BackgroundThere is little consensus on how to make a diagnosis announcement of severe chronic disease in neurology. Other medical specialties, such as oncology, have developed assessment methods similar to the Objective Structured Clinical Examination (OSCE) to address this issue. Here we report the implementation of an OSCE focused on the diagnosis announcement of chronic disease in neurology by residents.ObjectiveWe aimed to evaluate the acceptability, feasibility and validity in routine practice of an OSCE combined with a theoretical course focused on diagnosis announcement in neurology.MethodEighteen neurology residents were prospectively included between 2019 and 2022. First, they answered a questionnaire on their previous level of training in diagnosis announcement. Second, in a practical session with a simulated patient, they made a 15-min diagnosis announcement and then had 5mins of immediate feedback with an expert observer, present in the room. The OSCE consisted of 4 different stations, with standardized scenarios dedicated to the announcement of multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Third, in a theory session, expert observers covered the essential theoretical points. All residents and expert observers completed an evaluation of the “practical session” and the “theory session”.ResultsResidents estimated their previous level of diagnosis announcement training at 3.1/5. The most feared announcements were AD and ALS. The “practical session” was rated at a mean of 4.1/5 by the residents and 4.8/5 by the expert observers, and the “theory session” at a mean of 4.7/5 by the residents and 5/5 by the expert observers. After the OSCEs, 11 residents felt more confident about making an announcement.ConclusionThis study has shown a benefit of using an OSCE to learn how to make a diagnosis announcement of severe chronic disease in neurology. OSCEs could be used in many departments in routine practice and seem adapted to residents.

Objective: Aim of this study is to characterise the neuronal, axonal, and glial damage in seronegative NMOSD in comparison with AQP4+NMOSD Background: serum GFAP and NfL define disease activity in different neurological conditions. These biomarkers increase in patients with AQP4+NMOSD during clinical attacks, with contradictory results in seronegative-NMOSD. Design/Methods: patients with double (i.e. for AQP4 and MOG-Abs) seronegative-NMOSD and age-matched AQP4+NMOSD with available onset/relapse serum samples (i.e. obtained within 3 months) were retrospectively enrolled. Clinical and radiological data were collected. Serum NfL, GFAP, Tau and UCH-L1 levels were determined using an ultrasensitive paramagnetic bead-based enzyme-linked immunosorbent assay (SIMOA). Statistical analysis was performed using parametric and non-parametric tests and ROC analysis Results: 27 seronegative-NMOSD and 24 AQP4+NMOSD patients were included. Median age at sampling was 36.2 years [IQR 27.0–49] with no statistical differences between groups. Most common syndromes at sampling in both seronegative-NMOSD and AQP4+NMOSD were myelitis (37% vs 54.2%) and optic neuritis (33.3% vs 37.5%). Median EDSS at sampling was 3.5 [IQR 2.5–7.0], with no significant difference between the two groups. Serum GFAP, Tau and UCH-L1 levels were significantly higher in AQP4+NMOSD compared to seronegative-NMOSD patients (median 304.1 vs 160.5 pg/mL p=0.005; median 24.8 vs 13.3 pg/mL, p= 0.002; and median 60 vs 37.3 pg/mL, p=0.021, respectively), as confirmed by ROC analysis, while NfL levels were similar (p=0.270). In the seronegative-NMOSD group, NfL and UCH-L1 levels correlated with EDSS at attack nadir (rho 0.438, p=0.032 and rho 0.429 p=0.036, respectively), while in the AQP4+NMOSD group this correlation was observed for NfL, UCH-L1, and GFAP levels (rho 0.745, p=0.010; rho 0.448, p=0.32, rho 525, p= 0.010, respectively). Conclusions: serum GFAP, Tau, and UCH-L1 levels discriminate between AQP4+NMOSD and seronegative-NMOSD. The different biomarkers profile suggests heterogeneity of diseases and provides useful data to improve our understanding of these diseases Disclosure: Dr. Carta has nothing to disclose. Dr. Dinoto has nothing to disclose. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Valentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche S.p.a.. Dr. Lo Re has nothing to disclose. Ms. Chiodega has nothing to disclose. Pierre Branger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NOVARTIS. Pierre Branger has received personal compensation in the range of $0-$499 for serving as a Consultant for BIOGEN. Pierre Branger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MERCK. Pierre Branger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Bertrand Audoin has nothing to disclose. Jennifer Aboab, 8220 has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for SANOFI. Caroline Papeix has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIOGEN . Caroline Papeix has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE . Caroline Papeix has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MERCK. Caroline Papeix has received personal compensation in the range of $0-$499 for serving as a Consultant for NOVARTIS . Nicolas Collongues, MD has nothing to disclose. Philippe Kerschen has nothing to disclose. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BIogen Idec. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for novartis. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BMS. Helene Zephir has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Alain Creange has nothing to disclose. Bertrand Bourre has nothing to disclose. The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received research support from Viela Bio. Dr. Flanagan has received research support from UCB. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Redenbaugh has nothing to disclose. Javier Villacieros-Álvarez has nothing to disclose. The institution of Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. The institution of Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage. The institution of Dr. Arrambide has received research support from Instituto de Salud Carlos III. Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving as a Travel support for scientific meetings with Novartis. Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving as a Travel support for scientific meetings with Roche. Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving as a Travel support for scientific meetings with ECTRIMS. Dr. Arrambide has a non-compensated relationship as a Member of the Executive Committee with iWiMS that is relevant to AAN interests or activities. Dr. Arrambide has a non-compensated relationship as a Member of the steering committee with BioMS-eu that is relevant to AAN interests or activities. Dr. Cobo Calvo has nothing to disclose. Sergio Ferrari has nothing to disclose. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Marignier has received personal compensation in the range of $0-$499 for serving as a Consultant for ALEXION. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HORIZON THERAPEUTICS. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROCHE. Dr. Mariotto has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.

Multiple sclerosis (MS) is the most common chronic inflammatory neurological disease. The emergence of disease-modifying therapies (DMTs) has greatly improved disease activity control and progression of disability in MS patients. DMTs differ in their mode of action, route of administration, efficacy, and safety profiles, offering multiple options for clinicians. Personalized medicine aims at tailoring the therapeutic strategy to patients' characteristics and disease activity but also patients' needs and preferences. New therapeutic options have already changed treatment paradigms for patients with active relapsing MS (RMS). The traditional approach consists in initiating treatment with moderate-efficacy DMTs and subsequently, escalating to higher-efficacy DMTs when there is evidence of clinical and/or radiological breakthrough activity. Recent real-world studies suggest that initiation of high-efficacy DMTs from disease onset can improve long-term outcomes for RMS patients. In this article, we review different treatment strategies and discuss challenges associated with personalized therapy.

BackgroundIn clinical practice, the diagnosis of secondary progressive multiple sclerosis (SPMS) is often delayed, retrospective and non-reproducible, as there are no consensus criteria that define the advent of SPMS. Early identification of SPMS is essential to improve patient care.MethodsEight regional board meetings in France involving 56 multiple sclerosis (MS) experts (neurologists) were convened to discuss diagnostic criteria for SPMS. Subsequently, a national board meeting of 13 neurologists (with an expert representing each geographical region) was held to review points of convergence or divergence between regions and to develop a national consensus document.ResultsBased on the discussions from the regional boards, the MS experts at the national board retained the worsening of the EDSS score, with compatible clinical features, as the only consensus criterion for the diagnosis of SPMS in clinical practice. The patient should have experienced during at least the previous 6 months and in the absence of any relapse, a worsening in the EDSS score of +1.0 point (if the previous EDSS was≤5.0) or of +0.5 point (if the previous EDSS was≥5.5), with a pyramidal or cerebellar functional system score≥2 and without setting a minimum EDSS score; or, in case of a stable EDSS score≥4.0, a worsening of a functional score. This worsening should be confirmed within 3 to 6 months. According to the MS experts, the patient's age, duration of illness and a minimal threshold EDSS score are only risk factors for transition to SPMS. Patient reports during consultation and cognitive impairment are important warning signs, which should trigger an objective assessment with specific tests or closer monitoring. Clinical relapse and/or MRI activities are non-discriminatory for making the diagnosis of SPMS.ConclusionsThe experts defined precise diagnostic criteria adapted to clinical practice for earlier identification of SPMS, paving the way for better management of this stage of the disease.

BACKGROUND:Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies.METHODS:Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed.RESULTS:Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption.CONCLUSIONS:This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

To establish recommendations on pregnancy in women with multiple sclerosis (MS)

Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

Background and aims: PRO-MSACTIVE (NCT03589105) is a phase IV study evaluating the efficacy, safety and impact of ocrelizumab (OCR), an anti-CD20 antibody, on patient reported outcomes in patients with active relapsing multiple sclerosis (RMS). We report the interim analysis findings. Methods: In PRO-MSACTIVE, patients with active RMS, ≥18 years, receive OCR infusions for a 48-weeks treatment period. The primary endpoint of the study was the percentage of patients free of disease activity at week (W) 48 (defined by no relapse since enrolment and no T1 gadolinium (Gd)-enhancing lesion and no new and/or enlarging T2 lesion as detected by brain MRI [without MRI rebaseline]) and was evaluated in this interim analysis using the population of patients who have completed the 48 weeks of treatment phase before France COVID-19 lockdown. Results: In total, 422 patients (375 RRMS, 47 SPMS;female 73.7%;mean (SD) age 39.7 years (10.5);25.1% naive of previous DMT;mean (SD) baseline EDSS 2.80 (2.04)) were enrolled. This interim analysis included data from 335 patients at W48. Most patients (65.1% [95%CI 59.7%-70.2%]) were free of all protocol-defined disease activity events. Regarding individual activity events, 87.2% of patients were relapse free at W48, 83.6% had no T1 Gd-enhancing lesion and 76.1% had no new/enlarging T2 lesion. The adjusted annualised relapse rate (0.13) was low. There were no deaths and safety results were consistent with prior studies. Conclusion: The efficacy of ocrelizumab in RMS patients was confirmed in a pragmatic setting and was in line with the other OCR study results. No safety signals were observed.

OBJECTIVES The main objective was to compare clinical features, disease course, myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab) dynamics, between children and adults with MOG-Ab-associated disease (MOGAD). METHODS Retrospective multicentric, national study including 98 children and 268 adults with MOGAD between January 2014, and September 2019. Cox's regression model for recurrent time-to-event data, and Kaplan-Meier curves for time to antibody negativity were performed for the objectives, respectively. RESULTS Isolated optic neuritis was the most frequent clinical presentation both in 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 a better recovery (EDSS ≥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 two years, 64.2% (95%CI 40.9-86.5) of non-relapsing children became MOG-Ab negative compared to 14.1% (95%CI 4.7-38.3) of relapsing ones, log-rank p<0.001, with no differences observed in adults (log-rank p=0.280). INTERPRETATION MOGAD 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 relapses and a worse functional recovery. Finally, children with monophasic disease became MOG-Ab negative earlier than relapsing ones, but not in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. This article is protected by copyright. All rights reserved.

Background and purposeAssessing patients’ disability in multiple sclerosis (MS) requires time‐consuming batteries of hospital tests. MSCopilot is a software medical device for the self‐assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC).MethodsThis multicentre, open‐label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end‐point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end‐point was the correlation of MSCopilot z‐scores with MSFC z‐scores.ResultsIn all, 116 PwMS and 69 HCs were analysed. The primary end‐point was achieved: MSCopilot performance was non‐inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test–retest study demonstrated the good reproducibility of MSCopilot.ConclusionThis study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS‐related disability.