regression.

Results

We included 1640 pregnancies from 1452 women. DMT used in the year before conception were none (n=346), low (n=845), moderate (n=207) and high-efficacy (n=242). Most common DMT in each class was interferon-beta (n=597), fingolimod (n=147) and natalizumab (n=219) for low, moderate and high-efficacy respectively. Conception EDSS ≥2 was more common in higher efficacy DMT groups (high: 41.3%; moderate 28.5%; low 22.4%; none 20.2%). For low-efficacy and no DMT groups, ARR fell through pregnancy. ARR of the moderate-efficacy group increased in the 1^st pregnancy trimester (0.55 [95% CI 0.36-0.80] vs 0.14 [95% CI 0.10-0.21] on low-efficacy), then decreased to a trough in the third. Conversely, ARR steadily increased throughout pregnancy for those on high-efficacy DMT (3^rd trimester: 0.42 [95% CI 0.25-0.66] vs 0.12 [95% CI 0.07-0.19] on low-efficacy). Higher efficacy DMT groups were associated with higher ARR in the early postpartum period (high: 0.84 [95% CI 0.62-1.1]; moderate: 0.90 [95% CI 0.65-1.2]; low: 0.47 [95% CI 0.38-0.58]). Preconception use of high and moderate-efficacy DMT and higher preconception ARR were predictors of relapse in pregnancy. But, continuation of high-efficacy DMT into pregnancy was protective against relapse (odds ratio 0.80 [95% CI 0.68-0.94]). Age ≥35 years was associated with reduced odds of relapse.

Conclusions

Women with RRMS treated with moderate or high-efficacy DMT are at greater risk of relapse during pregnancy. Careful pregnancy management, and use of long-acting high-efficacy DMT preconception, or continuing natalizumab into pregnancy, may prevent relapse in pregnancy.

Background

The concept of no evidence of disease activity-3 (absence of brain MRI and clinical disease activity; NEDA-3) in multiple sclerosis (MS) reflects disease activity with limited sensitivity. The added value of neurofilament light chain levels in serum (sNfL) to NEDA-3 has not yet been investigated.

Objectives

To assess whether sNfL allows to identify among patients with and without NEDA-3 status those at higher risk of future disease activity and accelerated brain volume loss.

Methods

We analyzed 369 samples from 155 early relapsing-remitting MS patients (SET study). sNfL levels and brain MRI scans were evaluated annually. The comparison of subgroups defined by high or low sNfL (>90^th or <90^th percentile of healthy controls of the same age) and NEDA-3 status was performed by generalized estimating equation models. Changes in global and regional brain volumes were calculated on three-dimensional T1-weighted scans.

Results

Patients with disease activity (EDA-3) in the preceding year and high sNfL, compared to those with low sNfL, had: a) higher odds of EDA-3 in the following year (87% versus 58%; OR 4.39, 95%-CI:2.18, 8.94; p<0.001), b) greater whole brain volume loss during the following year (0.39%, 95%-CI:-0.63, -0.16; p<0.001) and c) greater whole brain volume loss (0.61%, 95%-CI:-0.66, -0.17; p<0.001) during the preceding year. Accordingly, NEDA-3 patients with high sNfL showed a trend for a return of disease activity (EDA-3) in the following year compared with those with low sNfL (57% versus 31%).

Conclusions

High sNfL levels are associated with increased future risk of disease activity and accelerated brain volume loss. Adding of sNfL improves the prognostic value of the NEDA-3 concept.

Background

Recent studies have described Multiple Sclerosis (MS) as a disconnection syndrome (Rocca et al. 2015). Modelling disconnectomes using brain networks enables to quantify connectivity loss using graph analysis. To build structural connectomes, high-quality diffusion Magnetic Resonance Imaging (dMRI) and robust tractography algorithms are typically required. However, high-quality dMRI is rarely acquired in clinical workups due to time constraints.

Objectives

We propose to use a tractography atlas to extract brain connectivity loss in response to lesions without requiring dMRI, and to model structural disconnectomes with brain graphs. Topological graph features are proposed as new radiological biomarkers and their relation with Total Lesion Volume (TLV) and Expanded Disability Status Scale (EDSS) are studied.

Methods

589 MS patients (159 males, age 28±8yo, EDSS 2.40±1.22, TLV 13.0±14.6mL) underwent MRI at 3T (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). Acquisition protocols included T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) and fluid-attenuated inversion recovery (FLAIR).

Lesions were segmented using LeMan-PV, a prototype lesion segmentation algorithm (Fartaria et al. 2016). The lesion masks were registered to standard MNI space and overlapped with the HCP842 tractography atlas (Yeh et al. 2018). Streamlines passing through lesions were isolated to define the affected connectivity.

The disconnectome graph was built using brain regions from the Brainnetome atlas (Fan et al. 2016) as nodes, whilst edges were weighted by the percent of unaffected streamlines connecting two nodes relative to the atlas connectivity. Topological features were extracted from the disconnectome graph and their Spearman’s correlations with TLV and EDSS were computed.

Results

Transitivity (T) and global efficiency (GE) decreased for larger TLV (R=-0.42 and R=-0.78), whereas the average shortest path length (PL) increased (R=0.78). When looking at correlations with EDSS, T (R=-0.17), GE (R=-0.24) and PL (R=0.23) showed stronger associations than lesion count (R=0.14) but were comparable to TLV (R=0.23). All correlations were significant (p<0.001).

Conclusions

We proposed an atlas-based disconnectome model which allowed to study connectivity loss in MS patients without requiring dMRI. Overall, patients showed a lower small-worldness and efficiency for larger TLV and worse disability. These observations were consistent with previous studies on diffusion-based connectomes and open new avenues of research for routine clinical data.

Background

Serum neurofilament light chain (sNfL) levels reflect only neuro-axonal injury that took place within 3-6 months prior to the date of sampling. Therefore, the frequency of assessment of sNfL levels for monitoring of disease activity warrants further investigation.

Objectives

To determine differences in accuracy of sNfL levels to detect radiological disease activity during the preceding 6 versus 12 months of follow-up.

Methods

This observational study included 148 patients with early relapsing-remitting multiple sclerosis (MS) from the SET cohort. Based on brain MRI performed at 0, 6 and 12 months, we assessed the ability of categorized sNfL measured at 12 months to reflect the presence of combined unique active lesions, defined as new/enlarging lesion compared with MRI performed in the previous 6 versus 12 months or contrast-enhancing lesion (e.g., active lesions).

Results

Together, 91% (95% CI=85-98%) of patients with ≥1 active lesion during the last 6 months and 84% (95% CI=77-92%) of patients with ≥1 active lesion during the last 12 months had sNfL≥30^th percentile. Among the patients with sNfL<30^th percentile, 14 (33.3%) developed ≥1 active lesion during the last 12 months, but only 6 (14.3%) developed ≥1 active lesion during the last 6 months. Among patients with sNfL<30^th percentile, 6 (14.3%) developed ≥2 active lesions during the last 12 months, but only 2 (4.8%) developed ≥2 active lesions during the last 6 months.

Conclusions

Low levels of sNfL better identified MS patients with the absence of recent radiological disease activity during the previous 6 than the previous 12 months. In the future, assessment of sNfL at least every 6 months may substitute the need for annual brain MRI monitoring to exclude brain lesion activity in clinically stable patients with low sNfL levels.

Background

Regional brain atrophy is a sensitive disability marker for MS patients. A previous study has shown that atrophy of the corpus callosum is an early marker for disease progression. However, the relationship between diffuse pathology in specific brain regions and the course of regional atrophy development remains poorly understood.

Objectives

To investigate quantitative T1 maps and entropy (amount of T1 inhomogeneity) in regional brain structures from diagnostic MRI (performed at disease onset) of MS patients and compare these findings with healthy controls (HC).

Methods

Fifty MS patients and 102 HC were examined on a 3T MRI scanner (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). The MRI protocol comprised 3D MP2RAGE, 3D MPRAGE, 3D FLAIR and 3D DIR. The calculation of T1 maps, brain structure segmentations and brain volume measurements were obtained from a single MP2RAGE scan. Lesion segmentation masks were obtained using the LeManPV prototype software (Siemens Healthcare, Erlangen, Germany). We evaluated T1 maps from normal-appearing white matter (excluding lesions) in the corpus callosum, the brain lobes, brainstem and cerebellum, as well as from normal-appearing gray matter (excluding lesions) in the thalami, basal ganglia, and cortical gray matter. We calculated median regional T1 relaxation times, T1 entropy and volume for the above-mentioned structures for the early-MS group and 50 age- and sex-matched HC subjects. Statistical comparison was performed using t-tests.

Results

The median T1 of the corpus callosum in the early MS group was 838 ms (SD 38.5), with entropy 8.42 (SD 0.24); compared to 810 ms (SD 25.2) and 8.23 (SD 0.13) in the HC group. Statistically significant differences were found in T1 times and entropy between the groups (p<0.001); volumes were, however, not statistically different. Smaller but also statistically significant differences in T1 maps and entropy were found for white matter of the brain lobes (p<0.001). Thalami volumes showed statistically significant differences between groups, but not median T1 times (MS group 1055 ms, SD 32.6 vs. HC 1049 ms, SD 21.2).

Conclusions

Pathology of the normal-appearing white matter in T1 relaxometry can already be detected at MS disease onset. In particular, corpus callosum T1 times were considerably higher at clinical onset of MS compared to HC. We hypothesize that early microstructural changes detected at disease onset lead to evolution of regional brain atrophy.

Background

The presence of infratentorial lesions early in the disease has been shown to have prognostic value for future disability in multiple sclerosis (MS). Quantitative imaging metrics such as T1 relaxometry might contribute to understanding the relationship between supratentorial (ST), infratentorial (IT), and spinal cord (SC) pathology.

Objectives

Our aim was to explore the association between ST, IT and SC pathology and microstructural tissue alterations assessed with T1 relaxometry in T2-hyperintense lesions as well as cerebral and cerebellar normal-appearing white matter (NAWM) in patients with recently diagnosed MS with- and without IT lesions.

Methods

Microstructural tissue alterations were assessed in 42 patients (mean age 33.6±8.0 years, median MS duration 0.2 years (0-2.3)) as deviations from normative T1 times, both obtained from the MP2RAGE sequence at 3T (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). The normative T1 values were voxel-wise modelled via a study-specific atlas based on spatially normalized data from 102 healthy individuals (21-59 years). Relationship between normalized IT volumes (mesencephalon, pons, medulla oblongata, cerebellum), SC volume, ST and IT lesion loads estimated by the Morphobox prototype, Scanview and LemanPV prototype, respectively and the deviations from normative T1 times expressed as z-score-derived metrics (volumes and means of voxels with z-scores above z-score 2 and below z-score 2) in lesions, cerebral and cerebellar NAWM were studied by partial correlations adjusted for age and brain lesion volume.

Results

Patients with IT lesions (n=23, 33.0±8.5 years) had larger lesion load, higher volumes of voxels with positive z-scores (> 2), higher mean of z-scores above 2 in lesions, and larger thalami than patients without IT lesions (n=19, 34.3±7.7 years). The remaining volumes and z-scores derived metrics did not differ between groups. Cerebellar volume correlated negatively with volume of voxels with negative z-scores (< 2) in cerebellar NAWM (partial correlation coefficient r=-.437, p=.005) only in patients with IT lesions. In patients without IT lesions, SC and pons volumes correlated negatively with volume of voxels with positive z-scores corresponding to areas of supratentorial T2 lesions (SC: r=-.669, p=.003, pons: r=-0.606, p=0.01).

Conclusions

Microstructural alterations identified as T1 z-scores relate differently to IT and SC volumes in MS patients with and without IT lesions. In the presence of IT lesions, changes in cerebellar NAWM (T1 shortening relative to healthy controls) are associated with lower cerebellar volume. In the absence of IT lesions, the association of cerebellar NAWM and cerebellar volume is not present. In patients without IT lesions, microstructural alterations in ST lesions (T1 prolongation) that might indicate the extent of tissue damage in lesions, are associated with lower pontine and SC volumes regardless of the T2 lesion load.

Background

Although conventional MRI acquisitions are of essence in the monitoring of MS, they show low specificity towards the microstructural nature of tissue alterations and exhibit rather low correlations with clinical metrics (“clinico-radiological paradox”). Conversely, recent advances in brain relaxometry allow characterizing microstructural alterations on a single-subject basis; the question yet remains whether such quantitative measurements can help bridging the gap between radiological and clinical findings.

Objectives

This study investigates whether automatically assessed alterations of T₁ relaxation times in brain lesions and normal-appearing white matter (NAWM) improve clinico–radiological correlations in early MS with respect to conventional measures.

Methods

102 healthy controls (65% female, [21-59] y/o) and 50 early-MS patients (76% female, [19-52] y/o) underwent MRI at 3T (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). The employed 3D protocol comprised MPRAGE, FLAIR (both used for lesion segmentation as in [Fartaria et al., 2017, MICCAI]), and MP2RAGE for T₁ mapping.

After the healthy controls’ data were spatially normalized into a study-specific template, reference T₁ values in healthy tissues were established by linear, voxel-wise modelling of the T₁ inter-subject variability [Piredda et al., MRM, 2020]. In the MS cohort, T₁ deviations from the established references were calculated as z-score maps.

Correlations between the EDSS and conventional measures, i.e. lesion volume and count, were compared against correlations with z-score-derived metrics in lesions and NAWM, namely the volume of voxels exceeding a given z-score threshold.

Results

Correlations between EDSS and lesion volume and count were found to be 0.23 and 0.18, respectively. Higher correlations were found between EDSS and the volume of voxels exceeding an absolute z-score threshold of 2, both in lesions and NAWM, with ρ=0.3 and ρ=0.33, respectively. Correlation further improved when considering only negative z-scores, ρ=0.36 for lesions and ρ=0.39 for NAWM. The highest correlation was found when considering absolute z-scores in the occipital lobe NAWM, ρ=0.47.

Conclusions

Microstructural alterations identified as T₁ z-scores were found to improve clinico–radiological correlation in comparison to conventional measures (lesion volume and count). Of notice, negative z-scores (i.e. abnormal T₁ shortening), which may be due to an increase in iron content, appear to be a potential predictor for the clinical state of an early MS patient.

Background

SC pathology occurs early in the course of MS. However, few studies have investigated the relationship between lesions, diffuse changes and mean upper cervical cord area (MUCCA) in MS patients with different levels of disability in detail.

Objectives

To explore spinal cord (SC) pathology in multiple sclerosis (MS) patients with different levels of disability and MS phenotypes.

Methods

638 MS patients with different degrees of disability and 102 healthy controls (HC) underwent MRI on a 3T (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). The MRI protocol comprised transversal 3D-T2WI for MUCCA, sagittal T2WI-Fat-Sat and PDWI for SC pathology, and 3D-MPRAGE for regional brain volume (BV). MUCCA was measured automatically between the C3 and C4 vertebra (ScanView.cz). Global and regional BVs were estimated by the fully automated MorphoBox prototype (Siemens Healthcare, Erlangen, Germany). Diffuse changes, number and location of SC lesions were assessed manually. Patients and HC were matched by sex and age using propensity scores. MUCCA, regional BVs and SC pathology were compared among matched subgroups of: 54 patients with mild disability (EDSS=<1.5), 54 patients with mild-to-moderate disability (EDSS 2-3.5), 54 patients with severe disability (EDSS 4-4.5), 54 patients with very severe disability (EDSS>=5), 18 primary progressive (PP) patients, and 54 controls from the HC group. ANOVA test was used for between-group comparison.

Results

There was a trend of lower MUCCA with higher disability level. Mean MUCCA was 76.5±10.8 mm² invery severe, 80.1±9.6 mm² in severe, 85.7±8.0 mm² in moderate, 85.6±8.5 mm² in mild disability, and 90±7.7 mm² in HC groups. There was a significant difference in MUCCA between HC and mild disability group (p<0.001). SC pathology was prominent in 64.1% of the patients with mild disability, compared to 90.4% patients with very severe disability. The percentage of diffuse changes varied greatly between the groups, with prevalence increasing almost four times between patients with mild and very severe disability.

Conclusions

SC pathology is present in all disability MS groups. MUCCA differentiated between patients with mild disability and healthy controls, suggesting that it may be promising for the implementation in diagnostic protocols. The evaluation of diffuse changes can help to predict disability. Low MUCCA together with prominent diffuse changes could help differentiate PP MS from other MS phenotypes.

Background

The dynamic of lesion activity and brain volume changes during the post-partum period in women with multiple sclerosis (MS) is not well understood.

Objectives

To describe the evolution of clinical and radiological disease activity, including brain volume loss during the pregnancy and post-partum period.

Methods

In this observational study of 62 women with relapsing-remitting MS, all 221 brain MRI scans were performed on the same 1.5-Tesla scanner. T2 lesion and brain volumes were analyzed by ScanView. MRI and clinical visits were scheduled at: late pre-pregnancy period: <24 and >6 months before pregnancy (56-measures); early pre-pregnancy period: <6 months before pregnancy (62-measures); early post-partum period: <3 months after delivery (62-measures); and late post-partum period: >12 and <24 months after delivery (41-measures). Differences in disease activity among time points were analyzed using the Wilcoxon signed-rank test.

Results

Eighteen (29.0%) women had a relapse during the year preceding pregnancy-onset, 9 (14.5%) women had a relapse during the pregnancy and 20 (32.3%) women had a relapse during the year following delivery. Disability status, as assessed by the expanded disability status scale (EDSS) remained unchanged during the follow-up. Women in early post-partum period (post) had higher T2 lesion volume (median: 0.94 ml vs 1.18 ml-post), greater annualized T2 lesion volume increase (0.0 ml vs 0.23 ml-post), lower brain parenchymal fraction (86.4% vs 85.7%-post) and greater annualized brain volume loss (-0.12% vs.-1.44%-post) compared with early pre-pregnancy period (all p>0.001). Forty-one women with available MRI data in late post-pregnancy (late-post) period had similar T2 lesion volume (1.18 ml vs 1.16 ml-late-post; p=0.14) and higher brain parenchymal fraction (85.6% vs. 86.0%-late-post; p=0.007) compared to early post-partum period.

Conclusions

The early post-partum period was associated with a transient increase in T2 lesion volume and accelerated brain volume loss compared to the pre-pregnancy period. In a proportion of women, newly accumulated T2 lesion volume and decreased brain parenchymal fraction did not return to its pre-pregnancy levels. These findings argue against any general protective effect of pregnancy on MS.

Background

Disease activity has been investigated in pregnant women with RRMS treated with low-efficacy or no therapy. How newer, more efficacious therapies affect relapse and disability progression risk after pregnancy remains understudied.

Objectives

To describe disease activity in a modern pregnancy cohort contrasted with historical cohorts. To determine the predictors of postpartum relapse and the predictors of six-month confirmed disability progression events in a contemporary pregnancy cohort.

Methods

Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 (modern cohort) were compared with those conceived between 2005-2010 and pre-2005. Annualised relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of time-to-relapse postpartum (1^st 3 months) and time to 6-month confirmed disability progression event were determined with clustered Cox regression analyses. Breastfeeding duration and time to DMT reinitiation were modelled as time-varying covariates.

Results

We included 1640 pregnancies from 1452 women (modern cohort). Disease-modifying therapy (DMT) used in the year before conception included interferon-beta (n=597), natalizumab (n=219) and fingolimod (n=147). Continuation of DMT up to conception increased over time (31% pre-2005 vs 54% modern cohort). Preconception ARR decreased across epochs (pre-2005: 0·58 [95% CI 0·49-0·70]; 2005-2010: 0·40 [95% CI 0·36-0·45]; modern: 0·29 [95% CI 0·27-0·32]). In all epochs, ARR decreased during pregnancy to reach similar troughs in the 3^rd trimester, and rebounded in the 1^st 3-months postpartum. Preconception use of high-efficacy DMT predicted early postpartum relapse (hazard ratio (HR) 2.1 [1.4-3.1]); although those on no DMT were also at risk of postpartum relapse, relative to women on low-efficacy DMT (HR 2.7 [1.2-5.9]). Conception EDSS ≥2, higher preconception and in-pregnancy ARR were also risk factors. DMT reinitiation, particularly of high-efficacy DMT (HR 0.17 [0.07-0.38]), was protective against postpartum relapse. Women who breastfed were less likely to relapse (HR 0.63 [0.42-0.94]). 4.5% of modern pregnancies had confirmed disability progression after delivery. This was predicted by higher pregnancy and postpartum ARR, with postpartum ARR remaining independently predictive in multivariable analysis (HR 1.5 [1.2-2.0]).

Conclusions

The early postpartum period remains a period of vulnerability for disease rebound in women with MS in the modern era. Early DMT reinitiation, particularly with high-efficacy treatment, is protective against postpartum relapse. Confirmed disability progression events after pregnnacy are uncommon in the modern era. Relapse activity is the key driver of these events.

Background

The concept of no evidence of disease activity-3 (absence of brain MRI and clinical disease activity; NEDA-3) in multiple sclerosis (MS) reflects disease activity with limited sensitivity. The added value of neurofilament light chain levels in serum (sNfL) to NEDA-3 has not yet been investigated.

Objectives

To assess whether sNfL allows to identify among patients with and without NEDA-3 status those at higher risk of future disease activity and accelerated brain volume loss.

Methods

We analyzed 369 samples from 155 early relapsing-remitting MS patients (SET study). sNfL levels and brain MRI scans were evaluated annually. The comparison of subgroups defined by high or low sNfL (>90^th or <90^th percentile of healthy controls of the same age) and NEDA-3 status was performed by generalized estimating equation models. Changes in global and regional brain volumes were calculated on three-dimensional T1-weighted scans.

Results

Patients with disease activity (EDA-3) in the preceding year and high sNfL, compared to those with low sNfL, had: a) higher odds of EDA-3 in the following year (87% versus 58%; OR 4.39, 95%-CI:2.18, 8.94; p<0.001), b) greater whole brain volume loss during the following year (0.39%, 95%-CI:-0.63, -0.16; p<0.001) and c) greater whole brain volume loss (0.61%, 95%-CI:-0.66, -0.17; p<0.001) during the preceding year. Accordingly, NEDA-3 patients with high sNfL showed a trend for a return of disease activity (EDA-3) in the following year compared with those with low sNfL (57% versus 31%).

Conclusions

High sNfL levels are associated with increased future risk of disease activity and accelerated brain volume loss. Adding of sNfL improves the prognostic value of the NEDA-3 concept.

Background

Serum neurofilament light chain (sNfL) levels reflect only neuro-axonal injury that took place within 3-6 months prior to the date of sampling. Therefore, the frequency of assessment of sNfL levels for monitoring of disease activity warrants further investigation.

Objectives

To determine differences in accuracy of sNfL levels to detect radiological disease activity during the preceding 6 versus 12 months of follow-up.

Methods

This observational study included 148 patients with early relapsing-remitting multiple sclerosis (MS) from the SET cohort. Based on brain MRI performed at 0, 6 and 12 months, we assessed the ability of categorized sNfL measured at 12 months to reflect the presence of combined unique active lesions, defined as new/enlarging lesion compared with MRI performed in the previous 6 versus 12 months or contrast-enhancing lesion (e.g., active lesions).

Results

Together, 91% (95% CI=85-98%) of patients with ≥1 active lesion during the last 6 months and 84% (95% CI=77-92%) of patients with ≥1 active lesion during the last 12 months had sNfL≥30^th percentile. Among the patients with sNfL<30^th percentile, 14 (33.3%) developed ≥1 active lesion during the last 12 months, but only 6 (14.3%) developed ≥1 active lesion during the last 6 months. Among patients with sNfL<30^th percentile, 6 (14.3%) developed ≥2 active lesions during the last 12 months, but only 2 (4.8%) developed ≥2 active lesions during the last 6 months.

Conclusions

Low levels of sNfL better identified MS patients with the absence of recent radiological disease activity during the previous 6 than the previous 12 months. In the future, assessment of sNfL at least every 6 months may substitute the need for annual brain MRI monitoring to exclude brain lesion activity in clinically stable patients with low sNfL levels.

Background

The dynamic of lesion activity and brain volume changes during the post-partum period in women with multiple sclerosis (MS) is not well understood.

Objectives

To describe the evolution of clinical and radiological disease activity, including brain volume loss during the pregnancy and post-partum period.

Methods

In this observational study of 62 women with relapsing-remitting MS, all 221 brain MRI scans were performed on the same 1.5-Tesla scanner. T2 lesion and brain volumes were analyzed by ScanView. MRI and clinical visits were scheduled at: late pre-pregnancy period: <24 and >6 months before pregnancy (56-measures); early pre-pregnancy period: <6 months before pregnancy (62-measures); early post-partum period: <3 months after delivery (62-measures); and late post-partum period: >12 and <24 months after delivery (41-measures). Differences in disease activity among time points were analyzed using the Wilcoxon signed-rank test.

Results

Eighteen (29.0%) women had a relapse during the year preceding pregnancy-onset, 9 (14.5%) women had a relapse during the pregnancy and 20 (32.3%) women had a relapse during the year following delivery. Disability status, as assessed by the expanded disability status scale (EDSS) remained unchanged during the follow-up. Women in early post-partum period (post) had higher T2 lesion volume (median: 0.94 ml vs 1.18 ml-post), greater annualized T2 lesion volume increase (0.0 ml vs 0.23 ml-post), lower brain parenchymal fraction (86.4% vs 85.7%-post) and greater annualized brain volume loss (-0.12% vs.-1.44%-post) compared with early pre-pregnancy period (all p>0.001). Forty-one women with available MRI data in late post-pregnancy (late-post) period had similar T2 lesion volume (1.18 ml vs 1.16 ml-late-post; p=0.14) and higher brain parenchymal fraction (85.6% vs. 86.0%-late-post; p=0.007) compared to early post-partum period.

Conclusions

The early post-partum period was associated with a transient increase in T2 lesion volume and accelerated brain volume loss compared to the pre-pregnancy period. In a proportion of women, newly accumulated T2 lesion volume and decreased brain parenchymal fraction did not return to its pre-pregnancy levels. These findings argue against any general protective effect of pregnancy on MS.