Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Role of the gut microbiota in the development of various neurological diseases.

INTRODUCTION: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. DEVELOPMENT: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.

[Mild encephalitis/encephalopathy syndrome with reversible splenial lesion associated with intraventricular bleeding secondary to cavernoma. Findings from the magnetic resonance brain scan]. / Síndrome de encefalitis/encefalopatía leve con lesión del esplenio reversible asociado a sangrado intraventricular secundario a cavernoma. Hallazgos en la resonancia magnética cerebral.

TITLE: Síndrome de encefalitis/encefalopatía leve con lesión del esplenio reversible asociado a sangrado intraventricular secundario a cavernoma. Hallazgos en la resonancia magnética cerebral.

The influence of interferon ß-1b on gut microbiota composition in patients with multiple sclerosis.

INTRODUCTION: The association between gut microbiota and animal models of multiple sclerosis has been well established; however, studies in humans are scarce. METHODS: We performed a descriptive, cross-sectional study comparing the relative composition of gut microbiota in 30 patients with multiple sclerosis (15 treated with interferon ß-1b, 15 not receiving this treatment) and 14 healthy controls using next generation sequencing. RESULTS: Patients with multiple sclerosis and controls showed differences in the proportion of Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, and Lentisphaerae phyla and in 17 bacterial species. More specifically, we found significant differences in the proportion of Firmicutes, Actinobacteria, and Lentisphaerae and 6 bacteria species between controls and untreated patients; however, these differences disappeared when compared with treated patients. Untreated patients showed a significant reduction in the proportion of Prevotella copri compared to controls, while the bacteria was significantly more abundant in patients treated with interferon ß-1b than in untreated patients, with levels resembling those observed in the healthy control group. CONCLUSION: We observed differences in gut microbiota composition between patients with multiple sclerosis and controls, and between patients treated and not treated with interferon ß-1b. In most cases, no differences were observed between treated patients and healthy controls, particularly for P. copri levels. This suggests that the clinical improvements observed in patients with multiple sclerosis receiving interferon ß-1b may result from the effect of the drug on gut microbiota. Longitudinal and functional studies are necessary to establish a causal relationship.

Role of the gut microbiota in the development of various neurological diseases. / Papel de la microbiota intestinal en el desarrollo de diferentes enfermedades neurológicas.

INTRODUCTION: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. DEVELOPMENT: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.

[Efficacy and safety of fingolimod in routine clinical practice in patients with relapsing-remitting multiple sclerosis in Spain: an intermediate analysis of the MS NEXT study]. / Efectividad y seguridad del fingolimod en la practica clinica habitual en pacientes con esclerosis multiple remitente recurrente en España: analisis intermedio del estudio MS NEXT.

INTRODUCTION: Fingolimod is a disease modifying therapies, which has showed clinical efficacy and an acceptable safety profile in clinical trials with relapsing-remitting multiple sclerosis (RRMS) patients. AIM: To assess fingolimod effectiveness and safety in patients with RRMS in clinical practice. PATIENTS AND METHODS: We present an interim analysis (July 2015) of MS NEXT, an observational, retrospective and multicenter study. 442 patients were included (mean age: 41 ± 9 years; median baseline EDSS: 3.0; 70% female; 284 previously treated with first-line disease modifying therapies, 139 with natalizumab and 19 without a previous treatment; mean fingolimod treatment duration: 25 ± 9 months) treated with fingolimod from November 2011 and with at least 12 months follow-up. 56 neurology-unit Spanish hospitals enrolled patients. Basal clinical and demographic data were recorded. Relapses, EDSS scores and radiological activity were recorded at baseline and annually. Adverse events were also recorded during the follow-up period. RESULTS: After two years of follow-up: annual relapse rates decreased by 76%, the proportion of relapse-free patients was 67%, of disability progression-free patients confirmed at 3 months was 91%, of relapse and disability progression-free patients was 63%, of radiological activity-free patients was 50%, and the proportion of relapse, disability progression and radiological activity-free patients was 35%. Only 3.9% of patients discontinued fingolimod permanently during the first year of treatment. CONCLUSIONS: In this interim analysis, most of patients treated with fingolimod in clinical practice had a controlled clinical disease activity, stable disability progression and high persistency.

TITLE: Efectividad y seguridad del fingolimod en la practica clinica habitual en pacientes con esclerosis multiple remitente recurrente en España: analisis intermedio del estudio MS NEXT.Introduccion. El fingolimod es un tratamiento modificador de la enfermedad que ha demostrado eficacia y seguridad en ensayos clinicos en pacientes con esclerosis multiple remitente recurrente (EMRR). Objetivo. Evaluar la efectividad y la seguridad del fingolimod en pacientes con EMRR en la practica clinica. Pacientes y metodos. Se presentan los resultados del analisis intermedio (julio de 2015) del MS NEXT, un estudio observacional, multicentrico y retrospectivo. Se incluyo a 442 pacientes (edad media: 41 ± 9 años; escala expandida del estado de discapacidad basal, mediana: 3; 70% mujeres; 284 previamente tratados con tratamientos modificadores de la enfermedad de primera linea, 139 con natalizumab y 19 naive; media de tratamiento con fingolimod: 25 ± 9 meses) tratados con fingolimod a partir de noviembre de 2011 y con al menos 12 meses de seguimiento. Participaron 56 hospitales españoles. Se recogieron datos demograficos y clinicos (basal y anualmente, numero de brotes, puntuacion en la escala expandida del estado de discapacidad y actividad radiologica). Tambien se registraron los efectos adversos durante el seguimiento. Resultados. Tras dos años de tratamiento, la tasa anualizada de brotes se redujo un 76%; el 67% de los pacientes estaba libre de brotes; el 91%, libre de progresion de la discapacidad confirmada a los tres meses; el 63%, libre de brotes y progresion de discapacidad; el 50%, libre de actividad radiologica, y el 35%, libre de brotes, progresion de discapacidad y actividad radiologica. Un 3,9% abandono el fingolimod permanentemente. Conclusiones. En este analisis intermedio, la mayoria de los pacientes tratados con fingolimod en la practica clinica presenta una actividad clinica controlada y una elevada persistencia al tratamiento.

Role of intestinal microbiota in the development of multiple sclerosis. / Papel de la microbiota intestinal en el desarrollo de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. DEVELOPMENT: We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. CONCLUSIONS: Multiple evidence points to the role of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us.

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

AIM: To evaluate the effectiveness and safety of fingolimod in clinical practice in Navarra, Gipuzkoa and La Rioja regions. PATIENTS AND METHODS: We conducted a retrospective multi-centre study with recurrent multiple sclerosis patients treated with fingolimod, following the product data sheet. The following data were evaluated: annualised relapse rate (ARR), percentage of patients free from relapses, disability using the Expanded Disability Status Scale (EDSS) and the percentage of patients without gadolinium-enhancing lesions. RESULTS: A total of 113 patients were treated with fingolimod: 6% were naive, and 58% and 35% were patients previously treated with an immunomodulator and natalizumab, respectively. Fingolimod lowered the ARR after the first (67%; 1 to 0.3; p < 0.0001) and second (89%; 1 to 0.1; p < 0.0001) years of treatment, and thus the number of patients free from relapses during the treatment increased. The baseline EDSS was 3 and after treatment with fingolimod was 2.5 in both years. The percentage of patients without gadolinium-enhancing lesions after the first year of treatment was 77%. Similar results were observed in naive patients and in those previously treated with an immunomodulator. In patients previously treated with natalizumab no changes were observed following the treatment. CONCLUSIONS: The use of fingolimod in clinical practice showed an effectiveness similar to that observed in clinical trials. There were no changes in the ARR after changing from natalizumab, and only one patient presented a 'relapse' after withdrawal of natalizumab. Fingolimod acts like a safe drug, with scarce side effects and a low percentage of drop-outs.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Navarra, Gipuzkoa y La Rioja.Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en las regiones de Navarra, Gipuzkoa y La Rioja. Pacientes y metodos. Estudio retrospectivo y multicentrico de pacientes con esclerosis multiple recurrente tratados con fingolimod, siguiendo la ficha tecnica. Se evaluo la tasa anualizada de brotes (TAB), el porcentaje de pacientes libres de brotes, la discapacidad usando la escala expandida del estado de discapacidad (EDSS) y el porcentaje de pacientes sin lesiones captantes de gadolinio. Resultados. Un total de 113 pacientes fueron tratados con fingolimod: el 6%, naive, y el 58% y 35%, pacientes tratados previamente con inmunomodulador y natalizumab, respectivamente. El fingolimod disminuyo la TAB tras el primer (67%; 1 a 0,3; p < 0,0001) y segundo (89%; 1 a 0,1; p < 0,0001) año de tratamiento, y aumento asi el porcentaje de pacientes libres de brotes durante el tratamiento. La EDSS basal fue 3 y despues del tratamiento con fingolimod fue 2,5 en ambos años. El porcentaje de pacientes sin lesiones captantes de gadolinio tras el primer año de tratamiento fue del 77%. Resultados similares se observaron en los pacientes naive y en los tratados previamente con inmunomodulador. En los pacientes tratados previamente con natalizumab no se observaron cambios tras el tratamiento. Conclusiones. El uso del fingolimod en la practica clinica mostro una efectividad similar a la eficacia observada en ensayos clinicos. No hubo cambios en la TAB al cambiar desde natalizumab, y solo un paciente tras suspender el natalizumab presento 'rebrote'. El fingolimod se comporta como un farmaco seguro, con escasos efectos adversos y con un bajo porcentaje de abandonos.

Epidemiological study of multiple sclerosis in La Rioja.

INTRODUCTION: Multiple sclerosis is a demyelinating disease that causes severe disability in younger patients. Many epidemiology studies have confirmed a variable prevalence. The objective of this study was to analyse the prevalence of this disease in La Rioja (Spain), using such variables as age and sex; type of progression, initial form of the disease, EDSS and number of relapses; disease-modifying treatment and reasons for treatment withdrawal; personal and family history of cancer; and incidence and mortality. METHODS: Analysis of patients in La Rioja diagnosed with MS (according to Poser criteria or the 2005 McDonald criteria) during a 10-year period (2001-2011). Data were collected from hospital records, multiple sclerosis associations, and personal records kept by neurologists. RESULTS: The MS prevalence rate in La Rioja is 65 patients/100 000 inhabitants with an incidence rate of 3.5 cases/100 000 residents per year. Relapsing-remitting MS is present in 67.6% of the patient total. Mean age of onset is 20-29 years (range, 12 to 70). Most EDSS scores were mostly ≤ 2. Untreated MS cases account for 47.6% of the total and the most commonly used therapy is interferon. We detected 4 haematological tumours and 7 families with multiple members affected by MS. CONCLUSIONS: Prevalence and incidence are similar to those found in other regions Spain. The average age at onset age for primary progressive MS is slightly higher than in other papers (40-49 years). In families with multiple patients, MS may be more aggressive. Disability in these patients remains very severe. We require more epidemiology studies with a variety of data gathering methods to support findings for prevalence obtained in different provinces.

[Intraparenchymal hematomas: specific features in children]. / Hematomas intraparenquimatosos: particularidades en los niños.

INTRODUCTION: Intraparenchymatous haemorrhages are rare in infancy, but their effects may be very harmful. The aetiology, clinical characteristics and prognosis regarding life and function are different from those in adults. OBJECTIVE: We decided to analyze the characteristics of this pathology in children and compare them with those in adults. MATERIAL AND METHODS: We reviewed the clinical histories of the patients under 13 years of age presenting with a spontaneous intraparenchymatous haemorrhage during a 10 year period. RESULTS: The study group was made up of 10 patients, 5 boys and 5 girls, aged between 23 days and 11 years. In 7 patients the aetiology was a burst arteriovenous malformation; in one a serious liver disorder due to alpha-l-antitrypsin deficiency; bleeding from an undiagnosed tumour caused another case and no aetiology was found in a further case. Two patients died, 6 patients had residual neurological defects and in the other two there were no sequelae. CONCLUSIONS: Intraparenchymatous haematomas in children have a high mortality (20%) and many sequelae. The figures are comparable with those for elderly persons aged over 70 and much greater than in the case of young adults. The commonest aetiology is an arteriovenous malformation, followed at a considerable distance by coagulopathies and tumours.

[Respiratory dyskinesia induced by veralipride]. / Discinesia respiratoria inducida por veralipride.

We describe the case of a patient whose menopause syndrome was treated with veralipride. After four months of this treatment she started to have bucco-lingual movements and marked dyspnea which caused difficult, irregular breathing and severe thoracic discomfort. After the drug was stopped there was progressive improvement and disappearance of the symptoms described. When the patient was taking a neuroleptic drug (veralipride) she developed bucco-lingual dyskinesia, considered to be the commonest late dyskinesia, together with marked respiratory dyskinesia. The latter is a type of dyskinesia seldom described, probably because it is only detected when it is severe enough to cause functional effects. It may pass unnoticed when the disorder is only slight or moderate. In the literature there are few references to disorders of movement induced by this drug, especially when compared with other benzamides which are frequently involved. However, in its mode of action there is a beneficial antigonadotropin activity together with an antidopaminergic effect which explains why they may cause such a reaction.

[Neurobrucellosis. A report of 13 cases]. / Neurobrucelosis. Aportación de 13 casos.

Thirteen patients with nervous system brucellosis are described. The clinical signs were heterogeneous: meningoencephalitis in 5 cases, meningoradiculitis in another 5, meningomyelitis with cranial neuropathy in 1 and of a vascular nature in 2 others. Neurologic signs appeared during the active phase in 5 patients and later in 8. Diagnosis was based on clinical manifestations, serum and cerebrospinal fluid (CSF) serology, quantitative changes in CSF and favorable response to treatment. Therapy consisted of a combination of 2 or 3 of the following drugs: rifampin, doxycycline, streptomycin and trimethoprim sulfamethoxazole. In spite of favorable evolution, 5 patients suffered sequelae. We suggest that brucellosis be investigated when neurologic deficit ensues with no known etiology, especially in endemic countries.