Publications by authors named "Jean-Christophe Ouallet"

26 Publications

  • Page 1 of 1

Association between familial Mediterranean fever and multiple sclerosis: A case series from the JIR cohort and systematic literature review.

Mult Scler Relat Disord 2021 Feb 10;50:102834. Epub 2021 Feb 10.

Sorbonne University; Internal Medicine Department; AP-HP; Hôpital Tenon; Paris; France; Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses Inflammatoire (CEREMAIA)-JIR Cohort; France. Electronic address:

Introduction: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disorder; and leads to the uncontrolled production of interleukin (IL)-1β. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system; and its development seems to be partly correlated with IL-1β levels. It is hypothesized that FMF could be associated with MS. We aim to describe the features of patients displaying both diseases and to investigate the MEFV mutation rate in MS patients.

Methods: Patients with definite MS were retrieved from the cohort of FMF patients in the Reference Center for Rare Auto-inflammatory Diseases and Amyloidosis (CEREMAIA). We also performed a systematic literature review of articles from PubMed that were published from 1990 to 2020.

Results: Twenty-four patients were included in the case series: five patients (1.3%) from our cohort of 364 and 19 patients from the literature. The sex ratio was 2:1. The mean age at diagnosis of FMF was 19 years old; and that for MS was 29 years old. Seven studies investigating the MEFV mutation rate in MS patients were included. Three studies found a higher mutation rate in MS patients than in the control group.

Conclusion: FMF and MS features were comparable to those of patients with unrelated diseases; and MEFV mutation carriage was not positively correlated with MS. However; MS prevalence in FMF patients was higher than was expected in a healthy population. To a lesser extent; FMF prevalence in MS patients was higher than expected in a healthy population and the difference might not be significant. These data suggest that FMF could be associated with MS; and further studies are needed to investigate a potential causal association.
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http://dx.doi.org/10.1016/j.msard.2021.102834DOI Listing
February 2021

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

JAMA Neurol 2020 09;77(9):1079-1088

Service de Neurologie, Clinical Investigation Center Institut National de la Santé et de la Recherche Médicale 1434, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France.

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities.

Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity.

Design, Setting, And Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020.

Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms.

Main Outcomes And Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes.

Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01).

Conclusions And Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.
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http://dx.doi.org/10.1001/jamaneurol.2020.2581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320356PMC
September 2020

Double-blind, randomized controlled trial of therapeutic plasma exchanges vs sham exchanges in moderate-to-severe relapses of multiple sclerosis.

J Clin Apher 2020 Aug 5;35(4):281-289. Epub 2020 May 5.

CHU de Bordeaux, Service de Neurologie, Bordeaux, France.

Introduction: No randomized controlled clinical trial of therapeutic plasma exchanges (TPE) has yet been performed for moderate-to-severe relapses of multiple sclerosis (MS).

Objective: To compare TPE to sham-TPE in patients with a recent steroid-resistant moderate-to-severe MS relapse.

Methods: Patients presenting with an MS relapse of less than 2 months without improvement and 15 days after a course of steroids were randomized. Specific criteria were used for each relapse type to define moderate-to-severe disability. The primary endpoint was the proportion of patients with at least a moderate improvement based on objective and functional evaluation after 1 month.

Results: Thirty-eight patients were randomized. The intention-to-treat analysis included 14 patients in the TPE group and 17 in the Sham-TPE group. The proportion of patients with at least moderate improvement at 1 month did not differ between the groups (P = .72), although 57.1% of the TPE group had full recovery compared with 17.6% of the sham group. Considering optic neuritis (ON), a significant difference in the proportion of different levels of improvement was observed in favor of the TPE group (P = .04). The combined Kurtzke's functional systems scores were significantly more improved in the TPE group than in the sham-TPE group at months 1 (P < .01), 3 (P < .05), and 6 (P < .05). No major side effects were observed.

Conclusions: A significant difference between TPE and Sham-TPE at the primary endpoint was only observed in patients with ON. Neurological function improved significantly more often in the TPE group than in the sham-TPE group.
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http://dx.doi.org/10.1002/jca.21788DOI Listing
August 2020

Evaluation of emotional disorders before and during treatment with interferon beta in patients with multiple sclerosis.

J Neurol Sci 2020 06 19;413:116739. Epub 2020 Feb 19.

Faculty of Economics, Louvain University, Belgium; Faculty of Medicine, University of Melbourne, Australia.

Background: Domains encompassing emotional disorders in relapsing-remitting MS (RRMS) patients are still unclear.

Methods: We performed a 24-month, multicenter, single-arm, prospective study. RRMS patients started IFN-β treatment at baseline. The primary endpoint was lack of emotional control, measured using the "Echelle d'HumeurDépressive" (EHD) scale three times at baseline and at 10 post-treatment visits. Secondary endpoints were emotional blunting, irritability, fatigue, depression and anxiety. A linear mixed covariance model assessed change from baseline on an intention-to-treat basis, under the assumption of no mood disorder effect (one-sided 97.5% level), in which autoregressive type of autocorrelation was tested.

Results: Out of 79 recruited patients, 70 were analyzed: 80% female; mean (SD) age, 37.0 (11.5) years. Mean (SD) lack of emotional control score at baseline and Month 24 was 12.7 (4.4) and 12.6 (5.5), respectively, versus 10.1 (3.2) in a healthy control population matched for age and sex. Stepwise analysis identified younger age, male sex and antidepressant use as significant predictors of higher lack of emotional control values.

Conclusions: Based on 24 months of prospective follow-up, the results of this study highlights a broad spectrum of emotional disorders in the MS population at the time of disease modifying drugs initiation but no major IFN-β-related emotional disorders (mood dyscontrol, anxiety, depression) were observed. However, sporadic occurrences of severe mood disorders and suicidality cannot be excluded.
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http://dx.doi.org/10.1016/j.jns.2020.116739DOI Listing
June 2020

Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement.

Rev Neurol (Paris) 2020 Jan - Feb;176(1-2):100-112. Epub 2019 Nov 19.

Service de neurologie, CHU de Nîmes, 30029 Nîmes, France; UMR5203, Inserm 1191, université de Montpellier, institut de génomique fonctionnelle, 34090 Montpellier, France.

The ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS.
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http://dx.doi.org/10.1016/j.neurol.2019.02.007DOI Listing
November 2020

First clinical inflammatory demyelinating events of the central nervous system in a population aged over 70 years: A multicentre study.

Mult Scler Relat Disord 2019 Feb 14;28:309-312. Epub 2018 Dec 14.

Service de Neurologie, CHU de Bordeaux, Place Amélie Raba Léon, F-33076, Bordeaux, France. Electronic address:

Background: Few data are available regarding patients with very late-onset inflammatory demyelinating events. (VLO-IDE).

Objectives: The aim of this study was to describe the clinical, biological, and radiological characteristics and aetiological diagnosis of very late first inflammatory demyelinating events of the central nervous system.

Methods: We conducted a national descriptive retrospective multicentre study on a case series of patients aged >70 years at the time of VLO-IDE. Patients were recruited from a national call on behalf of the 'Société Francophone de la Sclérose en Plaques' (French Multiple Sclerosis Society).

Results: Twenty-five patients were referred (F:M sex ratio 2.1:1). The most frequent clinical impairment was a spinal cord deficit (23/25), usually severe (disability score, median EDSS 4.5 [2-9.5]). Spinal cord lesions were usually extensive, spanning at least three segments (11/25), and large brain lesions were also observed (lesions >20 mm in 6/25). The final aetiological diagnoses comprised multiple sclerosis (9/25), neuromyelitis optica spectrum disorders (7/25), neurosystemic lupus erythematosus (2/25), transverse myelitis without aetiological diagnosis (6/25) and optic neuritis (1/25).

Conclusions: This study highlights a particular phenotype of first clinical inflammatory demyelinating events in predominantly female patients aged >70 years who have severe motor impairment with common longitudinal extensive myelitis and large and common very active radiological inflammatory lesions. Neuromyelitis optica spectrum disorders seem overrepresented.
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http://dx.doi.org/10.1016/j.msard.2018.12.016DOI Listing
February 2019

Preliminary evidence of the cerebellar role on cognitive performances in clinically isolated syndrome.

J Neurol Sci 2018 02 2;385:1-6. Epub 2017 Dec 2.

CHU de Bordeaux, INSERM-CHU CIC-P 0005, Service de Neurologie, Bordeaux F-33076, France; Université de Bordeaux, Bordeaux F-33076, France; Neurocentre Magendie, INSERM U1215, Team Glia-neuron Interactions, Bordeaux F-33077, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jns.2017.11.037DOI Listing
February 2018

Microstructural analyses of the posterior cerebellar lobules in relapsing-onset multiple sclerosis and their implication in cognitive impairment.

PLoS One 2017 8;12(8):e0182479. Epub 2017 Aug 8.

Univ. Bordeaux, Bordeaux, France.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182479PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549727PMC
October 2017

Double-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive Multiple Sclerosis.

PLoS One 2017 3;12(1):e0168834. Epub 2017 Jan 3.

Service de Neurologie et INSERM-CHU CIC-P 0005, CHU de Bordeaux, Bordeaux, France.

Background: Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far.

Objective: To compare CPM to methylprednisolone (MP) in SPMS.

Methods: Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area-MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model.

Results: Due to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 [95% CI: 0·31-1·22](p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely ([1·14-4.29]; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17-0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected.

Conclusion: Although the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability.

Trial Registration: Clinicaltrials.gov NCT00241254.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168834PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207788PMC
August 2017

CD62L test at 2 years of natalizumab predicts progressive multifocal leukoencephalopathy.

Neurology 2016 12 4;87(23):2491-2494. Epub 2016 Nov 4.

From the CHU Toulouse Purpan (B.P., F.B., D.B., D.A.-P., D.B.), Pôle Neurosciences; INSERM U1043-CNRS UMR 5282 (B.P., F.B., D.B.), Université Toulouse III, Centre de Physiopathologie Toulouse Purpan, France; University of Münster (N.S., T.S.-H., H.W.), Germany; University of Lille (O.O., H.Z., P.V.); Hôpital Civil (J.-C. Ongagna, J.d.S.), Strasbourg; CHU Pellegrin (B.B., J.-C. Ouallet), Bordeaux; CHU Nancy (M.D., S.P.); CHU Caen (G.D., N.D.); CH St Vincent (P.H.), GHICL, Lille; CHU Reims (A.T.); CHU Montpellier (P.L.); CHU Nîmes (G.C., W.C., O.C.); CHRU Clermont Ferrand (P.C.); CHU Besançon (E.B.); Aix Marseille University (J.P., A.R.), APHM, CHU Timone, Marseille; CHU Nantes (D.L., S.W.); CHU Grenoble (E.T.); CHU Dijon (T.M., A.F.); CHU Lyon (S.V.), Bron; Hôpital de la Salpêtrière (C.P.), Paris, France; Centre d'Esclerosi Múltiple de Catalunya (CEMCAT) (M.C.), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; and CHU Nice (C.L.-F.), France.

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http://dx.doi.org/10.1212/WNL.0000000000003401DOI Listing
December 2016

Posterior lobules of the cerebellum and information processing speed at various stages of multiple sclerosis.

J Neurol Neurosurg Psychiatry 2017 Feb 27;88(2):146-151. Epub 2016 Oct 27.

University Bordeaux, Bordeaux, France.

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 (R=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.
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http://dx.doi.org/10.1136/jnnp-2016-313867DOI Listing
February 2017

Deciphering Depressive Mood in Relapsing-Remitting and Progressive Multiple Sclerosis and Its Consequence on Quality of Life.

PLoS One 2015 10;10(11):e0142152. Epub 2015 Nov 10.

INSERM U.862, Neurocentre Magendie, Université de Bordeaux, Bordeaux, France.

Background: Depressive mood and other emotional symptoms are common in multiple sclerosis (MS). The patient-reported outcome version of the "Echelle d'Humeur Dépressive" (EHD-PRO) aims to differentiate between two dimensions of depressive mood in people living with MS (PwMS).

Objectives: First, to compare EHD-PRO assessment and its two dimensions, lack of emotional control and emotional blunting, between a large sample of healthy controls (HCs) and two samples of PwMS, relapsing-remitting MS (RRMS) and primary progressive MS (PPMS); and second, to analyse the relationships between EHD-PRO scores with neurological disability, cognitive function, fatigue and health-related quality of life (HR-QOL).

Results: Regardless of their phenotype, PwMS had significantly higher EHD-PRO scores than HCs. EHD-PRO scores did not differ between the two MS groups. EHD-PRO scores did not correlate with disability and fatigue scores, disease duration or cognitive z scores. In RRMS, the lack of emotional control was independently associated with a decrease in HR-QOL.

Conclusion: The EHD-PRO is able to easily detect depressive mood and to differentiate between two clinical dimensions, emotional blunting and lack of emotional control. The scale is sensitive and seems robust to confounding factors. Lack of emotional control seems to contribute significantly to altered HR-QOL in RRMS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142152PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640551PMC
June 2016

Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability.

J Neurol 2015 Oct 21;262(10):2329-35. Epub 2015 Jul 21.

Pole des Neurosciences, CHU Toulouse and UMR 1043, Université de Toulouse III, Toulouse, France.

Neuromyelitis optica (NMO) is a life-threatening disease without any validated treatment strategy. Recent retrospective studies suggested the efficacy of B cell depletion without any distinction between first-line or rescue therapy. To assess whether rituximab as first-line therapy in NMO could efficiently control the occurrence of relapses. A retrospective analysis of NMO patients from NOMADMUS network found 32 patients receiving rituximab as first-line therapy. Main measures were number of relapse-free patients, changes in the annualized relapse rate (ARR), and changes in the EDSS. Tolerance was reported. At baseline, NMO patients were 45 ± 12.1 years old, with a sex ratio of 5.4, and 87.5 % of them had AQP4 antibodies. The median disease duration was 6.5 months (1-410), the mean EDSS was 5.8 ± 2.4 and the mean ARR was 3.8 ± 4.3. After rituximab with a mean follow-up of 28.7 ± 21 months, twenty-seven patients (84.3 %) were relapse free. Patients presented a 97 % decrease of ARR (p = 0.00001). EDSS decreased significantly to 3.9 ± 2.6 (p = 0.01). No relevant side effect was noted. New retrospective data are presented on RTX use in NMOSD. When used as first-line therapy RTX is highly effective and well tolerated.
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http://dx.doi.org/10.1007/s00415-015-7852-yDOI Listing
October 2015

Adherence to, and effectiveness of, subcutaneous interferon β-1a administered by RebiSmart® in patients with relapsing multiple sclerosis: results of the 1-year, observational SMART study.

Expert Opin Drug Deliv 2015 Aug 22;12(8):1239-50. Epub 2015 Jun 22.

Department of Neurology, Klinikum Augsburg , Stenglinstr 2, D-86156, Augsburg , Germany +49 821 400 3892 ; +49 821 400 2691 ;

Background: Patients with multiple sclerosis who have poor adherence to treatment have a higher risk of relapse than adherent patients. This study assessed adherence to, and effectiveness and convenience of, treatment with subcutaneous (sc) interferon (IFN) β-1a (Rebif®, Merck Serono SA) 44 or 22 μg three times weekly in patients with relapsing multiple sclerosis (RMS) using the RebiSmart® electronic, multidose, autoinjector for 1 year.

Study Design: European, multicentre, observational study among neurologists: inclusion criteria included RMS, Expanded Disability Status Scale score ≤ 6, sc IFN β-1a administered by RebiSmart for ≤ 6 weeks. The primary endpoint was cumulative adherence recorded by RebiSmart.

Results: The safety population included 912 patients, 77.4% (n = 823) of whom completed the Month-12 visit. Mean (± standard deviation) cumulative adherence was 97.1 ± 7.3% (n = 791). The most common reason for missed injection was 'forgot to inject' (37.0%). At Month 12/ED, 79.5% of patients were relapse-free. Of 353 patients who rated the convenience of the device, 68.3% found injecting 'very easy'. No unknown safety issues were detected.

Conclusions: Patients with RMS self-injecting sc IFN β-1a with RebiSmart had excellent adherence at Month 12/ED, which was associated with good clinical outcomes and no unexpected safety issues. Patients rated RebiSmart as convenient and easy to use.
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http://dx.doi.org/10.1517/17425247.2015.1057567DOI Listing
August 2015

Does cerebrospinal fluid analysis add predictive value to magnetic resonance imaging for long term irreversible disability in patients with early multiple sclerosis?

J Neurol Sci 2015 Jul 2;354(1-2):51-5. Epub 2015 May 2.

CHU de Bordeaux, Service de Neurologie, Bordeaux, France; INSERM U 862, Université de Bordeaux, France. Electronic address:

Background: The independent prognostic value of cerebrospinal fluid analysis in multiple sclerosis is not established.

Objective: To determine the prognostic value of intrathecal synthesis in a cohort of patients with relapsing-onset MS taking into consideration demographic and imaging parameters.

Methods: In this prospective cohort study conducted from 1993 to 2013, we analyzed the time to confirmed disability (persistent above 6 months) and irreversible disability (persistent for the entire disease course) of two disability milestones, Expanded Disability Status Scale score ≥ 4 or 6, and the time to secondary progressive onset in 579 patients with relapsing-onset multiple sclerosis. Demographic parameters (age at onset, gender) and imaging parameters (periventricular lesions) were included in the Cox models.

Results: 447 patients (77.2%) had intrathecal synthesis (oligoclonal bands and/or increased immunoglobulin G index value). No statistically significant relation was found between intrathecal synthesis and the time to reach each disability milestone or secondary progressive onset. An age older than 40 years and more than 3 periventricular lesions predicted a worse prognosis.

Conclusions: Cerebrospinal fluid analysis did not predict the time to disability milestones in relapsing-onset multiple sclerosis independently of age and imaging data.
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http://dx.doi.org/10.1016/j.jns.2015.04.044DOI Listing
July 2015

Meralgia paresthetica after subcutaneous injection of glatiramer acetate.

Muscle Nerve 2015 Jul;52(1):150-1

Department of Neurology, Groupe hospitalier Pellegrin, Bordeaux, France.

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http://dx.doi.org/10.1002/mus.24614DOI Listing
July 2015

An unusual case of CSF leak following post-traumatic rupture of a sacral meningeal cyst.

Cephalalgia 2015 Oct 8;35(12):1130-2. Epub 2015 Jan 8.

Université de Bordeaux, Inserm U862, Neurocentre Magendie, France Service de Neuroimagerie Diagnostique et Thérapeutique, CHU de Bordeaux, France.

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http://dx.doi.org/10.1177/0333102414566202DOI Listing
October 2015

Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients.

Brain 2015 Feb 19;138(Pt 2):284-92. Epub 2014 Dec 19.

1 Département de Neurologie, CHU de Montpellier, 34295 Montpellier, France

Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.
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http://dx.doi.org/10.1093/brain/awu353DOI Listing
February 2015

Cognitive impairment, health-related quality of life and vocational status at early stages of multiple sclerosis: a 7-year longitudinal study.

J Neurol 2013 Mar 19;260(3):776-84. Epub 2012 Oct 19.

INSERM U.1049 Neuroinflammation, Imagerie et Thérapie de la Sclérose en plaques, Université de Bordeaux, Case 78, 146 rue Léo Saignat, 33076, Bordeaux cedex, France.

The association between cognitive impairment, health-related quality of life (HRQoL) and vocational status has been studied in recent years in cross-sectional studies in multiple sclerosis (MS), but longitudinal data are still lacking. This study assesses this association in a sample of 65 newly diagnosed MS patients followed longitudinally. Each patient underwent a standardised clinical assessment, cognitive tests and the HRQoL SEP-59 questionnaire six months after the MS diagnosis (baseline) and seven years later (y7).Vocational status was also established at baseline and at y7 in MS patients. The HRQoL at baseline was severely reduced in MS patients compared with healthy subjects. The independent predictors for HRQoL composite scores at y7 were the baseline depression score and the memory Z-score. Accordingly, 81.5 % of MS patients worked at baseline and only 54.4 % worked at y7. Among the MS patients who did not work at y7, 72.7 % of them were cognitively impaired, while 27.3 % were unimpaired at baseline. The vocational status at y7 was significantly associated with the baseline IPS Z-score, EDSS and age. Vocational status at y7 and its change over 7 years was significantly associated with cognitive deterioration. IPS or memory dysfunction in the early stages of MS is correlated with a decreased level in health perception, independent of fatigue, depression and physical disability. Cognitive impairment at the diagnosis of MS increases the risk of changing vocational status in MS patients seven years later.
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http://dx.doi.org/10.1007/s00415-012-6705-1DOI Listing
March 2013

Increased risk of multiple sclerosis relapse after in vitro fertilisation.

J Neurol Neurosurg Psychiatry 2012 Aug 11;83(8):796-802. Epub 2012 Jun 11.

Service de Neurologie, Centre Hospitalier Universitaire de Nantes, Hôpital Laennec, Nantes Cedex, France.

Background: Exogenous sexual steroids together with pregnancy have been shown to influence the risk of relapses in multiple sclerosis (MS). Treatments used during assisted reproductive techniques may consequently influence the short term evolution of MS by modifying the hormonal status of the patient. The objective of this study was to determine if there was an increased risk of developing exacerbations in women with MS after in vitro fertilisation (IVF).

Methods: MS and IVF data were either automatically extracted from 13 French university hospital databases or obtained from referring neurologists. After matching databases, patient clinical files were systematically reviewed to collect information about MS and the treatments used for IVF. The association between IVF and the occurrence of MS relapses was analysed in detail using univariate and multivariate statistical tests.

Findings: During the 11 year study period, 32 women with MS had undergone 70 IVF treatments, 48 using gonadotrophin releasing hormone (GnRH) agonists and 19 using GnRH antagonists. A significant increase in the annualised relapse rate (ARR) was observed during the 3 month period following IVF (mean ARR 1.60, median ARR 0) compared with the same period just before IVF (mean ARR 0.80, median ARR 0) and to a control period 1 year before IVF (mean ARR 0.68, median ARR 0). The significant increase in relapses was associated with the use of GnRH agonists (Wilcoxon paired test, p=0.025) as well as IVF failure (Wilcoxon paired test, p=0.019).

Interpretation: An increased relapse rate was observed in this study after IVF in patients with MS and may be partly related both to IVF failure and the use of GnRH agonists.
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http://dx.doi.org/10.1136/jnnp-2012-302235DOI Listing
August 2012

Predictive factors for multiple sclerosis in patients with clinically isolated spinal cord syndrome.

Mult Scler 2011 Mar 11;17(3):312-8. Epub 2010 Nov 11.

Services de Neurologie et de Neuro-imagerie, Hôpital Pellegrin, CHU de Bordeaux, 33076, Bordeaux cedex, France.

Objectives: To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord clinically isolated syndrome.

Methods: The predictive values for conversion to MS of clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) variables in 114 patients with acute partial myelitis confirmed by a spinal cord lesion on MRI were studied. Other causes of cord syndromes were excluded.

Results: MS was diagnosed in 78 patients (86%) during 4.0 ± 1.9 years of follow-up. Some 67 of these patients had a second clinical episode. The diagnosis of isolated myelitis was maintained for 36 patients, 78% of whom (28 cases) were followed for at least 2 years, comparable to the MS patients. Age, bladder involvement, ≥ 2 cord lesions on MRI, ≥ 9 brain lesions, ≥ 3 periventricular lesions and intrathecal IgG synthesis predicted conversion to clinically definite MS. Multivariate logistic analysis identified three predictors of MS diagnosis: age ≤ 40 years, inflammatory CSF and ≥ 3 periventricular lesions on brain MRI.

Conclusion: Two out of three baseline factors (age, periventricular lesions and inflammatory CSF) predicted conversion to MS with better accuracy than the revised McDonald criteria for dissemination in space.
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http://dx.doi.org/10.1177/1352458510386999DOI Listing
March 2011

Pain and quality of life in the early stages after multiple sclerosis diagnosis: a 2-year longitudinal study.

Clin J Pain 2009 Mar-Apr;25(3):211-7

EA 2966, Neurobiology of Myelin Disorders Laboratory, Bordeaux, France.

Background: Pain is a frequent symptom during the course of multiple sclerosis (MS) but its frequency and impact at the early clinical stages remain unknown.

Objectives: The aim of this study was to establish prevalence and severity of pain in a cohort of patients recently diagnosed with MS and to determine the evolution of pain prevalence over 2 years. Other objectives were to investigate the presence of baseline clinical predictors of pain after 2 years and to establish its impact on quality of life (QOL).

Methods: In a population-based sample of 69 patients recently diagnosed with MS (<6 mo), pain was measured using questions from the SEP-59 QOL questionnaire. A standardized bedside neurologic examination was performed to establish sensory function, sensory Kurtzke functional system score, and disability scales. Patients were reassessed after 1 and 2 years.

Results: Pain was reported by 73.5% of MS patients at baseline and by 70.6% and 61.8% at 1 and 2-year follow-ups, respectively. Clinically significant pain (grades between 3 and 6 using a 6-graded verbal scale) was reported by 63.2% of patients at baseline and by 51.5% and 45.6%, at 1 and 2-year follow-ups, respectively. Pain significantly altered daily activities in 44% of patients. Low overall QOL scores were significantly associated with pain. At 2 years time point, occurrence of pain was associated with baseline depressive symptoms after controlling for the presence of pain at baseline.

Conclusions: Pain is frequent in the early stages of MS and affects the daily QOL.
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http://dx.doi.org/10.1097/AJP.0b013e3181891347DOI Listing
June 2009

Quantitative cerebral perfusion using the PRESTO acquisition scheme.

J Magn Reson Imaging 2004 Dec;20(6):930-40

Department of Molecular and Functional Imaging (IMF) ERT CNRS, University Victor Segalen 2, Bordeaux, France.

Purpose: To evaluate the feasibility of using the rapid principles of echo shifting with a train of observations (PRESTO) sequence for measurements of cerebral hemodynamic parameters based on first pass of a contrast agent.

Materials And Methods: Simulations were performed to investigate potential resolution loss due to relaxation effects. Experimental evaluation was conducted in healthy monkey brains using PRESTO and echo-planar imaging (EPI).

Results: For short echo trains, an insignificant contribution of the longitudinal and transversal relaxation rates to the signal amplitude in white matter and gray matter was found, whereas a contribution as large as 40% was found in large vessels. Simulations of the point spread function demonstrated that PRESTO, despite its shorter readout trains, only has a small advantage in terms of maintenance of image resolution during bolus passage compared to EPI as long as the EPI echo train can be kept similar to the T2* value at the top of the bolus. Experimental studies revealed that the PRESTO and EPI gray matter to white matter ratio were similar with respect to cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT).

Conclusion: The study showed that PRESTO and EPI led to comparable quantitative perfusion parameters.
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http://dx.doi.org/10.1002/jmri.20206DOI Listing
December 2004

Frontline: Epitope recognition on the myelin/oligodendrocyte glycoprotein differentially influences disease phenotype and antibody effector functions in autoimmune demyelination.

Eur J Immunol 2004 Aug;34(8):2072-83

Department of Neurology, School of Medicine, University of California-San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA.

Preliminary observations of humoral immunity against the myelin oligodendrocyte glycoprotein (MOG) in experimental allergic encephalomyelitis (EAE) and human multiple sclerosis (MS) suggest that a subset of anti-MOG autoantibodies directed against conformational epitopes is of pathogenic predominance. Here, we provide proof that in marmoset EAE, autoantibodies reactive against conformational epitopes of MOG are not only responsible for aggravating demyelination, but also an essential factor for disease dissemination in space within the central nervous system, a hallmark for typical forms of human MS. In terms of effector mechanisms, IgG deposition and complement activation occur exclusively in association with presence of these conformational antibodies, while microglial/macrophage activation appears to be a common immunopathological finding regardless of the fine determinant specificity of anti-MOG antibodies. These findings highlight for the first time the complex heterogeneity of function and pathogenicity in the polyclonal anti-MOG antibody repertoire of outbred species. Because the linear and conformational antibody determinants of MOG are shared between marmosets and humans, these results are directly relevant to understanding effector mechanisms of organ damage in MS.
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http://dx.doi.org/10.1002/eji.200425050DOI Listing
August 2004