Cognitive impairment in multiple sclerosis: diagnosis and monitoring.

INTRODUCTION: Cognitive impairment (CI) has a prevalence of 45-70% in people with multiple sclerosis (MS), producing a negative impact on their quality of life, personal life, and work. Early detection of CI has become an important aspect to be considered for an adequate follow-up, to optimize social adaptation and to implement specific cognitive rehabilitation strategies. The aim of this work is to propose a suitable cognitive evaluation of patients with MS based on available and efficient tools for diagnosis and monitoring purposes well supported by literature review and clinical experience. METHODS: A multidisciplinary panel of professionals from the field of neurology, neuropsychology, and neuroimaging performed a literature review of the topic of cognitive impairment assessment. This was combined and completed with their clinical experience to produce a set of recommendations. RESULTS: Some limitations to cognitive evaluation are described: shortage of time and resources during the neurology consultation, scarceness or absence of specialized professionals' availability, importance of tests adaptation, and doubts about its use to define therapeutic efficiency. We recommend a baseline and annual screening evaluation, and we suggest a baseline and periodic neuropsychological assessment. The latter ought to change to a recommendation with the presence of either positive screening test, or subjective to cognitive complaints, screening-test results and patient or family report mismatch, or in specific social/work situations. CONCLUSIONS: Cognitive evaluation should be performed on all patients diagnosed with MS and throughout follow-up. It is necessary to support the creation of multidisciplinary MS teams to optimize the evaluation and follow-up of MS patients.

Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: DISCOVER study.

BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.

Treatment of multiple sclerosis with rituximab: A Spanish multicenter experience.

Introduction: Rituximab (RTX) is considered a potential therapeutic option for relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). The main objective of this work was to investigate the effectiveness and safety of rituximab in MS. Patients and methods: Observational multicenter study of clinical and radiological effectiveness and safety of rituximab in RRMS and PMS. Results: A total of 479 rituximab-treated patients were included in 12 Spanish centers, 188 RRMS (39.3%) and 291 (60.7%) PMS. Despite standard treatment, the annualized relapse rate (ARR) the year before RTX was 0.63 (SD: 0.8) and 156 patients (41%) had at least one gadolinium-enhanced lesion (GEL) on baseline MRI. Mean EDSS had increased from 4.3 (SD: 1.9) to 4.8 (SD: 1.7) and almost half of the patients (41%) had worsened at least one point. After a median follow-up of 14.2 months (IQR: 6.5-27.2), ARR decreased by 85.7% (p < 0.001) and GEL by 82.9%, from 0.41 to 0.07 (p < 0.001). A significant decrease in EDSS to 4.7 (p = 0.046) was observed after 1 year of treatment and this variable remained stable during the second year of therapy. There was no evidence of disease activity in 68% of patients. Infusion-related symptoms were the most frequent side effect (19.6%) and most were mild. Relevant infections were reported only in 18 patients (including one case of probable progressive multifocal leukoencephalopathy). Conclusion: Rituximab could be an effective and safe treatment in RRMS, including aggressive forms of the disease. Some selected PMS patients could also benefit from this treatment.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

Case Report: Exacerbation of Relapses Following mRNA COVID-19 Vaccination in Multiple Sclerosis: A Case Series.

Introduction: mRNA coronavirus disease 2019 (COVID-19) vaccination has been widely used to arrest the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Rarely, autoimmune events such as relapses in patients with multiple sclerosis (MS) have been reported after vaccination. However, the possible effects of vaccination in a patient already experiencing the symptoms of a relapse represent an unusual scenario that has not been described. Patients and Methods: This is a retrospective case series of four patients from three major tertiary referral centers that received mRNA COVID-19 vaccination after starting with symptoms of acute demyelination of the central nervous system due to non-recognized MS. A detailed description of each case, including MRI studies, serum light-neurofilament levels, and cerebrospinal fluid (CSF) cytokine profile, is provided. Case Description: All patients presented exacerbation of ongoing symptoms after vaccination (range 14-112 days first dose). All patients presented MRI features suggestive of highly active MS and fulfilled McDonald 2017 criteria at the time of presentation. All patients presented high serum light-neurofilament levels and oligoclonal G bands restricted to the CSF. Higher levels of interleukin-6 in the CSF were present in the more severe cases. Discussion: We describe exacerbation of relapses after mRNA COVID-19 vaccination. We hypothesize RNA sensors such as Toll-like receptor 7 may be activated and contribute to amplify the inflammatory response during a relapse. Conclusion: Patients should seek medical attention if experiencing acute neurological symptoms, especially before vaccination. Fast diagnostic procedures and prompt treatment should be performed in these patients. Pharmacovigilance and further study are warranted to confirm causality.

Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology.

Objective: To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS). Methods: Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula. Results: More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels. Conclusion: Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.

Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients. METHODS: This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study. MRI scans were performed within 3 months before enrollment and at month 12. RESULTS: Gray matter volume of declive and white matter volumes adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus significantly decreased from baseline to month 12. Baseline white matter volumes adjacent to right amygdala and left cuneus significantly differed between patients with and without disability progression, as well as baseline gray matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Baseline gray matter volumes of right cuneus and right superior temporal gyrus positively correlated with 12-month Selective Reminding Test and Word List Generation performance, respectively. Gray matter changes in right superior semilunar lobe and white matter adjacent to left declive and right cerebellar tonsil also positively correlated with Word List Generation scores, while white matter change in left inferior semilunar lobe positively correlated with Symbol Digit Modalities Test performance after 12 months. CONCLUSIONS: White and gray matter volumes of specific brain regions could predict disability progression and cognitive performance of PPMS patients after one year.

Short-term data on disease activity, cognition, mood, stigma and employment outcomes in a cohort of patients with primary progressive multiple sclerosis (UPPMS study).

BACKGROUND: Primary progressive multiple sclerosis (PPMS) has long been defined by progressive disability accrual in the absence of initial relapses. However, its underlying neurodegenerative process seems to be accompanied by central nervous system inflammation. A new classification defined multiple sclerosis courses according to clinical/radiological activity and progression. We provide further insight into PPMS activity according to this classification and other daily living aspects. METHODS: This was a multicentre, prospective, cohort study including 55 adult patients with PPMS according to 2010 McDonald criteria, within ten years from neurologic symptom onset and not receiving disease-modifying therapies during the past six months, who were followed up for 12 months. The primary study endpoint was the percentage of patients with active disease based on clinical relapses and/or magnetic resonance activity. Disability progression, cognitive function, physical/psychological impact, depression symptoms, stigma and employment were secondary endpoints. RESULTS: Eleven (25.6%) patients exhibited multiple sclerosis activity throughout the 12-month study follow-up. Fourteen showed non-active multiple sclerosis without progression, 11 non-active multiple sclerosis with progression, 6 active multiple sclerosis without progression and 4 active multiple sclerosis with progression; one patient with disease activity was not assessable for progression. Cognitive function scores remained unchanged or increased, disease physical impact was maintained and disease psychological impact significantly decreased. The proportion of patients with depression symptoms or stigma remained without significant changes as well as employment outcomes. CONCLUSION: This study shows that one-fourth of PPMS patients may exhibit disease activity over one year, with disability progression in approximately one-third but without worsening of cognitive function, disease impact, depression, stigma or employment outcomes.

Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS.

OBJECTIVE: To analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS). METHODS: In this multicenter prospective study including 53 patients with PPMS who initiated ocrelizumab treatment, we determined effector, memory, and regulatory cells by flow cytometry at baseline and after 6 months of therapy. Wilcoxon matched paired tests were used to assess differences between baseline and 6 months' results. p Values were corrected using the Bonferroni test. RESULTS: Ocrelizumab reduced the numbers of naive and memory B cells (p < 0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNFα) (p < 0.0001 in all cases). By contrast, the proportions of plasmablasts and B cells producing GM-CSF and TNFα increased significantly, suggesting the need for treatment continuation. We also observed a decrease in CD20+ T-cell numbers (p < 0.0001) and percentages (p < 0.0001), and a clear remodeling of the T-cell compartment characterized by relative increases of the naive/effector ratios in CD4+ (p = 0.002) and CD8+ (p = 0.002) T cells and relative decreases of CD4+ (p = 0.03) and CD8+ (p = 0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p = 0.002), but no changes were observed in those producing inflammatory cytokines. The immunologic variations were associated with a reduction of serum neurofilament light chain (sNfL) levels (p = 0.008). The reduction was observed in patients with Gd-enhanced lesions at baseline and in Gd- patients with baseline sNfL >10 pg/mL. CONCLUSIONS: In PPMS, effector B-cell depletion changed T-cell response toward a low inflammatory profile, resulting in decreased sNfL levels.

CSF chitinase 3-like-1 association with disability of primary progressive MS.

OBJECTIVE: To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS). METHODS: We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer's instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up. RESULTS: Increasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118-0.742, p = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063-0.725, p = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999-1.017, p = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = -0.366, 95% CI -0.676-0.054, p = 0.086). There was no correlation with regard to NfL levels. CONCLUSIONS: This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.

Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis.

BACKGROUND AND OBJECTIVES: Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice. METHODS: Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values. RESULTS: After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81-0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85-0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89-0.95; p <0.0001) and 0.92 (0.88-0.95; p <0.0001) respectively. All centres obtained z-scores≤0.5 for both biomarkers. CONCLUSION: Homogenous percentages of CD19+CD5+ B cells and CD8 perforin+ T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.

[Therapeutic plasma exchange: applications in neurology]. / Recambio plasmático terapéutico: aplicaciones en neurología.

INTRODUCTION: Plasma exchange is a technique used in the treatment of some neurological autoimmune disorders since the 80s, especially in acute conditions. In recent years new data about it use has been published in many diseases with autoimmune basis, expanding the range of use of this technique. AIM: To update the current indications of this technique in the treatment of neurological diseases. DEVELOPMENT: We conducted a thorough review of all articles about the efficacy of plasma exchange in the treatment of different neurological diseases published since the 80s. We have also carried out a detailed analysis of recommendations and evidence of the use of this procedure by analyzing the guidelines of different scientific societies. CONCLUSIONS: Plasma exchange has proven to be an effective alternative treatment with high grade scientific evidence in diseases such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. It has been effective in treating acute demyelinating episodes unresponsive to other therapies, neuromyelitis optica relapses and other central nervous system diseases induced by antibodies. In comparative studies with intravenous immunoglobulin efficacy of both therapies is similar. Comparative studies should continue to be conducted in order to better understand the mechanisms of action, prioritize indications and compare the cost-effectiveness ratio of both procedures.

TITLE: Recambio plasmatico terapeutico: aplicaciones en neurologia.Introduccion. El recambio plasmatico es una tecnica utilizada en el tratamiento de algunas enfermedades neurologicas de base autoinmune desde los años ochenta, especialmente en situaciones agudas. En los ultimos años se han publicado nuevos datos sobre su empleo en numerosas entidades con base autoinmune, ampliando, con ello, el espectro de utilizacion. Objetivo. Actualizar las indicaciones de esta tecnica en el tratamiento de las enfermedades neurologicas. Desarrollo. Se ha realizado una revision exhaustiva de todos los articulos publicados desde los años ochenta sobre la eficacia del recambio plasmatico en el tratamiento de las diferentes enfermedades neurologicas. Tambien se ha efectuado un analisis detallado de las recomendaciones y evidencias de la utilizacion de este procedimiento por parte de las diferentes sociedades cientificas. Conclusiones. El recambio plasmatico ha demostrado ser una alternativa eficaz con evidencia cientifica de primer nivel en enfermedades como el sindrome de Guillain-Barre, la polineuropatia desmielinizante inflamatoria cronica o la miastenia grave. Ha mostrado ser eficaz en el tratamiento de episodios desmielinizantes agudos sin respuesta a otras terapias, en los brotes de neuromielitis optica y en otras enfermedades del sistema nervioso central producidas por anticuerpos. En los estudios comparativos con inmunoglobulinas intravenosas, la eficacia de ambas terapias es similar. Es preciso seguir realizando estudios comparativos para conocer mejor los mecanismos y establecer indicaciones prioritarias y comparar la relacion coste-eficacia de ambos procedimientos.

Tratamiento de la esclerosis múltiple remitente recurrente con fingolimod en la práctica clínica habitual / Treatment of relapsing-remitting multiple sclerosis with fingolimod in routine clinical practice

Introducción. El fingolimod es un inmunosupresor selectivo dirigido contra el receptor SP-1, indicado en el tratamiento de la esclerosis múltiple remitente recurrente (EMRR) agresiva y tras el fracaso del tratamiento con fármacos de primera línea. Objetivo. Investigar la seguridad y efectividad del fingolimod en condiciones de práctica clínica habitual. Pacientes y métodos. Estudio observacional con seguimiento prospectivo de pacientes con EMRR que recibieron fingolimod desde enero de 2011 hasta febrero de 2014. Se evaluó la tasa anual de brotes (TAB), la discapacidad medida por la escala expandida del estado de discapacidad (EDSS), la actividad en la resonancia magnética y la aparición de efectos adversos. Resultados. Incluimos 122 pacientes, el 79,5% mujeres y con una edad media de 26,8 años. Se clasificaron según el último tratamiento recibido en: naïve (EMRR agresiva; n = 17), fracaso a terapias previas (n = 67) y retirada de natalizumab por riesgo de leucoencefalopatía multifocal progresiva (n = 38). Tras un seguimiento medio de 29,9 ± 15,9 meses, se redujo de forma significativa la TAB y la aparición de nuevas lesiones con realce de gadolinio en el grupo naïve y el de fracaso a terapias previas. No ha habido diferencias en la evolución de la EDSS ni en el tiempo hasta el primer brote o el fracaso terapéutico entre los diferentes subgrupos. El riesgo a fracaso terapéutico es mayor con la EDSS basal > 3 (hazard ratio: 4,24; p = 0,001) y presencia de bandas oligoclonales IgM (hazard ratio: 2,45; p < 0,022). Conclusiones. El fingolimod es un fármaco eficaz y seguro en la EMRR en condiciones de práctica clínica habitual. Tener una EDSS basal > 3 y bandas oligoclonales IgM predice una mala respuesta al fingolimod (AU)

Introduction. Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. Aim. To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. Patients and methods. We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014. Data assessed were the annualised relapse rate (ARR), disability measured by the Expanded Disability Status Scale (EDSS), magnetic resonance activity and the appearance of side effects. Results. Our sample consisted of 122 patients, 79.5% of them females and with a mean age of 26.8 years. They were classified, according to the last treatment received, as being: naïve (aggressive RRMS; n = 17), previous treatment failure (n = 67) and withdrawal of natalizumab due to risk of progressive multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 ± 15.9 months, the ARR and the appearance of new lesions with gadolinium enhancement were reduced in both the naïve and the previous treatment failure groups. There were no differences between the various subgroups as regards the progression of EDSS or the time elapsed until the first attack or treatment failure. The risk of treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p = 0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022). Conclusions: Fingolimod is an effective and well-tolerated drug under conditions of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal bands is predictive of a poor response to fingolimod (AU)

Recambio plasmático terapéutico: aplicaciones en neurología / Therapeutic plasma exchange: applications in neurology

Introducción. El recambio plasmático es una técnica utilizada en el tratamiento de algunas enfermedades neurológicas de base autoinmune desde los años ochenta, especialmente en situaciones agudas. En los últimos años se han publicado nuevos datos sobre su empleo en numerosas entidades con base autoinmune, ampliando, con ello, el espectro de utilización. Objetivo. Actualizar las indicaciones de esta técnica en el tratamiento de las enfermedades neurológicas. Desarrollo. Se ha realizado una revisión exhaustiva de todos los artículos publicados desde los años ochenta sobre la eficacia del recambio plasmático en el tratamiento de las diferentes enfermedades neurológicas. También se ha efectuado un análisis detallado de las recomendaciones y evidencias de la utilización de este procedimiento por parte de las diferentes sociedades científicas. Conclusiones. El recambio plasmático ha demostrado ser una alternativa eficaz con evidencia científica de primer nivel en enfermedades como el síndrome de Guillain-Barré, la polineuropatía desmielinizante inflamatoria crónica o la miastenia grave. Ha mostrado ser eficaz en el tratamiento de episodios desmielinizantes agudos sin respuesta a otras terapias, en los brotes de neuromielitis óptica y en otras enfermedades del sistema nervioso central producidas por anticuerpos. En los estudios comparativos con inmunoglobulinas intravenosas, la eficacia de ambas terapias es similar. Es preciso seguir realizando estudios comparativos para conocer mejor los mecanismos y establecer indicaciones prioritarias y comparar la relación coste-eficacia de ambos procedimientos (AU)

Introduction. Plasma exchange is a technique used in the treatment of some neurological autoimmune disorders since the 80s, especially in acute conditions. In recent years new data about it use has been published in many diseases with autoimmune basis, expanding the range of use of this technique. Aim. To update the current indications of this technique in the treatment of neurological diseases. Development. We conducted a thorough review of all articles about the efficacy of plasma exchange in the treatment of different neurological diseases published since the 80s. We have also carried out a detailed analysis of recommendations and evidence of the use of this procedure by analyzing the guidelines of different scientific societies. Conclusions. Plasma exchange has proven to be an effective alternative treatment with high grade scientific evidence in diseases such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. It has been effective in treating acute demyelinating episodes unresponsive to other therapies, neuromyelitis optica relapses and other central nervous system diseases induced by antibodies. In comparative studies with intravenous immunoglobulin efficacy of both therapies is similar. Comparative studies should continue to be conducted in order to better understand the mechanisms of action, prioritize indications and compare the cost-effectiveness ratio of both procedures (AU)