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Journal Article

  • MAAROUF A., AUDOIN B., PARIOLLAUD F., GHERIB S., RICO A., SOULIER E., CONFORT-GOUNY S., GUYE M., SCHAD L., PELLETIER J., RANJEVA J. - P., ZAARAOUI W. “Increased total sodium concentration in gray matter better explains cognition than atrophy in MS.”. Neurology [En ligne]. 17 January 2017. Vol. 88, n°3, p. 289-295. Disponible sur : < > (consulté le 18 August 2017)
    Résumé : Objective: To investigate whether brain total sodium accumulation assessed by 23Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS). Methods: Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using 23Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and 1H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction). Results: The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0–4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively. Conclusions: This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex.
    Mots-clés : crmbm, snc.


Journal Article

  • FAIVRE A., ROBINET E., GUYE M., ROUSSEAU C., MAAROUF A., LE TROTER A., ZAARAOUI W., RICO A., CRESPY L., SOULIER E., CONFORT-GOUNY S., PELLETIER J., ACHARD S., RANJEVA J. - P., AUDOIN B. “Depletion of brain functional connectivity enhancement leads to disability progression in multiple sclerosis: A longitudinal resting-state fMRI study.”. Multiple Sclerosis (Houndmills, Basingstoke, England) [En ligne]. November 2016. Vol. 22, n°13, p. 1695-1708. Disponible sur : < > (consulté le no date)
    Résumé : BACKGROUND: The compensatory effect of brain functional connectivity enhancement in relapsing-remitting multiple sclerosis (RRMS) remains controversial. OBJECTIVE: To characterize the relationships between brain functional connectivity changes and disability progression in RRMS. METHODS: Long-range connectivity, short-range connectivity, and density of connections were assessed using graph theoretical analysis of resting-state functional magnetic resonance imaging (fMRI) data acquired in 38 RRMS patients (disease duration: 120 ± 32 months) and 24 controls. All subjects were explored at baseline and all patients and six controls 2 years later. RESULTS: At baseline, levels of long-range and short-range brain functional connectivity were higher in patients compared to controls. During the follow-up, decrease in connections' density was inversely correlated with disability progression. Post-hoc analysis evidenced differential evolution of brain functional connectivity metrics in patients according to their level of disability at baseline: while patients with lowest disability at baseline experienced an increase in all connectivity metrics during the follow-up, patients with higher disability at baseline showed a decrease in the connectivity metrics. In these patients, decrease in the connectivity metrics was associated with disability progression. CONCLUSION: The study provides two main findings: (1) brain functional connectivity enhancement decreases during the disease course after reaching a maximal level, and (2) decrease in brain functional connectivity enhancement participates in disability progression.
    Mots-clés : crmbm, cvs, Disability, Functional connectivity, Functional MRI, graph theory, Multiple sclerosis.


Journal Article

  • CAUCHETEUX N., MAAROUF A., GENEVRAY M., LERAY E., DESCHAMPS R., CHAUNU M. P., DAELMAN L., FERRÉ J. C., GOUT O., PELLETIER J., PIEROT L., EDAN G., TOURBAH A. “Criteria improving multiple sclerosis diagnosis at the first MRI.”. Journal of Neurology [En ligne]. 17 February 2015. Vol. 262, n°4, p. 979-987. Disponible sur : < > (consulté le 3 June 2016)
    Résumé : The introduction of the McDonald criteria has enabled earlier diagnosis of multiple sclerosis (MS). However, even with the 2010 revised criteria, nearly 50 % of patients remain classified as “possible MS” following the first MRI. The present study aimed to demonstrate that time to MS diagnosis could be shorter than 2010 revised criteria, and established after a single early MRI in most patients with the association of the symptomatic lesion and at least one suggestive asymptomatic lesion. We also evaluated the short-term predictive capacity of an individual suggestive lesion on disease activity. We analyzed initial MRI results from 146 patients with MS from a multicenter retrospective study. Visualization of the symptomatic lesion was used as a primary criterion. Secondary criteria included one suggestive lesion (SL) aspect or topography on MRI, or one non-specific lesion associated with positive CSF. The proposed criteria led to a positive diagnosis of MS in 100 % of cases, from information available from the time of the first MRI for 145 patients (99.3 %). At least one SL was observed for 143 patients (97.9 %), and positive CSF for the 3 others. Compared to the McDonald criteria, the proposed criteria had 100 % sensitivity, with a significantly shorter mean time to reach a positive diagnosis. Furthermore, the simultaneous presence of corpus callosum, temporal horn, and ovoid lesions was associated with radiological or clinical activity after a year of follow-up. The proposed diagnostic criteria are easy to apply, have a good sensitivity, and allow an earlier diagnosis than the 2010 McDonald criteria. Nevertheless, prospective studies are needed to establish specificity and to confirm these findings.
    Mots-clés : Diagnosis, Multiple sclerosis, Neurology, Neuroradiology, Neurosciences, Prognosis, Relapsing-remitting, snc.

  • COMMOWICK O., MAAROUF A., FERRÉ J. - C., RANJEVA J. - P., EDAN G., BARILLOT C. “Diffusion MRI abnormalities detection with orientation distribution functions: A multiple sclerosis longitudinal study.”. Medical Image Analysis [En ligne]. 2015. Vol. 22, n°1, p. 114-123. Disponible sur : < > (consulté le 17 April 2015)
    Résumé : We propose a new algorithm for the voxelwise analysis of orientation distribution functions between one image and a group of reference images. It relies on a generic framework for the comparison of diffusion probabilities on the sphere, sampled from the underlying models. We demonstrate that this method, combined to dimensionality reduction through a principal component analysis, allows for more robust detection of lesions on simulated data when compared to classical tensor-based analysis. We then demonstrate the efficiency of this pipeline on the longitudinal comparison of multiple sclerosis patients at an early stage of the disease: right after their first clinically isolated syndrome (CIS) and three months later. We demonstrate the predictive value of ODF-based scores for the early detection of lesions that will appear or heal.
    Mots-clés : Diffusion MRI, Orientation distribution functions, Patient to controls comparison, snc.

  • MAAROUF A., FERRÉ J. - C., ZAARAOUI W., LE TROTER A., BANNIER E., BERRY I., GUYE M., PIEROT L., BARILLOT C., PELLETIER J., TOURBAH A., EDAN G., AUDOIN B., RANJEVA J. - P. “Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in clinically isolated syndrome.”. Multiple Sclerosis (Houndmills, Basingstoke, England) [En ligne]. 9 October 2015. Disponible sur : < > (consulté le no date)
    Résumé : 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.
    Mots-clés : clinically isolated syndrome, crmbm, macrophage, MRI, Multiple sclerosis, snc, USPIO.


Journal Article

  • CRIMI A., COMMOWICK O., MAAROUF A., FERRÉ J. - C., BANNIER E., TOURBAH A., BERRY I., RANJEVA J. - P., EDAN G., BARILLOT C. “Predictive value of imaging markers at multiple sclerosis disease onset based on gadolinium- and USPIO-enhanced MRI and machine learning.”. PloS One [En ligne]. 2014. Vol. 9, n°4, p. e93024. Disponible sur : < > (consulté le no date)
    Résumé : OBJECTIVES: A novel characterization of Clinically Isolated Syndrome (CIS) patients according to lesion patterns is proposed. More specifically, patients are classified according to the nature of inflammatory lesions patterns. It is expected that this characterization can infer new prospective figures from the earliest imaging signs of Multiple Sclerosis (MS), since it can provide a classification of different types of lesions across patients. METHODS: The method is based on a two-tiered classification. Initially, the spatio-temporal lesion patterns are classified. The discovered lesion patterns are then used to characterize groups of patients. The patient groups are validated using statistical measures and by correlations at 24-month follow-up with hypointense lesion loads. RESULTS: The methodology identified 3 statistically significantly different clusters of lesion patterns showing p-values smaller than 0.01. Moreover, these patterns defined at baseline correlated with chronic hypointense lesion volumes by follow-up with an R(2) score of 0.90. CONCLUSIONS: The proposed methodology is capable of identifying three major different lesion patterns that are heterogeneously present in patients, allowing a patient classification using only two MRI scans. This finding may lead to more accurate prognosis and thus to more suitable treatments at early stage of MS.

  • MAAROUF A., AUDOIN B., KONSTANDIN S., RICO A., SOULIER E., REUTER F., TROTER A. L., CONFORT-GOUNY S., COZZONE P. J., GUYE M., SCHAD L. R., PELLETIER J., RANJEVA J. - P., ZAARAOUI W. “Topography of brain sodium accumulation in progressive multiple sclerosis.”. Magnetic Resonance Materials in Physics, Biology and Medicine [En ligne]. 1 February 2014. Vol. 27, n°1, p. 53-62. Disponible sur : < > (consulté le 30 October 2014)
    Résumé : Object Sodium accumulation is involved in neuronal injury occurring in multiple sclerosis (MS). We aimed to assess sodium accumulation in progressive MS, known to suffer from severe neuronal injury. Materials and methods 3D-23Na-MRI was obtained on a 3T-MR-scanner in 20 progressive MS patients [11 primary-progressive (PPMS) and nine secondary-progressive (SPMS)] and 15 controls. Total sodium concentrations (TSC) within grey matter (GM), normal-appearing white matter (WM) and lesions were extracted. Statistical mapping analyses of TSC abnormalities were also performed. Results Progressive MS patients presented higher GM–TSC values (48.8 ± 3.1 mmol/l wet tissue vol, p < 0.001) and T2lesions-TSC values (50.9 ± 2.2 mmol/l wet tissue vol, p = 0.01) compared to GM and WM of controls. Statistical mapping analysis showed TSC increases in PPMS patients confined to motor and somatosensory cortices, prefrontal cortices, pons and cerebellum. In SPMS, TSC increases were associated with areas involving: primary motor, premotor and somatosensory cortices; prefrontal, cingulate and visual cortices; the corpus callosum, thalami, brainstem and cerebellum. Anterior prefrontal and premotor cortices TSC were correlated with disability. Conclusion Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.
    Mots-clés : Adult, Aged, Biomedical Engineering, Brain, Brain Mapping, Case-Control Studies, Computer Appl. in Life Sciences, crmbm, Disability, Female, Grey matter, Health Informatics, Humans, Imaging / Radiology, Magnetic Resonance Imaging, Male, Middle Aged, MRI, Multiple sclerosis, Nerve Fibers, Myelinated, Neurons, Progressive multiple sclerosis, Sodium, Solid State Physics.

  • WANONO R., DAELMAN L., MAAROUF A., CAUCHETEUX N., CHAUNU M. - P., TOURBAH A. “Un syndrome « huit et demi plus » révélateur de sclérose en plaques.”. Revue Neurologique [En ligne]. 2014. Vol. 170, n°8–9, p. 553-554. Disponible sur : < > (consulté le 9 March 2015)


Journal Article

  • CAUCHETEUX N., MAAROUF A., DAELMAN L., TOUPANCE O., LAVAUD S., TOURBAH A. “Acute disseminated encephalomyelitis in two renal transplant patients: is there a role for Epstein-Barr virus reactivation?”. Multiple Sclerosis Journal [En ligne]. 1 August 2013. Vol. 19, n°9, p. 1222-1225. Disponible sur : < > (consulté le 29 October 2014)
    Résumé : Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system, usually occurring after a vaccination or infectious disease. It has been exceptionally described in transplanted patients. The pathophysiology remains incompletely understood. We report the clinical, biological and magnetic resonance imaging (MRI) presentation and evolution of two kidney-transplanted patients with ADEM associated with local Epstein-Barr virus (EBV) reactivation. ADEM may occur in transplanted patients with favorable evolution. Its pathophysiology is uncertain, and the implication of EBV is discussed.
    Mots-clés : acute disseminated encephalomyelitis, Epstein-Barr virus, immunodeficiency, Kidney, physiopathology, transplantation.


Journal Article

  • DAELMAN L., MAITROT A., MAAROUF A., CHAUNU M. P., PAPEIX C., TOURBAH A. “Severe multiple sclerosis reactivation under fingolimod 3 months after natalizumab withdrawal.”. Multiple sclerosis (Houndmills, Basingstoke, England) [En ligne]. November 2012. Vol. 18, n°11, p. 1647-1649. Disponible sur : < > (consulté le no date)
    Résumé : We report the case of a woman with multiple sclerosis who developed a severe neurological condition following natalizumab (NZB) withdrawal and soon after fingolimod (FTY) initiation. FTY was started 3.5 months after a two-year NZB treatment. Fifteen days later, she suffered partial repetitive seizures followed by a tonicoclonic seizure. This was associated with attention difficulties and an increased asthenia. Brain MRI follow-up disclosed large demyelinating active lesions in favour of disease reactivation. This case suggests that FTY introduction may occur less than three months after NZB withdrawal.

  • EHRLÉ N., MAAROUF A., CHAUNU M. - P., SABBAGH-PEIGNOT S., BAKCHINE S. “[Acquired and developmental Gerstmann syndrome. Illustration from a patient with multiple sclerosis].”. Revue neurologique [En ligne]. November 2012. Vol. 168, n°11, p. 852-860. Disponible sur : < > (consulté le no date)
    Résumé : Gerstmann's syndrome (GS) is defined by a clinical tetrad including acalculia, finger anomia, left-right disorientation and agraphia. In this article, we describe the case of a 42-year-old woman suffering from an aggressive relapsing-remitting multiple sclerosis in which a systematic neuropsychological assessment revealed Gertsmann's syndrome amongst other cognitive disturbances. Brain MRI showed a high concentration of plaques within a left subcortical parietal region that has recently been considered as a crucial node for GS appearance. However, history, taking provided information suggesting that an important part of the GS, may have been present since childhood, evoking a possible neurodevelopmental origin in this patient. This article reviews the role of the GS concept in contemporary literature, with a special attention to pathophysiological hypotheses and to precautions necessary to study such cases.
    Mots-clés : Adult, Diagnosis, Differential, Female, Gerstmann Syndrome, Humans, Multiple sclerosis, Neuropsychological Tests.


Journal Article

  • MAAROUF A., HADJ-HENNI L., CAUCHETEUX N., RENKES C., SERRE I., BAKCHINE S., TOURBAH A. “[NeuroBehcet disease with corpus callosum involvement].”. Revue neurologique [En ligne]. July 2011. Vol. 167, n°6-7, p. 533-536. Disponible sur : < > (consulté le no date)
    Résumé : INTRODUCTION: Behçet's disease is a multi-system vascular-inflammatory disease with possible involvement of the central nervous system. Lesions of the corpus callosum on MRI have been rarely reported in this disease. CASE REPORT: A 47-year-old woman was admitted for a sudden right hemiplegia and confusion revealing a Behcet's disease. MRI showed a pedonculo-thalamic lesion and a white matter hypersignals, which was suggestive of the disease. Besides, involvement of the corpus callosum was observed. CONCLUSION: This case demonstrates that Behcet's disease should be considered among diseases with corpus callosum involvement.
    Mots-clés : Adrenal Cortex Hormones, Azathioprine, Behcet Syndrome, Colchicine, Confusion, Corpus Callosum, Female, Hemiplegia, Humans, Immunosuppressive Agents, Magnetic Resonance Imaging, Middle Aged, Tegmentum Mesencephali, Thalamus, Treatment Failure.
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