Neurocentre Magendie


Tél : 33(0)5 57 57 37 41
Envoyer un email

14 publication(s) depuis Mai 2012:

Trier par

* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en

30/01/2018 | Neuroimage   IF 5.8
Deciphering the microstructure of hippocampal subfields with in vivo DTI and NODDI: Applications to experimental multiple sclerosis.
Crombe A, Planche V, Raffard G, Bourel J, Dubourdieu N, Panatier A, Fukutomi H, Dousset V, Oliet S, Hiba B, Tourdias T

The hippocampus contains distinct populations of neurons organized into separate anatomical subfields and layers with differential vulnerability to pathological mechanisms. The ability of in vivo neuroimaging to pinpoint regional vulnerability is especially important for better understanding of hippocampal pathology at the early stage of neurodegenerative disorders and for monitoring future therapeutic strategies. This is the case for instance in multiple sclerosis whose neurodegenerative component can affect the hippocampus from the early stage. We challenged the capacity of two models, i.e. the classical diffusion tensor imaging (DTI) model and the neurite orientation dispersion and density imaging (NODDI) model, to compute quantitative diffusion MRI that could capture microstructural alterations in the individual hippocampal layers of experimental-autoimmune encephalomyelitis (EAE) mice, the animal model of multiple sclerosis. To achieve this, the hippocampal anatomy of a healthy mouse brain was first explored ex vivo with high resolution DTI and NODDI. Then, 18 EAE mice and 18 control mice were explored 20 days after immunization with in vivo diffusion MRI prior to sacrifice for the histological quantification of neurites and glial markers in each hippocampal layer. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) maps were computed from the DTI model while the orientation dispersion index (ODI), the neurite density index (NDI) and the volume fraction of isotropic diffusivity (isoVF) maps were computed from the NODDI model. We first showed in control mice that color-coded FA and ODI maps can delineate three main hippocampal layers. The quantification of FA, AD, RD, MD, ODI, NDI and isoVF presented differences within these 3 layers, especially within the molecular layer of the dentate gyrus which displayed a specific signature based on a combination of AD (or MD), ODI and NDI. Then, the comparison between EAE and control mice showed a decrease of AD (p=0.036) and of MD (p=0.033) selectively within the molecular layer of EAE mice while NODDI indices did not present any difference between EAE and control mice in any layer. Histological analyses confirmed the differential vulnerability of the molecular layer of EAE mice that exhibited decreased dendritic length and decreased dendritic complexity together with activated microglia. Dendritic length and intersections within the molecular layer were independent contributors to the observed decrease of AD (R(2)=0.37 and R(2)=0.40, p<0.0001) and MD (R(2)=0.41 and R(2)=0.42, p<0.0001). We therefore identified that NODDI maps can help to highlight the internal microanatomy of the hippocampus but NODDI still presents limitations in grey matter as it failed to capture selective dendritic alterations occurring at early stages of a neurodegenerative disease such as multiple sclerosis, whereas DTI maps were significantly altered.

13/01/2018 | Hum Brain Mapp   IF 4.5
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.

15/11/2017 | J Neurol Sci   IF 2.3
Improvement of quality of life and its relationship with neuropsychiatric outcomes in patients with multiple sclerosis starting treatment with natalizumab: A 3-year follow-up multicentric study.
Planche V, Moisset X, Morello R, Dumont E, Gibelin M, Charre-Morin J, Saubusse A, Mondou A, Reuter F, Defer G, Pelletier J, Brochet B, Clavelou P

BACKGROUND: Health-related quality of life (HRQoL) is impaired in multiple sclerosis (MS) but can be improved by disease-modifying therapies such as natalizumab. However, the predictive factors and neuropsychiatric correlates of HRQoL improvement are unknown. METHODS: In this study, 48 patients with relapsing-remitting MS were included in a 3-year open-label, single group, multicenter, clinical trial (NCT01392872). HRQoL was measured by the disease-specific MusiQoL questionnaire, together with physical disability, cognition, fatigue, anxiety and depression scores at baseline, 6months, 12months, 18months and 36months after starting natalizumab therapy. RESULTS: Compared to baseline, global HRQoL, as measured with the index of the MusiQoL, was significantly increased 6months after the beginning of natalizumab therapy, with medium effect-size (58.6+/-16.2 vs 69.8+/-18.9, p<0.001, Cohen's d=0.63). This improvement was maintained over time for up to 3years and mainly concerned activity of daily living, psychological well-being, symptoms and coping (p<0.001 for every dimensions). The variation of global HRQoL after 3years was negatively correlated with the variation of fatigue score (r=-0.44, p=0.015). Furthermore, a higher fatigue score at baseline was correlated with improvement in global HRQoL 3years afterwards (r=0.34, p=0.041), independently of age, educational level, disease duration and disability at baseline (beta=2.45, p=0.020). Disability at baseline, cognitive impairment, anxiety and depression failed to predict or correlate with global HRQoL improvement in multivariate analyses. CONCLUSION: Natalizumab improved HRQoL quickly and sustainably in patients with relapsing-remitting MS. In terms of HRQoL, natalizumab seems to benefit mostly patients with more marked fatigue at baseline.

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.

2017 | PLoS ONE   IF 2.8
Microstructural analyses of the posterior cerebellar lobules in relapsing-onset multiple sclerosis and their implication in cognitive impairment.
Moroso A, Ruet A, Lamargue-Hamel D, Munsch F, Deloire M, Coupe P, Charre-Morin J, Saubusse A, Ouallet JC, Planche V, Tourdias T, Dousset V, Brochet B

BACKGROUND: The posterior cerebellar lobules seem to be the anatomical substrate of cognitive cerebellar processes, but their microstructural alterations in multiple sclerosis (MS) remain unclear. OBJECTIVES: To correlate diffusion metrics in lobules VI to VIIIb in persons with clinically isolated syndrome (PwCIS) and in cognitively impaired persons with MS (CIPwMS) with their cognitive performances. METHODS: Sixty-nine patients (37 PwCIS, 32 CIPwMS) and 36 matched healthy subjects (HS) underwent 3T magnetic resonance imaging, including 3D T1-weighted and diffusion tensor imaging (DTI). Fractional anisotropy (FA) and mean diffusivity (MD) were calculated within each lobule and in the cerebellar peduncles. We investigated the correlations between cognitive outcomes and the diffusion parameters of cerebellar sub-structures and performed multiple linear regression analysis to predict cognitive disability. RESULTS: FA was generally lower and MD was higher in the cerebellum and specifically in the vermis Crus II, lobules VIIb and VIIIb in CIPwMS compared with PwCIS and HS. In hierarchical regression analyses, 31% of the working memory z score variance was explained by FA in the left lobule VI and in the left superior peduncle. Working memory was also associated with MD in the vermis Crus II. FA in the left lobule VI and right VIIIa predicted part of the information processing speed (IPS) z scores. CONCLUSION: DTI indicators of cerebellar microstructural damage were associated with cognitive deficits in MS. Our results suggested that cerebellar lobular alterations have an impact on attention, working memory and IPS.

12/11/2016 | Brain Behav Immun   IF 6
Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.
Planche V, Panatier A, Hiba B, Ducourneau EG, Raffard G, Dubourdieu N, Maitre M, Leste-Lasserre T, Brochet B, Dousset V, Desmedt A, Oliet SH, Tourdias T

Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis.

27/10/2016 | J Neurol Neurosurg Psychiatry   IF 7.3
Posterior lobules of the cerebellum and information processing speed at various stages of multiple sclerosis.
Moroso A, Ruet A, Lamargue-Hamel D, Munsch F, Deloire M, Coupe P, Ouallet JC, Planche V, Moscufo N, Meier DS, Tourdias T, Guttmann CR, Dousset V, Brochet B

BACKGROUND: Cerebellar damage has been implicated in information processing speed (IPS) impairment associated with multiple sclerosis (MS) that might result from functional disconnection in the frontocerebellar loop. Structural alterations in individual posterior lobules, in which cognitive functioning seems preponderant, are still unknown. Our aim was to investigate the impact of grey matter (GM) volume alterations in lobules VI to VIIIb on IPS in persons with clinically isolated syndrome (PwCIS), MS (PwMS) and healthy subjects (HS). METHODS: 69 patients (37 PwCIS, 32 PwMS) and 36 HS underwent 3 T MRI including 3-dimensional T1-weighted MRIs. Cerebellum lobules were segmented using SUIT V.3.0 to estimate their normalised GM volume. Neuropsychological testing was performed to assess IPS and main cognitive functions. RESULTS: Normalised GM volumes were significantly different between PwMS and HS for the right (p<0.001) and left lobule VI (p<0.01), left crus I, right VIIb and entire cerebellum (p<0.05 for each comparison) and between PwMS and PwCIS for all lobules in subregions VI and left crus I (p<0.05). IPS, attention and working memory were impaired in PwMS compared with PwCIS. In the whole population of patients (PwMS and PwCIS), GM loss in vermis VI (R2=0.36; p<0.05 when considering age and T2 lesion volume as covariates) were associated with IPS impairment. CONCLUSIONS: GM volume decrease in posterior lobules (especially vermis VI) was associated with reduced IPS. Our results suggest a significant impact of posterior lobules pathology in corticocerebellar loop disruption resulting in automation and cognitive optimisation lack in MS. TRIAL REGISTRATION: Clinicaltrail NCT01207856, NCT01865357; Pre-results.

25/10/2016 | Mult Scler   IF 4.8
Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis.
Planche V, Ruet A, Coupe P, Lamargue-Hamel D, Deloire M, Pereira B, Manjon JV, Munsch F, Moscufo N, Meier DS, Guttmann CR, Dousset V, Brochet B, Tourdias T

OBJECTIVE: We investigated whether diffusion tensor imaging (DTI) could reveal early hippocampal damage and clinically relevant correlates of memory impairment in persons with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: A total of 37 persons with CIS, 32 with MS and 36 controls prospectively included from 2011 to 2014 were tested for cognitive performances and scanned with 3T-magnetic resonance imaging (MRI) to assess volumetric and DTI changes within the hippocampus, whole brain volume and T2-lesion load. RESULTS: While there was no hippocampal atrophy in the CIS group, hippocampal fractional anisotropy (FA) was significantly decreased compared to controls. Decrease in hippocampal FA together with increased mean diffusivity (MD) was even more prominent in MS patients. In CIS, hippocampal MD was correlated with episodic verbal memory performance (r = -0.57, p = 0.0002 and odds ratio (OR) = 0.058, 95% confidence interval (CI) = 0.0057-0.59, p = 0.016 adjusted for age, gender, depression and T2-lesion load), but not with cognitive tasks unrelated to hippocampal functions. Hippocampal MD was the only variable discriminating memory-impaired from memory-preserved persons with CIS (area under the curve (AUC) = 0.77, sensitivity = 90.0%, specificity = 70.3%, positive predictive value (PPV) = 52.9%, negative predictive value (NPV) = 95.0%). CONCLUSION: DTI alterations within the hippocampus might reflect early neurodegenerative processes that are correlated with episodic memory performance, discriminating persons with CIS according to their memory status.

2016 | Eur Neurol   IF 1.7
Who Performs Lumbar Puncture, How Many Do They Perform, How and Why? A Retrospective Study of 6,594 Cases.
Moisset X, Ruet A, Brochet B, Planche V, Jaffeux P, Gilleron V, Ong N, Clavelou P

BACKGROUND: The number and indications of lumbar punctures (LPs) performed nowadays are unknown. The primary aim of this work was to report the number of LPs performed in each of the departments of 2 French university hospitals, their indications and the prevalence of atraumatic spinal needles used. METHODS: We carried out a retrospective study of all the LPs performed in 2014. The clinical department in which the intervention was performed and the final diagnosis was made from the Medical Information Department. The type of needles (cutting or atraumatic) used during the study period was also available. RESULTS: In 2014, 6,594 LPs were performed. Overall, 80% were performed for diagnostic purposes. Twenty percent of these LPs were performed in the Neurology Department and were usually carried out at routine check-ups. Overall, atraumatic needles were used in 8.0% of cases. Overall, 1.4 LPs per 100 hospital stays were performed and 0.8 LP for 100 Emergency department admissions. CONCLUSION: LP is a routine procedure for many clinicians and although neurologists perform the largest number of LPs, they are doing only one fifth of all procedures. Atraumatic needles are underused.

BACKGROUND AND PURPOSE: Few studies have investigated the differences in cognitive skills between the three subtypes of multiple sclerosis (MS) and they confounded the course of the disease with the duration of the disease and the physical disability. Moreover, they were not population based. METHODS: This was a retrospective analysis of cognitive testing from the database of a French programme for MS care. The pattern and the frequency of cognitive impairment in secondary progressive (SP), primary progressive (PP) and late relapsing-remitting (LRR, disease duration of more than 10 years) MS were compared. RESULTS: A total of 101 patients with MS (41 LRRMS, 37 SPMS, 23 PPMS) were included. 63.0% had a significant cognitive impairment. After controlling for age, sex, Expanded Disability Status Scale, disease duration and education level, patients with SPMS were at least 2-fold more frequently impaired than patients with LLRMS in information processing speed (P = 0.005), executive functions (P = 0.04), verbal fluency (P = 0.02), verbal episodic memory (P = 0.04), working memory (P = 0.02) and visuospatial construction (P = 0.01). The number of patients with at least one or two deficient cognitive domain(s) was higher in the SPMS group than in the LRRMS group (P = 0.002 and P < 0.001). Patients with PPMS were more frequently impaired in verbal fluency (P = 0.046) than patients with LRRMS and they more often presented at least one impaired cognitive domain (P = 0.03). SPMS and PPMS groups differed only for visuospatial construction (P = 0.02). CONCLUSION: In this population-based study, patients with a progressive subtype of MS were more frequently and more severely impaired than patients with RRMS, even after more than 10 years of disease.