The Response Study: A French registry on pregnancy in women with MS and related disorders and their children up to 6 years-Protocol, recruitment status, and baseline characteristics.

BACKGROUND: Counseling on pregnancy is still challenging, particularly regarding the use of disease-modifying treatments (DMTs). We are lacking long-term outcomes in children exposed to DMTs. OBJECTIVES: This study aimed to set up a French pregnancy registry for women with multiple sclerosis (MS) and related disorders nested within the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. METHODS: Prospective, observational, multicentric, epidemiological study in France. Neurological visits are organized according to routine practice. Data are collected on the OFSEP minimal datasheet. Auto-questionnaires on pregnancy are completed by patients at Months 5-6 and 8 during pregnancy, and Months 3, 6, and 12 postpartum. A specific survey on analgesia is completed by anesthesiologists. Pediatric data are collected from the child's health book, where visits on Day 8, Month 9, and 24 are mandatory. Parents complete neurodevelopmental questionnaires at Year 1, Years 2 and 6. RESULTS: The RESPONSE study started in August 2019. On 7 April 2023, 515 women were included. Baseline demographics are presented. CONCLUSIONS: RESPONSE will provide rich information on the global management of pregnancy in France and prospective data on children until the age of 6 years, exposed or not to a DMT, including data on neurodevelopment that can be compared to the general population. STUDY FUNDING: EDMUS and ARSEP Foundation, Biogen, Roche.

COVID-19 outcomes in patients with multiple sclerosis: Understanding changes from 2020 to 2022.

BACKGROUND: Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021. OBJECTIVES: We aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022. METHODS: This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity. RESULTS: Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave (p < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = [1.25-1.64] per 10 years), male sex (OR = 2.01, 95% CI = [1.51-2.67]), obesity (OR = 2.36, 95% CI = [1.52-3.68]), cardiac comorbidities (OR = 2.36, 95% CI = [1.46-3.83]), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = [1.43-3.06] for EDSS 3-5.5 and OR = 4.53, 95% CI = [3.04-6.75] for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = [1.85-3.87]) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = [0.60-0.69]) or off (RR = 0.32, 95% CI = [0.30-0.33]) anti-CD20. DISCUSSION: In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status.

Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network.

BACKGROUND: Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time. METHODS: All patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3-4. RESULTS: A total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria. CONCLUSIONS: Contrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.

Pseudocystic inflammatory demyelinating lesions in multiple sclerosis: A clinical, radiological, and pathological description.

BACKGROUND: Pseudocystic inflammatory demyelinating lesions (PIDLs) are poorly described in MS and might represent a diagnostic challenge. OBJECTIVES: We described the clinical, radiological, pathological, and follow-up characteristics of 13 PIDL in 9 MS patients. METHODS: We constituted a single-center retrospective case series of PIDLs in MS, defined on MRI as expansive cyst-like lesions, with a fluid-signal content, and a diameter of 1 cm or more. RESULTS: PIDL often occurred at first event (56%), were often asymptomatic (69%), and encircled by a hypo-T2 diffusion-restricted rim and a thin ring-like gadolinium enhancement (100%) on magnetic resonance imaging (MRI). Associated typical MS lesions were constant. Biopsies from two PIDLs displayed classical features of active MS, except for unusual edema. CONCLUSION: PIDLs are clinically unremarkable and associated with a good outcome. Their easily recognizable MRI features could help avoid biopsy.

ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. OBJECTIVE: To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

Pregnancy and post-partum in patients with myelin-oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND AND OBJECTIVE: Myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) frequently initiates during childbearing years. This study investigated the impact of pregnancy and post-partum on MOGAD activity. METHODS: Retrospective analysis of clinical and demographic data from a multicenter French cohort of adult patients with MOGAD. All adult female patients who had a pregnancy after disease onset or in the year before disease onset were included. The annualized relapse rate was evaluated in patients who had a pregnancy after disease onset, to evaluate the impact of pregnancy and post-partum on MOGAD course. RESULTS: Twenty-five informative pregnancies after disease onset were identified. No relapse was recorded during these pregnancies and only three relapses occurred during the first 3 months post-partum. The annualized relapse rate decreased from 0.67 (95% confidence interval: 0.40-1.10) during the pre-pregnancy period to 0 (95% confidence interval: 0-0.21) during pregnancy and to 0.22 (95% confidence interval: 0.09-0.53) during the first year post-partum. Among 144 female patients in their childbearing age recorded in the database, 18 (12.5%) reported their first symptoms during pregnancy or in the 12 months post-partum. DISCUSSION: Our study suggests a marked reduction of MOGAD relapse rate during pregnancy and the post-partum period. Prospective studies on the role of pregnancy and delivery in MOGAD course are needed.

Pregnancy and multiple sclerosis: 2022 recommendations from the French multiple sclerosis society.

OBJECTIVE: The objective of this study was to develop evidence-based recommendations on pregnancy management for persons with multiple sclerosis (MS). BACKGROUND: MS typically affects young women in their childbearing years. Increasing evidence is available to inform questions raised by MS patients and health professionals about pregnancy issues. METHODS: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and university databases (January 1975 through June 2021). The RAND/UCLA appropriateness method was developed to synthesise the scientific literature and expert opinions on healthcare topics; it was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS: A strong agreement was reached for all 104 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, locoregional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses and disease-modifying treatments. CONCLUSION: The 2022 recommendations of the French MS society should be helpful to harmonise counselling and treatment practice for pregnancy in persons with MS, allowing for better and individualised choices.

Improving the decision to switch from first- to second-line therapy in multiple sclerosis: A dynamic scoring system.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. OBJECTIVE: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. METHODS: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). RESULTS: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09-0.22) for the waiting group and 0.40 (95% CI 0.32-0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30-0.46) and 0.44 (95% CI 0.37-0.52), respectively. CONCLUSIONS: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.

Pregnancy and neuromyelitis optica spectrum disorders: 2022 recommendations from the French Multiple Sclerosis Society.

BACKGROUND: In 2020, the French Multiple Sclerosis (MS) Society (SFSEP) decided to develop a national evidence-based consensus on pregnancy in MS. As neuromyelitis optica spectrum disorders (NMOSD) shares a series of commonalities with MS, but also some significant differences, specific recommendations had to be developed. OBJECTIVES: To establish recommendations on pregnancy in women with NMOSD. METHODS: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and universities databases (January 1975 through June 2021). The RAND/UCLA appropriateness method, which was developed to synthesise the scientific literature and expert opinions on health care topics, was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A sub-group of nine NMOSD experts was dedicated to analysing available data on NMOSD. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS: A strong agreement was reached for all 66 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, loco-regional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses, and disease-modifying treatments. CONCLUSION: Physicians and patients should be aware of the new and specific evidence-based recommendations of the French MS Society for pregnancy in women with NMOSD. They should help harmonise counselling and treatment practise, allowing for better individualised choices.

European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs.

BACKGROUND AND PURPOSE: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. We aimed to develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). METHODS: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. RESULTS: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in subpopulations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. CONCLUSION: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.

Minor Salivary Gland Biopsy for the Diagnosis of Neurosarcoidosis.

INTRODUCTION: The definite diagnosis of neurosarcoidosis is challenging since it requires a compatible histology of the nervous system. When neurosarcoidosis is suspected, other systemic manifestations are investigated to confirm the diagnosis. A minor salivary gland biopsy (MSGB) is often performed since it is minimally invasive. The objective of the present study was to assess its performance for the diagnosis of neurosarcoidosis. METHODS: A retrospective single-center study included patients who underwent a MSGB in a tertiary neurological university hospital (Lyon, France) between 2015 and 2018. Clinical presentations unlikely to be compatible with neurosarcoidosis were excluded. Positive cases of neurosarcoidosis were defined as definite, probable, and possible cases, according to the latest international neurosarcoidosis diagnostic criteria from the Neurosarcoidosis Consortium Consensus Group. RESULTS: A total of 529 patients underwent a MSGB for clinical manifestations compatible with neurosarcoidosis. Among the 13 who fulfilled the criteria for neurosarcoidosis, only one had a positive MSGB. The sensitivity of MSGB was 7.7% (95% CI [0.2-36.0%]) and the specificity was 100.0% (95% CI [99.3-100%]). CONCLUSION: Considering the low sensitivity of MSGB for the diagnosis of NS, MSGB should be performed in selected indications, including a suspicion of spinal cord sarcoidosis, or when there is a strong clinical, laboratory, and radiological suspicion of NS. MSGB should rather not be performed when the chest CT-scan does not show signs of pulmonary or lymph node sarcoidosis.

Treatment regimens for neuromyelitis optica spectrum disorder attacks: a retrospective cohort study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy. METHODS: We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as "good" if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome. RESULTS: We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was "good" in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response. CONCLUSIONS: We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids.

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

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.

Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica.

INTRODUCTION: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. CASE SERIES: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. DISCUSSION: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021.

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Disability Progression in Multiple Sclerosis Patients using Early First-line Treatments.

BACKGROUND: Therapeutic management of relapsing-remitting multiple sclerosis (RRMS) has evolved towards early treatment. The objective was to assess the impact of early treatment initiation on disability progression among RRMS first-line treated patients. METHODS: This study included all incident RRMS cases starting interferon or glatiramer acetate for the first time from 1996/01/01 to 2012/31/12 (N=5,279) from ten MS expert OFSEP centers (Observatoire Français de la Sclérose en Plaques). The delay from treatment start to attain an irreversible Expanded Disability Status Scale score of 3.0 were compared between "Early" group (N= 1,882; treated within 12 months following MS clinical onset) and "Later" group using propensity score weighted Kaplan-Meier methods, overall and stratified by age. RESULTS: Overall, the restricted mean time before reaching EDSS 3.0 (RMST) from treatment start was 11 years and two months for patients treated within the year following MS clinical onset and 10 years and seven months for patients treated later. Thus, early treated patients gained 7 months (95% CI: [4-11] months) in the time to reach EDSS 3.0 compared to patients treated later (treatment start delayed by 28 months). The difference in RMST was respectively six months (95% CI: [1-10] months) and 14 months (95% CI: [4-24] months) in the "≤40 years" age group and in the ">40 years" age group, in favour of early group. . CONCLUSIONS: Early treatment initiation resulted in a significant reduction of disability progression among patients with RRMS, and also among older patients.

Multiple sclerosis lesions segmentation from multiple experts: The MICCAI 2016 challenge dataset.

MRI plays a crucial role in multiple sclerosis diagnostic and patient follow-up. In particular, the delineation of T2-FLAIR hyperintense lesions is crucial although mostly performed manually - a tedious task. Many methods have thus been proposed to automate this task. However, sufficiently large datasets with a thorough expert manual segmentation are still lacking to evaluate these methods. We present a unique dataset for MS lesions segmentation evaluation. It consists of 53 patients acquired on 4 different scanners with a harmonized protocol. Hyperintense lesions on FLAIR were manually delineated on each patient by 7 experts with control on T2 sequence, and gathered in a consensus segmentation for evaluation. We provide raw and preprocessed data and a split of the dataset into training and testing data, the latter including data from a scanner not present in the training dataset. We strongly believe that this dataset will become a reference in MS lesions segmentation evaluation, allowing to evaluate many aspects: evaluation of performance on unseen scanner, comparison to individual experts performance, comparison to other challengers who already used this dataset, etc.

Cumulative effects of therapies on disability in relapsing multiple sclerosis.

BACKGROUND: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. OBJECTIVE: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function. RESULTS: At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT). CONCLUSION: Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.

Clinical significance of a single cerebrospinal fluid immunoglobulin band: A retrospective study.

BACKGROUND: To demonstrate an inflammatory process in the central nervous system, the presence of at least two immunoglobulin (Ig) bands in the cerebrospinal fluid (CSF) is required. So far, the presence of a single abnormal Ig band is considered as negative. OBJECTIVE: The objective was to assess retrospectively the significance of a single CSF Ig band in clinical practice. METHODS AND RESULTS: Out of 10,286 CSF analyses, we retained 214 results with single Ig. An inflammatory neurological disorder was diagnosed in 41% of patients. CONCLUSION: Despite a modest sensitivity, the presence of a single CSF Ig band may be a biomarker of an inflammatory mechanism and, as such, may prompt the clinician to repeat the analysis when the clinical context remains suggestive.

Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network.

BACKGROUND: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. OBJECTIVE: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. METHODS: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. RESULTS: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients' group. CONCLUSION: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.