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Aurélie RUET

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38 publication(s) since Mars 2010:

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05/2019 | Mult Scler   IF 5.3
Efficacy of rituximab in refractory RRMS.
Durozard P, Maarouf A, Boutiere C, Ruet A, Brochet B, Vukusic S, Carra-Dalliere C, Labauge P, Mathey G, Debouverie M, Papeix C, Maillart E, Lubetzki C, Bensa C, Gout O, Giannesini C, Stankoff B, Ciron J, Brassat D, Pelletier J, Rico Lamy A, Audoin B

OBJECTIVE: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). METHODS: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts. RESULTS: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5-6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4-18.4) months after rituximab ( p < 0.0001). CONCLUSION: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

23/04/2019 | J Neurol   IF 3.8
Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions.
Ayrignac X, Rigau V, Lhermitte B, Vincent T, de Champfleur NM, Carra-Dalliere C, Charif M, Collongues N, de Seze J, Hebbadj S, Ahle G, Oesterle H, Cotton F, Durand-Dubief F, Marignier R, Vukusic S, Taithe F, Cohen M, Guennoc AM, Kerbrat A, Edan G, Carsin-Nicol B, Allou T, Sablot D, Thouvenot E, Ruet A, Magy L, Boncoeur-Martel MP, Labauge P, Kremer S

BACKGROUND: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. OBJECTIVES: Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. METHODS: We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. RESULTS: Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Balo-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1-12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. DISCUSSION: Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.

The relationships between cognitive impairment that exist during the clinical course of multiple sclerosis (MS) remain poorly described. The effect of disease duration has been studied in a few longitudinal cohorts and some cross-sectional studies that suggest that cognitive deficits tend to extend with disease duration. However, the effect of disease duration seems to be confounded by the effect of age. At the pre-clinical stage, cognitive deficits have been observed in patients with radiologically isolated syndromes, and their profile is similar than in clinically isolated syndromes (CIS) and relapsing-remitting MS (RRMS). The frequency of cognitive impairment tends to be higher in RRMS than in CIS. In these phenotypes, slowness of information processing speed (IPS) and episodic verbal and visuo-spatial memory deficits are frequently observed, but executive functions, and in particular verbal fluency, could also be impaired. More frequent and severe deficits are reported in SPMS than in RRMS with more severe deficits for memory tests, working memory and IPS. Similarly to what is observed in SPMS, patients with primary progressive MS (PPMS) present with a wide range of cognitive deficits in IPS, attention, working memory, executive functions, and verbal episodic memory with more tests and domains impaired than RRMS patients. Altogether these data suggested that not only the duration of the disease and age play an important role in the cognitive profile of patients, but also the phenotype itself, probably because of its specific pathological mechanism.

27/11/2018 | Mult Scler   IF 5.3
Longitudinal study of functional brain network reorganization in clinically isolated syndrome.
Koubiyr I, Deloire M, Besson P, Coupe P, Dulau C, Pelletier J, Tourdias T, Audoin B, Brochet B, Ranjeva JP, Ruet A

BACKGROUND:: There is a lack of longitudinal studies exploring the topological organization of functional brain networks at the early stages of multiple sclerosis (MS). OBJECTIVE:: This study aims to assess potential brain functional reorganization at rest in patients with CIS (PwCIS) after 1 year of evolution and to characterize the dynamics of functional brain networks at the early stage of the disease. METHODS:: We prospectively included 41 PwCIS and 19 matched healthy controls (HCs). They were scanned at baseline and after 1 year. Using graph theory, topological metrics were calculated for each region. Hub disruption index was computed for each metric. RESULTS:: Hub disruption indexes of degree and betweenness centrality were negative at baseline in patients ( p < 0.05), suggesting brain reorganization. After 1 year, hub disruption indexes for degree and betweenness centrality were still negative ( p < 0.00001), but such reorganization appeared more pronounced than at baseline. Different brain regions were driving these alterations. No global efficiency differences were observed between PwCIS and HCs either at baseline or at 1 year. CONCLUSION:: Dynamic changes in functional brain networks appear at the early stages of MS and are associated with the maintenance of normal global efficiency in the brain, suggesting a compensatory effect.

06/2018 | Rev Neurol (Paris)   IF 1.8
Update on pediatric-onset multiple sclerosis.
Ruet A

Pediatric-onset multiple sclerosis (POMS) has distinctive features compared with adult-onset multiple sclerosis (AOMS), and warrants caution despite being a rare form of MS. POMS diagnostic criteria are somewhat different from those used in AOMS, with acute disseminated encephalomyelitis being a key differential diagnosis of MS in children. Other differential diagnoses that have to be ruled out before diagnosing MS include demyelinating syndromes, autoimmune and systemic pathologies, and infectious, genetic, metabolic and neoplastic diseases. Compared with AOMS, POMS has several different clinical, biological and imaging findings. At onset, high-level inflammatory activity is mainly reported, and patients with POMS are also at high risk of developing early physical disabilities and early cognitive impairment. Yet, treating patients with POMS is challenging due to a lack of randomized controlled trials. Some of the disease-modifying drugs currently prescribed are analogous to therapies used in adults, and are associated with good tolerability in pediatric patients. However, a few clinical trials dedicated to POMS are now in progress, and the future outlook is to improve the long-term prognosis of POMS patients with early effective and safe treatments.

BACKGROUND: Cognitive impairment (CI) is frequent in patients with multiple sclerosis (PwMS) and could negatively affect family social and vocational activities. Detecting CI is clinically relevant, so the emerging question is the strategy for assessing cognition in MS. OBJECTIVE: An update on cognitive assessment in PwMS with use of standard neuropsychological (NP) tests and ecological tools. RESULTS: The minimal cognitive assessment in MS should include at least NP tests assessing information processing speed (IPS) and verbal and visuospatial episodic memory. The IPS could be easily and quickly evaluated with symbol digit substitution tests by using paper for the oral version of the Symbol Digit Modalities Test or a laptop for the Computerised Speed Cognitive Test. The comprehensive NP battery must be performed by a qualified neuropsychologist to adequately characterize the extent and severity of CI in PwMS. The quiet and controlled environment used for this standardized assessment could be a limitation for generalizing the results because it does not reflect real daily life conditions. Thus, this context could decrease the ability to detect some cognitive deficits that could occur only in more complex situations. Thus, ecological evaluation seems a complementary and promising approach for detecting cognitive abnormalities in daily activities. CONCLUSION: Recent efforts have been made to detect and characterize cognitive deficits in PwMS. Some IPS and episodic memory NP tests have been validated in MS and should be proposed to patients in the clinical setting. Besides NP tests, ecological tools are becoming important for detecting cognitive dysfunction in everyday-like conditions. Further research is needed to validate relevant tools for monitoring cognition in MS and the ability to detect clinically meaningful change in longitudinal studies.

15/02/2018 | J Neurol Sci   IF 2.4
Preliminary evidence of the cerebellar role on cognitive performances in clinically isolated syndrome.
Moroso A, Ruet A, Lamargue-Hamel D, Munsch F, Deloire M, Ouallet JC, Cubizolle S, Charre-Morin J, Saubusse A, Tourdias T, Dousset V, Brochet B

BACKGROUND: Cerebellar and cognitive dysfunction can occur early in clinically isolated syndrome (CIS). Eye tracking is a reliable tool for the evaluation of both subtle cerebellar symptoms and cognitive impairment. OBJECTIVES: To investigate the early cognitive profile using neuropsychological and ocular motor (OM) testing in CIS with and without cerebellar dysfunction with OM testing compared to healthy subjects (HS). METHODS: Twenty-eight patients and 12 HC underwent OM and neuropsychological testing. Cerebellar impairment was defined by the registration of saccadic intrusions and/or at least 10% of dysmetria during ocular motor recording. Visually guided saccade (VGS), memory-guided saccade (MGS) and antisaccade (AS) paradigms were compared to neuropsychological assessments. RESULTS: The group of patients with cerebellar dysfunction (n=16) performed worse on MGS latencies and error rates, and had worse working memory, executive function and information processing speed (IPS) z scores than patients without cerebellar dysfunction. IPS was correlated with the AS error rate in all patients and with the VGS error rate and the MGS final eye position ratio in cerebellar patients. CONCLUSION: Eye tracking is a sensitive tool to assess cognitive and cerebellar dysfunctions in CIS. In CIS patients, cerebellar impairment is associated with working memory, executive functions and IPS slowness.

13/01/2018 | Hum Brain Mapp   IF 4.9
Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.
Planche V, Koubiyr I, Romero JE, Manjon JV, Coupe P, Deloire M, Dousset V, Brochet B, Ruet A, Tourdias T

BACKGROUND: Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. METHOD: We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. RESULTS: At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R(2) = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ss = 0.87, p < .05). CONCLUSION: The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance.

2018 | front neurol   IF 3.5
Differential Gray Matter Vulnerability in the 1 Year Following a Clinically Isolated Syndrome.
Koubiyr I, Deloire M, Coupe P, Dulau C, Besson P, Moroso A, Planche V, Tourdias T, Brochet B, Ruet A

Background and purpose: Whether some gray matter (GM) regions are differentially vulnerable at the early stages of MS is still unknown. The objective of this study is to investigate whether deep and cortical GM are differentially vulnerable after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: Fifty-six patients with CIS (PwCIS) and 38 healthy controls (HC) had conventional and diffusion tensor imaging (DTI) at baseline and 46 PwCIS and 20 HC were rescanned after 1 year. Deep GM (DGM) volumes, cortical thickness (CTh), and DTI metrics (FA: fractional anisotropy; MD: mean diffusivity) within these structures were calculated for each participant at each time-point and compared between PwCIS and HC. Linear regression models were used to investigate whether baseline DTI parameters could predict GM volume loss over time. Results: At baseline, GM volumes did not differ between PwCIS and HC, but hippocampal MD was higher in PwCIS than HC (p < 0.01). Over 1 year, GM alterations became more widespread with putamen and hippocampus volumes decreasing in PwCIS (p < 0.01), and cortical thinning in different parts of the cortex along with a significant increase of MD. Hippocampus MD at baseline could predict its volume loss (R (2) = 0.159; p < 0.05) and cortical thinning was associated to microstructural damage (Spearman's rho ranging from -0.424 to -0.603 with p < 0.003). Conclusion: Along with MS being a diffuse inflammatory disease, GM showed a differential vulnerability at the early stage spreading from hippocampus to the cortex. Hippocampus volume loss could be predicted by its MD at baseline.

12/2017 | Neuroimage   IF 5.4
Performance of five research-domain automated WM lesion segmentation methods in a multi-center MS study.
de Sitter A, Steenwijk MD, Ruet A, Versteeg A, Liu Y, van Schijndel RA, Pouwels PJW, Kilsdonk ID, Cover KS, van Dijk BW, Ropele S, Rocca MA, Yiannakas M, Wattjes MP, Damangir S, Frisoni GB, Sastre-Garriga J, Rovira A, Enzinger C, Filippi M, Frederiksen J, Ciccarelli O, Kappos L, Barkhof F, Vrenken H

BACKGROUND AND PURPOSE: In vivoidentification of white matter lesions plays a key-role in evaluation of patients with multiple sclerosis (MS). Automated lesion segmentation methods have been developed to substitute manual outlining, but evidence of their performance in multi-center investigations is lacking. In this work, five research-domain automated segmentation methods were evaluated using a multi-center MS dataset. METHODS: 70 MS patients (median EDSS of 2.0 [range 0.0-6.5]) were included from a six-center dataset of the MAGNIMS Study Group ( which included 2D FLAIR and 3D T1 images with manual lesion segmentation as a reference. Automated lesion segmentations were produced using five algorithms: Cascade; Lesion Segmentation Toolbox (LST) with both the Lesion growth algorithm (LGA) and the Lesion prediction algorithm (LPA); Lesion-Topology preserving Anatomical Segmentation (Lesion-TOADS); and k-Nearest Neighbor with Tissue Type Priors (kNN-TTP). Main software parameters were optimized using a training set (N = 18), and formal testing was performed on the remaining patients (N = 52). To evaluate volumetric agreement with the reference segmentations, intraclass correlation coefficient (ICC) as well as mean difference in lesion volumes between the automated and reference segmentations were calculated. The Similarity Index (SI), False Positive (FP) volumes and False Negative (FN) volumes were used to examine spatial agreement. All analyses were repeated using a leave-one-center-out design to exclude the center of interest from the training phase to evaluate the performance of the method on 'unseen' center. RESULTS: Compared to the reference mean lesion volume (4.85 +/- 7.29 mL), the methods displayed a mean difference of 1.60 +/- 4.83 (Cascade), 2.31 +/- 7.66 (LGA), 0.44 +/- 4.68 (LPA), 1.76 +/- 4.17 (Lesion-TOADS) and -1.39 +/- 4.10 mL (kNN-TTP). The ICCs were 0.755, 0.713, 0.851, 0.806 and 0.723, respectively. Spatial agreement with reference segmentations was higher for LPA (SI = 0.37 +/- 0.23), Lesion-TOADS (SI = 0.35 +/- 0.18) and kNN-TTP (SI = 0.44 +/- 0.14) than for Cascade (SI = 0.26 +/- 0.17) or LGA (SI = 0.31 +/- 0.23). All methods showed highly similar results when used on data from a center not used in software parameter optimization. CONCLUSION: The performance of the methods in this multi-center MS dataset was moderate, but appeared to be robust even with new datasets from centers not included in training the automated methods.