Neuropsychological syndromes in multiple sclerosis

Síndromes neuropsicológicos en la esclerosis múltiple. Antecedentes: entre el 45-65% de los pacientes con esclerosis múltiple (EM) manifiestan déficits cognitivos en velocidad de procesamiento de la información (VPI), atención, memoria, funciones ejecutivas (FE) y visuoconstrucción. La alteración del lenguaje y la gnosis visual es infrecuente y poco reconocida. El objetivo es la descripción cognitiva, clínica y radiológica de cinco pacientes con EM con síndromes neuropsicológicos (SNPS). Método: revisión retrospectiva de pacientes de EM con SNPS estudiados mediante test específicos de atención, memoria, VPI, FE, visuoconstrucción, gnosis visual y lenguaje. Resultados: la muestra incluyó cuatro mujeres (3 EM remitente recurrente, 1 EM secundaria progresiva) y un varón con EM primaria progresiva (edades entre 30-55 años). Los déficits cognitivos fueron el síntoma inicial en 3 casos. Tres presentan agnosia aperceptiva y apraxia constructiva, uno alexia con agrafi a y el quinto afasia motora. Cuatro asocian disfunción cognitiva “típica” de EM. En resonancia magnética observamos alto volumen lesional en secuencias potenciadas en T1 y T2 y correlación entre los déficits cognitivos y la localización de las lesiones en 4 de ellos. Conclusiones: los SNPS pueden ser la queja inicial en la EM, con frecuencia se asocian a otros déficits cognitivos y manifiestan una estrecha relación con la localización de la lesión

Assisted Reproductive Techniques in Multiple Sclerosis: Recommendations from an Expert Panel

Introduction Multiple sclerosis (MS) is mainly diagnosed in women of reproductive age. However, there is a paucity of guidelines jointly prepared by neurologists and gynaecologists on managing women with MS and the desire for motherhood. Therefore, in this review we propose recommendations for such cases, with an particular focus on those requiring assisted reproductive techniques (ART). Methods A group of seven MS experts (4 neurologists and 3 gynaecologists) came together for three discussion sessions to achieve consensus. Results The recommendations reported here focus on the importance of early preconception counselling, the management of disease-modifying therapies before and during ART procedures, important considerations for women with MS regarding ART (intrauterine insemination, in vitro fertilisation and oocyte cryopreservation) and the paramount relevance of multidisciplinary units to manage these patients. Conclusions Early preconception consultations are essential to individualising pregnancy management in women with MS, and an early, well-planned, spontaneous pregnancy should be the aim whenever possible. The management of women with MS and the desire for motherhood by multidisciplinary units is warranted to ensure appropriate guidance through the entire pregnancy.Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA funded this work without participating in its design, data analysis or manuscript preparation. Merck, S.L.U also funded the journal’s Rapid Service Fee

Risk and prognostic factors for SARS-CoV-2 infection in Spanish population with multiple sclerosis during the first five waves.

Background: Data on coronavirus disease 2019 (COVID-19) incidence in patients with multiple sclerosis (MS) during the first wave have been published but are scarce for the remaining waves. Factors associated with COVID-19 infection of any grade are also poorly known. The aim of this study was to analyze the incidence, clinical features, and risk factors for COVID-19 infection of any grade in patients with MS (pwMS) during waves 1–5. Methods: This study prospectively analyzes the cumulative incidence of COVID-19 from the first to the fifth waves by periodic case ascertainment in pwMS followed at the University Hospital of Getafe (UHG). Global and stratified cumulative incidence was calculated. Logistic regression models were used to estimate the weight of selected variables as risk and prognostic factors. Results: We included 431 pwMS, of whom 86 (20%) were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall cumulative incidence of confirmed cases was similar to that of Madrid (13,689 vs. 13,307 per 100,000 habitants) but 3 times higher during the first wave and slightly lower from the second to the fifth waves. The majority (86%) of pwMS developed mild forms of COVID-19. Smoking was the only factor associated with a decreased risk of SARS-CoV2 infection of any grade [odds ratio (OR) 0.491; 95% CI 0.275–0.878; p = 0.017]. Risk factors associated with severe forms were Expanded Disability Severity Scale (EDSS) ≥3.5 (OR 7.569; 95% CI 1.234–46.440) and pulmonary disease (OR 10.763; 95% CI 1.27–91.254). Conclusion: The incidence of COVID-19 was similar in this MS cohort to the general population. Smoking halved the risk of being infected. Higher EDSS and pulmonary comorbidity were associated with an increased risk of severe forms.post-print983 K

microRNA Expression and Its Association With Disability and Brain Atrophy in Multiple Sclerosis Patients Treated With Glatiramer Acetate.

Background: MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis. Objective: To correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis. Methods: Cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant® . Results: We found an association between miR.146a.5p (rs:0.434, p=0.03) and miR.9.5p (rs:0.516, p=0.028) with EDSS; and miR-146a.5p (rs:-0.476, p=0.016) and miR-126.3p (rs:-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (rs:-0.545, p=0.036); miR.200c.3p with pallidum (rs:-0.68, p=0.002) and cerebellum (rs:-0.472, p=0.048); miR-138.5p with amygdala (rs:0.73, p=0.016) and pallidum (rs:0.64, p=0.048); and miR-223.3p with caudate (rs:0.46, p=0.04). Conclusions: These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis.post-print1410 K

Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.

The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline and after 12 and 24 months of DMF treatment. MS patients presented lower levels of 2-AG and PEA compared to HD. 2-AG increased at 24 months, reaching HD levels. AEA and PEA remained stable at 12 and 24 months. OEA increased at 12 months and returned to initial levels at 24 months. Patients who achieved no evidence of disease activity (NEDA3) presented the same modulation over time as EDA3 patients. PEA was modulated differentially between females and males. Our results show that the ECS is dysregulated in MS patients. The increase in 2-AG and OEA during DMF treatment suggests a possible role of DMF in ECS modulation.post-print1392 K

Estudio prospectivo sobre la efectividad y seguridad del dimetilfumarato en práctica clínica habitual en pacientes con esclerosis múltiple

Tesis inédita presentada en la Universidad Europea de Madrid. Escuela de Doctorado e Investigación. Programa de Doctorado en Biomedicina y Ciencias de la SaludNo data 2022UE

Psicothema

Resumen tomado de la publicaciónLa esclerosis múltiple (EM) es una enfermedad inflamatoria crónica del sistema nervioso central muy heterogénea en sus manifestaciones. A diferencia de los déficits sensitivos-motores, muy bien estudiados, los aspectos cognitivos están siendo analizados sólo en las últimas décadas. A 28 pacientes con EM recurrente-remitente (EMRR) (tiempo de evolución, mediana 7 años; EDSS, mediana 2) se les realizó una evaluación de atención, función ejecutiva y memoria mediante una batería neuropsicológica específica. Se evaluaron también el grado de depresión (BDI), ansiedad (STAI) y fatiga (EGF). Veinticinco fueron seleccionados para el estudio por presentar alteración en algún aspecto cognitivo. El 24 por ciento mostraba disminución en memoria y el 80 por ciento en atención y funciones ejecutivas relacionadas con regiones prefrontales. No se observaron dificultades globales de memoria, salvo en memoria inmediata visual de elementos complejos (Figura de Rey reproducción inmediata), sin afectarse la prueba de reproducción visual I de la WMS-R. En pacientes con EMRR con un tiempo medio de evolución y bajo nivel de incapacidad, las alteraciones cognitivas afectan fundamentalmente a funciones atribuidas a regiones prefrontales. Las dificultades en memoria inmediata visual de elementos complejos se explicarían también por un fallo de estas áreas al alterarse la organización y uso estratégico del material a codificar.AsturiasColegio Oficial de Psicólogos de Asturias; Calle Ildefonso Sánchez del Río, 4-1 B; 33001 Oviedo; Tel. +34985285778; Fax +34985281374;ES

Decision making under explicit risk and prefrontal and thalamus volumes in multiple sclerosis patients

Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS)(34th, 2018, Berlin

Predicting conversion to multiple sclerosis by assessing cognitive impairment in radiologically isolated syndrome

Up to a third of patients with radiologically isolated syndrome (RIS) exhibit lower-than-expected cognitive performances in neuropsychological evaluations, but the relationship between cognitive impairment (CI) and quantitative magnetic resonance (MRI) measures has not been stablished. Furthermore, the prognostic role of CI in RIS for conversion to MS is currently unknown. We assessed 17 patients with RIS and 17 matched healthy controls (HC) with a neurophychological battery and a 3T MRI. Six patients (35,3%) fulfilled our criterion for CI (scores 2 SDs below the mean of HC in at least two cognitive tests) (ci-RIS). The ci-RIS subgroup showed lower values of normalized brain and gray matter volumes when compared to HC. After a median follow-up time of 4.5 years, the ci-RIS subgroup presented a higher conversion rate to MS, suggesting that CI might be an independent risk factor for conversion to MS

Relationship between episodic memory and volume of the brain regions of two functional cortical memory systems in multiple sclerosis

Background/objective: Two functional networks are proposed as neuronal support for the complex processes of memory: the anterior temporal and the medial posterior systems. We examined the atrophy of hippocampus (HC) and of those areas constituting the two functional memory systems in multiple sclerosis (MS) patients with low disability. Methods: Episodic memory (EM) was assessed in 88 relapsing MS patients and in 40 healthy controls using Wechsler Memory Scale III (Spanish adaptation). FreeSurfer software was used to calculate normalized volume of total cortex, grey matter, white matter, subcortical grey matter (thalamus and striatum), HC and both the anterior temporal (entorhinal, ventral temporopolar, lateral orbitofrontal, amygdala) and posterior medial systems (thalamus, parahippocampal, posterior cingulate, precuneus, lateral parietal and medial prefrontal). Linear regression analysis was used to identify predictors of memory performance. Results: Total grey matter and cortex volumes correlated with all subtypes of EM, and the precuneus volume correlated with overall, immediate and delayed memories. Univariant regression analysis identified an association between the volumes of the posterior medial memory network regions and EM scores. The volume of the left precuneus area was the unique and independent predictor for all EM subtypes except for visual memory, for which left HC volume was also an independent predictor. Conclusion: Left precuneus volume was the best predictor of memory in relapsing MS patients with low disability and mild deficits in EM.Sin financiación4.204 JCR (2018) Q1, 41/199 Clinical Neurology1.432 SJR (2018) Q1, 66/378 Neurology (clinical)No data IDR 2018UE