Early beginning of alemtuzumab: Changing the multiple sclerosis treatment paradigm. Interim analysis of the LEMVIDA study.

INTRODUCTION: LEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain. METHODS: This is an interim analysis evaluating the baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria. RESULTS: 161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed). CONCLUSIONS: Unlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.

Incidence and prevalence of multiple sclerosis in China and other Asian countries.

The prevalence of multiple sclerosis (MS) in Asian countries is thought to be lower than in Western countries, with Asian populations presenting 80% less risk of MS than white populations. Incidence and prevalence rates in Asian countries are therefore not well defined and their association with rates in neighboring countries, as well as with ethnic, environmental, and socioeconomic factors, are not well understood. We performed a comprehensive literature review of epidemiological data from China and neighbouring countries to study the frequency of the disease, focusing on prevalence, and the progression over time and the influence of sex-related, environmental, dietary, and sociocultural factors. Prevalence rates in China range between 0.88 cases/100,000 population in 1986 and 5.2 cases/100,000 population in 2013, with a non-significant upwards trend (p = .08). The increase observed in Japan, where figures ranged between 8.1 and 18.6 cases/100,000 population was highly significant (p < .001). Prevalence rates in countries with predominantly white populations are considerably higher and have increased over time, reaching 115 cases/100,000 population in 2015 (r2 = 0.79, p < .0001). In conclusion, the prevalence of MS in China appears to have risen in recent years, although Asian populations (including Chinese and Japanese populations, among others) appear to present less risk than other populations. Within Asia, geographical latitude appears not to be a determining factor for developing MS.

Attentional networks in neurodegenerative diseases: anatomical and functional evidence from the Attention Network Test.

INTRODUCTION: Understanding alterations to brain anatomy and cognitive function associated with neurodegenerative diseases remains a challenge for neuroscience today. In experimental neuroscience, several computerised tests have been developed to contribute to our understanding of neural networks involved in cognition. The Attention Network Test (ANT) enables us to measure the activity of 3 attentional networks (alertness, orienting, and executive function). OBJECTIVES: The main aim of this review is to describe all the anatomical and functional alterations found in diverse neurological diseases using the ANT. MATERIAL AND METHODS: We collected studies published since 2010 in the PubMed database that employed the ANT in different neurological diseases. Thirty-two articles were obtained, addressing multiple sclerosis, epilepsy, and Parkinson's disease, among other disorders. CONCLUSIONS: Some of the anatomical structures proposed in the 3 attentional networks model were confirmed. The most relevant structures in the alertness network are the prefrontal cortex, parietal region, thalamus, and cerebellum. The thalamus is also relevant in the orienting network, together with posterior parietal regions. The executive network does not depend exclusively on the prefrontal cortex and anterior cingulate cortex, but also involves such subcortical structures as the basal ganglia and cerebellum and their projections towards the entire cortex.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

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.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain. / Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España.

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.

Effectiveness of monopolar dielectric transmission of pulsed electromagnetic fields for multiple sclerosis-related pain: a pilot study.

INTRODUCTION: 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. MATERIAL AND 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.

Incidence and prevalence of multiple sclerosis in China and other Asian countries. / Incidencia y prevalencia de la esclerosis múltiple en China y países asiáticos.

The prevalence of multiple sclerosis (MS) in Asian countries is thought to be lower than in Western countries, with Asian populations presenting 80% less risk of MS than white populations. Incidence and prevalence rates in Asian countries are therefore not well defined and their association with rates in neighboring countries, as well as with ethnic, environmental, and socioeconomic factors, are not well understood. We performed a comprehensive literature review of epidemiological data from China and neighbouring countries to study the frequency of the disease, focusing on prevalence, and the progression over time and the influence of sex-related, environmental, dietary, and sociocultural factors. Prevalence rates in China range between 0.88 cases/100,000 population in 1986 and 5.2 cases/100,000 population in 2013, with a non-significant upwards trend (p = .08). The increase observed in Japan, where figures ranged between 8.1 and 18.6 cases/100,000 population was highly significant (p < .001). Prevalence rates in countries with predominantly white populations are considerably higher and have increased over time, reaching 115 cases/100,000 population in 2015 (r2 = 0.79, p < .0001). In conclusion, the prevalence of MS in China appears to have risen in recent years, although Asian populations (including Chinese and Japanese populations, among others) appear to present less risk than other populations. Within Asia, geographical latitude appears not to be a determining factor for developing MS.

Attentional networks in neurodegenerative diseases: anatomical and functional evidence from the Attention Network Test. / Redes neurales atencionales en enfermedades neurodegenerativas: evidencias anatómico-funcionales empleando el Attention Network Test.

INTRODUCTION: Understanding alterations to brain anatomy and cognitive function associated with neurodegenerative diseases remains a challenge for neuroscience today. In experimental neuroscience, several computerised tests have been developed to contribute to our understanding of neural networks involved in cognition. The Attention Network Test (ANT) enables us to measure the activity of 3 attentional networks (alertness, orienting, and executive function). OBJECTIVES: The main aim of this review is to describe all the anatomical and functional alterations found in diverse neurological diseases using the ANT. MATERIAL AND METHODS: We collected studies published since 2010 in the PubMed database that employed the ANT in different neurological diseases. Thirty-two articles were obtained, addressing multiple sclerosis, epilepsy, and Parkinson's disease, among other disorders. CONCLUSIONS: Some of the anatomical structures proposed in the 3 attentional networks model were confirmed. The most relevant structures in the alertness network are the prefrontal cortex, parietal region, thalamus, and cerebellum. The thalamus is also relevant in the orienting network, together with posterior parietal regions. The executive network does not depend exclusively on the prefrontal cortex and anterior cingulate cortex, but also involves such subcortical structures as the basal ganglia and cerebellum and their projections towards the entire cortex.

Free kappa light chains in cerebrospinal fluid as a biomarker to assess risk conversion to multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) initiates with a first attack or clinically isolated syndrome (CIS). The importance of an early treatment in MS leads to the search, as soon as possible, for novel biomarkers which can predict conversion from CIS to MS. OBJECTIVE: The purpose of this study was to assess the predictive value of the kappa index ([Formula: see text] index), using kappa free light light chains ([Formula: see text]FLCs) in cerebrospinal fluid (CSF), for the conversion of CIS patients to MS, and compare its accuracy with other parameters used in clinical practice. METHODS: FLC levels were analysed in CSF from 176 patients: 70 as control group, 77 CIS, and 29 relapsing-remitting MS. FLC levels were quantified by nephelometry. RESULTS: [Formula: see text] Index sensitivity and specificity (93.1%; 95.7%) was higher than those from the immunoglobulin G (IgG) index (75.9%; 94.3%), and lower than those from oligoclonal IgG bands (OCGBs) (96.5%; 98.6%). The optimal cut-off for [Formula: see text] index was 10.62. Most of the CIS patients with [Formula: see text] index >10.62 presented OCGBs, IgG index >0.56 and fulfilled magnetic resonance imaging (MRI) criteria. CONCLUSION: CIS patients above [Formula: see text] index cut-off of 10.62 present 7.34-fold risk of conversion to MS than CIS below this value. The [Formula: see text] index correlated with positive OCGBs, IgG index above 0.56 and MRI criteria.

[Spinal metastatic tumor in a patient with tuberous sclerosis complex]. / Tumoración intrarraquídea metastásica en paciente con esclerosis tuberosa.

Most of the cauda equina tumors are primary tumors and metastases (especially from some tumors like renal carcinoma [RC]) are very unusual. We report a 28-yearold- man with tuberous sclerosis complex (TSC) who had undergone a left nephrectomy one year before for the treatment of RC. He presented with a 2-3 month history of lower back pain that radiated to both legs and weakness in lower limbs. He denied bowel and bladder symptoms. A magnetic resonance scan of the dorsolumbar spine revealed an intradural extramedullary cauda equina mass that demonstrated uniform homogeneous enhancement, which was a metastasis. Therapeutical and diagnostic aspects are discussed. We review the previous literature on this topic.

[Cost-utility analisys of multiple sclerosis treatment with glatiramer acetate or interferon beta in Spain]. / Análisis coste utilidad del tratamiento de la esclerosis múltiple remitente-recidivante con acetato de glatiramero o interferón beta en España.

OBJECTIVE: To carry out a cost-utility analysis of the treatment of relapsing-remitting multiple sclerosis (RRMS) with glatiramer acetate (copaxone) or interferon beta (all, avonex, rebif and betaferon). METHODS: A pharmacoeconomic Markov model was used to compare treatment options by simulating the life of a hypothetical cohort of women aged 30, from the societal perspective. The transition probabilities, utilities, resource utilisation and costs (direct and indirect) were obtained from Spanish sources and from bibliography. Univariant sensitivity analyses of the base case were performed. RESULTS: In the base case analysis, the average cost per patient (euro in 2001) for a lifetime treatment, considering a life expectancy of 53 years, would be 1,243,906 euros (euro), 1,818,149 euros, 1,763,263 euros, 1,987,153 euros and 1,704,031 euros with copaxone, all interferons, avonex, rebif and betaferon, respectively. Therefore, the saving with copaxone would range between 460,000 and 737,000 euros approximately. The quality-adjusted life years (QALY) obtained with copaxone or interferons would be 10.977 and 6.917, respectively, with an average gain of 4.060 QALY patient with copaxone. The sensitivity analyses confirmed the robustness of the base case. The interferons would only be superior to copaxone in the unlikely hypothetical case that they delay the progression of the illness by 20% more than that actually observed in clinical trials. CONCLUSIONS: For a typical patient with RRMS, treatment with copaxone would be more efficient than interferons and would dominate (would be more efficacious with lower costs) interferon beta.

[Immunosuppressants and multiple sclerosis]. / Inmunosupresores y esclerosis múltiple.

AIMS: Technological progress, improvements in the design of clinical trials and in MRI have led to a great variety of therapeutical approaches in dealing with multiple sclerosis (MS), some of which have been successful while others less so, despite promising results from animal models. DEVELOPMENT: In this paper we review the present state of therapy with immunosuppressants in MS and special attention is paid to trials conducted with cladribine, linomide, sulfasalazine, ciclophosphamide, mitoxantrone, cyclosporine A and azatioprine. CONCLUSION: Severe, unspecific immunosuppression lowers the anatomopathological and clinical activity of the disease, with slight improvements in the seizure rates and the MRI. While no effects have been found on the progression, serious short and long term side effects have been observed which, in some cases, prevent it from being administered. However, it is true that proof of the efficiency of these products may not have been possible owing to methodological problems they might be more useful alone or in combination with immunomodulators.

[The treatment of myasthenia gravis by video thoracoscopic thymectomy. The technic and the initial results]. / Tratamiento de la miastenia grave mediante timectomía videotoracoscópica. Técnica y resultados iniciales.

The primary role of thymectomy for the treatment of myasthenia gravis is currently undisputed. Traditionally, the approach of choice has been sternotomy, although a transcervical route has also been advocated because of its lower rate of associated morbidity. Our department performed thymectomy using a video-assisted thoracoscopic technique in 7 patients (2 men and 5 women) between March 1993 and October 1995. The patients' mean age was 43.4 years (range 20 to 66 years). Complications were few, consisting of 2 cases of pneumothorax due to contralateral opening of the pleura, resolved by pleural drainage. No deaths occurred. Clinical results over periods of observation ranging from 14 to 44 months were excellent in 2 cases of complete remission; good in 3 patients with considerable reduction in drug requirements; and fair in 2 patients who continued to need the same doses of medication throughout the 14 months after thymectomy. The technique we propose is less aggressive than mid-sternotomy, offering incontrovertible advantages and leading to faster. No patient required assisted ventilation for longer than 4 hours and the maximum time spent in the intensive care unit was 24 hours. We therefore suggest that thymectomy to treat myasthenia gravis be performed by thoracoscopy.

[Bilateral frontal infarct with imitation and utilization syndrome in a case of giant cell arteritis]. / Infarto frontal bilateral con síndrome de imitación y utilización en un caso de arteritis de células gigantes.

Giant cell arteritis (GCA) is a vasculitis which involves in a systemic fashion the mean and medium sized arteries. Intracranial vessels are exceptionally involved. Thus, stroke is an uncommon complication. We report a patient with typical GCA with blindness due to occlusion of the central artery of the retina, who developed an imitation and utilization behavior attributable to bilateral frontal infarction without accompanying neurological symptoms. Although histological study was not available, this case fulfilled all of Russi's criteria for GCA localized in the CNS. This lends support to the suspicion that the bilateral frontal infarction might be due to it.