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Short-chain fatty acids (SCFAs) can have pro- or anti-inflammatory properties, but their relationship with multiple sclerosis (MS) relapses during pregnancy remains unknown. This study aimed to explore SCFA profiles in MS patients during pregnancy and to assess their association with the appearance of relapses during pregnancy and postpartum.We prospectively included 53 pregnant MS patients and 21 healthy control women. Patients were evaluated during pregnancy and puerperium. SCFAs were measured by liquid chromatography-mass spectrometry.Sixteen patients (32%) had relapses during pregnancy or puerperium, and 37 (68%) did not. All MS patients showed significant increases in acetate levels during pregnancy and the postpartum period compared to non-MS women. However, propionate and butyrate values were associated with disease activity. Their values were higher in nonrelapsing patients and remained similar to the control group in relapsing patients. The variable that best identified active patients was the propionate/acetate ratio. Ratios of0.36 during the first trimester were associated with higher inflammatory activity (odds ratio = 165, 95% confidence interval = 10.2-239.4, p 0.01). Most nonrelapsing patients showed values of0.36, which were similar to those in healthy pregnant women.Low propionate/acetate ratio values during the first trimester of gestation identified MS patients at risk of relapses during pregnancy and the postpartum period.

Resumen Introduccion La esclerosis multiple (EM) es una enfermedad neurologica de origen autoinmune, degenerativa y cronica que aparece en adultos jovenes. Su manejo sanitario es complejo, ya que la enfermedad presenta una sintomatologia muy heterogenea y las necesidades de los pacientes son distintas segun la fase de la enfermedad en que se encuentren. En ocasiones las necesidades medicas pueden ser diferentes a las necesidades personales de los pacientes, por lo que es importante tener en consideracion su opinion sobre todo el proceso. Objetivos Conocer la experiencia de los pacientes con EM y sus familiares en relacion con la atencion recibida en el Hospital General Universitario Gregorio Maranon. Metodo Estudio cualitativo realizado en la consulta de Enfermedades Desmielinizantes del Servicio de Neurologia del Hospital General Universitario Gregorio Maranon. Se organizaron 3 grupos focales con un total de 26 personas provenientes de la mencionada consulta: 8 con una discapacidad fisica baja, 8 con mayor discapacidad fisica y 10 familiares/cuidadores de personas con EM. Se identifican 3 bloques tematicos a tratar: la informacion, la atencion recibida y el equipo sanitario. Resultados Los resultados muestran como la satisfaccion es alta con muchos de los servicios, asi como con los profesionales. Agradecen algunas de las iniciativas de intervencion, pero definen necesidades importantes en otras como la rehabilitacion fisica y la asistencia psicologica, tanto para pacientes como para familiares/cuidadores. Identifican la transdisciplinariedad como objetivo a futuro. Conclusiones Con estos datos buscamos reforzar los aspectos mejor calificados y trabajar posteriormente para cubrir y adaptar los procesos ofrecidos a los pacientes con EM.

Introduction Multiple sclerosis (MS) is an immunological, degenerative and chronic neurological disease that is frequently diagnosed in young adults. Medical care might be challenging as MS symptoms are heterogenic and sometimes medical-care team requirements might not meet MS patients’ needs. Objectives To learn the experience of patients and their caregivers of the medical care received in the Gregorio Maranon Hospital Demyelinating Unit. Method we designed a focus group with 26 participants incidentally recruited from the Gregorio Maranon Hospital Demyelinating Unit: 8 with low physical disability, 8 with high physical disability and 10 caregivers. Information was collected regarding three main topics: information, clinical care and medical team. Results High satisfaction was found among all participants with most of the medical care and with the professionals of the MS Unit. They agreed with the interventions they were offered but they considered that physical rehabilitation and psychological support must be offered, not only to MS patients but also to their caregivers and family. They also asked to emphasize transdisciplinary care. Conclusions This information defined the aspects of medical care that participants perceived as quality-care and the goals the Unit needs to achieve in the future.

Resumen Introduccion En esclerosis multiple (EM), la exposicion fetal a farmacos modificadores de la enfermedad (FME) conlleva distintos grados de riesgo. Objetivo: analizar nuestra experiencia en relacion con los casos de exposicion fetal involuntaria a FME. Pacientes y metodos Estudio observacional. Se analizaron los datos clinico-obstetricos de una cohorte de pacientes con EM, entre 2007 y 2017. Grupo EM: pacientes con EM con embarazos expuestos a FME. Grupo control: pacientes con EM no expuestas y embarazadas sanas. Resultados Hubo un total de 68 embarazos en pacientes con EM. Control: 56 mujeres sanas. Grupo EM expuestas a FME durante embarazo: 13; bajo peso al nacer: 2(15%); parto pretermino: 0. Grupo EM no expuestas a FME: 55; 22 (40%) suspendieron FME previo embarazo; 33 (60%) naive; bajo peso al nacer: 5 (9%); pretermino: 7 (12%). Grupo mujeres sanas: bajo peso al nacer, 6 (11%); parto pretermino, 6 (11%). No hubo diferencias clinicas estadisticamente significativas entre pacientes EM. Tampoco hubo diferencias en peso al nacer, tiempo de gestacion o morbilidad obstetrica en expuestas a FME. Conclusiones No hubo diferencias clinicas estadisticamente significativas, ni mayor morbilidad obstetrica, entre pacientes expuestas a FME, no expuestas y embarazadas sanas.

Background In multiple sclerosis (MS), fetal exposure to DME carries varying degrees of risk. We aim to analyze the clinical and obstetric outcomes of MS patients (MSp) exposed to DMDs during pregnancy. Methods Observational study. We analyzed clinical-obstetric data of a cohort MSp, who became pregnant between 2007-2017. They were prospectively followed during pregnancy and postpartum. Control group: healthy pregnant women (HPW). Results Sixty-eight pregnancies in MSp. Fifty-six HPW. Thirteen MSp were exposed to DMDs during pregnancy. Obstetric outcome: 2(15%) infants had low birth weight, no preterm deliveries. Fifty-five MSp were not exposed to DMDs: 22(40%) discontinued DMD before pregnancy, 33(60%) naive. Five infants (9%) had low birth weight and 7(12%) were preterm. HPW: 56. Low birth weight 6 (11%), preterm delivery 6 (11%). There were no differences in relapse incidence during pregnancy-puerperium between MSp groups. There were no differences in birth weight, gestation time, delivery-cesarean section. We found no special obstetric morbidity in women exposed to DMDs. Conclusions There were no significant differences in the clinical and obstetric variables analyzed between pregnant women exposed to DMDs, unexposed, and HPW.

It has been suggested that bilingualism is beneficial for executive control and could have positive long-term effects by delaying the onset of symptoms of degenerative diseases. This research investigates, for the first time, the impact of bilingualism on executive control (monitoring and inhibitory control) in individuals with Multiple Sclerosis (MS), a neurodegenerative disease which commonly causes deficiencies in the cognitive system. Bilingual and monolingual adults, with and without an MS diagnosis, performed a flanker task with two degrees of monitoring demands (high monitoring vs. low monitoring). Results showed that bilingual MS patients had inhibitory control and monitoring abilities that were similar to healthy bilingual controls. In contrast, monolingual MS patients showed similar inhibitory control but significantly worse monitoring abilities compared to monolingual healthy controls. We propose that the similar behaviour between bilingual groups suggests that bilingualism might counteract cognitive deficits related to MS, especially with respect to monitoring. The high monitoring cost observed in monolingual patients seems related to underlying deficits in monitoring and possibly switching, executive control abilities commonly impaired in MS patients from early stages. Our findings provide some preliminary evidence for the cognitive reserve hypothesis in bilingual MS patients.

Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited.The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting.We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated.Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy.Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.

Fibrinogen is a protein that plays a key role in blood coagulation and thrombosis and it is involved in several inflammatory processes; in multiple sclerosis (MS) may be related with blood-brain barrier (BBB) disruption. We analysed the relationship between plasma fibrinogen levels and the presence of active lesions on magnetic resonance imaging (MRI) during relapses of multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients.We collected data of patients admitted to a tertiary-care hospital with relapse of MS and CIS from 2008 to 2013 and we analysed the relation between plasma fibrinogen levels (normal: 200mg/dl-417mg/dl) and the presence of active lesions on brain or spinal MRI.A total of 58 patients were included, 45 (77%) CIS patients, 12 (21%) relapsing-remitting MS (RR-MS) and 1 (2%) active progressive MS (P-MS). 17 patients had high plasma fibrinogen levels (417mg/dl). Among total of patients with elevated plasma fibrinogen, 15 (88%) had active lesions on MRI and only 2 (12%) did not have active lesion on MRI (p = 0,013) with a specificity of 95%. All patients with fibrinogen417mg/dl were CIS (p =0.05).We observed that high plasma fibrinogen levels had a high specificity high specificity, but low sensitivity (only 40%) for detection of active lesions on MRI during relapses of MS. These findings support the hypothesis that fibrinogen could play an important role on the development of MS lesions, however, additional studies are needed to confirm these results.

The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (&ndash, 2.3-fold and &ndash, 1.3-fold, respectively) and relapsing disease (&ndash, 2.2-fold and &ndash, 1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn&rsquo, s disease (CD) (&minus, 4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (&ndash, 2.2-fold, &ndash, 1.4-fold, &ndash, 1.6-fold, and &ndash, 1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.

Background: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. Objective: The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. Methods: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. Results: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. Conclusions: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies. Sin financiación 5.754 JCR (2020) Q1, 36/208 Clinical Neurology 1.565 SJR (2020) Q1, 61/372 Neurology (clinical) No data IDR 2020 UEM

The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (–2.3-fold and –1.3-fold, respectively) and relapsing disease (–2.2-fold and –1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn’s disease (CD) (−4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (–2.2-fold, –1.4-fold, –1.6-fold, and –1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.

Plasma exchange (PLEX) is a therapeutic option in the treatment of acute attacks of Demyelinating Diseases of the Central Nervous System (DDCNS). Factors related with PLEX response are not well established. Descriptive and retrospective study. We included patients treated with PLEX for acute attacks of DDCNS between 2008 and 2017. We recorded demographics, clinical and treatment-related data, and Expanded Disability Status Scale (EDSS) score at admission, at discharge, and at 6 months. We included 64 patients. Forty-eight (75%) were female with a mean age of 48.28 ± 11.5 years. Half of our patients were diagnosed with multiple sclerosis. Clinical improvement was achieved in 51.6% at discharge and 62.5% at 6 months. The logistic regression model showed that EDSS score > 3 at admission (p = 0.04) and early clinical improvement with PLEX (p = 0.00) were predictors of good response to PLEX at discharge and at 6 months, respectively. No serious adverse effects were identified. PLEX is a safe and effective treatment for acute attacks of DDCNS. EDSS score at admission and early clinical improvement with PLEX were factors associated with good response to PLEX.

Key Clinical Message Hepatotoxicity is a rare adverse event of methylprednisolone that should be considered in clinical practice. In patients at risk, we propose liver function surveillance, by measuring hepatic enzymes concentration 15–30 days after methylprednisolone administration. Additionally, we propose ACTH, dexamethasone, or plasma exchange as alternate treatment options for these patients.

Objective To explore the serum cytokine profile associated with disease activity during pregnancy and postpartum in MS, and to assess any potential biomarkers predicting the occurrence of relapses during this period. Methods We included 53 MS pregnant women recruited between 2007 and 2018. Interferon-gamma, Tumor necrosis factor-alpha, interleukin-17, granulocyte/macrophage-colony stimulating factor, Activin-A, interleukin-10, and programmed-death-ligand-1 (PD-L1) were measured quarterly in serum by ELISA. Results Seventeen patients (32%) experienced relapses during pregnancy or puerperium and 37(68%) did not. We did not found differences in clinical characteristics or treatment status between the two groups. However, relapsing patients showed at the first trimester of pregnancy considerably lower levels of serum Activin-A (336.4 pg/dl [289.6–491.7], median [IQR] vs. 760.0 pg/dl [493.2–1108.0],p = .003), which correlated positively with serum PD-L1 (r = 0.53,p = .0005) and IL-10 (r = 0.43,p = .004) values. Activin-A levels lower than 515 pg/ml at the first trimester identified patients with high probability of relapsing during pregnancy and postpartum (OR = 13.75, CI: 2.5–76.8, p = .001). Conclusions MS patients with no relapses during pregnancy and puerperium showed an early triggering of a tolerogenic innate immune response evidenced by high serum Activin-A concentrations during the first trimester of pregnancy. Thus, serum Activin-A can be a useful biomarker to predict clinical activity during this period.

Palatal tremor (PT) is a rare movement disorder that involves pharynx, tongue, and other facial muscles. Symptomatic PT is due to lesions on the dentate-rubro-olivary pathways. We present an illustrative case of PT due to degenerative olivary hypertrophy after ependymoma surgery.