BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

BACKGROUND: 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.
METHODS: 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.

BACKGROUND: A growing number of studies have evaluated the effects of transcranial magnetic stimulation (TMS) for the symptomatic treatment of multiple sclerosis (MS).
METHODS: We performed a PubMed search for articles, recent books, and recommendations from the most relevant clinical practice guidelines and scientific societies regarding the use of TMS as symptomatic treatment in MS.
CONCLUSIONS: Excitatory electromagnetic pulses applied to the affected cerebral hemisphere allow us to optimise functional brain activity, including the transmission of nerve impulses through the demyelinated corticospinal pathway. Various studies into TMS have safely shown statistically significant improvements in spasticity, fatigue, lower urinary tract dysfunction, manual dexterity, gait, and cognitive deficits related to working memory in patients with MS; however, the exact level of evidence has not been defined as the results have not been replicated in a sufficient number of controlled studies. Further well-designed, randomised, controlled clinical trials involving a greater number of patients are warranted to attain a higher level of evidence in order to recommend the appropriate use of TMS in MS patients across the board. TMS acts as an adjuvant with other symptomatic and immunomodulatory treatments. Additional studies should specifically investigate the effect of conventional repetitive TMS on fatigue in these patients, something that has yet to see the light of day.

BACKGROUND: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population.
OBJECTIVE: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS.
RESULTS: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P=.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P=.001, P<.001, P<.001, and P=.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P=.002, P=.017, P=.013, and P=.009, respectively).
CONCLUSIONS: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS.

BACKGROUND: 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.
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.

BACKGROUND: Commercial video games are considered an effective tool to improve postural balance in different populations. However, the effectiveness of these video games for patients with multiple sclerosis (MS) is unclear.
OBJECTIVE: To analyse existing evidence on the effects of commercial video games on postural balance in patients with MS.
METHODS: We conducted a systematic literature search on 11 databases (Academic-Search Complete, AMED, CENTRAL, CINAHL, WoS, IBECS, LILACS, Pubmed/Medline, Scielo, SPORTDiscus, and Science Direct) using the following terms: \"multiple sclerosis\", videogames, \"video games\", exergam*, \"postural balance\", posturography, \"postural control\", balance. Risk of bias was analysed by 2 independent reviewers. We conducted 3 fixed effect meta-analyses and calculated the difference of means (DM) and the 95% confidence interval (95% CI) for the Four Step Square Test, Timed 25-Foot Walk, and Berg Balance Scale (BBS).
RESULTS: Five randomised controlled trials were included in the qualitative systematic review and 4 in the meta-analysis. We found no significant differences between the video game therapy group and the control group in Four Step Square Test (DM: -.74; 95% CI, -2.79 to 1.32; P=.48; I2=0%) and Timed 25-Foot Walk scores (DM: .15; 95% CI, -1.06 to .76; P=.75; I2=0%). We did observe intergroup differences in BBS scores in favour of video game therapy (DM: 5.30; 95% CI, 3.39-7.21; P<.001; I2=0%), but these were not greater than the minimum detectable change reported in the literature.
CONCLUSIONS: The effectiveness of commercial video game therapy for improving postural balance in patients with MS is limited.

BACKGROUND: In recent years, there has been an increase of studies dedicated to cognitive rehabilitation in patients with multiple sclerosis (MS); however, few of these analyze the impact on such variables as cognitive reserve. The study aims to explore the effects of a cognitive rehabilitation program comprising a combination of cognitive and physical exercises, as well as group sessions to improve cognitive performance, emotional state, and cognitive reserve index.
METHODS: Fifty patients with MS were subdivided into 2 groups: the control group, which performed aerobic exercise (n=25), and the experimental group (n=25), which participated in the integrated cognitive rehabilitation program (ICRP). All participants were evaluated 3 times (baseline, post-treatment, and long-term) with the Brief Repeatable Battery of Neuropsychological Tests, Cognitive Reserve Scale, Beck Depression Inventory, and a scale evaluating trait and state anxiety.
RESULTS: Compared with the control group, patients in the experimental group showed improvements in cognitive function, with significant changes in measures of information processing speed, attention, memory, cognitive reserve index, and long-term mood.
CONCLUSIONS: The ICRP was effective in improving cognitive and emotional function in MS, and increased the cognitive reserve index.

BACKGROUND: Pain is highly prevalent in patients with multiple sclerosis (MS); it is chronic in 50% of cases and is classified as nociceptive, neuropathic, or mixed-type. Pain affects quality of life, sleep, and the activities of daily living. Electrotherapy is an interesting alternative or complementary treatment in the management of pain in MS, with new innovations constantly appearing.
METHODS: This study evaluates the effectiveness of treatment with monopolar dielectric transmission of pulsed electromagnetic fields (PEMF) for pain associated with MS. We performed a randomised, placebo-controlled clinical trial including 24 patients, who were assessed with the Brief Pain Inventory, the Multiple Sclerosis International Quality of Life questionnaire, the Beck Depression Inventory, and the Modified Fatigue Impact Scale.
RESULTS: Statistically significant improvements were observed in maximum and mean pain scores, as well as in the impact of pain on work, personal relationships, and sleep and rest. Not significant differences were found between the treatment and placebo groups.
CONCLUSIONS: Treatment with PEMF may be effective in reducing pain in patients with MS, although further research is necessary to confirm its effectiveness over placebo and to differentiate which type of pain may be more susceptible to this treatment.

OBJECTIVE: To describe non-relapse-related emergency consultations of patients with multiple sclerosis (MS): causes, difficulties in the diagnosis, clinical characteristics, and treatments administered.
METHODS: We performed a retrospective study of patients who attended a multiple sclerosis day hospital due to suspected relapse and received an alternative diagnosis, over a 2-year period. Demographic data, clinical characteristics, final diagnosis, and treatments administered were evaluated. Patients who were initially diagnosed with pseudo-relapse and ultimately diagnosed with true relapse were evaluated specifically. As an exploratory analysis, patients who consulted with non-inflammatory causes were compared with a randomly selected cohort of patients with true relapses who attended the centre in the same period.
RESULTS: The study included 50 patients (33 were women; mean age 41.4 ± 11.7 years). Four patients (8%) were initially diagnosed with pseudo-relapse and later diagnosed as having a true relapse. Fever and vertigo were the main confounding factors. The non-inflammatory causes of emergency consultation were: neurological, 43.5% (20 patients); infectious, 15.2% (7); psychiatric, 10.9% (5); vertigo, 8.6% (4); trauma, 10.9% (5); and miscellaneous, 10.9% (5).
CONCLUSIONS: MS-related symptoms constituted the most frequent cause of non-inflammatory emergency consultations. Close follow-up of relapse and pseudo-relapse is necessary to detect incorrect initial diagnoses, avoid unnecessary treatments, and relieve patients\' symptoms.

BACKGROUND: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease.
METHODS: We performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined.
RESULTS: Relapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed.
CONCLUSIONS: The incidence of COVID-19 was slightly higher in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined.