Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Progression of a series of patients with relapsing-remitting multiple sclerosis treated for 7 years with natalizumab using the "no evidence of disease activity" parameter.

INTRODUCTION: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. OBJECTIVE: To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters. PATIENTS AND METHODS: We performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions. RESULTS: The study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti-JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy. CONCLUSIONS: Natalizumab is highly effective as measured by the NEDA long-term remission parameter.

Evolución de una serie de pacientes con esclerosis múltiple remitente-recurrente tratados con natalizumab durante 7 años mediante el parámetro no evidencia enfermedad activa / Progression of a series of patients with relapsing-remitting multiple sclerosis treated for 7 years with natalizumab using the “no evidence of disease activity” parameter

Introducción: La efectividad y seguridad de natalizumab en pacientes con esclerosis múltiple remitente recurrente (EMRR) se demostró en ensayos clínicos. Sin embargo, por las limitaciones de estos es importante saber cómo se comporta en condiciones de práctica clínica a largo plazo.ObjetivoConocer la eficacia a largo plazo de natalizumab en pacientes con EMRR mediante la evaluación anual del no evidence of disease activity (NEDA), que incluye número de brotes, discapacidad medida con EDSS y parámetros de RM cerebral.Pacientes y métodosEstudio retrospectivo y multicéntrico (n = 3) de pacientes con EMRR tratados con una o más dosis de natalizumab. Se evaluó el estado NEDA cada año y la seguridad a partir del porcentaje de pacientes que discontinuaron y que presentaron efectos adversos.ResultadosIncluimos 89 pacientes, la mayoría recibieron tratamiento durante 2 a 4 años, con una duración del seguimiento de hasta 7 años. Natalizumab reduce significativamente la progresión radiológica y clínica de la enfermedad, así como la tasa anual de brotes, demostrándose su eficacia con el parámetro NEDA, 75,28% al primer año y 66,67% al séptimo año. Veinticinco pacientes (28,1%) han abandonado el estudio en una mediana de tiempo de 4 años, 14 pacientes (56%) por aparición de anticuerpos contra el virus JC, como causa única o asociada a otro motivo, 4 abandonos (16%) fueron por ineficacia, un paciente falleció a causa de LMP.ConclusionesNatalizumab presenta una alta eficacia medida mediante el parámetro de remisión NEDA a largo plazo. (AU)

Introduction: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions.ObjectiveTo determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the “no evidence of disease activity” (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters.Patients and methodsWe performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions.ResultsThe study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti–JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy.ConclusionsNatalizumab is highly effective as measured by the NEDA long-term remission parameter. (AU)

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Development and validation of a brief electronic screening test for cognitive impairment in multiple sclerosis (SCI-MS Test).

OBJECTIVE: Although cognitive impairment (CI) is common in multiple sclerosis (MS), it is difficult to suspect in patients with low disability and there is a lack of brief and effective CI screening tools with a define cut-off point to be used during routine clinic visits. This study aims to validate the Electronic Screening Cognitive Impairment in Multiple Sclerosis (SCI-MS) test for CI among MS patients. METHODS: Cross-sectional, observational study that included adult patients, diagnosed with MS, Expanded Disability Status Scale (EDSS) score ≤6.5, without relapses within the last 2 months and no depression symptoms. The SCI-MS test consists of two modules: questionnaire (SCI-MS-Q) and pictogram matching tool (SCI-MS-P) measured for score and time. At inclusion, patients completed the Beck Depression Inventory (BDI-II test), the Brief Repeatable Battery of Neuropsychological Test (BRB-N) and the SCI-MS. The SCI-MS feasibility, test-retest reliability and predictive validity were assessed. RESULTS: A total of 194 patients (59.3% female) were included: mean (SD) age of 42 (9) years, mean time since diagnosis of 10 (7) years, 89.7% relapsing-remitting MS, and median (Q1-Q3) EDSS of 2.0 (1.0-3.5). According to BRB-N, 26.8% of patients had CI. Internal consistency was high (Cronbach alpha: 0.97). The intra-class correlation coefficient was 0.88 for the SCI-MS-Q, 0.09 for the SCI-MS-P score and 0.48 for the SCI-MS-P time, corresponding to AUC of the ROC curves of 0.571, 0.574 and 0.714, respectively. For a clinically significant cut-off point of ≥60 seconds, the reached CI sensitivity of SCI-MS-P time was 0.75 and the specificity 0.51. CONCLUSION: SCI-MS showed good psychometric properties. SCI-MS-P time of pictogram completion had an acceptable diagnostic accuracy of CI in MS patients with low disability. SCI-MS-P time of pictogram completion tool is an easy and quick score that can help neurologists to early identify CI in MS patients that should be further assessed to confirm CI diagnosis and to describe its characteristics and mainly affected domains.

[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Galicia]. / Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Galicia.

INTRODUCTION: The effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) have been proven in clinical trials. Yet, due to their limitations, it is important to know how it behaves under everyday clinical practice conditions. Hence, the aim of this study is to evaluate the effectiveness and safety of fingolimod after 12 months' usage in clinical practice in Galicia. PATIENTS AND METHODS: We conducted a retrospective, multi-centre study (n = 8) of patients with RRMS who were treated with one or more doses of fingolimod, 0.5 mg/day. Effectiveness was assessed -annualised relapse rate (ARR), changes in the score on the Expanded Disability Status Scale (EDSS), percentage of patients free from relapses, free from progression of disability and free from activity in resonance- for the total number of patients and according to previous treatment. Safety was assessed based on the percentage of patients who withdrew and presented adverse side effects. RESULTS: After 12 months' use, fingolimod reduced the ARR by 87% (1.7 to 0.23; p < 0.0001) and, consequently, 81% of patients were free from relapses. The score was reduced by 9%. In all, 91% of patients were free from progression of disability and 72% were free from resonance activity. No signs of disease activity were found in 43% of the patients. Most of the benefits of fingolimod differed depending on previous treatment. About a third of the patients reported adverse side effects, but only 2% of them withdrew for this reason. CONCLUSIONS: In clinical practice, most of the results on the effectiveness of the clinical trials conducted with fingolimod were observed during the first 12 months of treatment. A better safety profile was observed than that reported in the clinical trials.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Galicia.Introduccion. La efectividad y seguridad del fingolimod en pacientes con esclerosis multiple remitente recurrente (EMRR) se demostro en ensayos clinicos. Sin embargo, por las limitaciones de estos, es importante saber como se comporta en condiciones de practica clinica habitual. Asi, el objetivo de este estudio es evaluar la efectividad y seguridad del fingolimod despues de 12 meses de uso en la practica clinica en Galicia. Pacientes y metodos. Estudio retrospectivo y multicentrico (n = 8) de pacientes con EMRR y tratados con una o mas dosis de fingolimod, 0,5 mg/dia. Se evaluo la efectividad ­tasa anualizada de brotes (TAB), cambio en la puntuacion de la escala expandida del estado de discapacidad (EDSS), porcentaje de pacientes libres de brotes, libres de progresion de discapacidad y libres de actividad en resonancia­ para el total de pacientes y segun tratamiento previo. Se evaluo la seguridad a partir del porcentaje de pacientes que discontinuaron y que presentaron efectos adversos. Resultados. Despues de 12 meses de uso, el fingolimod redujo un 87% la TAB (de 1,7 a 0,23; p < 0,0001) y, en consecuencia, un 81% de pacientes estuvo libre de brotes. La puntuacion de la EDSS disminuyo un 9%. Un 91% de pacientes estuvo libre de progresion de discapacidad y un 72%, libre de actividad en resonancia. En el 43% de los pacientes no se evidenciaron signos de la actividad de la enfermedad. La mayoria de los beneficios del fingolimod difirieron segun el tratamiento previo. Alrededor de un tercio de los pacientes comunicaron efectos adversos, pero solo el 2% discontinuo debido a ellos. Conclusiones. La mayoria de los resultados de efectividad de los ensayos clinicos del fingolimod se observa durante los 12 primeros meses de tratamiento en la practica clinica. Se observo un mejor perfil de seguridad al comunicado en los ensayos clinicos.