Publications by authors named "Mar Tintore"

145 Publications

CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event.

Mult Scler 2021 Apr 19:13524585211010082. Epub 2021 Apr 19.

Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis.

Objective: To assess the relationship between iron rims and levels of chitinase 3-like 1 (CHI3L1), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with a first demyelinating event.

Methods: Iron rims were identified using 3T susceptibility-weighted imaging. Serum NfL and GFAP levels were measured by single-molecule array assays. CSF (cerebrospinal fluid) CHI3L1 levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Sixty-one patients were included in the study. The presence of iron rims was associated with higher T2 lesion volume and higher number of gadolinium-enhancing lesions. In univariable analysis, having ⩾2 iron rims (vs 0) was associated with increased CSF CHI3L1 levels (β = 1.41; 95% confidence interval (CI) = 1.10-1.79; < 0.01) and serum NfL levels (β = 2.30; 95% CI = 1.47-3.60; < 0.01). In multivariable analysis, however, only CSF CHI3L1 levels remained significantly associated with the presence of iron rim lesions (β = 1.45; 95% CI = 1.11-1.90; < 0.01). The presence of ⩾2 iron rims was not associated with increased serum GFAP levels in univariable or multivariable analyses.

Conclusion: These findings support an important contribution of activated microglia/macrophages to the pathophysiology of chronic active lesions with iron rims in patients with a first demyelinating event.
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http://dx.doi.org/10.1177/13524585211010082DOI Listing
April 2021

Scoring the 10-year risk of ambulatory disability in multiple sclerosis: the RoAD score.

Eur J Neurol 2021 Mar 31. Epub 2021 Mar 31.

Centre d'Esclerosi Multiple de Catalunya (Cemcat), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.

Background And Purpose: Both baseline prognostic factors and short-term predictors of treatment response can influence the long-term risk of disability accumulation in patients with relapsing-remitting multiple sclerosis (RRMS). The objective was to develop and validate a scoring system combining baseline prognostic factors and 1-year variables of treatment response into a single numeric score predicting the long-term risk of disability.

Methods: We analysed two independent datasets of patients with RRMS who started interferon beta or glatiramer acetate, had an Expanded Disability Status Scale (EDSS) score <4.0 at treatment start and were followed for at least 10 years. The first dataset ('training set') included patients attending three MS centres in Italy and served as a framework to create the so-called RoAD score (Risk of Ambulatory Disability). The second ('validation set') included a cohort of patients followed in Barcelona, Spain, to explore the performance of the RoAD score in predicting the risk of reaching an EDSS score ≥6.0.

Results: The RoAD score (ranging from 0 to 8) derived from the training set (n = 1225), was based on demographic (age), clinical baseline prognostic factors (disease duration, EDSS) and 1-year predictors of treatment response (number of relapses, presence of gadolinium enhancement and new T2 lesions). The best cut-off score for discriminating patients at higher risk of reaching the disability milestone was ≥4. When applied to the validation set (n = 296), patients with a RoAD score ≥4 had an approximately 4-fold increased risk for reaching the disability milestone (p < 0.001).

Discussion: The RoAD score is proposed as an useful tool to predict individual prognosis and optimize treatment strategy of patients with RRMS.
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http://dx.doi.org/10.1111/ene.14845DOI Listing
March 2021

Impact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey.

Mult Scler 2021 Mar 25:13524585211005339. Epub 2021 Mar 25.

Department of Neurofarba, University of Florence, Florence, Italy/IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.

Background: The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS).

Objectives: To collect data about the impact of COVID-19 emergency on access to care for PwMS and on MS treatment practices.

Methods: Between March and July 2020, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) promoted an online survey covering patient access to care, management of relapses and visits, disease-modifying therapy (DMT) and experience with COVID-19.

Results: Three-hundred and sixty neurologists from 52 countries (68% from Europe) completed the survey. 98% reported COVID-19-related restrictions. Telemedicine was adopted to overcome the limited access to care and was newly activated (73%) or widely implemented (17%). 70% reported changes in DMT management. Interferons and glatiramer were considered safe. Dimethyl fumarate, teriflunomide and fingolimod were considered safe except for patients developing lymphopenia. No modifications were considered for natalizumab in 64%, cladribine in 24%, anti-CD20 in 22% and alemtuzumab in 17%; 18% (for alemtuzumab and cladribine) and 43% (for anti-CD20) considered postponing treatment.

Conclusion: The ECTRIMS survey highlighted the challenges in keeping standards of care in clinical practice. Telemedicine clearly needs to be implemented. Gathering data on DMT safety will remain crucial to inform treatment decisions.
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http://dx.doi.org/10.1177/13524585211005339DOI Listing
March 2021

Menopause does not modify disability trajectories in a longitudinal cohort of women with clinically isolated syndrome and multiple sclerosis followed from disease onset.

Eur J Neurol 2021 Feb 20. Epub 2021 Feb 20.

Neurology-Neuroimmunology Department, Centro de Esclerosis Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background And Purpose: To evaluate the effect of menopause on disability accumulation in women followed from their clinically isolated syndrome (CIS).

Methods: We examined the longitudinal changes in Expanded Disability Status Scale (EDSS) scores from CIS until the last follow-up in women belonging to the Barcelona CIS prospective cohort, followed through their menopausal transition. The analysis is based on 13,718 EDSS measurements, with an average of 28 EDSS measurements per patient. Differences in EDSS trajectories between menopausal and nonmenopausal women, controlling for age and disease duration, were evaluated. We performed two sensitivity analyses in women with confirmed MS and in those experiencing early menopause.

Results: From 764 eligible women, 496 (65%) responded to the questionnaire, and 74 (14.9%) reached menopause over the follow-up. We did not find a significant inflection point in EDSS trajectories around menopause (slope change -0.009; 95% CI -0.066; 0.046). The annual increase in EDSS over the complete course of the disease was significantly higher in menopausal women (0.049; 95% CI, 0.026-0.074) versus nonmenopausal (0.019; 95% CI, 0.008-0.031; interaction p value 0.025). This difference was lost when controlling for age and disease duration (EDSS annual increase of 0.059; 95% CI, 0.025-0.094 vs. 0.038; 95% CI, 0.021-0.057, respectively; interaction p value 0.321). No inflection point was detected when the analysis was restricted to women with confirmed MS or with earlier menopause.

Conclusions: Menopause is not associated with an increased risk of disability in a CIS population, considering EDSS trajectories throughout the course of the disease together with age and disease duration.
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http://dx.doi.org/10.1111/ene.14782DOI Listing
February 2021

The frequency and characteristics of MS misdiagnosis in patients referred to the multiple sclerosis centre of Catalonia.

Mult Scler 2021 May 10;27(6):913-921. Epub 2021 Feb 10.

Section of Neuroradiology, Radiology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Multiple sclerosis (MS) misdiagnosis may cause physical and emotional damage to patients.

Objectives: The objective of this study is to determine the frequency and characteristics of MS misdiagnosis in patients referred to the Multiple Sclerosis Centre of Catalonia.

Methods: We designed a prospective study including all new consecutive patients referred to our centre between July 2017 and June 2018. Instances of misdiagnosis were identified, and referral diagnosis and final diagnosis were compared after 1 year of follow-up. Association of misdiagnosis with magnetic resonance imaging (MRI) findings, presence of comorbidities and family history of autoimmunity were assessed.

Results: A total of 354 patients were referred to our centre within the study period, 112 (31.8%) with 'established MS'. Misdiagnosis was identified in eight out of 112 cases (7.1%). MRI identified multifocal white matter lesions, deemed non-specific or not suggestive of MS in all misdiagnosed cases. Patients with MS misdiagnosis had more comorbidities in general than patients with MS ( = 0.026) as well as a personal history of autoimmunity ( < 0.001).

Conclusion: A low frequency of MS misdiagnosis was found in our clinical setting. Multifocal non-specific white matter lesions in referral MRI examinations and the presence of comorbidities, including a personal history of autoimmunity, seem to be contributing factors to misdiagnosis.
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http://dx.doi.org/10.1177/1352458520988148DOI Listing
May 2021

Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years.

Mult Scler Relat Disord 2021 Apr 24;49:102717. Epub 2020 Dec 24.

Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.

Background: Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]).

Methods: Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years).

Results: Compared with SC IFNB-1a over 2 years across age cohorts, alemtuzumab lowered annualized relapse rates (ARR; 0.22-0.24 vs. 0.38-0.51), improved or stabilized disability (freedom from 6-month confirmed disability worsening [CDW]: 85%-92% vs. 62%-88%; achievement of 6-month confirmed disability improvement [CDI]: 20%-31% vs. 13%-25%), increased proportions free of MRI disease activity (70%-86% vs. 42%-63% per year), and slowed brain volume loss (BVL; -0.45% to -0.87% vs. -0.50% to -1.39%). Through Year 2, the treatment effect with alemtuzumab did not significantly differ among age groups for ARR (p-interaction=0.6325), 6-month CDW-free (p-interaction=0.4959), 6-month CDI (p-interaction=0.9268), MRI disease activity-free (p-interaction=0.6512), and BVL (p-interaction=0.4970). Alemtuzumab remained effective on outcomes through Year 8 across age groups. Age-related increases in malignancies (≤45 years: 0.9%-2.2% vs. >45 years: 8.1%) and deaths (0%-1.7% vs. 7.0%) were observed. Serious infections also increased from the youngest (5.1%) to oldest (12.8%) age cohorts.

Conclusions: Alemtuzumab had greater efficacy than SC IFNB-1a over 2 years across comparable age groups, with no significant differences between alemtuzumab-treated age groups. Efficacy on relapse, disability, and MRI outcomes continued through Year 8 across age groups. Age-related increases in serious infections, malignancies, and deaths were observed.
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http://dx.doi.org/10.1016/j.msard.2020.102717DOI Listing
April 2021

Prognostication and contemporary management of clinically isolated syndrome.

J Neurol Neurosurg Psychiatry 2020 Dec 24. Epub 2020 Dec 24.

Department of Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK.

Clinically isolated syndrome (CIS) patients present with a single attack of inflammatory demyelination of the central nervous system. Recent advances in multiple sclerosis (MS) diagnostic criteria have expanded the number of CIS patients eligible for a diagnosis of MS at the onset of the disease, shrinking the prevalence of CIS. MS treatment options are rapidly expanding, which is driving the need to recognise MS at its earliest stages. In CIS patients, finding typical MS white matter lesions on the patient's MRI scan remains the most influential prognostic investigation for predicting subsequent diagnosis with MS. Additional imaging, cerebrospinal fluid and serum testing, information from the clinical history and genetic testing also contribute. For those subsequently diagnosed with MS, there is a wide spectrum of long-term clinical outcomes. Detailed assessment at the point of presentation with CIS provides fewer clues to calculate a personalised risk of long-term severe disability.Clinicians should select suitable CIS cases for steroid treatment to speed neurological recovery. Unfortunately, there are still no neuroprotection or remyelination strategies available. The use of MS disease modifying therapy for CIS varies among clinicians and national guidelines, suggesting a lack of robust evidence to guide practice. Clinicians should focus on confirming MS speedily and accurately with appropriate investigations. Diagnosis with CIS provides an opportune moment to promote a healthy lifestyle, in particular smoking cessation. Patients also need to understand the link between CIS and MS. This review provides clinicians an update on the contemporary evidence guiding prognostication and management of CIS.
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http://dx.doi.org/10.1136/jnnp-2020-323087DOI Listing
December 2020

COVID-19 in multiple sclerosis patients: susceptibility, severity risk factors and serological response.

Eur J Neurol 2020 Dec 19. Epub 2020 Dec 19.

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background And Purpose: Information regarding multiple sclerosis (MS) patients with the 2019 novel coronavirus disease (COVID-19) is scarce. The study objective was to describe the incidence and characteristics of MS patients with COVID-19, to identify susceptibility and severity risk factors and to assess the proportion of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologies according to disease-modifying treatments.

Methods: This was a retrospective study of an MS cohort analysing data collected between February and May 2020. Cases were identified through an email survey and clinical visits. The relationship of demographic and MS characteristics with COVID-19 and of the disease-modifying treatments with SARS-CoV-2 serostatus were examined.

Results: Data from 48 suspected cases out of 758 valid respondents and from 45 COVID-19 cases identified through clinical visits were collected. Incidence was 6.3%. Nineteen (20.3%) patients were hospitalized and two (2.2%) died. Multivariable models determined that age (odds ratio [OR] per 10 years 0.53, 95% confidence interval [CI] 0.34-0.85), contact with a confirmed case (OR 197.02, 95% CI 56.36-688.79), residence in Barcelona (OR 2.23, 95% CI 1.03-4.80), MS duration (OR per 5 years 1.41, 95% CI 1.09-1.83) and time on anti-CD20 treatment (OR per 2 years 3.48, 95% CI 1.44-8.45) were independent factors for presenting COVID-19 and age (OR per 10 years 2.71, 95% CI 1.13-6.53) for a severe COVID-19. Out of the 79 (84.9%) with serological test, 45.6% generated antibodies, but only 17.6% of those on anti-CD20 therapies. Lymphopaenia or immunoglobulin levels did not relate to COVID-19.

Conclusions: Multiple sclerosis patients present similar incidence, risk factors and outcomes for COVID-19 as the general population. Patients treated with an anti-CD20 therapy for a longer period of time might be at a higher risk of COVID-19 and less than 20% generate an antibody response. Only age was related to severity.
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http://dx.doi.org/10.1111/ene.14690DOI Listing
December 2020

Optic Nerve Topography in Multiple Sclerosis Diagnosis: The Utility of Visual Evoked Potentials.

Neurology 2021 01 16;96(4):e482-e490. Epub 2020 Dec 16.

From the Servicio de Neurología-Neuroinmunología (A V.-J., G.A., S.O.-R., J.R., M.C., C.N., J.C., I.G., S.C., B.R.-A., A.Z., L.M., J.S.-G., X.M., M.T.), Centro de Esclerosis Múltiple de Catalunya (Cemcat), Sección de Neuroradiologia (A.R., C.A.), Servei de Radiologia, Servicio de Medicina Preventiva y Epidemiologia (S.O.-R.), and Servicio de Neurofisiología Clínica (D.M., K.R., V.T.), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; and Division of Neurology (X.M.), St. Michael's Hospital. University of Toronto, Ontario, Canada.

Objective: To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria.

Methods: From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis).

Results: The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS.

Conclusion: The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity.
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http://dx.doi.org/10.1212/WNL.0000000000011339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905792PMC
January 2021

Adding brain volume measures into response criteria in multiple sclerosis: the Río-4 score.

Neuroradiology 2020 Nov 25. Epub 2020 Nov 25.

Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035, Barcelona, Spain.

Purpose: Brain volume changes (BVC) on therapy in MS are being considered as predictor for treatment response at an individual level. We ought to assess whether adding BVC as a factor to monitor interferon-beta response improves the predictive ability of the (no) evidence of disease activity (EDA-3) and Río score (RS-3) criteria for confirmed disability progression in a historical cohort.

Methods: One hundred one patients from an observational cohort treated with interferon-beta were assessed for different cutoff points of BVC (ranged 0.2-1.2%), presence of active lesions (≥ 1 for EDA/≥ 3 for RS), relapses, and 6-month confirmed disability progression (CDP), measured by the Expanded Disability Status Scale, after 1 year. Sensitivity, specificity, and positive and negative predictive values for predicting confirmed disability progression at 4 years in original EDA (EDA-3) and RS (RS-3) as well as EDA and RS including BVC (EDA-4 and RS-4) were compared.

Results: Adding BVC to EDA slightly increased sensitivity, but not specificity or predictive values, nor the OR for predicting CDP; only EDA-3 showed a trend for predicting CDP (OR 3.701, p = 0.050). Adding BVC to RS-3 (defined as ≥ 2 criteria) helped to improve sensitivity and negative predictive value, and increased OR for predicting CDP using a cutoff of ≤ - 0.86% (RS-3 OR 23.528, p < 0.001; RS-4 for all cutoffs ranged from 15.06 to 32, p < 0.001). RS-4 showed areas under the curve larger than RS-3 for prediction of disability at 4 years.

Conclusion: Addition of BVC to RS improves its prediction of response to interferon-beta.
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http://dx.doi.org/10.1007/s00234-020-02604-8DOI Listing
November 2020

Clinical Features and Risk of Relapse in Children and Adults with Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Ann Neurol 2021 01 15;89(1):30-41. Epub 2020 Oct 15.

Department of Neurology, Multiple Sclerosis and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Lyon Civil Hospices, Lyon, France.

Objective: The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG-Ab-associated disease (MOGAD).

Methods: This retrospective multicentric, national study included 98 children and 268 adults with MOGAD between January 2014 and September 2019. Cox regression model for recurrent time-to-event data and Kaplan-Meier curves for time to antibody negativity were performed for the objectives.

Results: Isolated optic neuritis was the most frequent clinical presentation in both children (40.8%) and adults (55.9%, p = 0.013), and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs 5.6%, p < 0.001). Compared to adults, children displayed better recovery (Expanded Disability Status Scale ≥ 3.0 at last follow-up reached only by 10 of 97 [10.3%] vs 66/247 [26.7%], p < 0.001). In the multivariate analysis, adults were at higher risk of relapse than children (hazard ratio = 1.41, 95% confidence interval [CI] = 1.12-1.78, p = 0.003). At 2 years, 64.2% (95% CI = 40.9-86.5) of nonrelapsing children became MOG-Ab negative compared to 14.1% (95% CI = 4.7-38.3) of relapsing children (log-rank p < 0.001), with no differences observed in adults (log-rank p = 0.280).

Interpretation: MOGAD patients differ in the clinical presentation at onset, showing an age-related shift in the clinical features across age groups. Compared to children, adults have a higher risk of relapse and worse functional recovery. Finally, children with monophasic disease become MOG-Ab negative earlier than relapsing children, but this is not true in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. ANN NEUROL 2021;89:30-41.
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http://dx.doi.org/10.1002/ana.25909DOI Listing
January 2021

Menopause and multiple sclerosis: Influence on prognosis and role of disease-modifying drugs and hormonal replacement therapy.

Mult Scler 2020 Aug 28:1352458520952022. Epub 2020 Aug 28.

Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Sex hormones play a role in both the risk and the prognosis of multiple sclerosis (MS). Considering all stages of women's reproductive life, data regarding the influence of menopause on MS and vice versa are scarce.

Objective: The aim of this study was to review the evidence addressing the relationship between menopause and MS.

Methods: A literature search through PubMed was conducted, selecting studies that assessed (1) the influence of menopause in the MS course, (2) the influence of MS and disease-modifying drugs (DMD) on the development of menopause and (3) the effect of hormone replacement therapy (HRT) on symptoms of menopausal MS patients.

Results: (1) Most studies suggest menopause may transitorily aggravate MS symptoms. Two studies found an inflexion point on the Expanding Disability Status Scale (EDSS) with clinical worsening during the menopausal transition. Another study considering full EDSS trajectories from clinically isolated syndrome to postmenopause did not find such an EDSS inflection; (2) MS and DMD do not seem to alter the age of menopause onset; and (3) HRT in menopausal MS patients has not shown consistent benefits.

Conclusion: Menopause seems to be associated with transient symptom worsening, but the existence of an inflection in disability progression is still controversial. Properly designed studies are necessary to achieve conclusive results.
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http://dx.doi.org/10.1177/1352458520952022DOI Listing
August 2020

Harnessing Real-World Data to Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS).

Front Neurol 2020 7;11:632. Epub 2020 Aug 7.

Biogen, Cambridge, MA, United States.

Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care. Institutional participation required the following: active MS patient census of ≥500, at least one Siemens 3T magnetic resonance imaging scanner, and willingness to standardize patient assessments, share standardized data for research, and offer universal enrolment to capture a representative sample. The eligible participants have diagnosis of MS, including clinically isolated syndrome, and consent for sharing pseudonymized data for research. MS PATHS incorporates a self-administered patient assessment tool, the Multiple Sclerosis Performance Test, to collect a structured history, patient-reported outcomes, and quantitative testing of cognition, vision, dexterity, and walking speed. Brain magnetic resonance imaging is acquired using standardized acquisition sequences on Siemens 3T scanners. Quantitative measures of brain volume and lesion load are obtained. Using a separate consent, the patients contribute DNA, RNA, and serum for future research. The clinicians retain complete autonomy in using MS PATHS data in patient care. A shared governance model ensures transparent data and sample access for research. As of August 5, 2019, MS PATHS enrolment included participants ( = 16,568) with broad ranges of disease subtypes, duration, and severity. Overall, 14,643 (88.4%) participants contributed data at one or more time points. The average patient contributed 15.6 person-months of follow-up (95% CI: 15.5-15.8); overall, 166,158 person-months of follow-up have been accumulated. Those with relapsing-remitting MS demonstrated more demographic heterogeneity than the participants in six randomized phase 3 MS treatment trials. Across sites, a significant variation was observed in the follow-up frequency and the patterns of disease-modifying therapy use. Through digital health technology, it is feasible to collect standardized, quantitative, and interpretable data from each patient in busy MS practices, facilitating the merger of research and patient care. This approach holds promise for data-driven clinical decisions and accelerated systematic learning.
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http://dx.doi.org/10.3389/fneur.2020.00632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426489PMC
August 2020

Multiple sclerosis management during the COVID-19 pandemic.

Mult Scler 2020 09 10;26(10):1163-1171. Epub 2020 Aug 10.

Division of Neuroimmunology and Neurological Infections, Johns Hopkins University, Baltimore, MA, USA.

Background: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services.

Objectives: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery.

Methods: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d'Hebron-Centre d'Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care.

Results: There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services.

Conclusion: Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption.
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http://dx.doi.org/10.1177/1352458520948231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424611PMC
September 2020

The apparently milder course of multiple sclerosis: changes in the diagnostic criteria, therapy and natural history.

Brain 2020 09;143(9):2637-2652

Department of Neurology, Hospital General Universitari Vall D'Hebron, Cemcat, Barcelona, Spain.

In the past decade, changes have occurred in the spectrum of multiple sclerosis courses. The natural history of multiple sclerosis appears milder from the first sign of demyelinating disease to the progressive course, probably as a result of an interplay between several factors including changes in the diagnostic criteria, changes in the epidemiology of multiple sclerosis, impact of early and appropriate disease-modifying treatment and improvement of the general state of health in the population. It has been suggested to regard incidental findings of demyelinating lesions in MRI in individuals without any history of clinical symptoms consistent with neurological dysfunction, so-called radiological isolated syndrome, as the initial course of multiple sclerosis. New diagnostic criteria have enabled the multiple sclerosis diagnosis in many patients at the first clinical demyelinating event, clinically isolated syndrome. The remaining patients with clinically isolated syndrome have a more benign prognosis, and for relapsing-remitting multiple sclerosis, the prognosis has become more favourable. Reduced disease activity in patients with relapsing-remitting multiple sclerosis can partly be ascribed to more efficacious new disease-modifying therapies but decrease in disease activity has also be seen in placebo-treated patients in clinical trials. This may be explained by several factors: change in the diagnostic criteria, more explicit inclusion criteria, exclusion of high-risk patients e.g. patients with co-morbidities, and more rigorous definitions of relapses and disease worsening. However, these factors also make the disease course in patients treated with disease-modifying therapies seem more favourable. In addition, change in the therapeutic target to stable disease (no evidence of disease activity = no relapses, no disease worsening and no MRI activity) could by itself change the course in relapsing-remitting multiple sclerosis. The effectiveness of disease-modifying drugs has reduced the transition from relapsing-remitting to secondary progressive multiple sclerosis. The concept of progressive multiple sclerosis has also evolved from two very distinct categories (primary progressive and secondary progressive multiple sclerosis) to a unified category of progressive multiple sclerosis, which can then be split into the categories of active or inactive. Also, an increasing tendency to treat progressive multiple sclerosis with disease-modifying therapies may have contributed to change the course in progressive multiple sclerosis. In conclusion, during the past decade the entire course of multiple sclerosis from the first sign of a demyelinating disorder through the progressive course appears to be milder due to a complex interplay of several factors.
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http://dx.doi.org/10.1093/brain/awaa145DOI Listing
September 2020

Sex effects across the lifespan in women with multiple sclerosis.

Ther Adv Neurol Disord 2020 1;13:1756286420936166. Epub 2020 Jul 1.

Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.
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http://dx.doi.org/10.1177/1756286420936166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331774PMC
July 2020

Keeping standards of multiple sclerosis care through the COVID-19 pandemic.

Mult Scler 2020 09 19;26(10):1153-1156. Epub 2020 Jun 19.

Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Edifici Cemcat, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1177/1352458520931785DOI Listing
September 2020

Aggressive multiple sclerosis (1): Towards a definition of the phenotype.

Mult Scler 2020 06 12:1352458520925369. Epub 2020 Jun 12.

Department of Clinical Neuroscience, Division of Neurology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.

While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and management. Here, we review previous attempts to define aggressive MS and present characteristics that might, with additional research, eventually help characterize it. A companion paper summarizes data regarding treatment and management.
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http://dx.doi.org/10.1177/1352458520925369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412876PMC
June 2020

Aggressive multiple sclerosis (2): Treatment.

Mult Scler 2020 06 12:1352458520924595. Epub 2020 Jun 12.

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.
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http://dx.doi.org/10.1177/1352458520924595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412878PMC
June 2020

A validation study of manual atrophy measures in patients with Multiple Sclerosis.

Neuroradiology 2020 Aug 3;62(8):955-964. Epub 2020 Apr 3.

Section of Neuroradiology and Magnetic Resonance Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Purpose: Manual measures such as corpus callosum index, normalized corpus callosum area, and width of the third ventricle are potential biomarkers for brain atrophy. In this work, we investigate their suitability to assess the neurodegenerative component of multiple sclerosis (MS) by comparing them to volumetric measures and expanded disability status scale (EDSS).

Methods: Fifty-eight patients with a clinically isolated syndrome, 48 MS patients treated with interferon β, and 26 treated with natalizumab underwent a brain MRI at baseline and after 1 year. Manual measures were evaluated by two observers using Jim v.6.0 at both time points. Volumetric tools (SIENA/x and Freesurfer) were used to calculate normalized brain volume, brain parenchymal fraction, annualized percentage of brain volume change, corpus callosum volume, ventricle volume, and volume of the third ventricle. Statistical analyses were performed with SPSS v.13.

Results: Usage of corpus callosum volume and third ventricle volume to validate normalized corpus callosum area and width of the third ventricle, respectively, showed very good correlations (r = 0.85, r = 0.83; p < 0.01). Width of the third ventricle, corpus callosum index, and normalized corpus callosum area correlations were significant with EDSS in all patients and moderate to strong with normalized brain volume and brain parenchymal fraction in natalizumab-treated patients (respectively r = - 0.54, r = - 0.61; r = 0.55, r = 0.67; and r = 0.58, r = 0.67; with p < 0.05).

Conclusion: Width of the third ventricle and normalized corpus callosum area seem the more robust manual measures regarding correlation with volumetric measures and EDSS, especially in patients with more advanced disease.
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http://dx.doi.org/10.1007/s00234-020-02401-3DOI Listing
August 2020

MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice.

Nat Rev Neurol 2020 Mar 24;16(3):171-182. Epub 2020 Feb 24.

Section of Neuroradiology and Magnetic Resonance Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.
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http://dx.doi.org/10.1038/s41582-020-0314-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054210PMC
March 2020

Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study.

Lancet Neurol 2020 03 10;19(3):234-246. Epub 2020 Feb 10.

Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Catalan Institute for Research and Advanced Studies, Barcelona, Spain. Electronic address:

Background: Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis.

Methods: In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies. All MOG antibody-positive cases were included in our study, which assessed syndromes, treatment and response to treatment (ie, number of relapses), outcomes (measured with the modified Rankin scale [mRS]), and phenotypes associated with poor prognosis. We used Fisher's exact and Wilcoxon rank sum tests to analyse clinical features, and survival Cox regression to analyse time to antibody negativity.

Findings: Between June 1, 2013, and Dec 31, 2018, 239 children with demyelinating syndromes (cohort A) and 296 with encephalitis other than ADEM (cohort B) were recruited. 116 patients had MOG antibodies, including 94 (39%) from cohort A and 22 (7%) from cohort B; 57 (49%) were female, with a median age of 6·2 years (IQR 3·7-10·0). Presenting syndromes in these 116 patients included ADEM (46 [68%]), encephalitis other than ADEM (22 [19%]), optic neuritis (20 [17%]), myelitis (13 [11%]), neuromyelitis optica spectrum disorders (six [5%]), and other disorders (nine [8%]). Among the patients with autoimmune encephalitis in cohort B (n=64), MOG antibodies were more common than all neuronal antibodies combined (22 [34%] vs 21 [33%]). After a median follow-up of 42 months (IQR 22-67), 33 (28%) of the 116 patients had relapses, including 17 (17%) of 100 diagnosed at first episode. Steroids, intravenous immunoglobulin, or plasma exchange were used in 100 (86%) patients at diagnosis, and 32 (97%) of 33 at relapses. Rituximab was mainly used at relapses (11 [33%]). 99 (85%) of 116 patients had substantial recovery (mRS <2) and 17 (15%) moderate to severe deficits (mRS >2; one died). Phenotypes of poor prognosis included ADEM-like relapses progressing to leukodystrophy-like features, and extensive cortical encephalitis evolving to atrophy. Time to antibody negativity was longer in patients with relapses (HR 0·18, 95% CI 0·05-0·59).

Interpretation: The spectrum of paediatric MOG antibody-associated syndromes is wider than previously reported and includes demyelinating syndromes and encephalitis. Recognition of these disorders has important clinical and prognostic implications.

Funding: Mutua Madrileña Foundation; ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Española de Esclerosis Múltiple; La Caixa Foundation; and Fundació CELLEX.
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http://dx.doi.org/10.1016/S1474-4422(19)30488-0DOI Listing
March 2020

SVM recursive feature elimination analyses of structural brain MRI predicts near-term relapses in patients with clinically isolated syndromes suggestive of multiple sclerosis.

Neuroimage Clin 2019 22;24:102011. Epub 2019 Oct 22.

Queen Square MS Centre, University College London, London, United Kingdom; National Institute of Health Research (NIHR), University College London Hospitals, Biomedical Research Centre, London, United Kingdom.

Machine learning classification is an attractive approach to automatically differentiate patients from healthy subjects, and to predict future disease outcomes. A clinically isolated syndrome (CIS) is often the first presentation of multiple sclerosis (MS), but it is difficult at onset to predict who will have a second relapse and hence convert to clinically definite MS. In this study, we thus aimed to distinguish CIS converters from non-converters at onset of a CIS, using recursive feature elimination and weight averaging with support vector machines. We also sought to assess the influence of cohort size and cross-validation methods on the accuracy estimate of the classification. We retrospectively collected 400 patients with CIS from six European MAGNIMS MS centres. Patients underwent brain MRI at onset of a CIS according to local standard-of-care protocols. The diagnosis of clinically definite MS at one-year follow-up was the standard against which the accuracy of the model was tested. For each patient, we derived MRI-based features, such as grey matter probability, white matter lesion load, cortical thickness, and volume of specific cortical and white matter regions. Features with little contribution to the classification model were removed iteratively through an interleaved sample bootstrapping and feature averaging approach. Classification of CIS outcome at one-year follow-up was performed with 2-fold, 5-fold, 10-fold and leave-one-out cross-validation for each centre cohort independently and in all patients together. The estimated classification accuracy across centres ranged from 64.9% to 88.1% using 2-fold cross-validation and from 73% to 92.9% using leave-one-out cross-validation. The classification accuracy estimate was higher in single-centre, smaller data sets than in combinations of data sets, being the lowest when all patients were merged together. Regional MRI features such as WM lesions, grey matter probability in the thalamus and the precuneus or cortical thickness in the cuneus and inferior temporal gyrus predicted the occurrence of a second relapse in patients at onset of a CIS using support vector machines. The increased accuracy estimate of the classification achieved with smaller and single-centre samples may indicate a model bias (overfitting) when data points were limited, but also more homogeneous. We provide an overview of classifier performance from a range of cross-validation schemes to give insight into the variability across schemes. The proposed recursive feature elimination approach with weight averaging can be used both in single- and multi-centre data sets in order to bridge the gap between group-level comparisons and making predictions for individual patients.
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http://dx.doi.org/10.1016/j.nicl.2019.102011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861587PMC
September 2020

Diagnosis of multiple sclerosis: what is changing?

Expert Rev Neurother 2020 08 11;20(8):743-746. Epub 2019 Nov 11.

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona , Barcelona, Spain.

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http://dx.doi.org/10.1080/14737175.2020.1691530DOI Listing
August 2020

An asymptomatic new lesion on MRI is a relapse and should be treated accordingly - Commentary.

Mult Scler 2019 12 1;25(14):1845-1847. Epub 2019 Nov 1.

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1177/1352458519885110DOI Listing
December 2019

The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS.

Mult Scler 2020 11 15;26(13):1658-1669. Epub 2019 Oct 15.

Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Servei de Neurologia/Neuroimmunologia, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain/Division of Neurology, University of Toronto, St Michael's Hospital, Toronto, ON, Canada.

Objective: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort.

Methods: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years).

Results: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL.

Conclusion: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS.
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http://dx.doi.org/10.1177/1352458519877810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604549PMC
November 2020

Head-to-head drug comparisons in multiple sclerosis: Urgent action needed.

Neurology 2019 10 7;93(18):793-809. Epub 2019 Oct 7.

From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK; Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain; Department of Medicine (T.K.), CORe, University of Melbourne, Australia; Department of Neurology (T.K.), Royal Melbourne Hospital, Australia; Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada; Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy; and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia.

Disease-modifying drugs are changing the natural history of multiple sclerosis (MS). However, currently available clinical trial data are insufficient to develop accurate personalized treatment algorithms to assign the best possible treatment to each person with MS according to disease features, treatment history, and comorbidities. Such accurate algorithms would require the presence of numerous head-to-head trials of long duration, which is virtually impossible, given the economic costs, required time, and difficulties with attrition. Thus, efforts are being made to compare relative treatment efficacy through observational designs, using large multicenter prospective cohorts or "big MS data," and network meta-analyses. Although such studies can yield useful information, they are liable to biases and their results should be confirmed in other study populations, including smaller, single-center cohorts, where some of these biases can be minimized. In this View article, we analyze the potential benefits and biases of all these strategies alternative to head-to-head trials in MS. Finally, we propose the combination of all these types of studies to obtain reliable head-to-head drug comparisons in the absence of randomized designs.
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http://dx.doi.org/10.1212/WNL.0000000000008319DOI Listing
October 2019

Oligoclonal bands do not represent dissemination in time in the 2017 revisions to the McDonald criteria.

Mult Scler 2019 10 16;25(12):1690-1691. Epub 2019 May 16.

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1177/1352458519846103DOI Listing
October 2019

Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome.

Mult Scler J Exp Transl Clin 2019 Jan-Mar;5(1):2055217319836664. Epub 2019 Mar 20.

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, USA.

Background: Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination.

Objectives: To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome.

Methods: We analysed an international historical cohort of 61 children with radiologically isolated syndrome (≤18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.2 ± 4.7 years). All index scans also met the 2017 magnetic resonance imaging dissemination in space criteria.

Results: Diagnostic indices (95% confidence intervals) for the 2005 dissemination in space criteria, with and without oligoclonal bands, were: sensitivity 66.7% (38.4-88.2%) versus 72.7% (49.8-89.3%); specificity 83.3% (58.6-96.4%) versus 53.9% (37.2-69.9%). For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1-93.2%) versus 100% (84.6-100%); specificity 72.7% (49.8-89.3%) versus 25.6% (13.0-42.1%).

Conclusions: Oligoclonal bands increased the specificity of magnetic resonance imaging criteria in children with Ped-RIS. Clinicians should consider testing cerebrospinal fluid to improve diagnostic certainty. There is rationale to include cerebrospinal fluid analysis for biomarkers including oligoclonal bands in planned prospective studies to develop optimal diagnostic criteria for radiologically isolated syndrome in children.
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http://dx.doi.org/10.1177/2055217319836664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429663PMC
March 2019