Hospital General Universitario Gregorio Marañón
Department of Neurology

Author Of 3 Presentations

Neuropsychology and Cognition Poster Presentation

P0801 - Default Mode Network functioning and Multiple Sclerosis: the importance of phenotypes and cognition (ID 1661)

Abstract

Background

There is controversial data on the differential activity of the default mode network (DMN) in patients with Multiple Sclerosis (MS), and how it is linked to cognitive status. For some authors, there could be an initial hypercompensation, followed by a late exhaustion of the DMN. More research is needed to clarify how those changes may be related to cognition and the different phenotypes of MS.

Objectives

To evaluate the functional connectivity of DMN of MS patients with different phenotypes (relapsing-remitting (RR), clinically isolated syndrome (CIS) and primary progressive (PP) compared to healthy controls (HC).

Methods

Sixty-two participants (16 HC, 16 RR, 15 CIS and 14 PP) were evaluated with a neuropsychological battery to establish their cognitive profile. A functional magnetic resonance (fMRI) with a seed-to-voxel approach was performed to study the DMN, as defined by the Human Connectome Project. We selected four regions of interest: Posterior cingulated cortex (PCC); Medial prefrontal cortex (MPFC); Lateral parietal cortex Left (L-LPC) and Lateral parietal cortex Right (R-LPC). Correlation of their functional connectivity was analyzed considering different groups according to the MS phenotype.

Results

MS patients and HC were equivalent in age, years of education and gender. A 35,5% of MS patients were cognitively preserved, whereas 24(64,5%) had cognitive impairment: 12 were mild(MCI) and 12 moderate(ModCI). RR patients were significantly younger (M=37,9 old; SD=7,3) compared to CIS (M=40,8; SD=9,9) and PP (M= 49,4; SD=7,8). CIS patients had a shorter duration of MS (M=4,3 years; SD=3,9; p=0,013) compared to RR (age M=9,5; SD=5,6) and PP (M=9,9; SD=6,9). Groups were not homogeneous in terms of physical disability, being PP the most disabled (Mode=6) vs RR (Mode=2) or CIS (Mode=0). Regarding global DMN connectivity, no differences were found between HC and MS patients. However, when focusing on phenotypes, we found that CIS had a trend to a higher connectivity than HC and that connectivity steadily decreased though RR to PP, so that PP activity was significantly lower than that of CIS (p=0,019). No differences were found based on cognitive impairment. Antero-posterior connectivity was significantly higher for CIS than RR (p=0,017) and PP (p=0,018); and in cognitively preserved vs ModCI (p=0,03).

Conclusions

Our data supports the dynamic theory for functional connectivity that suggests an initial overcompensation followed by a gradual decline, which is elicited by studying MS phenotypes. Within the DMN, anterior-posterior connectivity was related to a worse cognitive performance.

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Pathogenesis – Immunology Poster Presentation

P0939 - Antibody titters against EBV and HHV-6A/B and expression of MSRV ENV in the serum of pregnant multiple sclerosis patients (ID 1197)

Abstract

Background

Pregnancy is a special period within the clinical course of multiple sclerosis (MS), characterized by a reduction in the relapse rate and slower disease progression. On the contrary, during puerperium, relapse rate increases again. Viruses have been related to the etiopathogenesis of the disease, especially with disease activity.

Objectives

To analyse the serum antibody titters against Epstein-Barr virus (EBV) (EBNA-1 and VCA) and human herpesvirus 6 A/B (HHV-6A/B), as well as the expression of the envelope protein of the MS-associated retrovirus (MSRV ENV) in pregnant MS patients during pregnancy and postpartum. To study their possible relationship with the disease activity during pregnancy and postpartum, as well as their potential role in predicting the risk of relapses.

Methods

Serum samples were collected from 71 pregnant women, 50 with MS and 21 healthy controls, at every trimester of pregnancy and in the postpartum. Antibody titters against the above mentioned viruses were analysed by ELISA commercial kits, following manufacturer instructions; gene expression of MSRV ENV was analysed by qRT-PCR.

Results

IgM titres against HHV-6A/B were higher in MS patients than in healthy controls in the three trimesters of pregnancy and in the postpartum period (U-Mann Whitney): p =0.00001 for the first trimester; p=0.021 for the second trimester; p = 0.000005 for the third trimester; p =0.001, for the postpartum period). Furthermore, IgM titres against HHV-6A/B in the first trimester were higher in patients with relapses (U Mann Whitney, p = 0.052). Regarding the expression of MSRV ENV, the percentage of positivity during the first trimester was significantly higher in MS patients with relapses during pregnancy compared to those who did not (Fisher, p = 0.038).

Conclusions

High IgM titters against HHV-6A/B and the expression of MSRV ENV during the first trimester of pregnancy could act as predictors of relapse risk during pregnancy / postpartum. Although further studies are needed to validate these results, this study support the relation between viruses and relapses in pregnant MS patients.

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Reproductive Aspects and Pregnancy Poster Presentation

P1138 - short-chain fatty acid during pregnancy in multiple sclerosis: a prospective cohort study (ID 1801)

Abstract

Background

Objective: Pregnancy reduces the annualized relapse rate (ARR) in multiple sclerosis (MS). However it is temporarily increased at puerperium. The exact mechanism underlying this clinical observation remains unknown.

Objectives

We aimed to explore the changes of the short-chain fatty acids (SCFAs) profiles in MS patients and healthy women (HCW) during pregnancy, and to assess any potential biomarker predicting the appearance of relapses during pregnancy and postpartum.

Methods

Methods: We included 53 pregnant MS patients and 21 HCW followed at Hospital Universitario Gregorio Marañón between 2007 and 2018. Patients were evaluated at every trimester of pregnancy and in the puerperium. Serum SCFAs were measured by liquid chromatography-mass spectrometry

Results

Results: Seventeen patients (32%) experienced relapses during pregnancy or puerperium (ACT group) and 37(68%) did not (NO-ACT group). We did not found differences in clinical characteristics or treatment status between the two groups. We observed differences in the SCFAs profile between ACT:NO-ACT groups during pregnancy and puerperium. Acetate levels were higher during the pregnancy-puerperium period in MS patients, regardless of clinical activity, compared to HCW (p: 0.0001). Interestingly, levels of propionate and butyrate below 1,985 μM (1,283 - 3.55) and 0.515 μM (0.01-2.943) respectively during the first trimester were associated with relapses during the pregnancy-puerperium period (p: 0.0001). The ACT group had a lower ratio of propionate/acetate and butyrate/acetate during pregnancy compared to NO-ACT group (<0.0001). The ROC curve showed that a propionate/acetate ratio of 0.36 (AUC 0.96, sensitivity 94%, specificity 92%;) has an OR=165 [CI: 10.2-239.4], p <0.0001) to predict relapses during pregnancy-puerperium.

Conclusions

Conclusions: SCFA levels during pregnancy may be associated with clinical activity in MS, and that their measurement could be useful in predicting the occurrence of relapses during this pregnancy-puerperium period

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