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Aurélie RUET

Senior Teacher/Researcher

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43 publication(s) since Mars 2010:

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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 5.8
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.

11/2017 | mult scler relat disord   IF 2.3
Treating asymptomatic bacteriuria before immunosuppressive therapy during multiple sclerosis: Should we do it?
Rouzaud C, Hautecoeur P, Donze C, Heinzlef O, Dinh A, Creange A, Abdullatif A, Audouin B, Tourbah A, Berger E, Bourre B, Brochet B, Mekies C, Cabre P, Papeix C, Casez O, Brassat D, Defer G, Derache N, De Seze J, Dive D, LePage E, Fromont A, Gouider R, Edan G, Pelletier J, Grimaud J, Guennoc AM, Camdessanche JP, Kwiatkowski A, Laplaud D, Lebrun C, Debouverie M, Coustans M, Gout O, La Rochelle OA, Heinzlef O, Ouallet JC, Cavelou P, Hautecoeur P, Labauge P, Vermersch P, Wiertlewski S, Vukusic S, Marignier R, Schluep M, Seeldrayers P, Slassi I, Stankoff B, Thaite F, Moreau T, Thouvenot E, Zephir H, Ciron J, Collongues N, Kerschen P, Cohen M, Gueguen A, Mathey G, Carra C, Bernady P, Faucheux JM, Planque E, Donze C, Ruet A, Mouzawakh C, Pittion S


10/2017 | J Neurol   IF 3.4
Optic neuritis in patients with anti-MOG antibodies spectrum disorder: MRI and clinical features from a large multicentric cohort in France.
Biotti D, Bonneville F, Tournaire E, Ayrignac X, Dalliere CC, Mahieu L, Vignal C, Dulau C, Brochet B, Ruet A, Ouallet JC, Gout O, Heran F, Menjot de Champfleur N, Tourdias T, Deneve M, Labauge P, Deschamps R


10/2017 | Ann Endocrinol (Paris)   IF 0.9

Ferriere A, Kerlan V, Tabarin A

The 2017 Endocrine Society annual meeting included several communications and debates on the conservative adrenal surgery in bilateral hereditary pheochromocytomas (BHP), bilateral adrenal macronodular hyperplasia (BAMH) and primary hyperaldosteronism (PHA). The general principle is to preserve a part of the adrenal cortex to prevent the occurrence of a definitive adrenal insufficiency. In BHP, cortical sparing surgery allows more than 50% of patients to maintain normal corticotropic function at 10 years with a low recurrence rate (~ 10%). Since the adrenal medulla cannot be removed entirely, recurrence seems inevitable and long-term follow-up is essential. Individual risk of malignancy must be taken into account. In BAMH responsible for Cushing syndrome, unilateral adrenalectomy induces a normalization of urinary free cortisol in 92 to 100% of cases and even corticotropic insufficiency in 40 to 100% of cases. This is most often transient. Late recurrences of Cushing's syndrome may occur in 13 to 60% of cases. Prolonged patient monitoring is therefore essential. In PAH with lateralized aldosterone production, minimally invasive partial adrenal surgery, which consists of removing only the adrenal adenoma visualized at TDM, allows an improvement blood pressure in about 94% of patients. However, failure or recurrence may occur. Its place therefore remains marginal in the treatment of the lateralized PAHs.

08/2017 | brain behav   IF 2.2
Pattern separation performance is decreased in patients with early multiple sclerosis.
Planche V, Ruet A, Charre-Morin J, Deloire M, Brochet B, Tourdias T

BACKGROUND: Hippocampal-dependent memory impairment is frequent and occurs early during the course of multiple sclerosis (MS). While mechanisms responsible for episodic memory dysfunction in patients with MS remain largely unknown, dentate gyrus structure has been suggested as particularly vulnerable at the early stage of the disease. If true, we hypothesized that the pattern separation component of episodic memory (a function known to be critically dependent to dentate gyrus function) would be impaired in patients with early MS (PweMS). METHODS: Thirty eight participants (19 PweMS and 19 healthy controls matched on age, gender and education level) were tested with a behavioral pattern separation task and also for information processing speed and visuospatial episodic memory. RESULTS: We report a significant decrease in pattern separation performance in PweMS compared to healthy controls (27.07 vs. 40.01, p = .030 after Holm-Bonferroni correction, d = 1.02) together with a significantly higher pattern completion rate (56.11 vs. 40.95, p = .004 after Holm-Bonferroni correction, d = 1.07) while no difference was found among groups for information processing speed and 'global' visuospatial episodic memory regarding learning, long-term recall or recognition. CONCLUSION: Our results suggest that behavioral pattern separation task can detect subtle memory decline in patients with MS and argue for early dentate gyrus dysfunction during the course of the disease.

08/2017 | Ann Neurol   IF 9.9
Matrix metalloproteinase 9 is decreased in natalizumab-treated multiple sclerosis patients at risk for progressive multifocal leukoencephalopathy.
Fissolo N, Pignolet B, Matute-Blanch C, Trivino JC, Miro B, Mota M, Perez-Hoyos S, Sanchez A, Vermersch P, Ruet A, de Seze J, Labauge P, Vukusic S, Papeix C, Almoyna L, Tourbah A, Clavelou P, Moreau T, Pelletier J, Lebrun-Frenay C, Montalban X, Brassat D, Comabella M

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.