Publications by authors named "Celia Oreja-Guevara"

106 Publications

Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus.

J Neurol 2021 Apr 12. Epub 2021 Apr 12.

MS Center and Neurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

Coronavirus disease (COVID-19) appeared in December 2019 in the Chinese city of Wuhan and has quickly become a global pandemic. The disease is caused by the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), an RNA beta coronavirus phylogenetically similar to SARS coronavirus. To date, more than 132 million cases of COVID19 have been recorded in the world, of which over 2.8 million were fatal ( https://coronavirus.jhu.edu/map.html ). A huge vaccination campaign has started around the world since the end of 2020. The availability of vaccines has raised some concerns among neurologists regarding the safety and efficacy of vaccination in patients with multiple sclerosis (MS) taking immunomodulatory or immunosuppressive therapies.
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http://dx.doi.org/10.1007/s00415-021-10545-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038920PMC
April 2021

Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD.

Ann Neurol 2021 Feb 14. Epub 2021 Feb 14.

Mayo Clinic, Rochester, MN.

Objective: During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy.

Methods: Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis.

Results: Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1-276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6-97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013-0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199-0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use.

Interpretation: This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021.
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http://dx.doi.org/10.1002/ana.26049DOI Listing
February 2021

Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment.

Mult Scler Relat Disord 2021 Jan 11;49:102747. Epub 2021 Jan 11.

Multiple Sclerosis Unit, Department of Neurology,Hospital Universitario Getafe, Carr. Madrid - Toledo, Km 12,500, 28905 Getafe, Madrid, Spain. Electronic address:

Background: Potential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS).

Objective: Detailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment.

Methods: We describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National Health System hospitals from February 2014 to May 2019. Local researchers were periodically contacted by the investigation team to monitor safety issues. Cancer histories were collected from the medical records and the information was updated at July 30 2020.

Results: Eight Caucasian women developed cancer, which accounts for 0.9% and an accumulated malignancy rate of 298.39 cases per 100,000 patient-years of DMF exposure. At the time of cancer diagnosis, age was between 33 to 67 years and median time on DMF treatment 16.5 months (range 1-53). Two patients had familiar history of cancer. No specific cancer lines were found (breast cancer in 2 cases, thyroid in 3, urothelial carcinoma, cervix and a progression to leiomyosarcoma from a mitotically active leiomyoma). DMF was withdrawn during cancer treatment in 6 patients and reintroduced later. All cancers except one are in complete remission. The patient with leiomyosarcoma died by cancer progression.

Conclusion: A relationship between cancers and DMF is unlikely because the malignancy rate was similar to that of the age-and sex-matched general population, and because of the absence of specific tumour cell lines. Nevertheless, as with other immunosuppressive DMTs, clinicians treating MS should be aware of any potential cancer symptom and demand proper testing.
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http://dx.doi.org/10.1016/j.msard.2021.102747DOI Listing
January 2021

A plea for equitable global access to COVID-19 diagnostics, vaccination and therapy: The NeuroCOVID-19 Task Force of the European Academy of Neurology.

Eur J Neurol 2021 Jan 18. Epub 2021 Jan 18.

Division of Neurology, CHU of Grenoble, Grenoble Institute of Neurosciences, Grenoble Alpes University, Grenoble, France.

Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.
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http://dx.doi.org/10.1111/ene.14741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014664PMC
January 2021

[Natural history and optic neuritis in multiple sclerosis].

An Pediatr (Barc) 2020 Dec 30. Epub 2020 Dec 30.

Servicio de Oftalmología, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España.

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http://dx.doi.org/10.1016/j.anpedi.2020.11.018DOI Listing
December 2020

Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial.

Mult Scler Relat Disord 2021 Jan 26;47:102641. Epub 2020 Nov 26.

Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address:

Background: Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT.

Methods: In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.

Results: The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.

Conclusion: Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.

Trial Registration: NCT01892345 (ClinicalTrials.gov).
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http://dx.doi.org/10.1016/j.msard.2020.102641DOI Listing
January 2021

Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study.

CNS Drugs 2020 12 23;34(12):1275-1286. Epub 2020 Nov 23.

Multiple Sclerosis Unit, Department of Neurology, S. de Neurología, Hospital Universitario de Getafe, Carretera Toledo Km 12.5, Getafe, 28905, Madrid, Spain.

Background: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited.

Objective: The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting.

Methods: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated.

Results: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy.

Conclusions: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.
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http://dx.doi.org/10.1007/s40263-020-00775-9DOI Listing
December 2020

Treatment Response Score to Glatiramer Acetate or Interferon Beta-1a.

Neurology 2021 01 6;96(2):e214-e227. Epub 2020 Oct 6.

From the Department of Health Sciences (DISSAL) (F.B., M.P.S.), University of Genoa, Italy; CORe (T.K., C.M.), Department of Medicine, University of Melbourne, Australia; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Biostatistics (G.C.), University of Alabama at Birmingham; Department of Neurology and Center for Clinical Neuroscience (D.H., E.K.H.), First Medical Faculty, Charles University, Prague, Czech Republic; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; Department of Neuroscience (A.P., M.G., P.D.), Faculty of Medicine, Université de Montréal, Quebec, Canada; Department of Neuroscience, Imaging, and Clinical Sciences (M.O.), University G. d'Annunzio, Chieti; IRCCS Istituto delle Scienze Neurologiche di Bologna (A.L.); Dipartimento di Scienze Biomediche e Neuromotorie (A.L.), Università di Bologna, Italy; Hospital Universitario Virgen Macarena (G. Izquierdo. S.E.), Sevilla, Spain; Department of Medical, Surgical Science and Advanced Technology "GF Ingrassia" (F.P.), University of Catania, Italy; Ondokuz Mayis University (M. Terzi), Department of Neurology, Samsun, Turkey; CISSS Chaudi're-Appalache (P.G.), Centre-Hospitalier, Levis, Quebec, Canada; IRCCS Mondino Foundation (R.B.), Pavia; Department of Neuroscience (P.S., D.F.), Azienda Ospedaliera Universitaria, Modena, Italy; Department of Neurology (S.O.), Dokuz Eylul University, Izmir, Turkey; Ospedali Riuniti di Salerno (G. Iuliano), Salerno, Italy; Department of Neurology (C.B.), Karadeniz Technical University, Trabzon, Turkey; Department of Neurology (R.H.), Zuyderland Medical Center, Sittard, the Netherlands; Neuro Rive-Sud (F.G.), Hôpital Charles LeMoyne, Greenfield Park, Quebec, Canada; Clinico San Carlos (C.O.-G), Madrid, Spain; Cliniques Universitaires Saint-Luc (V.v.P.); Université Catholique de Louvain (V.v.P.), Brussels, Belgium; UOC Neurologia (E.C.), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Kommunehospitalet (T.P.), Arhus C, Denmark; Koc University (A.A.), School of Medicine; Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases (A.S.), Istanbul, Turkey; Hospital Germans Trias i Pujol (C.R.-T.), Badalona, Spain; University of Queensland (P.M.), Brisbane, Australia; Haydarpasa Numune Training and Research Hospital (R.T.), Istanbul, Turkey; Central Clinical School (H.B.), Monash University, Melbourne, Australia; The University of Texas Health Science Center at Houston (J.S.W.); Rehabilitation Unit (C.S.), "Mons. L. Novarese" Hospital, Moncrivello; and IRCCS Ospedale Policlinico San Martino (M.P.S.), Genoa, Italy.

Objective: To compare the effectiveness of glatiramer acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments.

Methods: Data from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-1a) and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.

Results: The overall ARR ratio of GA to IFN-β-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration, and Expanded Disability Status Scale score) detected differential response of GA vs IFN-β-1a: in the trial, patients with the largest benefit from GA vs IFN-β-1a (lower score quartile) had an ARR ratio of 0.40 (95% confidence interval [CI] 0.25-0.63), those in the 2 middle quartiles of 0.90 (95% CI 0.61-1.34), and those in the upper quartile of 1.14 (95% CI 0.59-2.18) (heterogeneity = 0.012); this result was validated on MSBase, with the corresponding ARR ratios of 0.58 (95% CI 0.46-0.72), 0.92 (95% CI 0.77-1.09,) and 1.29 (95% CI 0.97-1.71); heterogeneity < 0.0001).

Conclusions: We demonstrate the possibility of a criterion, based on patients' characteristics, to choose whether to treat with GA or IFN-β-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.
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http://dx.doi.org/10.1212/WNL.0000000000010991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905777PMC
January 2021

Skin Phototype Could Be a Risk Factor for Multiple Sclerosis.

J Clin Med 2020 Jul 26;9(8). Epub 2020 Jul 26.

Instituto de Investigación Biomédica de Málaga-IBIMA, 29009 Málaga, Spain.

Environmental and genetic factors are assumed to be necessary for the development of multiple sclerosis (MS), however its interactions are still unclear. For this reason here, we have not only analyzed the impact on increased risk of MS of the best known factors ( allele, sun exposure, vitamin D levels, smoking habit), but we have included another factor (skin phototype) that has not been analyzed in depth until now. This study included 149 MS patients and 147 controls. A multivariate logistic regression (LR) model was carried out to determine the impact of each of the factors on the increased risk of MS. Receiver Operating Characteristics (ROC) analysis was performed to evaluate predictive value of the models. Our multifactorial LR model of susceptibility showed that females with light brown skin (LBS), smokers and who had allele had a higher MS risk (LBS: OR = 5.90, IC95% = 2.39-15.45; smoker: OR = 4.52, IC95% = 2.69-7.72; presence of : OR = 2.39, IC95% = 1.30-4.50; female: OR = 1.88, IC95% = 1.08-3.30). This model had an acceptable discriminant value with an Area Under a Curve AUC of 0.76 (0.69-0.82). Our study indicates that MS risk is determined by complex interactions between sex, environmental factors, and genotype where the milieu could provide the enabling proinflammatory environment that drives an autoimmune attack against myelin by self-reactive lymphocytes.
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http://dx.doi.org/10.3390/jcm9082384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464407PMC
July 2020

Teriflunomide vs injectable disease modifying therapies for relapsing forms of MS.

Mult Scler Relat Disord 2020 Aug 13;43:102158. Epub 2020 May 13.

Stony Brook University, Stony Brook, NY, USA.

Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory disease affecting the white and gray matter of the central nervous system. Several disease modifying therapies (DMTs) have been shown to significantly reduce relapse rates, slow disability worsening, and modify the overall disease course of MS. Decision-making when initiating a DMT should be shared between the patient and physician. Important factors such as prognostic indicators, safety, patient preferences, adherence, and convenience should also be considered. Treatment guidelines recommend switching a DMT when a patient experiences breakthrough disease activity, but also for patients who experience adverse events. Compared with injectable therapies, oral DMTs are often associated with increased treatment adherence and patient satisfaction, due to a less burdensome route of administration and greater tolerability. This review will summarize the available scientific evidence for injectable DMTs and the oral DMT teriflunomide, including considerations for both treatment-naïve patients initiating a DMT and patients switching from an injectable DMT.
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http://dx.doi.org/10.1016/j.msard.2020.102158DOI Listing
August 2020

Highlights from the 2019 European Congress on Treatment and Research in Multiple Sclerosis (ECTRIMS 2019).

Mult Scler 2020 06 4;26(7):859-868. Epub 2020 May 4.

Department of Neurology, Hospital Clínico San Carlos, Madrid, Spain/Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid (UCM) and IdISSC, Madrid, Spain.

The 2019 ECTRIMS Congress, in Stockholm, has had record-breaking figures for both attendance and scientific production. There were 9361 participants from 100 different countries for a total of 1541 abstracts. Upon invitation of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) executive committee, the authors of this meeting report assessed abstracts from all poster and oral presentations for novelty, scientific quality and relevance for basic and clinical multiple sclerosis (MS) research. The objective of this report is to highlight a selection of basic, translational and clinical studies out of the many outstanding projects that were presented. Abstracts and references cited in our report were chosen at the discretion of the authors and all co-authors and the ECTRIMS executive committee agreed on the selection. In the event of discrepancies between the abstract and the uploaded poster or presentation, we aimed to present data derived from the poster or presentation. All abstracts are accessible through the ECTRIMS online library ( https://onlinelibrary.ectrimscongress.eu/ectrims/#!*menu=36*browseby=3*sortby=2*ce_id=160 ) and also published in this journal (Volume 25 Issue 2_suppl, September 2019; https://journals.sagepub.com/toc/msja/25/2_suppl ). A few additional references from the literature were added but were restricted to the ones that authors considered as absolutely required for an optimized understanding of the topics highlighted.
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http://dx.doi.org/10.1177/1352458520918377DOI Listing
June 2020

Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population.

J Neurol 2020 Aug 29;267(8):2362-2371. Epub 2020 Apr 29.

Multiple Sclerosis Unit, Department of Neurology, University Hospital of Getafe, Madrid, Spain.

Background: Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population.

Objective: To evaluate DMF tolerability, safety and persistence in MS in a real-world setting.

Methods: We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect data on most frequent adverse events (AE). Regression models were used to analyze the effect of demographic and clinical characteristics on risk of AEs and DMF discontinuation.

Results: We collected data of 886 patients (2681 patients/years-exposition) with median 39.5 (IQR 23, 51.5) months on DMF exposure; 25.3% were treatment naïve and 74.7% switched to DMF from other disease-modifying therapies. DMF was discontinued in 29.9% of patients, in 13.2% due to AEs and in 13.5% to inefficacy. AEs were experienced by 71.2%, being flushing the most frequent (44.1%), 5.4% developed grade III lymphopenia, without cases of grade IV. Females showed a higher risk of flushing and gastroenteric symptoms (OR 1.49, p = 0.011; OR 1.69, p = 0.001, respectively); lymphopenia was associated with older age (OR 1.04, p < 0.001), and a higher EDSS with lymphopenia (OR 1.10, p = 0.035) and DMF withdrawal (HR 1.43, p = 0.012). No safety problems were reported.

Conclusions: Our findings confirm good tolerability and safety of DMF in real-world setting and suggest that women have an increased risk of AEs and higher baseline disability involves greater risk of drug discontinuation.
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http://dx.doi.org/10.1007/s00415-020-09848-7DOI Listing
August 2020

Spanish real-world experience with fingolimod in relapsing-remitting multiple sclerosis patients: MS NEXT study.

PLoS One 2020 2;15(4):e0230846. Epub 2020 Apr 2.

Novartis Farmacéutica S.A., Barcelona, Spain.

Purpose: The objective of this study was to characterize the demographic and clinical profile of RRMS patients receiving fingolimod in Spain, and to evaluate drug effectiveness and safety in clinical practice.

Methods: This observational, retrospective, multicentre, nationwide study was performed at 56 Spanish hospitals and involved 804 RRMS patients who received oral fingolimod (0.5 mg) since November 2011, with a minimum follow-up of 12 months.

Results: The mean annualized relapse rate (ARR) in the year before fingolimod was 1.08 and the median EDSS was 3; patients were exposed to fingolimod for 2.2 years as average; regarding magnetic resonance imaging (MRI) activity, more than half of the patients had >20 lesions at baseline. Patients were previously treated with first-line injectable DMTs (60.3%), or natalizumab (31.3%), and 8.3% were naïve patients. Overall, the ARR significantly decreased to 0.28, 0.22 and 0.17 (74.1%, 79.7% and 83.5% of relative reduction, respectively) after 12, 24 and 36 months of treatment, P<0.001. The ARR of patients who switched from natalizumab to fingolimod was stable over the study. Most of the patients (88.7%) were free from confirmed disability and MRI activity (67.3%) after 24 months. The persistence after 12 months on fingolimod was 93.9%.

Conclusions: The subgroups of patients analysed showed differential baseline demographic and clinical characteristics. The analysis of patients who received fingolimod in routine clinical practice confirmed adequate efficacy and safety, even for long-term treatment. The present data also confirmed the positive benefit/risk balance with fingolimod in real-world clinical practice setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230846PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117743PMC
July 2020

Family planning is the second most relevant factor for treatment decisions after disease activity - No.

Mult Scler 2020 05 21;26(6):642-643. Epub 2020 Feb 21.

Department of Neurology, Hospital Clínico San Carlos, Madrid, Spain/Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid (UCM), IdISSC, Madrid, Spain.

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http://dx.doi.org/10.1177/1352458520902343DOI Listing
May 2020

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder.

Mult Scler Relat Disord 2020 Feb 25;38:101868. Epub 2019 Nov 25.

CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. Electronic address:

Background: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD.

Method: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.

Results: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).

Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.
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http://dx.doi.org/10.1016/j.msard.2019.101868DOI Listing
February 2020

Joint Healthcare Professional and Patient Development of Communication Tools to Improve the Standard of MS Care.

Adv Ther 2019 11 5;36(11):3238-3252. Epub 2019 Sep 5.

Member of the MS in the 21st Century Steering Group, Southampton, UK.

Introduction: Effective communication between patients and healthcare professionals (HCPs) is important to enhance outcomes in multiple sclerosis (MS). However, in practice, patients often report a disconnect in communication. Communication tools to aid patient-HCP communication have a long history of use in many chronic conditions. For example, symptom diaries have been shown to enhance outcomes in cancer, headache and sleep disorder management. MS in the 21st Century, a Steering Group of HCP specialists and patients with MS (PwMS), has created two communication tools designed for use by both patients and their HCPs.

Methods: The Steering Group first identified prominent issues in patient-HCP communication through group discussions and survey data. Following this, a series of workshops led to the development of two communication tools as potential solutions to these identified issues in communication.

Results: The two most prominent issues identified were HCP time constraints during appointments and the misalignment of patient and HCP priorities-the communication tools developed through the workshops were created to address these. The "myMS priorities" tool [see supplementary materials] is designed to maximize the use of consultation time while the "myMS commitments" tool [see supplementary materials] aims to improve patient-HCP shared decision-making.

Conclusions: The MS in the 21st Century Steering Group adopted a broad, iterative and collaborative approach in the development of these tools to help ensure they would be as useful as possible to both HCPs and PwMS. These tools have been developed through shared patient-HCP expertise and are based on existing tools in other therapy areas as well as a review of the existing literature and data from MS in the 21st Century Steering Group surveys. The next steps will focus on the validation of these tools through testing them in real-world environments and clinical trials.

Funding: Merck KGaA, Darmstadt, Germany.
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http://dx.doi.org/10.1007/s12325-019-01071-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822792PMC
November 2019

Single-subject structural cortical networks in clinically isolated syndrome.

Mult Scler 2020 10 24;26(11):1392-1401. Epub 2019 Jul 24.

Centre for Medical Image Computing (CMIC), UCL Medical Physics and Biomedical Engineering, University College London, London, UK/NIHR University College London Hospitals Biomedical Research Centre, London, UK/Alzheimer Center Amsterdam, Department of Neurology, Amsterdam University Medical Centers, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands/UCL Institute of Healthcare Engineering and UCL Queen Square Institute of Neurology, University College London, London, UK.

Background: Structural cortical networks (SCNs) represent patterns of coordinated morphological modifications in cortical areas, and they present the advantage of being extracted from previously acquired clinical magnetic resonance imaging (MRI) scans. SCNs have shown pathophysiological changes in many brain disorders, including multiple sclerosis.

Objective: To investigate alterations of SCNs at the individual level in patients with clinically isolated syndrome (CIS), thereby assessing their clinical relevance.

Methods: We analyzed baseline data collected in a prospective multicenter (MAGNIMS) study. CIS patients ( = 60) and healthy controls ( = 38) underwent high-resolution 3T MRI. Measures of disability and cognitive processing were obtained for patients. Single-subject SCNs were extracted from brain 3D-T1 weighted sequences; global and local network parameters were computed.

Results: Compared to healthy controls, CIS patients showed altered small-world topology, an efficient network organization combining dense local clustering with relatively few long-distance connections. These disruptions were worse for patients with higher lesion load and worse cognitive processing speed. Alterations of centrality measures and clustering of connections were observed in specific cortical areas in CIS patients when compared with healthy controls.

Conclusion: Our study indicates that SCNs can be used to demonstrate clinically relevant alterations of connectivity in CIS.
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http://dx.doi.org/10.1177/1352458519865739DOI Listing
October 2020

Cognitive Dysfunctions and Assessments in Multiple Sclerosis.

Front Neurol 2019 4;10:581. Epub 2019 Jun 4.

Unidad de Esclerosis Múltiple y Neuroinmunología de Girona, Servicio de Neurología, IDIBGI, Hospital Universitario Dr. Josep Trueta, Girona, Spain.

Cognitive impairment has been reported at all phases and all subtypes of multiple sclerosis. It remains a major cause of neurological disability in young and middle-aged adults suffering from the disease. The severity and type of cognitive impairment varies considerably among individuals and can be observed both in early and in later stages. The areas which have commonly shown more deficits are: information processing speed, complex attention, memory, and executive function. Even though an alteration in both the white matter and in the gray matter has been found in patients with multiple sclerosis and cognitive impairment, the underlying process still remains unknown. Standardized neurological examinations fail to detect emerging cognitive deficits and self-reported cognitive complaints by the patients can be confounded by other subjective symptoms. This review is a comprehensive and short update of the literature on cognitive dysfunctions, the possible confounders and the impact of quality of life in patients with multiple sclerosis.
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http://dx.doi.org/10.3389/fneur.2019.00581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558141PMC
June 2019

Management strategies for female patients of reproductive potential with multiple sclerosis: An evidence-based review.

Mult Scler Relat Disord 2019 Jul 5;32:54-63. Epub 2019 Apr 5.

Brigham and Women's Hospital, Harvard Medical School, Brookline, MA, USA.

Multiple sclerosis (MS) is an inflammatory, demyelinating, neurodegenerative, immune-mediated disease primarily diagnosed in early adulthood. Multiple sclerosis mostly impacts women of reproductive potential, with pregnancy and birth outcomes being major concerns for many patients. While there is ample evidence that the disease itself has no impact on pregnancy, many women living with MS still question their ability to have children, and the impact of childbearing on their disease in the short and long term. Such questions emphasize the importance of proper guidance from healthcare professionals, particularly neurologists. Management considerations are also complicated by the growing list of available treatment options. This review will summarize current evidence and expert opinion around the management of female MS patients of reproductive potential, from family planning to the postpartum period. Current guidelines on the use of disease-modifying therapies throughout pregnancy will be discussed, as well as other general medical recommendations, to minimize MS disease activity in the peripartum period.
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http://dx.doi.org/10.1016/j.msard.2019.04.003DOI Listing
July 2019

Best Practices for Long-Term Monitoring and Follow-Up of Alemtuzumab-Treated MS Patients in Real-World Clinical Settings.

Front Neurol 2019 22;10:253. Epub 2019 Mar 22.

Rehabilitation & MS-Centre Overpelt, Hasselt University, Hasselt, Belgium.

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in the absence of continuous treatment and with a consistent safety profile. There is an increased incidence of autoimmune events in patients treated with alemtuzumab (mainly thyroid events, but also immune thrombocytopenia and nephropathy), which imparts a need for mandatory safety monitoring for 4 years following the last treatment. The risk management strategy for alemtuzumab-treated patients includes laboratory monitoring and a comprehensive patient education and support program that enables early detection and effective management of autoimmune events, yielding optimal outcomes for MS patients. Here we provide an overview of tools and techniques that have been implemented in real-world clinical settings to reduce the burden of monitoring for both patients and healthcare providers, including customized educational materials, the use of social media, and interactive online databases for managing healthcare data. Many practices are also enhancing patient outreach efforts through coordination with specialized nursing services and ancillary caregivers. The best practice recommendations for safety monitoring described in this article, based on experiences in real-world clinical settings, may enable early detection and management of autoimmune events, and help with implementation of monitoring requirements while maximizing the benefits of alemtuzumab treatment for MS patients.
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http://dx.doi.org/10.3389/fneur.2019.00253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439479PMC
March 2019

Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial.

Proc Natl Acad Sci U S A 2019 04 8;116(17):8463-8470. Epub 2019 Apr 8.

Center of Neuroimmunology, Institut d'Investigacions Biomediques August Pi Sunyer, 08036 Barcelona, Spain;

There are adaptive T-cell and antibody autoimmune responses to myelin-derived peptides in multiple sclerosis (MS) and to aquaporin-4 (AQP4) in neuromyelitis optica spectrum disorders (NMOSDs). Strategies aimed at antigen-specific tolerance to these autoantigens are thus indicated for these diseases. One approach involves induction of tolerance with engineered dendritic cells (tolDCs) loaded with specific antigens. We conducted an in-human phase 1b clinical trial testing increasing concentrations of autologous tolDCs loaded with peptides from various myelin proteins and from AQP4. We tested this approach in 12 patients, 8 with MS and 4 with NMOSD. The primary end point was the safety and tolerability, while secondary end points were clinical outcomes (relapses and disability), imaging (MRI and optical coherence tomography), and immunological responses. Therapy with tolDCs was well tolerated, without serious adverse events and with no therapy-related reactions. Patients remained stable clinically in terms of relapse, disability, and in various measurements using imaging. We observed a significant increase in the production of IL-10 levels in PBMCs stimulated with the peptides as well as an increase in the frequency of a regulatory T cell, known as Tr1, by week 12 of follow-up. In this phase 1b trial, we concluded that the i.v. administration of peptide-loaded dendritic cells is safe and feasible. Elicitation of specific IL-10 production by peptide-specific T cells in MS and NMOSD patients indicates that a key element in antigen specific tolerance is activated with this approach. The results warrant further clinical testing in larger trials.
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http://dx.doi.org/10.1073/pnas.1820039116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486735PMC
April 2019

Antiphospholipid Antibodies Overlapping in Isolated Neurological Syndrome and Multiple Sclerosis: Neurobiological Insights and Diagnostic Challenges.

Front Cell Neurosci 2019 19;13:107. Epub 2019 Mar 19.

Department of Clinical Immunology and IdISSC, Hospital Clínico San Carlos, Madrid, Spain.

Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy morbidity and fetal loss caused by pathogenic autoantibodies directed against phospholipids (PL) and PL-cofactors. Isolated neurological APS may represent a significant diagnostic challenge, as epidemiological, clinical and neuroimaging features may overlap with those of multiple sclerosis (MS). In an open view, MS could be considered as an organ-specific anti-lipid (phospholipid and glycosphingolipid associated proteins) disease, in which autoreactive B cells and CD8+ T cells play a dominant role in its pathophysiology. In MS, diverse autoantibodies against the lipid-protein cofactors of the myelin sheath have been described, whose pathophysiologic role has not been fully elucidated. We carried out a review to select clinical studies addressing the prevalence of antiphospholipid (aPL) autoantibodies in the so-called MS-like syndrome. The reported prevalence ranged between 2% and 88%, particularly aCL and aβ2GPI, with predominant IgM isotype and suggesting worse MS prognosis. Secondarily, an updated summary of current knowledge on the pathophysiological mechanisms and events responsible for these conditions is presented. We draw attention to the clinical relevance of diagnosing isolated neurological APS. Prompt and accurate diagnosis and antiaggregant and anticoagulant treatment of APS could be vital to prevent or at least reduce APS-related morbidity and mortality.
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http://dx.doi.org/10.3389/fncel.2019.00107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433987PMC
March 2019

Single-arm study to assess comprehensive infusion guidance for the prevention and management of the infusion associated reactions (IARs) in relapsing-remitting multiple sclerosis (RRMS) patients treated with alemtuzumab (EMERALD).

Mult Scler Relat Disord 2019 Apr 6;29:7-14. Epub 2019 Jan 6.

Department of Neurology, Hospital Clínico San Carlos, IdISSC, Departamento de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain.

Background: Alemtuzumab is a humanized IgG monoclonal antibody approved in more than 60 countries for patients with relapsing remitting multiple sclerosis (RRMS). In phase 2 and 3 clinical trials (CAMMS223 (NCT00050778), CARE-MS I (NCT00530348), and CARE-MS II (NCT00548405)), patients receiving alemtuzumab demonstrated significantly greater improvements on clinical and MRI outcomes versus SC IFNβ-1a; mild to moderate infusion-associated reactions (IARs) were the most frequently reported adverse events (AEs) associated with alemtuzumab. EMERALD (NCT02205489) was a phase 4, multicenter, multinational, single-arm study designed to assess an algorithm for the prevention and management of IARs in RRMS patients treated with alemtuzumab.

Methods: Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H and/or H antagonists or equivalent gastroprotection (proton pump inhibitors) were given 1 day before alemtuzumab infusion, 1 h prior to the infusion, and post-infusion. Methylprednisolone was given orally 1 day before infusion, 1 h prior to the infusion, and as needed post-infusion. Antipyretics were given 1 h before infusion and as needed post-infusion. Anti-emetics and normal saline were given as needed during and post-infusion.

Results: Of the 61 patients screened, 58 (95.1%) were enrolled into the study. Of the 58 patients who received the first infusion of Period 1, 57 (98.3%) completed the 5 days of Course 1. A total of 54 patients received the first infusion of Period 2 and 53 completed the 3-day course. All patients (n = 58) completed the Month 6 visit and 54 the Month 12 visit. 93.1% of patients had at least one IAR (91.4% in Period 1 and 81.5% in Period 2), the majority of which were grade 1 (69.1%) or grade 2 (28.0%). The three most common IARs of headache, pyrexia, and rash occurred in 48.8%, 40.7%, and 24.1% of patients during the first course and 14.8%, 17.2%, and 5.6% of patients during the second course, respectively. The majority of IARs occurred within 6 h after the start of alemtuzumab infusion, with a peak during the first 2 h. The types and overall incidence of IARs were consistent with phase 2 and 3 trials. Frequency and distribution of rash were reduced in the EMERALD study compared with previous clinical trials. Serious IARs occurred in 15.5%, a higher rate than reported in clinical trials of alemtuzumab.

Conclusion: Although most alemtuzumab-treated patients experienced IARs as in previous controlled clinical studies, there was an improvement in the frequency and distribution of alemtuzumab-associated rash, which may have been associated with this study's prophylaxis regimen.
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http://dx.doi.org/10.1016/j.msard.2019.01.019DOI Listing
April 2019

Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study.

Mult Scler Relat Disord 2019 Feb 3;28:235-243. Epub 2019 Jan 3.

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, Alfred Hospital, Melbourne, Australia; Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, Australia. Electronic address:

Background: Exposure to disease-modifying therapy (DMT) during early pregnancy in women with relapsing-remitting MS (RRMS) may be increasing.

Objective: To retrospectively determine incidence of pregnancy, DMT exposure and pregnancy outcomes in women with RRMS.

Methods: We identified all women with RRMS aged 15-45 years in the MSBase Registry between 2005-2016. Annualised pregnancy incidence rates were calculated using Poisson regression models. DMT exposures and pregnancy outcomes were assessed.

Results: Of 9,098 women meeting inclusion criteria, 1,178 (13%) women recorded 1,521 pregnancies. The annualised incidence rate of pregnancy was 0.042 (95% CI 0.040, 0.045). A total of 635 (42%) reported pregnancies were conceived on DMT, increasing from 27% in 2006 to 62% in 2016. The median duration of DMT exposure during pregnancy was 30 days (IQR: 9, 50). There were a higher number of induced abortions on FDA pregnancy class C/D drugs compared with pregnancy class B and no DMT (p = 0.010); but no differences in spontaneous abortions, term or preterm births.

Conclusions: We report low pregnancy incidence rates, with increasing number of pregnancies conceived on DMT over the past 12-years. The median duration of DMT exposure in pregnancy was relatively short at one month.
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http://dx.doi.org/10.1016/j.msard.2019.01.003DOI Listing
February 2019

Prolonged-release fampridine in multiple sclerosis: clinical data and real-world experience. Report of an expert meeting.

Ther Adv Neurol Disord 2018 5;11:1756286418803248. Epub 2018 Oct 5.

Center of Clinical Neuroscience, Department of Neurology, MS Center Dresden, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.

Prolonged-release (PR) fampridine is the only approved medication to improve walking in multiple sclerosis (MS), having been shown to produce a clinically meaningful improvement in walking ability in the subset of MS patients with Expanded Disability Status Scale 4-7. Recent responder subgroup analyses in the phase III ENHANCE study show a large effect size in terms of an increase of 20.58 points on the patient-reported 12-item MS Walking Scale in the 43% of patients classified as responders to PR-fampridine, corresponding to a standardized response mean of 1.68. Use of PR-fampridine in clinical practice varies across Europe, depending partly on whether it is reimbursed. A group of European MS experts met in June 2017 to discuss their experience with using PR-fampridine, including their views on the patient population for treatment, assessment of treatment response, re-testing and re-treatment, and stopping criteria. This article summarizes the experts' opinions on how PR-fampridine can be used in real-world clinical practice to optimize the benefits to people with MS with impaired walking ability.
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http://dx.doi.org/10.1177/1756286418803248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174649PMC
October 2018

Three-Tesla MRI does not improve the diagnosis of multiple sclerosis: A multicenter study.

Neurology 2018 07 20;91(3):e249-e257. Epub 2018 Jun 20.

From the Departments of Neurology (M.H.J.H., J.B., J.K.) and Radiology and Nuclear Medicine (I.D.K., M.L.d.V., M.P.W., F.B.), MS Centre Amsterdam, and Department of Epidemiology and Biostatistics (B.I.L.-W.), VU University Medical Centre; Department of Radiology and Nuclear Medicine (I.D.K.), Onze Lieve Vrouwen Gasthuis, Amsterdam, the Netherlands; Queen Square Multiple Sclerosis Centre (N.C., O.C.) and Institutes of Neurology & Healthcare Engineering (F.B.), UCL Institute of Neurology, London, UK; Department of Neurology and Psychiatry (E.S., P.P.), Sapienza University of Rome, Italy; Department of Neurology (M. Andelova, M. Amann) and Division of Neuroradiology, Department of Radiology (M. Amann, J.M.L.), University Hospital Basel; Medical Image Analysis Centre (M. Amann), Basel, Switzerland; Istituto Neurologico Mediterraneo (P.P.), Neuromed, Pozzilli (IS), Italy; Department of Neurology (C.O.-G.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; National Institute for Health Research (O.C., F.B.), University College London Hospitals (UCLH) Biomedical Research Centre (BRC), UK; Department of Neurosciences (C.G.), San Camillo-Forlanini Hospital, Rome, Italy; and Department of Diagnostic and Interventional Radiology and Nuclear Medicine (C.L.), St. Josef Hospital, Ruhr University, Bochum, Germany.

Objective: In the work-up of patients presenting with a clinically isolated syndrome (CIS), 3T MRI might offer a higher lesion detection than 1.5T, but it remains unclear whether this affects the fulfilment of the diagnostic criteria for multiple sclerosis (MS).

Methods: We recruited 66 patients with CIS within 6 months from symptom onset and 26 healthy controls in 6 MS centers. All participants underwent 1.5T and 3T brain and spinal cord MRI at baseline according to local optimized protocols and the MAGNIMS guidelines. Patients who had not converted to MS during follow-up received repeat brain MRI at 3-6 months and 12-15 months. The number of lesions per anatomical region was scored by 3 raters in consensus. Criteria for dissemination in space (DIS) and dissemination in time (DIT) were determined according to the 2017 revisions of the McDonald criteria.

Results: Three-Tesla MRI detected 15% more T2 brain lesions compared to 1.5T ( 0.001), which was driven by an increase in baseline detection of periventricular (12%, 0.015), (juxta)cortical (21%, 0.005), and deep white matter lesions (21%, 0.001). The detection rate of spinal cord lesions and gadolinium-enhancing lesions did not differ between field strengths. Three-Tesla MRI did not lead to a higher number of patients fulfilling the criteria for DIS or DIT, or subsequent diagnosis of MS, at any of the 3 time points.

Conclusion: Scanning at 3T does not influence the diagnosis of MS according to McDonald diagnostic criteria.
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http://dx.doi.org/10.1212/WNL.0000000000005825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059032PMC
July 2018

Familial multiple sclerosis and association with other autoimmune diseases.

Brain Behav 2018 01 19;8(1):e00899. Epub 2017 Dec 19.

Department of Neurology Institute of Neurosciences Hospital Clínico San Carlos Madrid Spain.

Objectives: Autoimmune diseases (AID) follow a complex, probably polygenic, pattern of inheritance and often cluster in families of patients with multiple sclerosis (MS). Our objective was to analyze family patterns and characteristics in families including more than one patient with MS.

Materials And Methods: We analyzed personal and family history of neurological, systemic, and autoimmune diseases in 84 MS patients from 40 different families. Families were classified in two groups: families with cases of MS in at least two different generations (15 families) and families in which cases of MS belonged to only one generation (25 families).

Results: The two previously established groups presented different clinical patterns and frequency of association with another AID. In one group, the second generation displayed a higher annual relapse rate than the first generation, higher frequency of progressive forms of MS, and more patients with another AID in addition to MS. Relapsing-remitting forms of MS (RRMS) were more frequent in the other group.

Conclusions: Families that include more than one MS patient may show two distinct patterns. This finding seems important for the compression and analysis of genetic information on MS.
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http://dx.doi.org/10.1002/brb3.899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853641PMC
January 2018

Impact of 3 Tesla MRI on interobserver agreement in clinically isolated syndrome: A MAGNIMS multicentre study.

Mult Scler 2019 03 12;25(3):352-360. Epub 2018 Jan 12.

Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

Background: Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases signal-to-noise ratio leading to improved image quality. However, its clinical relevance in clinically isolated syndrome suggestive of multiple sclerosis remains uncertain.

Objectives: The purpose of this study was to investigate how 3 T MRI affects the agreement between raters on lesion detection and diagnosis.

Methods: We selected 30 patients and 10 healthy controls from our ongoing prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain and spinal cord MRI. Patients also received follow-up brain MRI at 3-6 months. Four experienced neuroradiologists and four less-experienced raters scored the number of lesions per anatomical region and determined dissemination in space and time (McDonald 2010).

Results: In controls, the mean number of lesions per rater was 0.16 at 1.5 T and 0.38 at 3 T ( p = 0.005). For patients, this was 4.18 and 4.40, respectively ( p = 0.657). Inter-rater agreement on involvement per anatomical region and dissemination in space and time was moderate to good for both field strengths. 3 T slightly improved agreement between experienced raters, but slightly decreased agreement between less-experienced raters.

Conclusion: Overall, the interobserver agreement was moderate to good. 3 T appears to improve the reading for experienced readers, underlining the benefit of additional training.
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http://dx.doi.org/10.1177/1352458517751647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393953PMC
March 2019