Effects of pulsed electromagnetic field therapy on fatigue, walking performance, depression, and quality of life in adults with multiple sclerosis: a randomized placebo-controlled trial.

BACKGROUND: Multiple sclerosis has a great disability burden. Management of the disease is complex, and patients often seek new conservative approaches. OBJECTIVE: To investigate the effect of low-frequency pulsed electromagnetic field (PEMF) therapy, compared to placebo, on the level of fatigue, walking performance, symptoms of depression, and quality of life (QOL) in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Forty-four adults with RRMS and minimal to significant disability were randomly assigned to a 4-week protocol using a PEMF or a placebo whole-body mat. The PEMF group were initially treated with 15Hz frequency, gradually increased to 30Hz (intensity between 25-35µT). The primary outcome was fatigue, assessed with the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Secondary measures included walking function (GAITRite system and Timed 25-Foot Walk test), the Beck Depression Inventory-II, and the Multiple Sclerosis International Quality of Life Questionnaire. Data were collected at baseline, after intervention, and at 3-months post-intervention (follow-up). RESULTS: There were no differences between groups for changes in fatigue symptoms from baseline to end of intervention (mean and 95% confidence interval FSS: -0.6, 95%CI: -1.3, 0.1; MFIS: -5.4, 95% CI: -15.1, 4.4) or at follow-up (FSS: -0.6, 95% CI: -1.4, 0.2; MFIS: -2.1, 95% CI: -10.9, 6.8). Similarly, both groups did not differ for any of the secondary outcomes at post-intervention or follow-up. CONCLUSIONS: Low-frequency PEMF therapy is no more effective than placebo to produce changes in fatigue, gait performance, severity of depression, and QOL in people with RRMS and minimal to significant disability.

Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry.

BACKGROUND: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON. METHODS: Via the MSBase Registry, data on patients from 41 centers was collected during routine clinical and research visits. Physical and visual disability were measured using the expanded disability status scale (EDSS) and the visual function score (VFS). Inclusion criteria for this analysis included age ≥ 18 years, clinically isolated syndrome (CIS), ON-onset, baseline visit within 6 months of onset, and at least one follow-up visit. Survival analysis was used to evaluate the association of disease-modifying treatment with time to conversion to clinically definite MS or sustained EDSS/VFS progression. RESULTS: Data from 60,933 patients were obtained from the MSBase registry in July 2019. Of these, 1317 patients met inclusion criteria; 935 were treated at some point in disease course, while 382 were never treated. At baseline, mean age was 32.3 ± 8.8 years, 74% were female, median EDSS was 2 (IQR 1-2), and median VFS was 1 (IQR 0-2). Median follow-up time was 5.2 years (IQR 2.4-9.3). Treatment was associated with reduced risk and delayed conversion to clinically definite MS (HR = 0.70, p < 0.001), sustained EDSS progression (HR = 0.46, p < 0.0001) and sustained VFS (HR = 0.41, p < 0.001) progression. CONCLUSIONS: In the MSBase cohort, treatment after ON was associated with better visual and neurological outcomes compared to no treatment. These results support early treatment for patients presenting with ON as the first manifestation of MS.

Evaluation of More Stamina, a Mobile App for Fatigue Management in Persons with Multiple Sclerosis: Protocol for a Feasibility, Acceptability, and Usability Study.

BACKGROUND: Multiple sclerosis (MS) is one of the world's most common neurologic disorders leading to severe disability in young adults. MS-related fatigue directly impacts on the quality of life and activity levels of people with MS. Self-management strategies are used to support them in the care of their health. Mobile health (mHealth) solutions can offer tools to help symptom management. Following a user-centered design and evidence-based process, an mHealth solution called More Stamina was created to help persons with MS manage their fatigue. OBJECTIVE: The overall study aims are to explore the feasibility, acceptability, and usability of More Stamina, a mobile app for fatigue self-management for persons with MS. METHODS: A mixed-methods, multicenter study will be used to assess the feasibility, acceptability, and usability of More Stamina. The study will take place during the third and fourth quarters of 2020 (Q3-Q4 2020) in 3 locations: Argentina, Spain, and Switzerland. A longitudinal cohort study will take place, and think-aloud protocols, open-ended interviews, and short answer questionnaires will be used. Persons with MS will be recruited from the different locations. This study seeks to enroll at least 20 patients that meet the criteria from each site for the longitudinal cohort study (total n=60). RESULTS: Ethical approval has been granted in Argentina and is pending in Spain and Switzerland. Outcomes will be published in peer-reviewed medical journals and presented at international conferences. CONCLUSIONS: Findings from this study will be used to help understand the role that mHealth can play in fatigue management in MS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04244214; https://clinicaltrials.gov/ct2/show/NCT04244214. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18196.

Effectiveness of Dry Needling versus Placebo on Gait Performance, Spasticity, Electromyographic Activity, Pain, Range-of-Movement and Quality of Life in Patients with Multiple Sclerosis: A Randomized Controlled Trial Protocol.

Dry needling (DN) is an emerging technique commonly used in neurological and musculoskeletal pain conditions, but there have been no previous studies in patients with multiple sclerosis (pwMS). This trial aims to assess the efficacy of deep DN, compared with sham placebo DN, on gait performance, spasticity level, pain, electromyographic activity, range-of-movement (ROM) and quality of life in pwMS. Forty adults with MS were randomly assigned to one study group. The DN group will undergo 2 sessions (once per week) using DN over the rectus femoris (RF) and gastrocnemius medialis (GM) muscles at the lower extremity with higher spasticity. The placebo group will receive the same protocol using a sham placebo needle (Dong Bang needle). Outcome measures will include gait performance, using the GaitRite® system, spasticity level with the Modified Ashworth Scale, superficial electromyographic activity of RF and GM, pain (pressure algometer), ROM (goniometer), and quality of life (Musiqol). This study is the first investigating the short-term effect of DN, compared with placebo, in pwMS, and taking into account the possible changes in the electromyographic activity of the lower limb. Therefore, the results may help to understand the suitability of using this technique in the clinical setting for this population. Trial registration: ACTRN12619000880145.

Validation and meta-analysis of kappa index biomarker in multiple sclerosis diagnosis.

The importance of studying the cerebrospinal fluid (CSF) in Multiple Sclerosis (MS) is included in the last McDonald criteria (2018). The study of oligoclonal IgG bands (OCGB) assay is strongly recommended in some situations in which MS diagnosis is uncertain. New biomarkers are developed during the last years. Kappa free light chains (FLC) can predict conversion to MS in patients with Clinically Isolated Syndrome (CIS). The aim of this work is to validate the clinical usefulness of the kappa index, and to establish the actual state of knowledge for kappa index as a biomarker of conversion in CIS patients by a meta-analysis. Kappa index seems more relevant than the mere concentration of kappa FLC in CSF. In the validation study, 334 patients were included; in which 100 were CIS patients. Patients were divided in two groups according kappa index cut-off of 10.62: group 1 (kappa index>10.62); group 2 (kappa index<10.62). In group 1 more patients had positive OCGB, IgG index>0.56 and fulfilled magnetic resonance imaging (MRI) criteria. In contrast, in group 2, more patients showed negative OCGB, IgG index<0.56 and did not fulfilled MRI criteria. While 67.6% of patients from group 1 converted to MS, only 12.5% of patients from group 2 converted to MS. An HR of 6.02 was obtained in the Kaplan-Meier analysis. In the meta-analysis, 8 studies were finally included. The SROC curve revealed a high diagnostic performance for the kappa index as a MS diagnostic biomarker. Despite heterogeneity found between studies, the global OR revealed a good discriminatory capacity of kappa index. In conclusion, kappa index has a great clinical sensitivity and specificity as a support in MS diagnosis. High kappa index increase the probability of CIS to MS conversion. A correct sample processing in the preanalytical stage is key to obtain right results and to allow establishing comparison between laboratories.

Gait pattern changes after six-minute walk test in persons with multiple sclerosis.

OBJECTIVE: To examine the effect of induced fatigue on spatiotemporal gait parameters in persons with multiple sclerosis (PwMS) by using 6-min walk test (6MWT). METHODS: A cross-sectional study with a control group (25 healthy persons) was performed. Fifty-six PwMS (37 female) were divided into three groups according to their level of disability, as measured by the expanded disability status scale (EDSS): mild (n = 23, EDSS = 1.0-3.5), moderate (n = 19, EDSS = 4.0-5.5), and severe (n = 12, EDSS = 6.0-6.5). Spatiotemporal gait parameters were measured by the GAITRite electronic walkway before and after 6MWT performance. In addition, to determine the level of fatigue in PwMS, the participants completed the questionnaire modified fatigue impact scale (MFIS) before performing the 6MWT. Statistical analyses were performed to compare intragroup and intergroup differences. RESULTS: Fatigue level was lower in the mild (37.6 ± 20.5) versus moderate (54.3 ± 17.2) versus severe (53.6 ± 12.9) groups (p < 0.05). Significant differences were found among all the groups in terms of the distance walked during the 6MWT (p = 0.001) and of the spatiotemporal gait parameters: gait velocity (cm/s), cadence (steps/min), and step length (cm) decreased and, on the contrary, step time (sec), stance, and double support time (% gait cycle) increased when EDSS scores were higher (p < 0.05). The percentage of change (%) in the spatiotemporal gait parameters, after 6MWT performance, was statistically significant in the moderate and severe groups: gait velocity (-8.8%, -25.9%) and step length (-6.5%, -13.4%) decreased, whereas step time (3.0%, 15.0%), double support time (8.8%, 19.1%), step time asymmetry (32.1%, 64.0%), and single support asymmetry (60.0%, 74.7%) increased (p < 0.05). CONCLUSIONS: Gait pattern worsen after performing a walking-induced fatigue test, such as 6MWT, in moderate-severe PwMS (EDSS ≥ 4.0). Identifying these gait alterations will allow physiotherapists to determine specific therapeutic objectives.

Retest reliability of individual alpha ERD topography assessed by human electroencephalography.

BACKGROUND: Despite the immense literature related to diverse human electroencephalographic (EEG) parameters, very few studies have focused on the reliability of these measures. Some of the most studied components (i.e., P3 or MMN) have received more attention regarding the stability of their main parameters, such as latency, amplitude or topography. However, spectral modulations have not been as extensively evaluated considering that different analysis methods are available. The main aim of the present study is to assess the reliability of the latency, amplitude and topography of event-related desynchronization (ERD) for the alpha band (10-14 Hz) observed in a cognitive task (visual oddball). Topography reliability was analysed at different levels (for the group, within-subjects individually and between-subjects individually). RESULTS: The latency for alpha ERD showed stable behaviour between two sessions, and the amplitude exhibited an increment (more negative) in the second session. Alpha ERD topography exhibited a high correlation score between sessions at the group level (r = 0.903, p<0.001). The mean value for within-subject correlations was 0.750 (with a range from 0.391 to 0.954). Regarding between-subject topography comparisons, some subjects showed a highly specific topography, whereas other subjects showed topographies that were more similar to those of other subjects. CONCLUSION: ERD was mainly stable between the two sessions with the exception of amplitude, which exhibited an increment in the second session. Topography exhibits excellent reliability at the group level; however, it exhibits highly heterogeneous behaviour at the individual level. Considering that the P3 was previously evaluated for this group of subjects, a direct comparison of the correlation scores was possible, and it showed that the ERD component is less reliable in individual topography than in the ERP component (P3).

Effect of Training Exercises Incorporating Mechanical Devices on Fatigue and Gait Pattern in Persons with Relapsing-Remitting Multiple Sclerosis.

Purpose: The aim of this study was to evaluate the effects of regular exercise incorporating mechanical devices on fatigue, gait pattern, mood, and quality of life in persons with relapsing-remitting multiple sclerosis (RRMS). Method: A total of 55 individuals with RRMS with an Expanded Disability Status Scale (EDSS) score of 0-4.5 and a Fatigue Severity Scale (FSS) score of 4.0 or more were randomly assigned to one of two exercise groups or a control group (n=18). Exercise programmes used aerobic, body weight, coordination, and balance exercises with either whole-body vibration (WBV; n=19; drop-outs, n=3) or the Balance Trainer system (n=18; drop-outs, n=4). Outcome measures included the FSS, Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory (BDI-II), and Multiple Sclerosis International Quality of Life (MusiQoL). Spatiotemporal gait parameters were assessed using the GAITRite electronic walkway. Pre- and post-intervention assessments were performed by a blinded assessor. Intra- and inter-group analysis was performed, using the paired-samples t-test, by calculating the effect size with Cohen's d analysis and one-way analysis of variance, respectively. Results: Significant improvements in fatigue and mood were identified for both intervention groups (p<0.05). Gait parameters also improved significantly in the WBV group: velocity and step length increased (12.8% and 6.5%, respectively; p<0.005), and step time, stance time, double support time, and step length asymmetry decreased (-5.3%, -1.4%, -5.9%, and -43.7%, respectively; p<0.005). Conclusions: The results of this study support the hypothesis that combined training programmes help to reduce fatigue and improve mood in persons with mild to moderate RRMS. WBV combined with a standard exercise programme significantly improves spatiotemporal gait parameters.

Objectif : la présente étude visait à évaluer les effets de l'exercice régulier incluant des appareils mécaniques sur la fatigue, les types de démarche, l'humeur et la qualité de vie de personnes ayant une sclérose en plaques rémittente (SPR). Méthodologie : au total, 55 personnes ayant une SPR, un score de 0 à 4,5 sur l'échelle étendue des incapacités (EDSS) et un score de 4,0 ou plus sur l'échelle de gravité de la fatigue (FSS) ont été divisées au hasard entre deux groupes d'exercices et un groupe témoin (CT, n=18). Les programmes d'exercices faisaient appel à l'aérobie, au poids du corps, à la coordination et aux exercices d'équilibre à l'aide de la vibration globale du corps (groupe WBV, n=19; abandons, n=3) ou du système d'entraînement à l'équilibre (groupe BT, n=18; abandons, n=4). Les mesures de résultats incluaient la FSS, l'échelle modifiée des répercussions sur la fatigue (MFIS), l'inventaire de dépression de Beck (BDI-II) et la qualité de vie de la fédération internationale de sclérose en plaques (MusiQoL). Les chercheurs ont évalué les paramètres de démarche spatiotemporelle au moyen de la piste électronique GAITRite. Un évaluateur a procédé à des évaluations à l'aveugle avant et après les interventions. Les chercheurs ont effectué des analyses intragroupes et intergroupes à l'aide du test de Student pour échantillons appariés, en calculant la taille de l'effet par l'analyse d de Cohen et l'analyse de variance unidirectionnelle, respectivement. Résultats : les chercheurs ont constaté une diminution significative de la fatigue et une amélioration significative de l'humeur dans les deux groupes d'intervention (p<0,05). Les paramètres de démarche se sont également améliorés de manière considérable dans le groupe de WBV : la vélocité et la longueur des pas ont augmenté (12,8 % et 6,5 %, respectivement; p<0,005), tandis que la durée des pas, la durée d'appui, la durée du double appui et l'asymétrie de la longueur des pas ont diminué (−5,3 %, −1,4 %, −5,9 % et −43,7 %, respectivement; p<0,005). Conclusion : les résultats de la présente étude appuient l'hypothèse selon laquelle des programmes d'entraînement combinés contribuent à réduire la fatigue et à améliorer l'humeur des personnes présentant une SPR. La WBV combinée à un programme d'exercices standard améliore considérablement les paramètres de la démarche spatiotemporelle.

Efficacy of the Treatments Used in Multiple Sclerosis: From Meta-analysis to Number Needed to Treat.

The aim of this study was to analyze the efficacy of drugs used in relapsing-remitting multiple sclerosis, first- and second-line drugs, using the number needed to treat (NNT) as a measure of efficacy. METHODS: Data from randomized clinical trials were analyzed for 3 categories of clinical efficacy outcomes: relapse, change in Expanded Disability Status Scale, and number of new lesions in magnetic resonance imaging. Meta-analysis results are expressed as odds ratios. RESULTS: The global odds ratio was 0.41 (95% confidence interval [CI], 0.34-0.49). For analyzed clinical outcomes, the odds ratio was less for second-line drugs (odds ratio, 2.0). For all studied clinical conditions, in the control group, 47 of 100 patients do not get benefits, compared with 25 (95% CI, 18-32 patients) of 100 for the active treatment group. The NNT was 5 patients (95% CI, 4-7 patients). For the proportion of patients free of relapses, in the control group, 56 of 100 patients had a relapse at 2 years, compared with 37 of 100 patients in the treatment group, with an NNT of 6 patients (95% CI, 5-8 patients). CONCLUSIONS: Active treatments produced statistically significant improvements compared with placebo.

Efectos específicos de la rehabilitación cognitiva en pacientes con esclerosis múltiple remitente-recidivante / Specific effects of cognitive rehabilitation in relapsing-remitting multiple sclerosis patients

Fundamento y objetivo: se ha demostrado la existencia de deterioro cognitivo en pacientes con esclerosis múltiple. Este estudio pretende comprobar si es posible generar mejoras en la capacidad atencional de estos pacientes y analizar si esta mejora es generalizable a más de un mecanismo atencional. Material y método: se distribuyó en dos grupos a 26 pacientes con esclerosis múltiple remitente-recidivante (EMRR): un grupo de tratamiento que participó en un programa de estimulación basado en el Attention Process Training durante 3 meses, y otro grupo control patológico que no recibió el programa. Completaron el estudio 18 controles sanos. Los beneficios de la aplicación del programa se evaluaron empleando dos pruebas computarizadas de evaluación, una de atención sostenida y otra de atención selectiva. Resultados: los pacientes del grupo de tratamiento mostraron mejoras en los tiempos de reacción tras la aplicación del programa solo en la tarea de atención selectiva. No se encontró ninguna mejora en la tarea de atención sostenida. Conclusiones: únicamente en la tarea de atención selectiva se obtuvo una mejora significativa en pacientes con EMRR. Esta asimetría en los beneficios del programa de estimulación cognitiva muestra las dificultades en la generalización de los beneficios a todos los mecanismos atencionales y el alto grado de especificidad en la rehabilitación de las funciones cognitivas (AU)

Background and objective: Cognitive impairment in patients with multiple sclerosis has been shown vastly. The aim of this study was to assess whether it is possible to generate improvements in attentional capacity of these patients, and to determine whether this improvement is generalizable to more than one attentional mechanism. Materials and method: 26 patients with relapsing-remitting multiple sclerosis (RRMS) were distributed in two groups. A treatment group who participated in a stimulation program based on the Attention Process Training program for three months. And another pathological control group who did not receive the program. 18 healthy controls completed the study. The benefits of implementing the program were evaluated using two computerized evaluation tasks, a sustained attention one and another of selective attention. Results: Patients in the treatment group showed improvements in reaction times after application of the program only in the selective attention task. No improvement was found in the sustained attention task. Conclusions: Only the selective attention task showed a significant improvement in patients with RRMS. This asymmetry in the benefits of cognitive stimulation program shows the difficulties in generalizing the benefits to all attentional mechanisms, as well as the high degree of specificity in the rehabilitation of cognitive functions (AU)

Esclerosis múltiple: impacto socioeconómico y en la calidad de vida de los pacientes / Multiple sclerosis: socioeconomic effects and impact on quality of life

La esclerosis múltiple (EM) es una enfermedad del sistema nervioso central que incide en adultos jóvenes, con un tiempo de supervivencia muy largo, por encima de los 35 años y, por ello, el impacto socioeconómico es importantísimo. En este artículo se tratan las enormes dificultades para realizar evaluaciones económicas en este campo, pero también los logros obtenidos en la investigación en él y las ventajas de hacer estudios socioeconómicos, las herramientas cada vez más perfeccionadas de las que disponemos. En este trabajo, también se plantea la necesidad de traducir costes indirectos e intangibles para convertirlos en calidad de vida y, en un segundo abordaje, en coste económico y, por tanto, en dinero, en nuestro caso en euros. Los datos de que disponemos indican que el enorme coste de la enfermedad (1.200 millones de euros al año) se debe más a gastos relacionados con la discapacidad que a la utilización de terapias, que aunque muy costosas no suponen más de un 16-18% del gasto total (200 millones de euros al año, aproximadamente). El aumento que supone el coste de la EM no se basa en un mayor gasto en los tratamientos, sino en un aumento de la incidencia y, especialmente, en la prevalencia de la enfermedad, y sobre todo no podemos olvidar que en los últimos años el porcentaje de pacientes que tienen indicación de tratamiento ha aumentado considerablemente. Por tanto, es necesario reflexionar acerca del uso que hacemos de los medicamentos en EM, ya que un ahorro en el gasto de productos más eficaces parece suponer un mayor gasto global en EM, mientras que gastar en productos más eficaces supone un ahorro a largo plazo (AU)

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that affects young adults. Survival is long, more than 35 years, and consequently the disease has a huge socioeconomic impact. The present article discusses the enormous difficulties of carrying out economic assessments in this field but also describes the advances made in research on this topic and the advantages of performing socioeconomic evaluations with increasingly sophisticated tools. We also discuss the need to quantify indirect and intangible costs to translate them into quality of life and subsequently into economic cost, expressed in euros in the case of Spain. The available data indicate that the enormous cost of the disease (1200 million euros per year) is due more to disability-related expenditure than to treatment, which -although expensive- does not represent more than 16-18% of the total expenditure (approximately 200 million euros per year). The increase represented by the cost of MS is not based on higher treatment expenditure but on an increase in the incidence and-especially-the prevalence of the disease. Above all, in the last few years, there has been a considerable rise in the percentage of patients with an indication for treatment. Reflection is therefore needed on the use of drug therapy in MS, since a saving in the most effective products seems to increase the overall cost of MS, while expenditure on these drugs represents a saving in the long-term (AU)

Estudio longitudinal del beneficio de un programa de rehabilitación atencional en pacientes con esclerosis múltiple / Longitudinal assessment of the benefit from an attentional rehabilitation program in multiple sclerosis patients

Fundamento y objetivo: los programas de rehabilitación cognitiva están rindiendo resultados esperanzadores en la recuperación del deterioro cognitivo en pacientes con esclerosis múltiple (EM). En el presente proyecto de investigación se pretende analizar si un programa adaptado en nuestra unidad hospitalaria permite mejorar la atención visual de los pacientes con EM. Material y método: un total de 20 pacientes con EM fueron distribuidos en dos grupos: a) grupo tratamiento (participaron en un programa de rehabilitación durante 3 meses) y b) grupo control patológico (no participaron el programa). Se completó el estudio con un grupo de control sano con variables sociodemográficassimilares. El programa de rehabilitación fue una adaptación del Attention Process Training (APT). Los beneficiosde la aplicación del programa se evaluaron empleando un test de atención selectiva computarizado. Resultados: los pacientes del grupo de tratamiento mostraron mejoras en los tiempos de reacción tras la aplicación del programa; en cambio, los pacientes del grupo de control patológico o los controles sanos no. El beneficio del programa de rehabilitación se mantuvo hasta 4 meses después del cese de su aplicación. Conclusiones: el programa de rehabilitación produce mejoras en la capacidad de atención selectiva de los pacientes con EM que se mantienen incluso meses después de la aplicación del programa (AU)

Background and objective: Cognitive rehabilitation programs are producing hopeful results in the recovery of the cognitive impairment in multiple sclerosis patients (MS). The main aim in the present research project is to analyze if a rehabilitation program customized in our clinical unit allows improving attention system in MS patients. Materials and method: 20 patients with MS were distributed in two groups: a) Treatment (these patients received a rehabilitation program for three months), and b) Pathological (no program was applied). A third healthy control group was included with similar sociodemographical parameters. Cognitive rehabilitation program was adapted from the Attention Program Training (APT). Benefits from the application of the program were assessed by a computerized selective attention test. Results: Patients from treatment group experienced a benefit in reaction time after the application of the rehabilitation program. This benefit lasted four months after the completion of the rehabilitation program. Conclusions: Cognitive rehabilitation program induces benefits in the selective attention in multiple sclerosis patients and persist even months after the end of the treatment (AU)

Estudio de las subpoblaciones linfocitarias y secreción intratecal en pacientes con esclerosis múltiple defnida / Study of lymphocyte subpopulations and intrathecal secretion in patients with defnite multiple sclerosis / Estudo das subpopulaþ§es de linfócitos e secreþÒo intratecal em pacientes com esclerose múltipla defnida

La esclerosis múltiple (EM) es una enfermedad infamatoria desmielinizante y autoinmune del sistema nervioso central que afecta al cerebro y a la médula espinal. El objetivo del estudio fue la cuantificación de subpoblaciones linfocitarias en líquido cefalorraquídeo y sangre de pacientes diagnosticados de esclerosis múltiple y en pacientes con enfermedades no degenerativas (controles), para encontrar variables o relaciones entre las mismas que permitan diferenciar el estado inmunológico de los pacientes de cada grupo. Este trabajo se ha llevado a cabo conjuntamente con el Hospital Universitario Virgen Macarena de Sevilla entre los años 2008 y 2010. Es un estudio de tipo descriptivo, transversal y de cohortes. La población seleccionada (n=142) estuvo compuesta por sujetos a los que se les realizó una punción lumbar y una citometría de fujo, tanto de LCR como de sangre. El Grupo 1 (n=70) fue el grupo control, Grupo 2: (n=53): pacientes con esclerosis múltiple remitente recidivante (EMRR), Grupo 3: (n=5), pacientes con esclerosis múltiple de tipo primaria progresiva y Grupo 4 (n=14), pacientes que presentaban un síndrome neurológico aislado. Los resultados mostraron un aumento de células B en LCR en pacientes con EM que sugirieron un aumento de la actividad infamatoria focal en el SNC. En cuanto a NKCD8- se observó una disminución de los niveles totales de NK, así como de los NKCD8 con respecto a los controles y un mayor valor del índice de IgG en los pacientes con EMRR.(AU)

Multiple sclerosis is an infammatory demyelinating autoimmune disease that affects the brain and spinal cord. The aim of the study was to quantify lym-phocyte subpopulations in cerebrospinal fuid and blood of patients diagnosed with multiple sclerosis and in patients whit degenerative diseases not (control) in order to fnd some relationships between them that make it possible to differentiate the immune status of patients in each group. This work was jointly carried out with Hospital Universitario Virgen Macarena in Seville during 2008, 2009 and 2010. It is a descriptive, transversal and cohort study. The selected population is composed of 142 subjects who were subjected to lumbar puncture and a blood sample. Group 1 (n=70), control, Group 2 (n=53), patients with relapsing remitting multiple sclerosis, Group 3 (n=5), patients with primary type progressive multiple sclerosis, and Group 4 (n=14) patients with isolated neurological syndrome. The results show an increase in CSF B cells in MS patients suggesting an increase in focal infammatory activity in the CNS. Regarding NKCD8, reduced total levels of NK and NKCD8 regard-ing controls were observed, and it showed an increased IgG index value in patients with RRMS.(AU)

A esclerose múltipla é uma doenþa infamatória desmielinizante autoimune do sistema nervoso central que afeta o cérebro e a medula espinhal. O objetivo do estudo foi quantificar subpopulaþ§es linfocitarias em líquido cefalorraquidiano e sangue de pacientes com diagnóstico de esclerose múltipla e em pacientes com doenþas nÒo degenerativas (controles) para encontrar variáveis ou relaþ§es entre as mesmas que permitam diferenciar o estado imunológico dos pacientes cada grupo. Este trabalho foi realizado em conjunto com o Hospital Uni-versitário Virgen Macarena de Sevilha, entre os anos 2008 e 2010. E um estudo de tipo descritivo, tranversal e de coortes. A populaþÒo selecionada é (n=142) foi constituída por indivíduos submetidos a punþÒo lombar e citometria de fuxo tanto de LCR como de sangue. O Grupo 1 (n=70), foi o grupo controle, o Grupo 2 (n=53): pacientes com esclerose múltipla recidivante-remitente (EMRR), o Grupo 3 (n=5), pacientes com esclerose múltipla de tipo primária progressiva e o Grupo 4 (n=14) pacientes com síndrome neurológica isolada. Os resultados mostraram um aumento de células B no LCR em pacientes com EM, sugerindo um aumento da atividade infamatória focal no SNC. Quanto a NKCD8, observou-se uma diminuiþÒo dos níveis totais de NK bem como dos NKCD8 com relaþÒo a controles e maior valor do índice de IgG nos pacientes com EMRR.(AU)

Estudio de las subpoblaciones linfocitarias y secreción intratecal en pacientes con esclerosis múltiple defnida / Study of lymphocyte subpopulations and intrathecal secretion in patients with defnite multiple sclerosis / Estudo das subpopulações de linfócitos e secreção intratecal em pacientes com esclerose múltipla defnida

La esclerosis múltiple (EM) es una enfermedad infamatoria desmielinizante y autoinmune del sistema nervioso central que afecta al cerebro y a la médula espinal. El objetivo del estudio fue la cuantificación de subpoblaciones linfocitarias en líquido cefalorraquídeo y sangre de pacientes diagnosticados de esclerosis múltiple y en pacientes con enfermedades no degenerativas (controles), para encontrar variables o relaciones entre las mismas que permitan diferenciar el estado inmunológico de los pacientes de cada grupo. Este trabajo se ha llevado a cabo conjuntamente con el Hospital Universitario Virgen Macarena de Sevilla entre los años 2008 y 2010. Es un estudio de tipo descriptivo, transversal y de cohortes. La población seleccionada (n=142) estuvo compuesta por sujetos a los que se les realizó una punción lumbar y una citometría de fujo, tanto de LCR como de sangre. El Grupo 1 (n=70) fue el grupo control, Grupo 2: (n=53): pacientes con esclerosis múltiple remitente recidivante (EMRR), Grupo 3: (n=5), pacientes con esclerosis múltiple de tipo primaria progresiva y Grupo 4 (n=14), pacientes que presentaban un síndrome neurológico aislado. Los resultados mostraron un aumento de células B en LCR en pacientes con EM que sugirieron un aumento de la actividad infamatoria focal en el SNC. En cuanto a NKCD8- se observó una disminución de los niveles totales de NK, así como de los NKCD8 con respecto a los controles y un mayor valor del índice de IgG en los pacientes con EMRR.

Multiple sclerosis is an infammatory demyelinating autoimmune disease that affects the brain and spinal cord. The aim of the study was to quantify lym-phocyte subpopulations in cerebrospinal fuid and blood of patients diagnosed with multiple sclerosis and in patients whit degenerative diseases not (control) in order to fnd some relationships between them that make it possible to differentiate the immune status of patients in each group. This work was jointly carried out with Hospital Universitario Virgen Macarena in Seville during 2008, 2009 and 2010. It is a descriptive, transversal and cohort study. The selected population is composed of 142 subjects who were subjected to lumbar puncture and a blood sample. Group 1 (n=70), control, Group 2 (n=53), patients with relapsing remitting multiple sclerosis, Group 3 (n=5), patients with primary type progressive multiple sclerosis, and Group 4 (n=14) patients with isolated neurological syndrome. The results show an increase in CSF B cells in MS patients suggesting an increase in focal infammatory activity in the CNS. Regarding NKCD8, reduced total levels of NK and NKCD8 regard-ing controls were observed, and it showed an increased IgG index value in patients with RRMS.

A esclerose múltipla é uma doença infamatória desmielinizante autoimune do sistema nervoso central que afeta o cérebro e a medula espinhal. O objetivo do estudo foi quantificar subpopulações linfocitarias em líquido cefalorraquidiano e sangue de pacientes com diagnóstico de esclerose múltipla e em pacientes com doenças não degenerativas (controles) para encontrar variáveis ou relações entre as mesmas que permitam diferenciar o estado imunológico dos pacientes cada grupo. Este trabalho foi realizado em conjunto com o Hospital Uni-versitário Virgen Macarena de Sevilha, entre os anos 2008 e 2010. É um estudo de tipo descritivo, tranversal e de coortes. A população selecionada é (n=142) foi constituída por indivíduos submetidos a punção lombar e citometria de fuxo tanto de LCR como de sangue. O Grupo 1 (n=70), foi o grupo controle, o Grupo 2 (n=53): pacientes com esclerose múltipla recidivante-remitente (EMRR), o Grupo 3 (n=5), pacientes com esclerose múltipla de tipo primária progressiva e o Grupo 4 (n=14) pacientes com síndrome neurológica isolada. Os resultados mostraram um aumento de células B no LCR em pacientes com EM, sugerindo um aumento da atividade infamatória focal no SNC. Quanto a NKCD8, observou-se uma diminuição dos níveis totais de NK bem como dos NKCD8 com relação a controles e maior valor do índice de IgG nos pacientes com EMRR.

Análisis de anticuerpos antifosfolipídicos y cistatina C en pacientes con esclerosis múltiple / Analysis of antiphospholipid antibodies and cystatin C in multiple sclerosis patients / Teste de anticorpos antifosfolípídes e cistatina C em pacientes com esclerose múltipla

La cistatina C es considerada el inhibidor fisiológico más importante de las proteasas de cisteína endógenas. Se cree que el papel de la cistatina C es el de modular la actividad de las proteasas secretadas o liberadas de células dañadas o en proceso de necrosis, siendo por tanto las cistatinas fundamentales para los procesos de regulación y prevención del potencial daño proteolítico local. Los anticuerpos antifosfolípidos se usan para esclarecer el diagnóstico de esclerosis múltiple (EM) ya que existen patologías que pueden cursar con sintomatología o hallazgos paraclínicos semejantes. El objetivo de este trabajo fue analizar la concentración de cistatina C y la presencia o ausencia de anticuerpos antifosfolipídicos en pacientes diagnosticados de esclerosis múltiple remitente recurrente (EMRR) como marcadores de desmielinización. Este trabajo se llevó a cabo conjuntamente por el laboratorio de Riesgo Vascular, el laboratorio de Autoinmunidad y la Unidad de Esclerosis Múltiple del Hospital Universitario Virgen Macarena de Sevilla, España, con una duración de un año. Se seleccionaron dos tipos de poblaciones: grupo 1, n=30 pacientes con EMRR y un segundo grupo, denominado grupo control, n=30. Se determinó cistatina C y anticuerpos antifosfolípidos IgG e IgM, anticuerpos anticardiolipina IgG e IgM y anticuerpos f>2 glicoproteína IgG e IgM. Los pacientes diagnosticados de EMRR presentan títulos negativos de anticuerpos antifosfolípidos IgG e IgM, anticardiolipina IgG e IgM y f>2 glicoproteína IgG e IgM. La concentración de cistatina C es menor en el grupo de pacientes diagnosticados de EM, lo que podría producir un déficit en la modulación de las proteasas de cisteína endógenas. Dicha desmielini-zación agudizaría el progreso de la EM.(AU)

Cystatin C is considered the most important physiological inhibitor of endogenous cysteine proteases; the role of cystatin C is believed to be to modulate the activity of proteases secreted or released from damaged cells or in the process of necrosis, therefore cystatins being fundamental regulatory processes and a potential prevention of local proteolytic damage. Antiphospholipid antibodies are used to clarify the diagnosis of diseases like multiple sclerosis (MS) and other pathologies could present similai symptoms or paraclinical findings. The objective of the present work is to analyze the concentration of cystatin C and the presence or absence of antiphospholipid antibodies in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) as markers of demyelization. This work was carried out jointly by the Vascular Risk Laboratory, the Laboratory of Autoimmunity and Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena in Seville in one year. Two types of people were selected: Group 1 (n = 30) RRMS group and a control group, n = 30. Cystatin C and antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM were determined. Patients showed negative titers of antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM. Cystatin C concentration is lower in the group of patients diagnosed with MS, which could give rise to a decrease in the modulation of endogenous cysteine proteases. This would exacerbate the progress of demyelization in MS.(AU)

A cistatina C é considerada o inibidor fisiológico das proteases de cisteína endógenas mais importante. Acredita-se que o papel da cistatina C é o de modular a atividade de proteases secretadas ou liberadas a partir de células danificadas ou em processo de necrose, sendo por isso as cistatinas fundamentais para os processos de regulagao e prevengao do potencial dano proteolítico local. Anticorpos antifosfolípides sao usados para esclarecer o diagnóstico de EM, visto que existem patologias que podem apresentar sintomas ou achados paraclínicos semelhantes. O objetivo deste trabalho foi o de analisar a concentra-gao de cistatina C e a presenga ou ausencia de anticorpos antifosfolípides em pacientes diagnosticados com esclerose múltipla recidivante - remitente (EMRR) como marcadores de desmielinizagao. Este trabalho foi realizado em conjunto pelo laboratório de Risco Vascular, o laboratório de Autoimunidade e a Unidade de Esclerose Múltipla do Hospital Universitario Virgen Macarena, de Sevilha, Espanha, com uma duragao de um ano. Foram selecionados dois tipos de populagdes-. Grupo 1 (n = 30) pacientes com EMRR e um segundo grupo, chamado de grupo controle, n = 30. Determinou-se cistatina C e anticorpos antifosfolípides IgG e IgM, anticorpos anticardiolipina IgG e IgM, e anticorpos $2 glicoproteína IgG e IgM. Pacientes diagnosticados com EMRR apresentam títulos negativos de anticorpos antifosfolípides IgG e IgM, anticardiolipina IgG e IgM e $2 glicoproteína IgG e IgM. A concentragao de cistatina C é menor no grupo de pacientes diagnosticados com EM, o que poderia produzir um déficit na modulagao das proteases de cisteína endógenas. Tal desmielinizagao agravaría o progresso da EM.(AU)

Análisis de anticuerpos antifosfolipídicos y cistatina C en pacientes con esclerosis múltiple / Analysis of antiphospholipid antibodies and cystatin C in multiple sclerosis patients / Teste de anticorpos antifosfolípídes e cistatina C em pacientes com esclerose múltipla

La cistatina C es considerada el inhibidor fisiológico más importante de las proteasas de cisteína endógenas. Se cree que el papel de la cistatina C es el de modular la actividad de las proteasas secretadas o liberadas de células dañadas o en proceso de necrosis, siendo por tanto las cistatinas fundamentales para los procesos de regulación y prevención del potencial daño proteolítico local. Los anticuerpos antifosfolípidos se usan para esclarecer el diagnóstico de esclerosis múltiple (EM) ya que existen patologías que pueden cursar con sintomatología o hallazgos paraclínicos semejantes. El objetivo de este trabajo fue analizar la concentración de cistatina C y la presencia o ausencia de anticuerpos antifosfolipídicos en pacientes diagnosticados de esclerosis múltiple remitente recurrente (EMRR) como marcadores de desmielinización. Este trabajo se llevó a cabo conjuntamente por el laboratorio de Riesgo Vascular, el laboratorio de Autoinmunidad y la Unidad de Esclerosis Múltiple del Hospital Universitario Virgen Macarena de Sevilla, España, con una duración de un año. Se seleccionaron dos tipos de poblaciones: grupo 1, n=30 pacientes con EMRR y un segundo grupo, denominado grupo control, n=30. Se determinó cistatina C y anticuerpos antifosfolípidos IgG e IgM, anticuerpos anticardiolipina IgG e IgM y anticuerpos f>2 glicoproteína IgG e IgM. Los pacientes diagnosticados de EMRR presentan títulos negativos de anticuerpos antifosfolípidos IgG e IgM, anticardiolipina IgG e IgM y f>2 glicoproteína IgG e IgM. La concentración de cistatina C es menor en el grupo de pacientes diagnosticados de EM, lo que podría producir un déficit en la modulación de las proteasas de cisteína endógenas. Dicha desmielini-zación agudizaría el progreso de la EM.

Cystatin C is considered the most important physiological inhibitor of endogenous cysteine proteases; the role of cystatin C is believed to be to modulate the activity of proteases secreted or released from damaged cells or in the process of necrosis, therefore cystatins being fundamental regulatory processes and a potential prevention of local proteolytic damage. Antiphospholipid antibodies are used to clarify the diagnosis of diseases like multiple sclerosis (MS) and other pathologies could present similai symptoms or paraclinical findings. The objective of the present work is to analyze the concentration of cystatin C and the presence or absence of antiphospholipid antibodies in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) as markers of demyelization. This work was carried out jointly by the Vascular Risk Laboratory, the Laboratory of Autoimmunity and Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena in Seville in one year. Two types of people were selected: Group 1 (n = 30) RRMS group and a control group, n = 30. Cystatin C and antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM were determined. Patients showed negative titers of antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM. Cystatin C concentration is lower in the group of patients diagnosed with MS, which could give rise to a decrease in the modulation of endogenous cysteine proteases. This would exacerbate the progress of demyelization in MS.

A cistatina C é considerada o inibidor fisiológico das proteases de cisteína endógenas mais importante. Acredita-se que o papel da cistatina C é o de modular a atividade de proteases secretadas ou liberadas a partir de células danificadas ou em processo de necrose, sendo por isso as cistatinas fundamentais para os processos de regulagao e prevengao do potencial dano proteolítico local. Anticorpos antifosfolípides sao usados para esclarecer o diagnóstico de EM, visto que existem patologias que podem apresentar sintomas ou achados paraclínicos semelhantes. O objetivo deste trabalho foi o de analisar a concentra-gao de cistatina C e a presenga ou ausencia de anticorpos antifosfolípides em pacientes diagnosticados com esclerose múltipla recidivante - remitente (EMRR) como marcadores de desmielinizagao. Este trabalho foi realizado em conjunto pelo laboratório de Risco Vascular, o laboratório de Autoimunidade e a Unidade de Esclerose Múltipla do Hospital Universitario Virgen Macarena, de Sevilha, Espanha, com uma duragao de um ano. Foram selecionados dois tipos de populagdes-. Grupo 1 (n = 30) pacientes com EMRR e um segundo grupo, chamado de grupo controle, n = 30. Determinou-se cistatina C e anticorpos antifosfolípides IgG e IgM, anticorpos anticardiolipina IgG e IgM, e anticorpos $2 glicoproteína IgG e IgM. Pacientes diagnosticados com EMRR apresentam títulos negativos de anticorpos antifosfolípides IgG e IgM, anticardiolipina IgG e IgM e $2 glicoproteína IgG e IgM. A concentragao de cistatina C é menor no grupo de pacientes diagnosticados com EM, o que poderia produzir um déficit na modulagao das proteases de cisteína endógenas. Tal desmielinizagao agravaría o progresso da EM.