Publications by authors named "Françoise Durand-Dubief"

48 Publications

Signal Intensity Evaluation in the Dentate Nucleus and Subcortical Gray Matter : Effect of Several Administrations of Gadoterate Meglumine in Multiple Sclerosis.

Clin Neuroradiol 2021 Feb 25. Epub 2021 Feb 25.

CREATIS-CNRS UMR5220 & INSERM U1206, INSA-Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.

Purpose: Several studies reported gadolinium deposition in the dentate nuclei (DN) and the globus pallidus (GP) that was associated to linear GBCA administrations rather than macrocyclic. It is therefore imperative to evaluate and assess the safety of cumulative administration of gadoterate meglumine (macrocyclic). Thus, T1-weighted images (T1WI) of multiple sclerosis (MS) patients longitudinally followed for 4 years were retrospectively analyzed.

Methods: In this study 44 patients, 10 with clinically isolated syndrome (CIS), 24 relapsing-remitting MS (RRMS) and 10 primary-progressive MS (PPMS) were examined every 6 months (first four scans) and then with a 1-year interval (last two scans). Image processing consisted in reorienting unenhanced T1WI to standard space, followed by B1 inhomogeneity correction. A patient-specific template was then generated to normalize T1WI signal intensity (SI) and segment the DN and subcortical GM structures. All structures were then transformed to each patient space in order to measure the SI in each region. The cerebellar peduncles (CP) and semi-oval (SO) white matter were then manually delineated and used as reference to calculate SI ratios in the DN and subcortical GM structures. A linear mixed-effect model was finally applied to longitudinally analyze SI variations.

Results: The SI measurements performed in all structures showed no significant increases with the cumulative GBCA administration.

Conclusion: This study showed no significant SI increases within the DN and subcortical GM structures of longitudinally followed MS patients even with the cumulative administration of the macrocyclic GBCA gadoterate meglumine.
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http://dx.doi.org/10.1007/s00062-021-00995-6DOI Listing
February 2021

The long-term outcome of MOGAD: An observational national cohort study of 61 patients.

Eur J Neurol 2021 Feb 2. Epub 2021 Feb 2.

Department of Neurology, Centre de référence des maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.

Background And Objective: The prognosis in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a matter of debate. Our aim was to assess the long-term outcomes of patients with MOGAD.

Methods: We retrospectively analysed the clinical and paraclinical data of patients from the French nationwide observatory study NOMADMUS who tested positive for MOG antibodies (MOG-IgG) and who had clinical follow-up of at least 8 years from their first episode.

Results: Sixty-one patients (median [range] age at onset 27 [3-69] years), with a median (mean; range) follow-up of 177 (212.8; 98-657) months, were included. Among 58 patients with a relapsing course, 26.3% relapsed in the first year after onset. Of the 61 patients, 90.2% experienced at least one episode of optic neuritis. At last visit, the median (mean; range) Expanded Disability Status Scale (EDSS) score was 1 (2.12; 0-7.5), 12.5% had an EDSS score ≥6 and 37.5% had an EDSS score ≥3. Of 51 patients with final visual acuity (VA) data available, 15.7% had VA ≤0.1 in at least one eye and 25.5% had VA ≤0.5 in at least one eye. Bilateral blindness (VA ≤0.1) was present in 5.9% of patients. Finally, 12.5% of patients presented bladder dysfunction requiring long-term urinary catheterization. No factor associated significantly with a final EDSS score ≥3 or with final VA ≤0.1 was found.

Conclusion: Overall long-term favourable outcomes were achieved in a majority of our patients, but severe impairment, in particular visual damage, was not uncommon.
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http://dx.doi.org/10.1111/ene.14746DOI Listing
February 2021

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study.

Mult Scler 2020 Dec 3:1352458520978218. Epub 2020 Dec 3.

INSERM U 1195, Le Kremlin-Bicêtre, France.

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy.

Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo.

Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo.

Results: Recruitment was stopped prematurely due to slow inclusions ( = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) ( = 0.79)).

Conclusion: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.
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http://dx.doi.org/10.1177/1352458520978218DOI Listing
December 2020

Clinical Features and Risk of Relapse in Children and Adults with Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Ann Neurol 2021 01 15;89(1):30-41. Epub 2020 Oct 15.

Department of Neurology, Multiple Sclerosis and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Lyon Civil Hospices, Lyon, France.

Objective: The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG-Ab-associated disease (MOGAD).

Methods: This retrospective multicentric, national study included 98 children and 268 adults with MOGAD between January 2014 and September 2019. Cox regression model for recurrent time-to-event data and Kaplan-Meier curves for time to antibody negativity were performed for the objectives.

Results: Isolated optic neuritis was the most frequent clinical presentation in both children (40.8%) and adults (55.9%, p = 0.013), and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs 5.6%, p < 0.001). Compared to adults, children displayed better recovery (Expanded Disability Status Scale ≥ 3.0 at last follow-up reached only by 10 of 97 [10.3%] vs 66/247 [26.7%], p < 0.001). In the multivariate analysis, adults were at higher risk of relapse than children (hazard ratio = 1.41, 95% confidence interval [CI] = 1.12-1.78, p = 0.003). At 2 years, 64.2% (95% CI = 40.9-86.5) of nonrelapsing children became MOG-Ab negative compared to 14.1% (95% CI = 4.7-38.3) of relapsing children (log-rank p < 0.001), with no differences observed in adults (log-rank p = 0.280).

Interpretation: MOGAD patients differ in the clinical presentation at onset, showing an age-related shift in the clinical features across age groups. Compared to children, adults have a higher risk of relapse and worse functional recovery. Finally, children with monophasic disease become MOG-Ab negative earlier than relapsing children, but this is not true in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. ANN NEUROL 2021;89:30-41.
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http://dx.doi.org/10.1002/ana.25909DOI Listing
January 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

Outcome and risk of recurrence in a large cohort of idiopathic longitudinally extensive transverse myelitis without AQP4/MOG antibodies.

J Neuroinflammation 2020 Apr 23;17(1):128. Epub 2020 Apr 23.

Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, and Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677, Lyon/Bron, France.

Background: Longitudinally extensive transverse myelitis (LETM) is classically related to aquaporin (AQP4)-antibodies (Ab) neuromyelitis optica spectrum disorders (NMOSD) or more recently to myelin oligodendrocyte glycoprotein (MOG)-Ab associated disease. However, some patients remain negative for any diagnosis, despite a large work-up including AQP4-Ab and MOG-Ab. Data about natural history, disability outcome, and treatment are limited in this group of patients. We aimed to (1) describe clinical, biological, and radiological features of double seronegative LETM patients; (2) assess the clinical course and identify prognostic factors; and (3) assess the risk of recurrence, according to maintenance immunosuppressive therapy.

Methods: Retrospective evaluation of patients with a first episode of LETM, tested negative for AQP-Ab and MOG-Ab, from the French nationwide observatory study NOMADMUS.

Results: Fifty-three patients (median age 38 years (range 16-80)) with double seronegative LETM were included. Median nadir EDSS at onset was 6.0 (1-8.5), associated to a median EDSS at last follow-up of 4.0 (0-8). Recurrence was observed in 24.5% of patients in the 18 following months, with a median time to first relapse of 5.7 months. The risk of recurrence was lower in the group of patients treated early with an immunosuppressive drug (2/22, 9%), in comparison with untreated patients (10/31, 32%).

Conclusions: A first episode of a double seronegative LETM is associated to a severe outcome and a high rate of relapse in the following 18 months, suggesting that an early immunosuppressive treatment may be beneficial in that condition.
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http://dx.doi.org/10.1186/s12974-020-01773-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178729PMC
April 2020

Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS: Response to the editor.

Mult Scler 2020 10 5;26(12):1610-1611. Epub 2020 Feb 5.

Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France.

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http://dx.doi.org/10.1177/1352458520904549DOI Listing
October 2020

New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions.

J Neuroradiol 2020 Jun 31;47(4):250-258. Epub 2020 Jan 31.

MRI center, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France; Observatoire Français de la Sclérose en Plaques, Lyon, France; Université Lyon 1, CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Purpose: New multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients' quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain.

Methods: A consensus report was established by neuroradiologists and neurologists from the French Observatory of MS, which aimed at reducing the number of Gd injections required during MS patient follow-up.

Recommendations: The French Observatory of MS recommends the use of macrocyclic Gd enhancement at time of diagnosis, when a new DMT is introduced, at 6-month re-baseline, and when previous scans are unavailable for comparison. Gd administration can be performed as an option in case of relapse or suspicion of intercurrent disease such as progressive multifocal leukoencephalopathy. Other follow-up MRIs do not require contrast enhancement, provided current and previous MRI acquisitions follow the same standardized protocol including 3D FLAIR sequences.
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http://dx.doi.org/10.1016/j.neurad.2020.01.083DOI Listing
June 2020

Prediction of Multiple Sclerosis Patient Disability from Structural Connectivity using Convolutional Neural Networks.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:2087-2090

Prediction of disability progression in multiple sclerosis patients is a critical component of their management. In particular, one challenge is to identify and characterize a patient profile who may benefit of efficient treatments. However, it is not yet clear whether a particular relation exists between the brain structure and the disability status.This work aims at producing a fully automatic model for the expanded disability status score estimation, given the brain structural connectivity representation of a multiple sclerosis patient. The task is addressed by first extracting the connectivity graph, obtained by combining brain grey matter parcellation and tractography extracted from Diffusion and T1-weighted Magnetic Resonance (MR) images, and then processing it via a convolutional neural network (CNN) in order to compute the predicted score. Experiments show that the herein proposed approach achieves promising results, thus resulting as an important step forward on the road to better predict the evolution of the disease.
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http://dx.doi.org/10.1109/EMBC.2019.8856845DOI Listing
July 2019

Frequency of myelin oligodendrocyte glycoprotein antibody in multiple sclerosis: A multicenter cross-sectional study.

Neurol Neuroimmunol Neuroinflamm 2020 03 13;7(2). Epub 2019 Dec 13.

From the Service de Neurologie (Á.C.-C., F.D.-D., S.V., R.M.), Sclérose en Plaques, Pathologies de La Myéline et Neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France; Centre de Référence pour Les Maladies Inflammatoires Rares Du Cerveau et de La Moelle (MIRCEM) (Á.C.-C., F.D.-D., S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France; Centre de Recherche en Neurosciences de Lyon (Á.C.-C., H.I., A.R., R.M.), U1028 INSERM, UMR5292 CNRS, Lyon, France; Département de Neurologie (N.C., L.K., J.D.S.), Centre Hospitalier Universitaire de Strasbourg, France; Biopathologie de La Myéline (N.C., J.D.S.), Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, France; Centre D'investigation Clinique (N.C., J.D.S.), INSERM U1434, Centre Hospitalier Universitaire de Strasbourg, France; Centre de Recherche en Neurosciences de Lyon (F.R., R.C., S.V.), Observatoire Français de La Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, Lyon, France; and Université Claude Bernard Lyon 1 (F.R., R.C., S.V.), F-69000 Lyon, France; Hospices Civils de Lyon, Lyon, France.

Objective: To address the frequency of myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) in an unselected large cohort of adults with MS.

Methods: This is a cross-sectional study in 2 MS expert centers (Lyon and Strasbourg University Hospitals, France) between December 1, 2017, and June 31, 2018. Patients aged ≥18 years with a definite diagnosis of MS according to 2010 McDonald criteria were tested for MOG-Ab by using a cell-based assay (CBA) in Lyon and subsequently included. Positive samples were tested by investigators blinded to the first result with a second assay in a different laboratory (Barcelona, Spain) by using the same plasmid and secondary Ab.

Results: Serum samples from 685 consecutive patients with MS were analyzed for MOG-Ab. Median disease duration at sampling was 11.5 (interquartile range, 5.8-17.7) years, and 72% were women. Two (0.3%) patients resulted to be MOG-Ab-positive. The 2 patients were women aged 42 and 38 at disease onset and were diagnosed with secondary and primary progressive forms of MS, respectively. This positive result was confirmed by the CBA in Barcelona.

Conclusion: Our findings indicate that MOG-Ab are exceptional in MS phenotype, suggesting that the MOG-Ab testing should not be performed in typical MS presentation.
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http://dx.doi.org/10.1212/NXI.0000000000000649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943364PMC
March 2020

Expert opinion: Criteria for second-line treatment failure in patients with multiple sclerosis.

Mult Scler Relat Disord 2019 Nov 19;36:101406. Epub 2019 Sep 19.

CHU de Montpellier, 191 Av. du Doyen Gaston Giraud, Montpellier, France.

Objectives: In the management of multiple sclerosis (MS), defining criteria for identification of suboptimal therapy responses and switching treatment is essential to avoid worsening. Despite the lack of a standardised definition, criteria for first-line treatment are well documented in the literature, based on clinical measures or magnetic resonance imaging (MRI) (gadolinium enhancing [Gd] lesions or new/enlarging T2 lesions) assessed during the first 6-18 months after treatment initiation. However, it is unknown whether the same criteria can be used for second-line treatment failure.

Methods: Five regional boards involving 36 French MS experts were convened to discuss published literature regarding criteria for first- and second-line treatment failure, and to identify differences in local therapeutic practices. A national board of 11 experts was subsequently conducted to identify convergences and differences between regions, and to propose second-line criteria for the definition of therapeutic failure.

Results: Published information is lacking regarding second-line treatment failure criteria. In light of this, regional differences in current therapeutic practices are justifiable. Due to the risk-benefit ratio of these treatments and limited options for third-line treatments, the authors recommend a different therapeutic approach when assessing second-line treatment failure. The treatment switch for second-line treatment should be informed by confirmed disease progression, after 6 months, or combined clinical and MRI outcomes, but only after at least 1 year of treatment.

Conclusions: Experts compared therapeutic attitudes and practices regarding second-line treatment failure between French regions. They identified convergences that were used to propose a national agreement on second-line treatment failure criteria, which should be evaluated in real-life prospective cohorts.
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http://dx.doi.org/10.1016/j.msard.2019.101406DOI Listing
November 2019

Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease.

J Neuroinflammation 2019 Jul 2;16(1):134. Epub 2019 Jul 2.

Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France.

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease.

Methods: This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment.

Results: Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab.

Conclusion: In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD.
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http://dx.doi.org/10.1186/s12974-019-1525-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607517PMC
July 2019

Classification of Multiple Sclerosis Clinical Profiles via Graph Convolutional Neural Networks.

Front Neurosci 2019 12;13:594. Epub 2019 Jun 12.

CREATIS, CNRS UMR5220, INSERM U1206, Université de Lyon, Université Lyon 1, INSA-Lyon, Villeurbanne, France.

Recent advances in image acquisition and processing techniques, along with the success of novel deep learning architectures, have given the opportunity to develop innovative algorithms capable to provide a better characterization of neurological related diseases. In this work, we introduce a neural network based approach to classify Multiple Sclerosis (MS) patients into four clinical profiles. Starting from their structural connectivity information, obtained by diffusion tensor imaging and represented as a graph, we evaluate the classification performances using unweighted and weighted connectivity matrices. Furthermore, we investigate the role of graph-based features for a better characterization and classification of the pathology. Ninety MS patients (12 clinically isolated syndrome, 30 relapsing-remitting, 28 secondary-progressive, and 20 primary-progressive) along with 24 healthy controls, were considered in this study. This work shows the great performances achieved by neural networks methods in the classification of the clinical profiles. Furthermore, it shows local graph metrics do not improve the classification results suggesting that the latent features created by the neural network in its layers have a much important informative content. Finally, we observe that graph weights representation of brain connections preserve important information to discriminate between clinical forms.
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http://dx.doi.org/10.3389/fnins.2019.00594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581753PMC
June 2019

Frequency and characteristics of short versus longitudinally extensive myelitis in adults with MOG antibodies: A retrospective multicentric study.

Mult Scler 2020 07 31;26(8):936-944. Epub 2019 May 31.

Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Bron, France; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle and INSERM U1028, CNRS UMR 5292, Lyon 1 University, Center for Research in Neuroscience of Lyon, Lyon, France.

Objectives: We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis.

Material And Methods: We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0.

Results: Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively),  = 0.007 and  = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group,  = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%),  < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0-4.0)) compared to SM patients (2.0, (1.0-3.0)),  = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01-1.95,  = 0.046).

Conclusion: SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.
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http://dx.doi.org/10.1177/1352458519849511DOI Listing
July 2020

Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS.

Mult Scler 2019 04 20;25(4):591-600. Epub 2018 Mar 20.

Service de Neurologie A, Hôpital Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France/Observatoire Français de la Sclérose en Plaques (OFSEP), Lyon, France/Centre de Recherche en Neurosciences de Lyon, INSERM U1028, CNRS UMR5292, Equipe Neuro-Oncologie et Neuro-Inflammation, Lyon, France/Université de Lyon 1, Lyon, France.

Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses.

Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy.

Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992-1995 and 2005-2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis.

Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78).

Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.
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http://dx.doi.org/10.1177/1352458518763080DOI Listing
April 2019

Spontaneous multiple cervical artery dissections after alemtuzumab.

Mult Scler 2020 03 9;26(3):381-383. Epub 2019 May 9.

Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation-Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France/Université Claude Bernard Lyon 1, Villeurbanne, France/Lyon Neuroscience Research Center, Observatoire Français de la Sclérose en Plaques, INSERM 1028 and CNRS UMR 5292, Lyon, France.

We report a case of multiple cervical artery dissections that occurred 4 days after a first course of alemtuzumab in a woman with relapsing-remitting multiple sclerosis and discuss its potential relationship and mechanisms of action. In particular, an arterial inflammatory process, secondary to cytokine release, could potentially lead to intimal thickening, luminal irregularities, stenosis, and ultimately occlusion. Occurrence of an unexpected serious adverse event, in our case, multiple cervical artery dissections, especially in a close time window after drug administration, questions a potential causal relationship with the drug or a simple coincidence.
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http://dx.doi.org/10.1177/1352458519828663DOI Listing
March 2020

Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions.

J Neurol 2019 Jul 23;266(7):1743-1755. Epub 2019 Apr 23.

Department of Radiology, Strasbourg University Hospital, Strasbourg, France.

Background: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear.

Objectives: Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions.

Methods: We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed.

Results: Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1-12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD.

Discussion: Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
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http://dx.doi.org/10.1007/s00415-019-09328-7DOI Listing
July 2019

Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome.

Mult Scler J Exp Transl Clin 2019 Jan-Mar;5(1):2055217319836664. Epub 2019 Mar 20.

Department of Neurology, Keck School of Medicine of University of Southern California, USA.

Background: Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination.

Objectives: To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome.

Methods: We analysed an international historical cohort of 61 children with radiologically isolated syndrome (≤18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.2 ± 4.7 years). All index scans also met the 2017 magnetic resonance imaging dissemination in space criteria.

Results: Diagnostic indices (95% confidence intervals) for the 2005 dissemination in space criteria, with and without oligoclonal bands, were: sensitivity 66.7% (38.4-88.2%) versus 72.7% (49.8-89.3%); specificity 83.3% (58.6-96.4%) versus 53.9% (37.2-69.9%). For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1-93.2%) versus 100% (84.6-100%); specificity 72.7% (49.8-89.3%) versus 25.6% (13.0-42.1%).

Conclusions: Oligoclonal bands increased the specificity of magnetic resonance imaging criteria in children with Ped-RIS. Clinicians should consider testing cerebrospinal fluid to improve diagnostic certainty. There is rationale to include cerebrospinal fluid analysis for biomarkers including oligoclonal bands in planned prospective studies to develop optimal diagnostic criteria for radiologically isolated syndrome in children.
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http://dx.doi.org/10.1177/2055217319836664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429663PMC
March 2019

Correction to: Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults.

J Neurol 2019 Apr;266(4):816

Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, 59 boulevard Pinel, BRON cedex, 69677, Lyon, France.

The original version of this article unfortunately contained a mistake.
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http://dx.doi.org/10.1007/s00415-019-09215-1DOI Listing
April 2019

Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults.

J Neurol 2019 Apr 3;266(4):806-815. Epub 2019 Jan 3.

Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, 59 boulevard Pinel, BRON cedex, 69677, Lyon, France.

Objective: To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions.

Methods: This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI.

Results: MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype.

Conclusion: High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels.
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http://dx.doi.org/10.1007/s00415-018-9160-9DOI Listing
April 2019

Multiple sclerosis with atypical MRI presentation: Results of a nationwide multicenter study in 57 consecutive cases.

Mult Scler Relat Disord 2019 Feb 18;28:109-116. Epub 2018 Dec 18.

MS Center and National Reference Center of adult Leukodystrophies, Department of Neurology, Montpellier University Hospital, 34 295 Montpellier Cedex 5, France. Electronic address:

Background: The recent 2017 modification have increased the sensitivity of McDonald criteria for MS. Nevertheless, some MS patients with atypical MRI findings have been identified, leading to prolonged delay to diagnosis and high costs to look for alternative diagnoses.

Objective: To describe a series of MS patients with atypical MRI presentation.

Material And Methods: Patients with atypical MS were identified through a nationwide retrospective study. We established a five groups classification: tumefactive demyelinating lesion (TDL)-onset MS, acute disseminated encephalomyelitis (ADEM)-like MS, cavitary MS and leukodystrophy-like MS. All the patients meeting our radiological criteria for atypical MS were included.

Results: A total of 57 patients met the inclusion criteria. 7 cases were classified in the TDL-onset group, 10 in the ADEM-like group, 26 in the cavitary group and 14 in the leukodystrophy-like group. Overall risk of conversion to MS after an isolated TDL was around 30% at five years. Patients in the TDL-onset and ADEM-like groups globally presented an acute onset and a relapsing-remitting evolution. Conversely, patients in the cavitary and leukodystrophy- groups largely evolved with a progressive and severe course.

Conclusion: A significant number of MS patients can have a striking atypical presentation and may be misdiagnosed. This preliminary analysis helps to refine the spectrum of atypical MS patients.
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http://dx.doi.org/10.1016/j.msard.2018.12.022DOI Listing
February 2019

Evidence of axonal damage in cerebellar peduncles without T2-lesions in multiple sclerosis.

Eur J Radiol 2018 Nov 17;108:114-119. Epub 2018 Sep 17.

CREATIS, UMR 5220 CNRS & U1206 INSERM, Université Claude Bernard - Lyon1, Université de Lyon, Villeurbanne, France; Département IRM, CERMEP-Imagerie du Vivant, Université de Lyon, Bron, France. Electronic address:

Background And Aim: Cerebellar peduncles (CP) can be probed by diffusion tensor imaging (DTI) to evaluate the integrity of cerebellar afferent and efferent networks. Damage to the CP in multiple sclerosis (MS) could lead to serious cognitive and mobility impairment. The aim of this study was to investigate the extent and the clinical impact of CP damage in MS.

Methods: Sixty-eight MS patients were included in this study along with 27 healthy controls (HC) and underwent an MRI on a 1.5T including T1, T2, FLAIR and DTI. Using DTI, the microstructural integrity within the CP regions (superior (SCP), inferior (ICP) and middle (MCP)) was probed while controlling for focal T2-lesions presence or absence. A general linear model was performed to test for associations between clinical scores and DTI metrics for each CP.

Results: Significantly decreased fractional anisotropy (FA) and increased radial diffusivity (RD) were found in the CP of all MS patients compared to those of HC, but to a lesser extent in non-lesioned CP than those with lesions. Axial diffusivity (AD) was significantly and similarly increased in both non-lesioned and lesioned CP, but only in the SCP and ICP. Expanded disability status scale (EDSS) significantly correlated with MCP's FA (p < 0.05) and RD (p < 0.05), while MS functional composite (MSFC) significantly correlated with SCP's FA (p < 0.01) and RD (p < 0.01).

Conclusion: The diffusion changes (FA and RD) measured in lesioned CP are probably directly related to the presence of inflammatory and/or demyelinating lesions. In contrast, the microstructural alterations reflected by AD increase in non-lesioned CP may result either from remote effects of cerebral white matter injury (diaschisis) or primary axonal degeneration, that are associated with cognitive, sensory and motor impairments of MS patients.
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http://dx.doi.org/10.1016/j.ejrad.2018.09.016DOI Listing
November 2018

Weekly enhanced T1-weighted MRI with Gadobutrol injections in MS patients: Is there a signal intensity increase in the dentate nucleus and the globus pallidus?

Eur J Radiol 2018 Aug 19;105:204-208. Epub 2018 Jun 19.

Faculté de médecine Lyon Est, Université Claude Bernard Lyon 1, Université de Lyon, 69008, Lyon, France; CREATIS, CNRS UMR 5220 - INSERM U1206, Université de Lyon, 69621, Villeurbanne, France; Service de Radiologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69310, Pierre Bénite, France. Electronic address:

Background And Purpose: Gadolinium-based contrast agents (GBCAs) administration have drastically improved the accuracy of Multiple Sclerosis (MS) diagnosis by highlighting any damage to the brain blood barrier, thereby differentiating between active and non-active lesions. Following multiple administrations of GBCAs, several MS studies have reported a signal intensity (SI) increase on unenhanced T1-weighted images in certain brain regions such as the dentate nucleus (DN) and the globus pallidus (GP). Our aim was therefore to determine the accumulation of macrocyclic GBCAs on enhanced T1-weighted images SI in the DN and the GP of MS patients injected eight times.

Materials And Methods: Five MS patients underwent eight weekly consecutive MRI scans. Enhanced 3D T1-weighted images with Gadobutrol as a macrocyclic GBCA, were acquired. A ROI-based approach was applied for the evaluation of SI in the DN to middle cerebellar peduncle (DN-MCP) and GP to semi-oval white matter (GP-SOWM) ratios. An analysis of variance on repeated measures was used for the statistical analysis of each ratio.

Results: No DN-MCP and GP-SOWM SI ratio differences were observed over the eight-weeks period using the macrocyclic GBCA.

Conclusion: Iterative and weekly injections of macrocyclic GBCAs are not associated with T1 signal increase in the DN and GP of MS patients. These results would suggest a no gadolinium accumulation in the brain using macrocyclic GBCA even after several close injections and promote the use of a macrocylcic GBCA rather than linear agents for MS patients.
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http://dx.doi.org/10.1016/j.ejrad.2018.06.011DOI Listing
August 2018

Focal and diffuse cervical spinal cord damage in patients with early relapsing-remitting MS: A multicentre magnetisation transfer ratio study.

Mult Scler 2019 07 18;25(8):1113-1123. Epub 2018 Jun 18.

IRISA, UMR CNRS 6074, VisAGeS U1228, INSERM, INRIA, Université Rennes I, Rennes, France.

Background: Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR).

Objectives: The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing-remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution.

Methods: We included 60 patients with RRMS <12  months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest.

Results: Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9  pu,   =  0.00005), even after excluding lesions (33.9  pu,   =  0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2-C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre.

Conclusion: Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.
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http://dx.doi.org/10.1177/1352458518781999DOI Listing
July 2019

Unusual neurologic presentation of aseptic abscesses syndrome.

Neurol Neuroimmunol Neuroinflamm 2018 Jul 5;5(4):e469. Epub 2018 Jun 5.

Service de Neurologie, sclérose en plaques (P.N., O.G., A.B., F.D.-D., R.M., S.V.), pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Centre des Neurosciences de Lyon (A.V., R.M.), INSERM 1028 et CNRS UMR5292, Equipe FLUID et Observatoire Français de la Sclérose en Plaques; Université de Lyon (A.V., R.M.); INSERM U1052 (G.R., E.J.), CNRS UMR5286, Cancer Research Center of Lyon; Fédération d'Endocrinologie (G.R., E.J.), Groupement Hospitalier Est, Hospices Civils de Lyon, Bron; Service de Radiologie (F.C.), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon1, Université de Lyon, Pierre Bénite; CREATIS (F.D.-D., F.C.), UMR 5220 CNRS & U1044 Inserm, Université Claude Bernard Lyon1, Université de Lyon, Villeurbanne; Service d'anatomie et cytologie pathologiques (C.D.), Centre Hospitalier de la Timone, France; Centre de Pathologie et Neuropathologie Est (A.V.), Groupement Hospitalier Est, Hospices Civils de Lyon, Bron; Service de dermatologie (S.D.), Centre Hospitalier Lyon Sud, 69495 Pierre Bénite; and Service de Neurochirurgie B (E.J.), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France.

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http://dx.doi.org/10.1212/NXI.0000000000000469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991774PMC
July 2018

Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study.

Neurology 2018 05 25;90(21):e1858-e1869. Epub 2018 Apr 25.

Objective: To describe clinical and radiologic features associated with myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in a large French nationwide adult cohort, to assess baseline prognostic features of MOG-Ab-associated diseases after a first acute demyelinating syndrome, and to evaluate the clinical value of MOG-Ab longitudinal analysis.

Methods: Clinical data were obtained from 197 MOG-Ab-positive patients ≥18 years of age. Complete imaging data were available in 108, and 54 serum samples were eligible for longitudinal evaluation. For survival analysis comparison, 169 aquaporin-4 antibody (AQP4-Ab)-positive patients from the NOMADMUS database were included.

Results: Median age at onset was 36.46 (range 18.0-76.8) years, and patients were predominantly white (92.9%) with male:female ratio, 1.1. Clinical phenotype at onset included optic neuritis or myelitis in 90.86%, isolated brainstem or encephalopathy syndromes in 6.6%, and a combination of syndromes in 2.5%. Distinctive brain MRI findings in MOG-Ab-positive patients were thalamic and pontine lesions. Cortical and leptomeningeal lesions were found in 16.3% and 6.1%, respectively. The probability of reaching a first relapse after 2 and 5 years was 44.8% and 61.8%, respectively. MOG-Ab-positive patients were at lower risk at presentation of further clinical relapse (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.26-0.79) compared to AQP4-Ab-positive individuals. MOG-Ab-positive individuals had a lower risk of reaching Disability Status Scale score of 3.0 (HR 0.46, 95% CI 0.22-0.94) and visual acuity of 20/100 (HR 0.23, 95% CI 0.07-0.72). Finally, MOG-Ab titers were higher at relapse than in remission ( = 0.009).

Conclusion: In adults, MOG-Ab-associated disease extends beyond clinical and radiologic abnormalities in the optic nerve and spinal cord. Despite the relapsing course, the overall visual and motor outcome is better compared with AQP4-Ab-positive patients.
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http://dx.doi.org/10.1212/WNL.0000000000005560DOI Listing
May 2018

Weekly follow up of acute lesions in three early multiple sclerosis patients using MR spectroscopy and diffusion.

J Neuroradiol 2018 Mar 13;45(2):108-113. Epub 2017 Oct 13.

CREATIS, UMR5520, U1206 Inserm, université Claude-Bernard-Lyon1, 69621 Lyon, France; CERMEP, Imagerie-du-Vivant, université de Lyon, 69677 Lyon, France. Electronic address:

Object: Pathophysiological mechanisms underlying multiple sclerosis (MS) lesion formation, including inflammation, demyelination/remyelination and axonal damage, and their temporal evolution are still not clearly understood. To this end, three acute white matter lesions were monitored using a weekly multimodal magnetic resonance (MR) protocol.

Materials And Methods: Three untreated patients with early relapsing-remitting MS and one healthy control subject were followed weekly for two months. MR protocol included conventional MR imaging (MRI), diffusion tensor imaging (DTI), and localized MR spectroscopy (MRS), performed on the largest gadolinium-enhancing lesion, selected at the first exam.

Results: Mean diffusivity increased and fractional anisotropy decreased in lesions compared to healthy control. Cho/Cr ratios remained elevated in lesions throughout the follow-up. In contrast, temporal profiles of mI/Cr ratios varied between patients' lesions. For patient 1, mI/Cr ratios were already elevated at the beginning of the follow-up. Patients 2 and 3 ratios increase was delayed by two and five weeks. Blood-brain barrier (BBB) recovery occurred after three weeks.

Conclusion: This multimodal MR follow-up highlighted the complementary role of DTI and MRS in identifying temporal relationships between BBB disruption, inflammation, and demyelination. Diffusion metrics showed high sensitivity to detect inflammatory processes. The different temporal profiles of mI suggested a potential better specificity to monitor pathological mechanisms occurring after lesion formation, such as glial proliferation and remyelination.
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http://dx.doi.org/10.1016/j.neurad.2017.06.010DOI Listing
March 2018

Radiologically isolated syndrome in children: Clinical and radiologic outcomes.

Neurol Neuroimmunol Neuroinflamm 2017 Nov 25;4(6):e395. Epub 2017 Sep 25.

Author affiliations are provided at the end of the article.

Objective: To describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed "radiologically isolated syndrome" or RIS).

Methods: Clinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS.

Results: We identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries. The mean follow-up time was 4.8 ± 5.3 years. The most common reason for initial neuroimaging was headache (20/38, 53%). A first clinical event consistent with CNS demyelination occurred in 16/38 children (42%; 95% confidence interval [CI]: 27%-60%) in a median of 2.0 years (interquartile range [IQR] 1.0-4.3 years). Radiologic evolution developed in 23/38 children (61%; 95% CI: 44%-76%) in a median of 1.1 years (IQR 0.5-1.9 years). The presence of ≥2 unique oligoclonal bands in CSF (hazard ratio [HR] 10.9, 95% CI: 1.4-86.2, = 0.02) and spinal cord lesions on MRI (HR 7.8, 95% CI: 1.4-43.6, = 0.02) were associated with an increased risk of a first clinical event after adjustment for age and sex.

Conclusions: We describe the clinical characteristics and outcomes of children with incidental MRI findings highly suggestive of CNS demyelination. Children with RIS had a substantial risk of subsequent clinical symptoms and/or radiologic evolution. The presence of oligoclonal bands in CSF and spinal cord lesions on MRI were associated with an increased risk of a first clinical event.
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http://dx.doi.org/10.1212/NXI.0000000000000395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614726PMC
November 2017

MOG antibody-related disorders: common features and uncommon presentations.

J Neurol 2017 Sep 2;264(9):1945-1955. Epub 2017 Aug 2.

Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677, Bron, France.

Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) (p = 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group (p = 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.
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http://dx.doi.org/10.1007/s00415-017-8583-zDOI Listing
September 2017

Machine Learning Approach for Classifying Multiple Sclerosis Courses by Combining Clinical Data with Lesion Loads and Magnetic Resonance Metabolic Features.

Front Neurosci 2017 11;11:398. Epub 2017 Jul 11.

CREATIS Centre National de la Recherche Scientifique UMR5220 & Institut National de la Santé et de la Recherche Médicale, U1206, Université de Lyon, Université Claude Bernard-Lyon 1, INSA-LyonVilleurbanne, France.

The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features. Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e.g., age, disease duration, Expanded Disability Status Scale), conventional magnetic resonance imaging and spectroscopic imaging. We extract -acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre) concentrations, and we compute three features for each spectroscopic grid by averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels. We built linear mixed-effects models to test for statistically significant differences between MS forms. We test nine binary classification tasks on clinical data, lesion loads, and metabolic features, using a leave-one-patient-out cross-validation method based on 100 random patient-based bootstrap selections. We compute F1-scores and BAR values after tuning Linear Discriminant Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and Random Forests. Statistically significant differences were found between the disease starting points of each MS form using four different response variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on clinical and lesion loads yields F1-scores of 71-72% for CIS vs. RR and CIS vs. RR+SP, respectively. For RR vs. PP we obtained good classification results (maximum F1-score of 85%) after training LDA on clinical and metabolic features, while for RR vs. SP we obtained slightly higher classification results (maximum F1-score of 87%) after training LDA and SVM-rbf on clinical, lesion loads and metabolic features. Our results suggest that metabolic features are better at differentiating between relapsing-remitting and primary progressive forms, while lesion loads are better at differentiating between relapsing-remitting and secondary progressive forms. Therefore, combining clinical data with magnetic resonance lesion loads and metabolic features can improve the discrimination between relapsing-remitting and progressive forms.
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http://dx.doi.org/10.3389/fnins.2017.00398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504183PMC
July 2017