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Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis., Objective: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain., Development: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group., Conclusion: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice., (Copyright © 2019 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Multiple sclerosis (MS) is a complex disease with a heterogeneous and unpredictable clinical course. Mobility impairment after progressive paralyses and muscle tone spasticity is common. Areas covered: The prevalence, assessment, and pharmacological management of gait impairment and spasticity in MS and their effects on health-related quality of life (HRQoL) are discussed. The roles of oral and intrathecal baclofen and of delta-9-tetrahydrocannabinol/cannabidiol (THC:CBD) oromucosal spray in treating MS spasticity-related gait impairment are reviewed. Expert commentary: Mobility impairment and spasticity are experienced by approximately 90% and 80% of MS patients, respectively, during the disease course. Prevalence and severity of gait impairment and spasticity increase as disease progresses. The symptoms are related and both impact negatively on HRQoL. Oral baclofen and tizanidine are generally used for first-line treatment of MS spasticity but are ineffective in approximately 40% of cases. Second-line therapy includes add-on THC:CBD spray for patients with resistant MS spasticity. Results of studies evaluating baclofen for treating MS spasticity gait impairment are equivocal. In studies of patients with resistant MS spasticity, THC:CBD spray consistently improved the timed 10-meter walk test and significantly improved multiple spatial-temporal and kinematic gait parameters. THC:CBD oromucosal spray warrants further investigation as a treatment for MS spasticity-related gait impairment.

Background: Alemtuzumab was superior on clinical and magnetic resonance imaging (MRI) outcomes versus subcutaneous interferon beta-1a in phase 3 trials in patients with relapsing-remitting multiple sclerosis., Objective: To examine quality-of-life (QoL) outcomes in the alemtuzumab phase 3 trials., Methods: Patients who were treatment naive (Comparison of Alemtuzumab and Rebif ® Efficacy in Multiple Sclerosis I [CARE-MS I]) or had an inadequate response to prior therapy (CARE-MS II) received annual courses of alemtuzumab 12 mg/day at baseline (5 days) and Month 12 (3 days) or subcutaneous interferon beta-1a 44 µg three times/week. QoL was measured every 6 or 12 months using Functional Assessment of Multiple Sclerosis (FAMS), European Quality of Life-5 Dimensions (EQ-5D) and its visual analog scale (EQ-VAS), and 36-Item Short-Form Survey (SF-36)., Results: Statistically significant improvements from baseline with alemtuzumab were observed on all three QoL instruments at the earliest post-baseline assessment and sustained through Year 2. Statistically significant greater QoL improvements over subcutaneous interferon beta-1a were seen at all time points in CARE-MS II with FAMS, EQ-VAS and SF-36 physical component summary, and in CARE-MS I with FAMS., Conclusion: Patients treated with alemtuzumab had improvements in physical, mental, and emotional QoL regardless of treatment history. Improvements were significantly greater with alemtuzumab versus subcutaneous interferon beta-1a on both disease-specific and general measures of QoL.

Objective: To assess the effectiveness and safety of fingolimod use in a Spanish clinical practice setting., Methods: Retrospective study with multiple sclerosis patients who received at least 1 fingolimod dose between January 2004 and January 2015. Effectiveness and safety data were collected during the entire treatment of each patient. Analysis was performed for the total population and stratified according to prior treatment, sex, and age at treatment initiation., Results: A total of 167 patients were included, 50.9% had prior immunomodulator use, 33.5% natalizumab use, and 15.6% were naive patients. The annual relapse rate (ARR) decreased for the total population at month 12 (62%) and month 24 (84%) (P < 0.0001, in both cases); for naive patients (P < 0.05) and patients with prior immunomodulator use (P < 0.0001); for patients with prior natalizumab use, the ARR kept low after treatment initiation (0.23). After 24 months, the proportion of relapse-free patients was 70% or greater and disability progression-free patients was 80% or greater. No significant differences were observed when the results were compared by prior treatment, sex, or age. Thirty-two patients (19.2%) reported adverse drug reactions and 9.6% discontinued: 4.8% due to adverse drug reactions and 4.8% for lack of effectiveness., Conclusions: The results support fingolimod use due to clinical effectiveness, tolerability, and ease of administration.

Aim: To create a national consensus checklist to assess newly diagnosed multiple sclerosis patients when considering treatment initiation in Spain., Materials & Methods: The Delphi consensus method was used. A scientific committee drafted items/domains, 52 experts evaluated their inclusion in the project checklist and 47 experts assessed checklist use in clinical practice., Results: Forty-eight items from seven dimensions were selected: sociodemographics, n = 3; medical history, n = 10; multiple sclerosis clinical factors, n = 14; laboratory/MRI, n = 8; multiple sclerosis signs affecting treatment, n = 4; multiple sclerosis signs affecting management, n = 1; treatment-related features, n = 8. Understanding, acceptance, ease of use, effectiveness and suitability of checklist use were favorably rated by ≥75.5% of experts., Conclusion: This project provides a consensus checklist gathering necessary information when considering multiple sclerosis treatment in newly diagnosed patients.

Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

Multiple sclerosis is the most frequent disabling neurological disease in young adults. Its development includes independent processes of inflammation, demyelination, neurodegeneration, gliosis and repair, which are responsible for the heterogeneity and individual variability in the expression of the disease, its prognosis and response to treatment. As part of personalised medicine, the progress made in the search for new biomarkers has identified promising candidates that may be useful for the early diagnosis of the disease, for detecting prognostic and developmental profiles of the disease, and for monitoring the response to treatment. Unfortunately, few of them have been validated adequately, which prevents them from being applied in clinical practice. In view of the latest findings, the experts recommend orienting research in another direction, not so much towards the discovery of new molecules or imaging techniques, but instead towards a clinical validation of these markers, with the aim of fostering translational research. This review offers an update on the information about the biomarkers in multiple sclerosis that have currently been validated and are thus potential candidates, as well as looking at their value in the diagnosis, prognosis, evaluation of the development of the disability caused by the disease and the response to therapy.

The new insights presented at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in November 2011. Further evidence from epidemiological studies yield a possible relationship between nutrition and alterations of the microbiota that may result in the development of multiple sclerosis (MS) and that may trigger the exacerbation of disease symptoms. Also show the magnitude of impact of comorbidities in multiple sclerosis course as well as the impact of early identification and management. Review of current data on chronic cerebrospinal venous insufficiency and MS sclerosis concludes that there is no role of chronic cerebrospinal venous insufficiency in either multiple sclerosis risk or MS severity. New diagnostic criteria for MS have simplified requirements for demonstrating dissemination of lesions in time. High-field magnetic resonance imaging improves cortical visualization and become a promising tool to detect remyelinization and cortical and medullary lesions, and optical coherence tomography is established as a powerful tool for neuroprotection trials. Diffuse meningeal inflammation through B-cell follicle-like structures is associated with cortical pathology and an accelerated clinical course in secondary progressive MS sclerosis. Systemic inflammation may contribute to neurodegeneration processes in MS, and with regard to grey matter damage recent findings conclude that occurs early in disease course, and correlates with future MS-related disability.

The classification of epilepsy includes a group of generalized idiopathic epilepsies that are triggered by a specific mode of activation, known as reflex epilepsies. Photosensitive epilepsy is the most common type. Some patients with photosensitive epilepsy use this sensitivity to induce seizures or epileptiform discharges on the electroencephalogram. In some patients, psychopharmacological treatment, for instance with selective serotonin reuptake inhibitors and neuroleptics, has demonstrated benefit insofar as self-induction of seizures is concerned. However, so far as we know, there are no documented cases of treatment with methylphenidate in patients with this type of seizure. Our purpose is to report the case of an 8-year-old girl with attention-deficit hyperactivity disorder (ADHD) and self-induced photosensitive epilepsy whose behavior in general, and self-inducing behavior in particular, improved dramatically following treatment with methylphenidate.

The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. The age is an important factor related to the course and prognosis of multiple sclerosis (MS). The evolution to progressive disease persists more than 50 years after diagnosis of MS and a reduction in the delay of diagnosis has been detected. Several strategies have been proposed in order to improve the efficacy of magnetic resonance regarding prognosis and course of disease. The studies presented at the Congress reflect the influence of gender on course and severity of disease symptoms, showing an increase of worldwide prevalence of MS in women. Neuroprotective action of estrogen receptor beta has been reported. The genome wide association studies have allowed investigators to identify numerous susceptible alleles. In this regard, HLA class II genes, seems to contribute to genetic risk for developing neutralizing antibodies against beta-interferon. Vitamin D deficiency and Epstein-Barr virus have been highlighted as risk factors for MS in the reported findings. On the subject of the ongoing controversy regarding the role of inflammation and degeneration in MS, several arguments have been found to support the role of CNS autoimmunity to explain the presence of inflammatory phenomenon. The available data hold the potential therapeutic role of mesenchymal cells given the involvement of these stem cells in CNS repair.

Schizencephaly is a rare disorder of neuronal migration that is characterized by the presence of clefts that extend from the ependymal surface of the lateral ventricles to the pial lining of the cortex. The authors present the case of a female patient with a prenatal diagnosis made by magnetic resonance imaging (MRI), her clinical course, and neurorradiological evolution following birth. A 6-year-old female, with right open lip schizencephaly, was diagnosed by means of prenatal cerebral magnetic resonance at the gestational age of 25 weeks. The patient does not present intellectual disability, reaching developmental mile-stones at normal time points. The MRI of the brain reveals right, perisylvian, closed lip schizencephaly. Prenatal MRI is remarkably useful in the diagnosis and prognostic approach to the condition. It is less useful in classifying the unilateral forms (open vs closed lips), and hence, its prognostic validity is more limited.

Much attention has been paid in recent years to the role of prenatal exposure to alcohol. Fetal alcohol syndrome is one of the most severe afflictions resulting from such exposure. The present report documents the cases of adopted children diagnosed with fetal alcohol syndrome who developed both Tourette syndrome and attention deficit-hyperactivity disorder. Out of a population of 138 adopted children with behavior issues whose clinical histories were reviewed retrospectively, 9 children (6.5%) presented this constellation. Epidemiologic data, clinical data, neurologic examination findings, complementary testing, and developmental data were recorded. All nine patients studied had initial psychomotor retardation, despite the frequent case of subsequent intelligence quotient normalization. From a behavioral perspective, half of the cases presented obsessive-compulsive disorder and problems with social relations. Aggressive behavior was common. These cases also presented a high degree of severity of both tics and hyperactivity. The most common drug treatment was methylphenidate. This constellation of fetal alcohol syndrome, Tourette syndrome, and attention deficit-hyperactivity disorder is scantly reported in the literature and is likely underdiagnosed. This particular constellation poses its own prognosis and requires its own treatment., (Copyright 2010 Elsevier Inc. All rights reserved.)

This article compiles the investigations carried out by a Research Group of the University of Granada, Spain. Its different projects on writing's cognitive social and cultural processes have been supported by the Spanish Government. This line of research joined together linguistic, psychological, social and cultural contributions to the development of writing from the 1970s. Currently, this line of research develops in collaboration with other European Universities: (a) Interuniversity Centre for Research On Cognitive Processing in Natural and Artificial Systems (ECONA), "La Sapienza" University of Rome (Italy); (b) Anadolu University, (Eskisehir, Turkey); (c) Coimbra University (Portugal); (d) University of Zaragoza (Spain); (e) the Institute of Education of the University of London (United Kingdom). The aforementioned collaboration is materializing into projects like the International Master on Multilingual Writing: Cognitive, Intercultural and Technological Processes of Written Communication ( http://www.multilingualwriting.com ) and the International Congress: Writing in the twenty-first Century: Cognition, Multilinguisim and Technologies, held in Granada ( http://www.asprogrades.org ). This research line is focussed on the development of strategies in writing development, basic to train twenty-first century societies' citizens. In these societies, participation in production media, social exchange and the development of multilingual written communication skills through new computer technologies spread multicultural values. In order to fulfil the social exigencies, it is needed to have the collaboration of research groups for designing and applying international research projects.