[Revista de Neurologia is celebrating its 50th anniversary]. / Revista de Neurología cumple medio siglo.

TITLE: Revista de Neurología cumple medio siglo.

Validation of a New Semiautomated Segmentation Pipeline Based on the Spinal Cord Toolbox DeepSeg Algorithm to Estimate the Cervical Canal Area.

BACKGROUND AND PURPOSE: As in the brain reserve concept, a larger cervical canal area may also protect against disability. In this context, a semiautomated pipeline has been developed to obtain quantitative estimations of the cervical canal area. The aim of the study was to validate the pipeline, to evaluate the consistency of the cervical canal area measurements during a 1-year period, and to compare cervical canal area estimations obtained from brain and cervical MRI acquisitions. MATERIALS AND METHODS: Eight healthy controls and 18 patients with MS underwent baseline and follow-up 3T brain and cervical spine sagittal 3D MPRAGE. The cervical canal area was measured in all acquisitions, and estimations obtained with the proposed pipeline were compared with manual segmentations performed by 1 evaluator using the Dice similarity coefficient. The cervical canal area estimations obtained on baseline and follow-up T1WI were compared; brain and cervical cord acquisitions were also compared using the individual and average intraclass correlation coefficients. RESULTS: The agreement between the manual cervical canal area masks and the masks provided by the proposed pipeline was excellent, with a mean Dice similarity coefficient mean of 0.90 (range, 0.73-0.97). The cervical canal area estimations obtained from baseline and follow-up scans showed a good level of concordance (intraclass correlation coefficient = 0.76; 95% CI, 0.44-0.88); estimations obtained from brain and cervical MRIs also had good agreement (intraclass correlation coefficient = 0.77; 95% CI, 0.45-0.90). CONCLUSIONS: The proposed pipeline is a reliable tool to estimate the cervical canal area. The cervical canal area is a stable measure across time; moreover, when cervical sequences are not available, the cervical canal area could be estimated using brain T1WI.

Assessing the Equivalence of Brain-Derived Measures from Two 3D T1-Weighted Acquisitions: One Covering the Brain and One Covering the Brain and Spinal Cord.

BACKGROUND AND PURPOSE: In MS, it is common to acquire brain and spinal cord MR imaging sequences separately to assess the extent of the disease. The goal of this study was to see how replacing the traditional brain T1-weighted images (brain-T1) with an acquisition that included both the brain and the cervical spinal cord (cns-T1) affected brain- and spinal cord-derived measures. MATERIALS AND METHODS: Thirty-six healthy controls (HC) and 42 patients with MS were included. Of those, 18 HC and 35 patients with MS had baseline and follow-up at 1 year acquired on a 3T magnet. Two 3D T1-weighted images (brain-T1 and cns-T1) were acquired at each time point. Regional cortical thickness and volumes were determined with FastSurfer, and the percentage brain volume change per year was obtained with SIENA. The spinal cord area was estimated with the Spinal Cord Toolbox. Intraclass correlation coefficients (ICC) were calculated to check for consistency of measures obtained from brain-T1 and cns-T1. RESULTS: Cortical thickness measures showed an ICC >0.75 in 94% of regions in healthy controls and 80% in patients with MS. Estimated regional volumes had an ICC >0.88, and the percentage brain volume change had an ICC >0.79 for both groups. The spinal cord area measures had an ICC of 0.68 in healthy controls and 0.92 in patients with MS. CONCLUSIONS: Brain measurements obtained from 3D cns-T1 are highly equivalent to those obtained from a brain-T1, suggesting that it could be feasible to replace the brain-T1 with cns-T1.

SWI as an Alternative to Contrast-Enhanced Imaging to Detect Acute MS Lesions.

BACKGROUND AND PURPOSE: Acute inflammatory activity of MS lesions is traditionally assessed through contrast-enhanced T1-weighted MR images. The aim of our study was to determine whether a qualitative evaluation of non-contrast-enhanced SWI of new T2-hyperintense lesions might help distinguish acute and chronic lesions and whether it could be considered a possible alternative to gadolinium-based contrast agents for this purpose. MATERIALS AND METHODS: Serial MR imaging studies from 55 patients with MS were reviewed to identify 169 new T2-hyperintense lesions. Two blinded neuroradiologists determined their signal pattern on SWI, considering 5 categories (hypointense rings, marked hypointensity, mild hypointensity, iso-/hyperintensity, indeterminate). Two different blinded neuroradiologists evaluated the presence or absence of enhancement in postcontrast T1-weighted images of the lesions. The Fisher exact test was used to determine whether each category of signal intensity on SWI was associated with gadolinium enhancement. RESULTS: The presence of hypointense rings or marked hypointensity showed a strong association with the absence of gadolinium enhancement (P < .001), with a sensitivity of 93.0% and a specificity of 82.9%. The presence of mild hypointensity or isohyperintensity showed a strong association with the presence of gadolinium enhancement (P < .001), with a sensitivity of 68.3% and a specificity of 99.2%. CONCLUSIONS: A qualitative analysis of the signal pattern on SWI of new T2-hyperintense MS lesions allows determining the likelihood that the lesions will enhance after administration of a gadolinium contrast agent, with high specificity albeit with a moderate sensitivity. While it cannot substitute for the use of contrast agent, it can be useful in some clinical settings in which the contrast agent cannot be administered.

Neuritis óptica: etiopatogenia, diagnóstico, pronóstico y manejo / Optic neuritis: aetiopathogenesis, diagnosis, prognosis and management

La neuritis óptica (NO) tiene como principales causas la esclerosis múltiple (EM), las enfermedades dentro del espectro de la neuromielitis óptica (NMOSD) y la enfermedad asociada a anticuerpos contra la proteína de la mielina del oligodendrocito, también conocida como MOGAD. Cuando todo el cribado es negativo, podemos hablar de NO idiopática, aunque este diagnóstico deberá ser provisional. La NO se puede diagnosticar clínicamente y no se requieren de forma rutinaria pruebas paraclínicas para confirmarla. Sin embargo, pruebas como la resonancia magnética (RM), los potenciales evocados visuales (PEV) y la tomografía de coherencia óptica (OCT) pueden dar soporte al diagnóstico si la presentación clínica es atípica. El uso de nuevas secuencias de RM, la OCT, los PEV multifocales y la determinación de neurofilamentos han posibilitado el uso de la NO como modelo de remielinización y neuroprotección, propiciando la realización de ensayos clínicos de fase II. Algunos de estos fármacos, como el opicinumab, la clemastina, la fenitoína o la simvastatina, han obtenido resultados positivos; no obstante, su efecto clínico está por definir. Se acepta que los corticoides no mejoran el pronóstico a largo plazo de la NO, aunque algunos estudios retrospectivos sugieren que existe una ventana terapéutica desde el inicio de los síntomas. La plasmaféresis también ha demostrado eficacia en pacientes con NO. En esta revisión abordaremos aspectos básicos del manejo de la NO, en el contexto fundamental de la EM, la NMOSD y la MOGAD, haciendo hincapié en las novedades etiopatogénicas, diagnósticas, pronósticas y terapéuticas.(AU)

The main causes of optic neuritis (ON) are multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease, also known as MOGAD. When all screening is negative, we can speak of idiopathic ON, although this diagnosis should be provisional. ON can be diagnosed clinically and paraclinical tests are not routinely required to confirm it. However, tests such as magnetic resonance imaging (MRI), visual evoked potentials (VEP) and optical coherence tomography (OCT) can lend support to the diagnosis if the clinical presentation is atypical. The use of new MRI sequences, OCT, multifocal VEPs and the determination of neurofilaments has allowed ON to be used as a model for remyelination and neuroprotection, leading to phase II clinical trials. Some of these drugs, such as opicinumab, clemastine, phenytoin or simvastatin, have shown positive results; however, their clinical effect remains to be defined. It is accepted that corticosteroids do not improve the long-term prognosis of ON, although some retrospective studies suggest that there is a therapeutic window from the onset of symptoms. Plasmapheresis has also been shown to be effective in patients with ON. In this review we will address basic aspects of the management of ON, in the fundamental context of MS, NMOSD and MOGAD, with emphasis on etiopathogenic, diagnostic, prognostic and therapeutic developments.(AU)

[Optic neuritis: aetiopathogenesis, diagnosis, prognosis and management]. / Neuritis óptica: etiopatogenia, diagnóstico, pronóstico y manejo.

The main causes of optic neuritis (ON) are multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease, also known as MOGAD. When all screening is negative, we can speak of idiopathic ON, although this diagnosis should be provisional. ON can be diagnosed clinically and paraclinical tests are not routinely required to confirm it. However, tests such as magnetic resonance imaging (MRI), visual evoked potentials (VEP) and optical coherence tomography (OCT) can lend support to the diagnosis if the clinical presentation is atypical. The use of new MRI sequences, OCT, multifocal VEPs and the determination of neurofilaments has allowed ON to be used as a model for remyelination and neuroprotection, leading to phase II clinical trials. Some of these drugs, such as opicinumab, clemastine, phenytoin or simvastatin, have shown positive results; however, their clinical effect remains to be defined. It is accepted that corticosteroids do not improve the long-term prognosis of ON, although some retrospective studies suggest that there is a therapeutic window from the onset of symptoms. Plasmapheresis has also been shown to be effective in patients with ON. In this review we will address basic aspects of the management of ON, in the fundamental context of MS, NMOSD and MOGAD, with emphasis on etiopathogenic, diagnostic, prognostic and therapeutic developments.

TITLE: Neuritis óptica: etiopatogenia, diagnóstico, pronóstico y manejo.La neuritis óptica (NO) tiene como principales causas la esclerosis múltiple (EM), las enfermedades dentro del espectro de la neuromielitis óptica (NMOSD) y la enfermedad asociada a anticuerpos contra la proteína de la mielina del oligodendrocito, también conocida como MOGAD. Cuando todo el cribado es negativo, podemos hablar de NO idiopática, aunque este diagnóstico deberá ser provisional. La NO se puede diagnosticar clínicamente y no se requieren de forma rutinaria pruebas paraclínicas para confirmarla. Sin embargo, pruebas como la resonancia magnética (RM), los potenciales evocados visuales (PEV) y la tomografía de coherencia óptica (OCT) pueden dar soporte al diagnóstico si la presentación clínica es atípica. El uso de nuevas secuencias de RM, la OCT, los PEV multifocales y la determinación de neurofilamentos han posibilitado el uso de la NO como modelo de remielinización y neuroprotección, propiciando la realización de ensayos clínicos de fase II. Algunos de estos fármacos, como el opicinumab, la clemastina, la fenitoína o la simvastatina, han obtenido resultados positivos; no obstante, su efecto clínico está por definir. Se acepta que los corticoides no mejoran el pronóstico a largo plazo de la NO, aunque algunos estudios retrospectivos sugieren que existe una ventana terapéutica desde el inicio de los síntomas. La plasmaféresis también ha demostrado eficacia en pacientes con NO. En esta revisión abordaremos aspectos básicos del manejo de la NO, en el contexto fundamental de la EM, la NMOSD y la MOGAD, haciendo hincapié en las novedades etiopatogénicas, diagnósticas, pronósticas y terapéuticas.

[Clinical monitoring of multiple sclerosis patients by means of digital technology, a field in the midst of a revolution]. / Monitorización clínica del paciente con esclerosis múltiple a través de la tecnología digital, un campo en plena revolución.

INTRODUCTION: Despite the great advances that have occurred in the diagnosis and treatment of ? multiple sclerosis (MS), few changes have taken place in terms of clinical monitoring. The lack of time and space in clinical practice limits the assessment of invisible symptoms and certain motor symptoms as manual dexterity and walking ability, which have a clear impact on the patient functional situation. OBJECTIVE: To review the potential role of technological tools in the clinical monitoring of MS patients. DEVELOPMENT: A bibliographic search was carried out through PubMed, selecting those studies focused on biosensors and digital tools aimed at evaluating the general functional situation, and specific aspects of the disease or certain functional systems. RESULTS: Different digital tools such as biosensors, mobile or web applications, both for remote and hospital use, self-completed or administered by healthcare personnel, seem to offer a more 'complete and real' picture of the functional situation of patients. Some studies have shown that digital technology could detect subclinical disability progression, which traditional tests, including the EDSS, fail to reflect, favouring the adoption of appropriate therapeutic measures and actions in an early and personalized manner. CONCLUSIONS: Digital tools, capable of collecting detailed and extensive clinical information, could play an important role in decision-making and clinical monitoring of patients with MS.

TITLE: Monitorización clínica del paciente con esclerosis múltiple a través de la tecnología digital, un campo en plena revolución.Introducción. A pesar de los grandes avances acontecidos en el área del diagnóstico y el tratamiento de la esclerosis múltiple (EM), pocos cambios se han gestado respecto al seguimiento clínico. La escasez de tiempo y espacio en la práctica clínica dificulta la valoración de síntomas invisibles y ciertos síntomas motores, como la destreza manual y la capacidad de marcha, que presentan un claro impacto en la situación funcional del paciente. Objetivo. Revisar el papel potencial de las herramientas tecnológicas en la monitorización clínica del paciente con EM. Desarrollo. Se realizó una búsqueda bibliográfica a través de PubMed, seleccionando los estudios centrados en biosensores y herramientas digitales destinadas a la evaluación de la situación funcional general, y de aspectos concretos de la enfermedad o de determinados sistemas funcionales. Resultados. Diferentes herramientas digitales en formato de biosensores, aplicaciones móviles o web, tanto de uso remoto como hospitalario, autocumplimentadas o administradas por el personal sanitario, parecen ofrecer una visión más 'completa y real' de la situación funcional de los pacientes. Algunos estudios han demostrado que la tecnología digital es capaz de detectar la progresión subclínica de la discapacidad, que las pruebas tradicionales, incluyendo la Escala expandida del estado de discapacidad, no consiguen reflejar, lo que favorece la adopción de medidas y acciones terapéuticas apropiadas de forma temprana y personalizada. Conclusiones. Las herramientas digitales, capaces de brindar información clínica amplia y detallada, podrían ocupar un papel importante en la toma de decisiones y el seguimiento clínico del paciente afecto de EM.

Monitorización clínica del paciente con esclerosis múltiple a través de la tecnología digital, un campo en plena revolución / Clinical monitoring of multiple sclerosis patients by means of digital technology, a field in the midst of a revolution

Introducción: A pesar de los grandes avances acontecidos en el área del diagnóstico y el tratamiento de la esclerosis múltiple (EM), pocos cambios se han gestado respecto al seguimiento clínico. La escasez de tiempo y espacio en la práctica clínica dificulta la valoración de síntomas invisibles y ciertos síntomas motores, como la destreza manual y la capacidad de marcha, que presentan un claro impacto en la situación funcional del paciente. Objetivo: Revisar el papel potencial de las herramientas tecnológicas en la monitorización clínica del paciente con EM. Desarrollo: Se realizó una búsqueda bibliográfica a través de PubMed, seleccionando los estudios centrados en biosensores y herramientas digitales destinadas a la evaluación de la situación funcional general, y de aspectos concretos de la enfermedad o de determinados sistemas funcionales. Resultados: Diferentes herramientas digitales en formato de biosensores, aplicaciones móviles o web, tanto de uso remoto como hospitalario, autocumplimentadas o administradas por el personal sanitario, parecen ofrecer una visión más ‘completa y real’ de la situación funcional de los pacientes. Algunos estudios han demostrado que la tecnología digital es capaz de detectar la progresión subclínica de la discapacidad, que las pruebas tradicionales, incluyendo la Escala expandida del estado de discapacidad, no consiguen reflejar, lo que favorece la adopción de medidas y acciones terapéuticas apropiadas de forma temprana y personalizada. Conclusiones: Las herramientas digitales, capaces de brindar información clínica amplia y detallada, podrían ocupar un papel importante en la toma de decisiones y el seguimiento clínico del paciente afecto de EM.(AU)

Introduction: Despite the great advances that have occurred in the diagnosis and treatment of ​ multiple sclerosis (MS), few changes have taken place in terms of clinical monitoring. The lack of time and space in clinical practice limits the assessment of invisible symptoms and certain motor symptoms as manual dexterity and walking ability, which have a clear impact on the patient functional situation.Objective: To review the potential role of technological tools in the clinical monitoring of MS patients. Development: A bibliographic search was carried out through PubMed, selecting those studies focused on biosensors and digital tools aimed at evaluating the general functional situation, and specific aspects of the disease or certain functional systems. Results: Different digital tools such as biosensors, mobile or web applications, both for remote and hospital use, self-completed or administered by healthcare personnel, seem to offer a more ‘complete and real’ picture of the functional situation of patients. Some studies have shown that digital technology could detect subclinical disability progression, which traditional tests, including the EDSS, fail to reflect, favouring the adoption of appropriate therapeutic measures and actions in an early and personalized manner. Conclusions: Digital tools, capable of collecting detailed and extensive clinical information, could play an important role in decision-making and clinical monitoring of patients with MS.(AU)

Optical coherence tomography measures correlate with brain and spinal cord atrophy and multiple sclerosis disease-related disability.

BACKGROUND AND PURPOSE: Both optical coherence tomography (OCT) and magnetic resonance imaging (MRI) volumetric measures have been postulated as potential biomarkers of multiple sclerosis (MS)-related disability. The aim of the study was to investigate the association between OCT and brain volume and spinal cord area (SCA) parameters in patients with relapsing MS and to assess their independent associations with disability. METHODS: This was a cross-sectional analysis of 90 patients with MS who underwent OCT and MRI examination. Values of peripapillary retinal nerve fibre layer (pRNFL), ganglion cell/inner plexiform layer (GCIPL) and inner nuclear layer of eyes without previous optic neuritis were obtained. SCA and brain parenchymal fraction (BPF), grey and white matter fractions were obtained. Multivariable regression analyses were conducted with disability as dependent variable. RESULTS: Lower pRNFL thickness and lower GCIPL volume as well as lower BPF, grey matter fraction and SCA were associated with a longer disease duration and a higher Expanded Disability Status Scale score. Lower pRNFL thickness and GCIPL volumes were associated with lower BPF and SCA. In the multivariable logistic regression analyses, pRNFL thickness and GCIPL volume outperformed MRI in predicting disability. CONCLUSIONS: The OCT measures correlate with brain and spinal cord atrophy and appear more closely associated with disability than MRI volumetric measures.

EAN guideline on palliative care of people with severe, progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. METHODS: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score > 6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. RESULTS: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. CONCLUSIONS: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

Value of 3T Susceptibility-Weighted Imaging in the Diagnosis of Multiple Sclerosis.

BACKGROUND AND PURPOSE: Previous studies have suggested that the central vein sign and iron rims are specific features of MS lesions. Using 3T SWI, we aimed to compare the frequency of lesions with central veins and iron rims in patients with clinically isolated syndrome and MS-mimicking disorders and test their diagnostic value in predicting conversion from clinically isolated syndrome to MS. MATERIALS AND METHODS: For each patient, we calculated the number of brain lesions with central veins and iron rims. We then identified a simple rule involving an absolute number of lesions with central veins and iron rims to predict conversion from clinically isolated syndrome to MS. Additionally, we tested the diagnostic performance of central veins and iron rims when combined with evidence of dissemination in space. RESULTS: We included 112 patients with clinically isolated syndrome and 35 patients with MS-mimicking conditions. At follow-up, 94 patients with clinically isolated syndrome developed MS according to the 2017 McDonald criteria. Patients with clinically isolated syndrome had a median of 2 central veins (range, 0-19), while the non-MS group had a median of 1 central vein (range, 0-6). Fifty-six percent of patients who developed MS had ≥1 iron rim, and none of the patients without MS had iron rims. The sensitivity and specificity of finding ≥3 central veins and/or ≥1 iron rim were 70% and 86%, respectively. In combination with evidence of dissemination in space, the 2 imaging markers had higher specificity than dissemination in space and positive findings of oligoclonal bands currently used to support the diagnosis of MS. CONCLUSIONS: A single 3T SWI scan offers valuable diagnostic information, which has the potential to prevent MS misdiagnosis.

The ACROSS study: Long-term efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: In chronic diseases such as multiple sclerosis requiring lifelong treatment, studies on long-term outcomes are important. OBJECTIVE: To assess disability and magnetic resonance imaging-related outcomes in relapsing multiple sclerosis patients from a Phase 2 study of fingolimod 10 or more years after randomization and to compare outcomes in patients who had a higher fingolimod exposure versus those with a lower fingolimod exposure. METHODS: ACROSS was a cross-sectional follow-up study of patients originally enrolled in a Phase 2 fingolimod proof-of-concept study (NCT00333138). Disability and magnetic resonance imaging-related outcomes were assessed in patients grouped according to fingolimod treatment duration, based on an arbitrary cut-off: ≥8 years (high exposure) and <8 years (low exposure). RESULTS: Overall, 175/281 (62%) patients participated in ACROSS; 104 (59%) of these were classified "high exposure." At 10 years, patients in the high-exposure group had smaller increases in Expanded Disability Status Scale (+0.55 vs. +1.21), and lower frequencies of disability progression (34.7% vs. 56.1%), wheelchair use (4.8% vs. 16.9%), or transition to secondary progressive multiple sclerosis (9.6% vs. 22.5%) than those in the low-exposure group. The high-exposure patients also had less progression in most magnetic resonance imaging-related outcomes. CONCLUSION: After 10 years of fingolimod treatment, disability progression was lower in the high-exposure group than in the low-exposure group.

Ratio of T1-Weighted to T2-Weighted Signal Intensity as a Measure of Tissue Integrity: Comparison with Magnetization Transfer Ratio in Patients with Multiple Sclerosis.

The study aim was to compare the ratio of T1WI to T2WI signal intensity (T1/T2) with magnetization transfer ratio, a marker of myelin integrity, in patients with multiple sclerosis. A moderate correlation (r = 0.50, P = .034) was found between the magnetization transfer ratio and T1/T2 in normal-appearing gray matter, and a strong correlation for normal-appearing white matter (r = 0.63, P = .005) and lesions (r = 0.70, P = .001). Results suggest that besides myelin integrity, other factors may be playing a role in T1/T2 measures.

Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis.

BACKGROUND AND PURPOSE: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. METHODS: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. RESULTS: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre-specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre-specified topics, 227 (40%) on additional topics (16 guideline-pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient-important outcomes and of taxing issues. CONCLUSIONS: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient-important outcomes.

[Remodelling of the Scientific Committee and a new series of neuroepidemiology reviews]. / Remodelacion del Comite Cientifico y nueva serie de revisiones de neuroepidemiologia.

TITLE: Remodelacion del Comite Cientifico y nueva serie de revisiones de neuroepidemiologia.

[Rituximab: its efficacy, effectiveness and safety in the treatment of multiple sclerosis]. / Rituximab: eficacia, efectividad y seguridad en el tratamiento de la esclerosis multiple.

INTRODUCTION: There is increasing evidence that B cells and humoral immunity play key roles in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, an anti-CD20 monoclonal antibody, has been shown to be effective in controlling the disease and has recently been aproved by the Food and Drug Administration for the treatment of primary progressive and relapsing MS. While awaiting its marketing authorization, the use of rituximab, with a similar mechanism of action, has expanded widely in the area of demyelinating diseases. AIM: To address the main aspects of efficacy, effectiveness and safety of rituximab in the treatment of MS. DEVELOPMENT: PubMed review of placebo-controlled clinical trials, prospective open label studies, retrospective observational studies, and case series using rituximab in adult MS affected populations were performed. Its impact on the clinical and radiological control of the disease was evaluated, as well as any relevant safety issues. CONCLUSIONS: In all of the studies reviewed, rituximab demonstrated a consistent benefit in controlling inflammatory activity, both clinically, reducing the incidence of relapses, and radiologically, avoiding the appearance of new and/or active lesions. On the contrary, with regards to the progression of disability, its effect is more controversial. Safety profile appears acceptable. Rituximab seems to be an effective and safe drug in the treatment of MS.

TITLE: Rituximab: eficacia, efectividad y seguridad en el tratamiento de la esclerosis multiple.Introduccion. Existe evidencia creciente de que las celulas B y la inmunidad humoral tienen un papel fundamental en la fisiopatogenia de la esclerosis multiple (EM). El ocrelizumab, un anticuerpo monoclonal anti-CD20, ha demostrado ser eficaz en el control de la enfermedad y recientemente ha sido aprobado por la Food and Drug Administration estadounidense para el tratamiento de las formas primariamente progresivas y las formas recidivantes de la EM. A la espera de su comercializacion, el uso del rituximab, con un mecanismo de accion similar, se ha expandido ampliamente en el area de las enfermedades desmielinizantes. Objetivo. Abordar los principales aspectos de eficacia, efectividad y seguridad del rituximab en el tratamiento de la EM. Desarrollo. Se realizo una revision bibliografica a traves de PubMed de los ensayos clinicos controlados con placebo, los estudios prospectivos abiertos, los estudios observacionales retrospectivos y las series de casos que utilizaron rituximab en poblaciones adultas afectas de EM. Se valoro su impacto en el control clinico y radiologico de la enfermedad, asi como los aspectos relevantes de seguridad. Conclusiones. En todos los estudios revisados, el rituximab demostro un beneficio consistente en cuanto al control de la actividad inflamatoria, tanto clinica, reduciendo la incidencia de brotes, como radiologica, evitando la aparicion de lesiones nuevas o activas. Por el contrario, respecto a la progresion de la discapacidad, su efecto es mas controvertido. No se hallaron alertas de seguridad destacables. El rituximab parece ser un farmaco eficaz, efectivo y seguro en el tratamiento de la EM.

Cervical Cord Atrophy and Long-Term Disease Progression in Patients with Primary-Progressive Multiple Sclerosis.

BACKGROUND AND PURPOSE: Cervical cord atrophy has been associated with clinical disability in multiple sclerosis and is proposed as an outcome measure of neurodegeneration. The aim of this study was to quantify the development of cervical cord atrophy and to evaluate its association with disability progression in patients with primary-progressive multiple sclerosis. MATERIALS AND METHODS: Thirty-one patients with primary-progressive multiple sclerosis underwent 1.5T brain and spinal cord MR imaging at baseline and 6-7 years later. The cervical spinal cord from C1 to C5 was segmented to evaluate the normalized overall cross-sectional area and the cross-sectional area of C2-C3, C3-C4, and C4-C5. The annualized rates of normalized cross-sectional area loss were also evaluated. To estimate clinical progression, we determined the Expanded Disability Status Scale score at baseline and at 2 and 14 years after baseline to compute the normalized area under the curve of the Expanded Disability Status Scale and the Expanded Disability Status Scale changes from baseline to the follow-up time points. Associations between the cord cross-sectional area and brain MR imaging and clinical measures were also investigated. Finally, the value of all these measures for predicting long-term disability was evaluated. RESULTS: Some normalized cross-sectional area measurements showed moderate correlations with the normalized area under the curve of the Expanded Disability Status Scale, ranging from -0.439 to -0.359 (P < .05). Moreover, the annualized rate of the normalized mean cross-sectional area loss and the baseline Expanded Disability Status Scale were independent predictors of long-term disability progression. CONCLUSIONS: These data indicate that development of cervical cord atrophy is associated with progression of disability and is predictive of this event in patients with primary-progressive MS.

Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates.

BACKGROUND: Population-based studies on neuromyelitis optica spectrum disorders (NMOSD) are limited, and it is unclear whether the rates have changed with the implementation of the new 2015 criteria. OBJECTIVES: To estimate the incidence and prevalence of NMOSD in Catalonia (Spain), using both the 2006 and the 2015 criteria. METHODS: In this clinic-based retrospective study, patients diagnosed with NMOSD between 2006 and 2015 were identified using multiple sources, including direct contact to all Catalan hospitals, identification of cases through the Catalan Health Surveillance System, and registry of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) in a reference laboratory. The incidence rate was calculated for the period 1 January 2006-1 January 2016 and prevalence for the date 1 January 2016. RESULTS: We identified 74 patients (by the 2015 criteria). Most patients were Caucasian (81%), and female (76%) with a median age at disease onset of 42 years (range, 10-76 years). In total, 54 (73%) patients were positive for AQP4-IgG, 11 (15%) double-seronegative, and 9 (12%) MOG-IgG-positive. Rates of incidence and prevalence (0.63/1,000,000 person-years and 0.89/100,000, respectively) were 1.5-fold higher than those reported by the 2006 criteria. Lowest rates were seen in children and elder people and highest in women and middle-aged people (40-59 years). The female predominance was lost in incident AQP4-IgG-seronegative children and AQP4-IgG-positive elder people. MOG-IgG and double-seronegativity contributed similarly but did not influence the long-term outcome. CONCLUSION: The new criteria increase the estimates, but NMOSD remains as a rare disease. The differences in age- and sex-specific estimates highlight the importance of the serologic classification.