Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders.

BACKGROUND: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. METHODS: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). RESULTS: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). CONCLUSIONS: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.

Frequency and characteristics of short versus longitudinally extensive myelitis in adults with MOG antibodies: A retrospective multicentric study.

OBJECTIVES: We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis. MATERIAL AND METHODS: We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0. RESULTS: Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0-4.0)) compared to SM patients (2.0, (1.0-3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01-1.95, p = 0.046). CONCLUSION: SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.

Matrix metalloproteinase 9 is decreased in natalizumab-treated multiple sclerosis patients at risk for progressive multifocal leukoencephalopathy.

OBJECTIVE: To identify biomarkers associated with the development of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab (NTZ). METHODS: Relapsing-remitting MS patients who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr) were included in the study. Cryopreserved peripheral blood mononuclear cells and serum samples collected at baseline, at 1- and 2-year treated time points, and during PML were analyzed for gene expression by RNA sequencing and for serum protein levels by Luminex and enzyme-linked immunosorbent assays, respectively. RESULTS: Among top differentially expressed genes in the RNA sequencing between pre-PML and NTZ-ctr patients, pathway analysis revealed a high representation of genes belonging to the following categories: proangiogenic factors (MMP9, VEGFA), chemokines (CXCL1, CXCL5, IL8, CCL2), cytokines (IL1B, IFNG), and plasminogen- and coagulation-related molecules (SERPINB2, PLAU, PLAUR, TFPI, THBD). Serum protein levels for these candidates were measured in a 2-step manner in a screening cohort and a validation cohort of pre-PML and NTZ-ctr patients. Only matrix metalloproteinase 9 (MMP9) was validated; in pre-PML patients, MMP9 protein levels were significantly reduced at baseline compared with NTZ-ctr patients, and levels remained lower at later time points during NTZ treatment. INTERPRETATION: The results from this study suggest that the proangiogenic factor MMP9 may play a role as a biomarker associated with the development of PML in MS patients treated with NTZ. Ann Neurol 2017;82:186-195.

USPIO-positive MS lesions are associated with greater tissue damage than gadolinium-positive-only lesions during 3-year follow-up.

BACKGROUND: Identifying in vivo the processes that determine lesion severity in multiple sclerosis (MS) remains a challenge. OBJECTIVES: To describe the dynamics of ultrasmall superparamagnetic iron oxide (USPIO) enhancement in MS lesions and the relationship between USPIO enhancement and microstructural changes over 3 years. METHODS: Lesion development was assessed at baseline, Months 3, 6, and 9, using magnetic resonance imaging (MRI) with gadolinium and USPIO. Microstructural changes were assessed at baseline, Months 3, 6, 9, 12, 18, 24, and 36, using relaxometry, magnetization transfer, and diffusion-weighted imaging. RESULTS: We included 15 patients with clinically isolated syndrome. In the 52 MRI scans acquired with USPIO, 22 lesions were USPIO and gadolinium positive, and 44 were USPIO negative but gadolinium positive. Lesions no longer exhibited sustained USPIO enhancement 3 months later. At baseline, lesions that were both USPIO and gadolinium positive had lower magnetization transfer ratio values (common language effect size = 0.84, p = 0.0005) and lower fractional anisotropy values (0.83, p = 0.001) than gadolinium-positive-only lesions. USPIO-positive lesions remained associated with greater damage than gadolinium-positive-only lesions throughout the 3-year follow-up. CONCLUSION: USPIO enhancement, mainly reflecting monocyte infiltration, is transient and is associated with persistent tissue damage after 3 years.

Social Cognition Abilities in Patients With Different Multiple Sclerosis Subtypes.

OBJECTIVES: Multiple sclerosis (MS) can be associated with impaired social cognition. However, social cognition skills have never been explored in the different subtypes of MS. The first aim of this study was to examine whether MS subtypes differ on the course of social cognition. The second aim was to explore the relationship between social cognition performances and executive abilities and mood variables. METHODS: Sixty-two patients with MS and 33 healthy matched controls performed experimental tasks assessing facial emotion recognition, theory of mind (ToM), and cognitive functioning, in particular executive functions. RESULTS: Patients differed from controls on both measures of social cognition. On the ToM measures, patients with progressive MS scored significantly lower than healthy participants. Patients with primary progressive MS performed worse than both healthy participants and patients with relapsing-remitting MS on the recognition of fearful facial expressions, while patients with secondary progressive MS performed worse on the recognition of facial expressions of sadness. Patients' social cognition difficulties were correlated with processing speed, working memory, and verbal fluency. CONCLUSIONS: These preliminary results suggested that there may be qualitative differences in social cognition difficulties among the phenotypes. Furthermore, these impairments were related to executive functions, but unrelated to patients' disability or level of depression. These data highlight the need for research to determine the real impact of these deficits on interpersonal relationships among patients and to confirm these disorders in a larger population with progressive forms of MS. (JINS, 2017, 23, 653-664).

The neuronal component of gray matter damage in multiple sclerosis: A [(11) C]flumazenil positron emission tomography study.

OBJECTIVE: Using positron emission tomography (PET) with [(11) C]flumazenil ([(11) C]FMZ), an antagonist of the central benzodiazepine site located within the GABAA receptor, we quantified and mapped neuronal damage in the gray matter (GM) of patients with multiple sclerosis (MS) at distinct disease stages. We investigated the relationship between neuronal damage and white matter (WM) lesions and evaluated the clinical relevance of this neuronal PET metric. METHODS: A cohort of 18 MS patients (9 progressive and 9 relapsing-remitting) was compared to healthy controls and underwent neurological and cognitive evaluations, high-resolution dynamic [(11) C]FMZ PET imaging and brain magnetic resonance imaging. [(11) C]FMZ binding was estimated using the partial saturation protocol providing voxel-wise absolute quantification of GABAA receptor concentration. PET data were evaluated using a region of interest (ROI) approach as well as on a vertex-by-vertex basis. RESULTS: [(11) C]FMZ binding was significantly decreased in the cortical GM of MS patients, compared to controls (-10%). Cortical mapping of benzodiazepine receptor concentration ([(11) C]FMZ Bmax) revealed significant intergroup differences in the bilateral parietal cortices and right frontal areas. ROI analyses taking into account GM volume changes showed extensive decrease in [(11) C]FMZ binding in bilateral parietal, cingulate, and insular cortices as well as in the thalami, amygdalae, and hippocampi. These changes were significant in both progressive and relapsing-remitting forms of the disease and correlated with WM T2-weighted lesion load. [(11) C]FMZ cortical binding correlated with cognitive performance. INTERPRETATION: This pilot study showed that PET with [(11) C]FMZ could be a promising and sensitive quantitative marker to assess and map the neuronal substrate of GM pathology in MS.

Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in clinically isolated syndrome.

BACKGROUND: Macrophages are important components of inflammatory processes in multiple sclerosis, closely linked to axonal loss, and can now be observed in vivo using ultra-small superparamagnetic iron oxide (USPIO). In the present 1-year longitudinal study, we aimed to determine the prevalence and the impact on tissue injury of macrophage infiltration in patients after the first clinical event of multiple sclerosis. METHODS: Thirty-five patients, 32 years mean age, were imaged in a mean of 66 days after their first event using conventional magnetic resonance imaging, gadolinium (Gd) to probe blood-brain barrier integrity, USPIO to study macrophage infiltration and magnetization transfer ratio (MTR) to assess tissue structure integrity. Statistics were performed using two-group repeated-measures ANOVA. Any patient received treatment at baseline. RESULTS: At baseline, patients showed 17 USPIO-positive lesions reflecting infiltration of macrophages present from the onset. This infiltration was associated with local higher loss of tissue structure as emphasized by significant lower MTRnorm values (p<0.03) in USPIO(+)/Gd(+) lesions (n=16; MTRnormUSPIO(+)/Gd(+)=0.78 at baseline, MTRnormUSPIO(+)/Gd(+)=0.81 at M12) relative to USPIO(-)/Gd(+) lesions (n=67; MTRnormUSPIO(-)/Gd(+)=0.82 at baseline, MTRnormUSPIO(-)/Gd(+)=0.85 at M12). No interaction in MTR values was observed during the 12 months follow-up (lesion type × time). CONCLUSION: Infiltration of activated macrophages evidenced by USPIO enhancement, is present at the onset of multiple sclerosis and is associated with higher and persistent local loss of tissue structure. Macrophage infiltration affects more tissue structure while tissue recovery during the following year has a similar pattern for USPIO and Gd-enhanced lesions, leading to relative higher persistent local loss of tissue structure in lesions showing USPIO enhancement at baseline.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. OBJECTIVE: To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. METHODS: Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. RESULTS: A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. CONCLUSION: MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated.

Brain networks disconnection in early multiple sclerosis cognitive deficits: an anatomofunctional study.

Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage.

Social cognition and executive functioning in multiple sclerosis: A cluster-analytic approach.

Multiple sclerosis (MS) is associated with deficits in social cognition, the process underlying social interaction and cognitive function. However, the relationships between executive impairment and social cognition remain unclear in MS. Previous studies exclusively focused on group comparisons between healthy controls and patients with MS, treating the latter as a homogeneous population. The variability of socio- and neurocognitive profiles in this pathology therefore remains underexplored. In the present study, we used a cluster analytic approach to explore the heterogeneity of executive and social cognition skills in MS. A total of 106 patients with MS were compared with 53 healthy matched controls on executive (e.g., working memory) and social cognition (facial emotion recognition and theory of mind) performances. A cluster analysis was then performed, focusing on the MS sample, to explore the presence of differential patterns of interaction between executive and social cognition difficulties and their links to sociodemographic, clinical and cognitive variables. We identified three distinct functional profiles: patients with no executive or social cognition deficits (Cluster 1); patients with difficulties in facial emotion recognition and theory of mind and, to a lesser extent, executive functioning (Cluster 2); and patients with executive functioning difficulties only (Cluster 3). Clinical characteristics (disease duration, disability, fatigue) did not differ between clusters. CONCLUSIONS: These results suggest that there are qualitative differences in the social cognition and executive difficulties that are commonly found among patients with MS. If replicated, the identification of these profiles in clinical practice could allow for more individualized rehabilitation.

Social cognition impairments in relapsing-remitting multiple sclerosis.

Theory of Mind (ToM) is the ability to attribute independent mental states to self and others to explain and predict behavior. Impairment of ToM is well established in developmental pathologies. In neurological populations, investigation of ToM is still rare but data suggest that ToM impairment could contribute to behavioral and social disturbances. In addition to neurological signs, multiple sclerosis (MS) presents with disorders of cognition and behavior directly related to brain damage. The aim of this study was to assess ToM abilities and recognition of facial emotional expression in adults with MS. We compared 64 patients with relapsing MS and 30 matched healthy controls on three levels of ToM tasks, a facial emotion recognition task, and a neuropsychological assessment. MS patients performed significantly worse than controls in emotion recognition and all ToM tasks (p < .02). These deficits were not correlated with demographic variables or neuropsychological test performance. These findings underscore the importance of assessing ToM and facial recognition in MS, as dysfunction in these areas may impact upon social interaction and, thus, impair quality of life for both patients with MS and their families.

MSCopilot: New smartphone-based digital biomarkers correlate with Expanded Disability Status Scale scores in people with Multiple Sclerosis.

BACKGROUND: A previous clinical study showed the high specificity, sensitivity and reliability of MSCopilot, a software medical device designed by Ad Scientiam for the self-assessment of people with Multiple Sclerosis (PwMS), compared to the traditional Multiple Sclerosis Functional Composite (MSFC). We conducted further analyses to assess MSCopilot's performance with respect to the Expanded Disability Status Scale (EDSS). METHODS: The data of 116 PwMS were analysed. We studied the correlations between MSCopilot scores and the EDSS, and their ability to distinguish PwMS with high and low EDSS through a study of the distribution of the digital test scores as well as logistic regression models. The same analyses were performed using the MSFC tests. RESULTS: MSCopilot composite scores were as highly correlated to the EDSS (|r| = 0.65, p < 0.01) as their MSFC counterparts, confirming the known correlation of the MSFC with the EDSS. In a linear regression framework, the Walking digital tests have good explanatory power, especially for PwMS with EDSS > 3.5 (R²adj=0.47). The mean values of each MSCopilot subscore were significantly different between patients with an EDSS > 3.5 and others (p < 0.05), which could not be proved for the MSFC Cognition tests. MSCopilot4 was the best model to predict an EDSS score > 3.5 (AUC = 0.92). CONCLUSION: These analyses confirm the reliability of MSCopilot and show interesting correlations with the EDSS (similar results obtained with the MSFC). MSCopilot was able to highlight nuances in the different stages of MS the MSFC could not capture.

Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab.

OBJECTIVES: The study aimed to assess the potential for serum neurofilament light chain (NFL) levels to predict the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab (NTZ)-treated patients with multiple sclerosis (MS) and to discriminate PML from MS relapses. METHODS: NFL levels were measured with single molecule array (Simoa) in 4 cohorts: (1) a prospective cohort of patients with MS who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr); (2) a cohort of patients whose blood was collected during PML; (3) an independent cohort of non-PML NTZ-treated patients with serum NFL determinations at 2 years (replication cohort); and (4) a cohort of patients whose blood was collected during exacerbations. RESULTS: Serum NFL levels were significantly increased after 2 years of NTZ treatment in pre-PML patients compared with NTZ-ctr. The prognostic performance of serum NFL levels to predict PML development at 2 years was similar in the NTZ-ctr group and replication cohort. Serum NFL levels also distinguished PML from MS relapses and were 8-fold higher during PML compared with relapses. CONCLUSIONS: These results support the use of serum NFL levels in clinical practice to identify patients with relapsing-remitting MS at higher PML risk and to differentiate PML from clinical relapses in NTZ-treated patients. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that serum NFL levels can identify NTZ-treated patients with MS who will develop PML with a sensitivity of 67% and specificity of 80%.

Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome.

Importance: Younger age, oligoclonal bands, and infratentorial and spinal cord lesions are factors associated with an increased 10-year risk of clinical conversion from radiologically isolated syndrome (RIS) to multiple sclerosis (MS). Whether disease-modifying therapy is beneficial for individuals with RIS is currently unknown. Objectives: To evaluate the 2-year risk of a clinical event (onset of clinical symptoms of MS) prospectively, identify factors associated with developing an early clinical event, and simulate the sample size needed for a phase III clinical trial of individuals with RIS meeting 2009 RIS criteria. Design, Setting, and Participants: This cohort study used data on prospectively followed-up individuals with RIS identified at 1 of 26 tertiary centers for MS care in France that collect data for the Observatoire Français de la Sclérose en Plaques database. Participants were aged 10 to 80 years with 2 or more magnetic resonance imaging (MRI) scans after study entry and an index scan after 2000. All diagnoses were validated by an expert group, whose review included a double centralized MRI reading. Data were analyzed from July 2020 to January 2021. Exposure: Diagnosis of RIS. Main Outcomes and Measures: Risk of clinical event and associated covariates at index scan were analyzed among all individuals with RIS. Time to the first clinical event was compared by covariates, and sample size estimates were modeled based on identified risk factors. Results: Among 372 individuals with RIS (mean [SD] age at index MRI scan, 38.6 [12.1] years), 354 individuals were included in the analysis (264 [74.6%] women). A clinical event was identified among 49 patients (13.8%) within 2 years, which was associated with an estimated risk of conversion of 19.2% (95% CI, 14.1%-24.0%). In multivariate analysis, age younger than 37 years (hazard ratio [HR], 4.04 [95% CI, 2.00-8.15]; P < .001), spinal cord lesions (HR, 5.11 [95% CI, 1.99-13.13]; P = .001), and gadolinium-enhancing lesions on index scan (HR, 2.09 [95% CI, 1.13-3.87]; P = .02) were independently associated with an increased risk of conversion to MS. Having 2 factors at the time of the index MRI scan was associated with a risk of 27.9% (95% CI, 13.5%-39.9%) of a seminal event within 2 years, increasing to 90.9% (95% CI, 41.1%-98.6%) for individuals with all 3 factors (3 risk factors vs none: HR, 23.34 [95% CI, 9.08-59.96]; P < .001). Overall, with 80% power to detect an effect size of 60% within 24 months, a total of 160 individuals with RIS were needed assuming an event rate of 20%. Conclusions and Relevance: This study found that age younger than age 37 years, spinal cord involvement, and gadolinium-enhancing lesions on index MRI scan were associated with earlier clinical disease and relevant to the number of enrolled patients needed to detect a potential treatment effect.

[Increased plasma C-reactive protein in a pregnant woman with multiple sclerosis: corticotherapy or not ?]. / Augmentation de la protéine C-réactive chez une femme enceinte atteinte de sclérose en plaques : corticothérapie ou non ?

We report the case of a 26 years old pregnant woman at 17 weeks amenorrhea, suffering from multiple sclerosis (MS) for 6 years, hospitalized for a relapse. Treatment of MS relapses is based on high dose corticosteroid infusions, A current infection would represent a contra-indication to this treatment. In our patient, C-reactive protein (CRP) levels were moderately increased (38 mg/L). This raised the question of the physiological CRP levels in pregnant woman. After reviewing the literature, we noticed that increased CRP levels may be found in normal pregnancy, however no consensual cut-off value is admitted up to date. Procalcitonin measurement may contribute to therapeutical decision, even if increased levels have also been reported during normal pregnancy.

Reasons for switching to fingolimod in patients relapsing-remitting multiple sclerosis in France: the ESGILE study.

BACKGROUND: Timely treatment switching is an important strategy in optimising management of patients with relapsing remitting multiple sclerosis (RRMS). Patient preferences, as well as clinical benefit, may contribute to the switch decision. Information on reasons determining switching choices and on outcome according to the reason for switching is scarce. Study objectives were to describe the consequences of switching to fingolimod in terms of clinical improvement according to the reasons underlying the switch and to evaluate treatment acceptability from the patient's perspective. METHODS: This prospective observational study was conducted by 71 neurologists in France and included patients with RRMS switching to fingolimod following ≥6 months treatment with a first-line disease modifying treatment (DMT). Reasons for switching were documented. Patients were evaluated at inclusion and 12 months after initiating fingolimod. Physicians documented clinical status by relapse activity, disability (EDSS) at each visit and improvement with the Clinical Global Impression - Change (CGI-C) at Month 12. Patients rated improvement at Month 12 with the Patient Global Impression - Change (PGI-C) and treatment acceptability with the ACCEPT® questionnaire. Adverse events reported during fingolimod treatment were documented. RESULTS: Overall 232 patients were recruited of whom 190 could be analysed. Multiple reasons for switching were frequently given; 113 patients (59.4%) switched from a first-line injectable DMT. Switching was motivated by disease worsening in 161 patients (84.7%), tolerability in 35 (18.4%) and patient preference in 58 (30.5%). During the follow-up period, 38 patients (20.0%) experienced at least one exacerbation. The mean EDSS score was stable (2.0 ± 1.3 at inclusion; 2.0 ± 1.5 at M12). With the CGI-C, 67 patients (38.7%) were considered improved and 23 (13.3%) worsened. Although no obvious differences in CGI-C ratings were observed as a function of the reason for switching, when patient preferences entered into the decision, the proportion of patients considered minimally improved was somewhat higher (37.7%) and the proportion considered unchanged somewhat lower (41.5%). With the PGI-C, more patients rated themselves improved than were rated as improved by the physician: of 64 patients rated as 'no change' on the CGI-C, 21 (32.8%) rated themselves as 'improved' and 10 (15.6%) as 'worsened'. The overall level of agreement between the two measures was moderate (κ = 0.48 [95% CI: 0.35 - 0.60]). The mean general treatment acceptability score on the ACCEPT® questionnaire was 42.7 [95%CI: 34.5 - 50.9] at inclusion (reflecting acceptability of the previous DMT) and 64.6 [95%CI: 57.6 - 71.6] at M12 (reflecting acceptability of fingolimod). Mean dimension scores ranged from 36.7 for effectiveness to 72.2 for medication inconvenience at inclusion and from 63.4 for effectiveness to 96.8 for medication inconvenience at M12. The frequency and nature of reported adverse events was consistent with the well-characterised safety profile of fingolimod. CONCLUSION: Most patients switching from a first DMT to fingolimod do so due to persistent disease activity during the initial treatment, although patient preferences are also important. Switching is followed by a reduction in disease activity, perceived improvement in the clinical state of the patient and improved acceptability of treatment.