Oligoclonal M bands and cervical spinal cord lesions predict early secondary progressive multiple sclerosis.

Objective: To determine baseline cerebrospinal fluid and magnetic resonance imaging (MRI) variables at the onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) that predict evolution to secondary progressive MS (SPMS). Methods: 276 CIS patients with a minimum follow-up of 10 years were studied. Baseline presence of oligoclonal IgG and IgM bands (OCGB and OCMB respectively); number of brain T2 lesions (B-T2L), brain gadolinium enhancement lesions (brain-GEL), cervical spinal cord T2 lesions (cSC-T2L); and fulfillment of 2017 McDonald criteria among other variables were collected. Results: 14 patients ended up with a non-MS condition. 138/276 CIS patients fulfilled 2017 McDonald criteria. Mean age was 32.4 years, 185 female. 227 received treatment, 95 as CIS. After a mean follow-up of 12 years, 36 patients developed SPMS. Conversion to SPMS was associated with OCGB (p = 0.02), OCMB (p = 0.0001); ≥ 9 B-T2L (p = 0.03), brain-GEL (p = 0.03), and cSC-T2L (p = 0.03). However, after adjusting for sex, age, BT2L, brain-GEL, SC-T2, and OCMB status, only OCMB (HR 4.4, 1.9-10.6) and cSC-T2L (HR 2.2, 1.0-6.2) suggested an independent association with risk of conversion to SPMS. Patients with both risk factors had a HR of 6.12 (2.8-12.9). Discussion: OCMB and SC-T2 lesions are potential independent predictors of conversion to SPMS.

Effectiveness of rituximab vs. ocrelizumab for the treatment of primary progressive multiple sclerosis: a real-world observational study.

INTRODUCTION: Ocrelizumab, an antiCD-20 antibody, is the only drug approved to treat patients with primary progressive multiple sclerosis (pwPPMS). Not all candidates receive this treatment due to prescription limitations. Rituximab, another antiCD-20 antibody, has been used off-label in pwPPMS before and after ocrelizumab approval. However, studies comparing effectiveness of both drugs are lacking. OBJECTIVE: To evaluate effectiveness of rituximab and ocrelizumab in pwPPMS under real-life conditions. METHODS: We conducted a multicentric observational study of pwPPMS that started ocrelizumab or rituximab according to clinical practice, with a minimum follow-up of 1 year. Data was collected prospectively and retrospectively. Primary outcome was time to confirmed disability progression at 3 months (CDW). Secondary outcome was serum neurofilament light chain levels (sNFL) at the end of follow-up. RESULTS: 95 out 111 pwPPMS fulfilled inclusion criteria and follow-up data availability: 49 (51.6%) received rituximab and 46 (48.4%) ocrelizumab. Rituximab-treated patients had significantly higher baseline EDSS, disease duration and history of previous disease-modifying treatment (DMT) than ocrelizumab-treated patients. After a mean follow-up of 18.3 months (SD 5.9), 26 patients experienced CDW (21.4%); 15 (30.6%) in the rituximab group; and 11 (23.9%) in the ocrelizumab group. Survival analysis revealed no differences in time to CDW. sNFL were measured in 60 patients and no differences between groups were found. INTERPRETATION: We provide real-world evidence of effectiveness of ocrelizumab and rituximab in pwPPMS. No differences in time to CDW were found between treatments. However, this study cannot establish equivalence of treatments and warrant clinical trial to confirm our findings.

Treatment of Multiple Sclerosis With Teriflunomide. Multicenter Study of Real Clinical Practice in the Valencian Community-Spain.

Introduction: We have different treatment alternatives for relapsing-remitting multiple sclerosis-RRMS-within the so-called platform drugs. It would be desirable to know the ideal drug for each patient. Real clinical practice studies provide us with data on drug efficacy in the medium and long term, safety beyond clinical trials, and can help us to know the patient profile appropriate for each therapy. Material and Methods: An observational multicenter study of real clinical practice in patients with RRMS who were treated with teriflunomide in the Valencian Community, since teriflunomide was authorized in Spain. The database created for this study collects retrospectively patients followed prospectively in the MS clinics. Objectives: To analyze the efficacy and safety of teriflunomide treatment in patients with RRMS under the conditions of real clinical practice, and to identify a patient profile responding to the treatment. Results: We obtained data from 340 patients who received at least one dose of 14 mg teriflunomide. The patients were 69.4% female to 30.6% male, had a mean age of 46.4 years, and a mean time of progression of MS of 11.5 years. The mean pre-teriflunomide relapse rate was 0.4 years, the mean EDSS scorewas 1.98, IgG Oligoclonal bands were present in the CSF of 66.2% of the patients, IgM Oligoclonal bands were present in 46.9%, and the mean number of gadolinium-enhancing lesions was 1.07 lesions per patient at the beginning of treatment. The average number of treatments previously received was 1.04, and 28.53% were naïve. After a follow-up of up to 4 years, a reduction in the annualized and cumulative annualized relapse rate was observed in the first year, in the second year, and in the third year, compared to the pre-treatment year. The EDSS scores were stabilized throughout the follow-up. Likewise, there was a reduction in gadolinium-enhancing lesions in the 1st and 2nd years compared to the pre-treatment period. Applying different generalized multiple linear regression models, we identified a profile of a responding patient to teriflunomide as a male without IgM oligoclonal bands in the CSF, a previous EDSS score of <3, and more than 5 years duration of MS.

Workplace difficulties, health-related quality of life, and perception of stigma from the perspective of patients with Multiple Sclerosis.

INTRODUCTION: In Multiple Sclerosis (MS), withdrawal from employment is a critical problem. This study explores relationships between disease characteristics, work difficulties, health-related quality of life, depression, and stigma and how these factors affect employment status. METHODS: A multicenter, non-interventional, cross-sectional study was conducted in adults with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS). Patient-reported questionnaires included: 23-item Multiple Sclerosis Work Difficulties Questionnaire, 29-item Multiple Sclerosis Impact Scale, Stigma Scale for Chronic Illness, and Beck Depression Inventory-Fast Screen. RESULTS: A total of 199 individuals (mean age = 43.9 ± 10.5 years, 60.8% female, 86.4% with RRMS) participated in the study. Mean time from diagnosis was 9.6 ± 7.2 years and median Expanded Disability Status Scale score was 2.0 (interquartile range: 1.0-3.5). Employment rate was 47.2% (n = 94). Mean physical and psychological MSIS-29 impact sub-scores were 40.38 ± 17.1 and 20.24 ± 7.8, respectively. Forty patients (19.9%) had at least one SSCI-8 item with a score of 4 or 5, suggesting the presence of stigma often or always. Eighty-one patients (40.7%) were depressed and 25 (12.6%) had moderate-to-severe depression. Work difficulties were higher in those with worse functional status, a diagnosis of PPMS, and lower educational levels. Employed participants had lower perceptions of stigma and depressive symptoms than those not employed. Higher perceptions of stigma were also strongly linked to higher physical and psychological impact on health-related quality of life and greater work difficulties. Depressive symptoms were also strongly related to work-related problems. CONCLUSIONS: Work difficulties, stigma and poor quality of life are common in MS patients, even in a population with low physical disability. Evaluation of these dimensions in clinical practice would allow the development of targeted rehabilitation and specific work plans for MS employers.

Functional and structural changes in the visual pathway in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a heterogeneous disease with an unpredictable course. Visual pathway is a target of the disease and may reflect mechanisms that lead to disability. Structural and functional changes in the visual pathway may be studied by noninvasive techniques such as optical coherence tomography (OCT), visual evoked potentials (VEP), or B-mode transorbital sonography (TOS). OBJECTIVES: The aim is to assess changes in the visual pathway in eyes of MS patients with and without a history of optic neuritis over a 3-year period and to explore their relationship with disability. MATERIALS AND METHODS: In total, 112 eyes from 56 patients with relapsing MS were recruited: 29 with, and 83 without a history of ON (hON and nhON, respectively). Several parameters were measured by OCT, VEP, and TOS. Baseline measurements were also compared to 29 healthy controls. At 36 months, measurements were repeated in all eyes. RESULTS: At baseline, all tests showed significant differences in optic nerve structure and function in both patient cohorts in all the parameters studied, suggestive of more impairment of the visual pathway among the hON cohort. OCT showed significant differences between healthy controls and the nhON cohort. At 36 months, the nhON cohort showed significant changes by OCT, VEP, and TOS suggestive of further visual pathway impairment. OCT measurements also correlated with baseline EDSS among the nhON cohort. CONCLUSIONS: OCT is the most suitable technique and outperforms VEP and TOS to detect subclinical damage in the visual pathway. It discriminated MS patients from healthy controls and showed a progressive decline in optic nerve thickness over time among these patients.

The first reported case of drug-induced hemolytic anemia caused by dimethyl fumarate in a patient with multiple sclerosis.

BACKGROUND: Drug-induced hemolytic anemia is a rare and potentially fatal complication of drug treatment. Specific laboratory tests are crucial to confirm the diagnosis. CASE REPORT: A 38-year-old woman on treatment with dimethyl fumarate for multiple sclerosis presented with a 7-day history of weakness and fatigue. Laboratory tests revealed profound hemolytic anemia with hemoglobin levels of 4.7 g/dL (reference, 12.5-16.0), decreased haptoglobin, increased reticulocyte count, and increased indirect bilirubin. A first direct antiglobulin test was negative. The patient was started on prednisone 1 mg/kg/day, and dimethyl fumarate was withdrawn. A blood sample was drawn on Day 7 and sent to a reference laboratory. A direct antiglobulin test performed 7 days later was positive. Furthermore, an indirect antiglobulin test was positive only in the presence of the drug. RESULTS: The patient did not receive a blood transfusion, recovered clinically during the following days, and was discharged on Day 7. On Day 36, the patient's RBCs had normalized. She was changed to another disease-modifying treatment for her multiple sclerosis, and at 10-month follow-up she remained stable without any notable adverse effects. CONCLUSION: This case describes the first report of a dimethyl fumarate-induced hemolytic anemia. Laboratory results should always be interpreted within the clinical context. Specific laboratory expertise is often needed, given the complexity of the field.

Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Observational Study of Switching from Natalizumab to Immunomodulatory Drugs.

OBJECTIVE: To determine the effect of disease-modifying drugs (DMDs) on disease activity rebound in patients discontinuing natalizumab (NTZ). METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis (RRMS) treated with NTZ for ≥1 year and who switched to DMDs (glatiramer acetate [GA] or interferon) were followed up for 12 months in clinical practice. Clinical outcomes after NTZ cessation were assessed every 3 months for 1 year and MRI was performed at 12 months. RESULTS: Twelve months after switching from NTZ to DMDs, there were no significant differences in the annualized relapse rate (ARR) compared to the days that NTZ was used (0.3 vs. 0.1; p = 0.083); and the ARR never reached similar values to those prior to NTZ use (1.61; p < 0.001). The percentage of relapse-free patients after switching from NTZ was 71.4%. These patients did not have lower disease activity before NTZ compared with those with clinical relapses (1.3 vs. 1.7; p = 0.302), but they had lower Expanded Disability Status Scale scores (3.4 vs. 5.7; p = 0.001). DMDs had beneficial effects on MRI parameters, as 10 of 16 patients (62.5%) presented no evidence of radiological activity 12 months after NTZ discontinuation. CONCLUSIONS: Patients with RRMS and moderate disability who discontinued NTZ for safety reasons may benefit from the DMDs GA and interferon with no known risk for progressive multifocal leukoencephalopathy.

Fatigue Improvement after Switching Multiple Sclerosis Treatment from Interferon-ß to Glatiramer Acetate in Clinical Practice.

BACKGROUND/AIMS: The immunomodulatory effect of glatiramer acetate may help in reducing multiple sclerosis (MS)-related fatigue; however, evidence to prove this notion especially after switching from another immunomodulatory therapy is limited. We assessed the 6-month effect of glatiramer acetate on MS-related fatigue in patients switching from interferon-ß (IFN-ß) in clinical practice. METHODS: This was an observational study including 54 patients with relapsing-remitting MS that showed moderate/severe fatigue primarily caused by MS before switching from IFN-ß to glatiramer acetate and received glatiramer acetate for ≥6 months in daily practice. Study data were retrospectively collected through chart review at treatment switch and over the following 6 months on glatiramer acetate. RESULTS: Over the 6-month administration of glatiramer acetate, scores on the Modified Fatigue Impact Scale decreased: overall (p < 0.001), physical scale (p < 0.001), cognitive scale (p < 0.001), and psychosocial scale (p < 0.001). The Work Productivity and Activity Impairment Questionnaire showed improvements in work (p = 0.009) and other daily activity impairment (p < 0.001). Health-related quality of life as per the Multiple Sclerosis Impact Scale also improved: physical score (p < 0.001) and psychological score (p < 0.001). CONCLUSION: Patients with moderate/severe fatigue switching from IFN-ß to glatiramer acetate may benefit from fatigue improvements that contribute to reduce their work/activity impairment and improve their quality of life.

Implicación de la cocaína en la patología vascular cerebral / Involvement of cocaine in cerebral vascular pathology

Objetivo. Describir la implicación de la cocaína en la patología vascular cerebral en pacientes jóvenes. Pacientes y métodos. Es un estudio descriptivo del papel de la cocaína en pacientes con ictus agudo menores de 50 años ingresados en el servicio de neurología durante cuatro años. Se analizan 18 pacientes con niveles de cocaína positivos en el momento del ingreso y 79 pacientes con niveles negativos. Se recogen y analizan distintas variables que definen el perfil de riesgo vascular, características del ictus y morbimortalidad asociada a éstos. Resultados. Se obtiene un predominio de varones y mayor proporción de factores de riesgo vascular no significativa en el grupo control (55,6% frente a 64,6%). El grupo de consumidores presenta de manera significativa una menor edad media (35,2 ± 8,9 frente a 41,5 ± 7,7 años), mayor consumo de tóxicos (tabaco, alcohol y cannabis), hiperCKemia (27,8% frente a 5,1%) y trastorno psiquiátrico (16,7% frente a 3,8%) (p < 0,05). Predomina el subtipo de ictus isquémico en territorio anterior para ambos grupos. Hay una clara tendencia a la normalidad de las pruebas complementarias, mayor índice de complicaciones (33,3% frente a 15,2%) y mortalidad (11,1% frente a 3,8%) en los consumidores (p > 0,05). Conclusiones. La cocaína es un factor de riesgo que hay que tener en cuenta en adultos jóvenes, asociado a ictus a edades más tempranas de lo habitual, con tendencia a la normalidad de las pruebas complementarias y una mayor morbimortalidad hospitalaria (AU)

Aim. To describe the involvement of cocaine in cerebral vascular pathology in young patients. Patients and methods. The work consists in a descriptive study of the role of cocaine in patients with acute stroke under the age of 50 years admitted to the neurology service over a period of four years. Eighteen patients with positive levels of cocaine on admission and 79 patients with negative levels were analysed. Different variables that define the profile of vascular risk, characteristics of the stroke and the morbidity and mortality associated to them are collected and analysed. Results. Males were predominant and there was a non-significant higher proportion of vascular risk factors in the control group (55.6% versus 64.6%). The group of consumers presented a significantly lower mean age (35.2 ± 8.9 versus 41.5 ± 7.7 years), higher consumption of toxic substances (tobacco, alcohol and cannabis), hyperCKemia (27.8% versus 5.1%) and psychiatric disorders (16.7% versus 3.8%) (p < 0.05). The ischaemic stroke in the anterior territory subtype was predominant in both groups. There was a clear tendency towards normality in complementary tests and a higher rate of complications (33.3% versus 15.2%) and mortality (11.1% versus 3.8%) among consumers (p > 0.05). Conclusions. Cocaine is a risk factor that must be taken into account in young adults: it is associated to stroke at earlier ages than is considered normal, with a tendency towards normality in complementary tests and a higher rate of hospital morbidity and mortality (AU)

[Involvement of cocaine in cerebral vascular pathology]. / Implicación de la cocaína en la patología vascular cerebral.

AIM: To describe the involvement of cocaine in cerebral vascular pathology in young patients. PATIENTS AND METHODS: The work consists in a descriptive study of the role of cocaine in patients with acute stroke under the age of 50 years admitted to the neurology service over a period of four years. Eighteen patients with positive levels of cocaine on admission and 79 patients with negative levels were analysed. Different variables that define the profile of vascular risk, characteristics of the stroke and the morbidity and mortality associated to them are collected and analysed. RESULTS: Males were predominant and there was a non-significant higher proportion of vascular risk factors in the control group (55.6% versus 64.6%). The group of consumers presented a significantly lower mean age (35.2 ± 8.9 versus 41.5 ± 7.7 years), higher consumption of toxic substances (tobacco, alcohol and cannabis), hyperCKemia (27.8% versus 5.1%) and psychiatric disorders (16.7% versus 3.8%) (p < 0.05). The ischaemic stroke in the anterior territory subtype was predominant in both groups. There was a clear tendency towards normality in complementary tests and a higher rate of complications (33.3% versus 15.2%) and mortality (11.1% versus 3.8%) among consumers (p > 0.05). CONCLUSIONS: Cocaine is a risk factor that must be taken into account in young adults: it is associated to stroke at earlier ages than is considered normal, with a tendency towards normality in complementary tests and a higher rate of hospital morbidity and mortality.