Publications by authors named "Cécile Dulau"

11 Publications

  • Page 1 of 1

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis.

Neurotherapeutics 2020 Sep 22. Epub 2020 Sep 22.

CHU de Clermont-Ferrand, F-63000, Clermont-Ferrand, France.

High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (p = 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (p = 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13311-020-00926-2DOI Listing
September 2020

Severe anti-GFAP meningo-encephalomyelitis following viral infection.

Mult Scler Relat Disord 2020 Oct 19;45:102448. Epub 2020 Aug 19.

Medical Intensive Care and Infectious Diseases Unit, Saint-Andre Hospital, CHU BORDEAUX, 1 rue Jean Burguet, 33075 BORDEAUX CEDEX, France.

Glial fibrillary acidic protein is a recently identified rare cause of autoimmune encephalomyelitis, in which the cerebrospinal fluid shows lymphocytic pleocytosis accompanied by linear perivascular radial gadolinium enhancement in the brain. We report a 19-year-old man admitted to the intensive care unit with suspected viral meningoencephalitis. Magnetic resonance imaging showed mild encephalopathy with a reversible splenial lesion. He quickly developed a coma and acute respiratory failure. Glial fibrillary acidic protein antibodies and human parainfluenza virus were detected by cerebrospinal fluid exams. He was treated with intravenous immunoglobulin, methylprednisolone pulses, plasma exchange and then six infusions of cyclophosphamide plus two of rituximab, which resulted in a total recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102448DOI Listing
October 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jca.21788DOI Listing
August 2020

MRI features of demyelinating disease associated with anti-MOG antibodies in adults.

J Neuroradiol 2019 Sep 20;46(5):312-318. Epub 2019 Jun 20.

Neuroradiology department, Pierre-Paul-Riquet/Purpan university hospital, 31300 Toulouse, France. Electronic address:

The spectrum of Myelin Oligodendrocytes Glycoprotein (MOG) antibody disease constitutes a recently described challenging entity, referring to a relatively new spectrum of autoimmune disorders with antibodies against MOG predominantly involving the optic nerve and spinal cord. The purpose of this article is to describe MRI features of MOG-AD involvement in the optic nerves, spinal cord and the brain of adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurad.2019.06.001DOI Listing
September 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2018.12.016DOI Listing
February 2019

Longitudinal study of functional brain network reorganization in clinically isolated syndrome.

Mult Scler 2020 02 27;26(2):188-200. Epub 2018 Nov 27.

University of Bordeaux, Bordeaux, France/Inserm U1215, Neurocentre Magendie, Bordeaux, France/CHU Pellegrin, CHU de Bordeaux, Bordeaux, France.

Background: There is a lack of longitudinal studies exploring the topological organization of functional brain networks at the early stages of multiple sclerosis (MS).

Objective: This study aims to assess potential brain functional reorganization at rest in patients with CIS (PwCIS) after 1 year of evolution and to characterize the dynamics of functional brain networks at the early stage of the disease.

Methods: We prospectively included 41 PwCIS and 19 matched healthy controls (HCs). They were scanned at baseline and after 1 year. Using graph theory, topological metrics were calculated for each region. Hub disruption index was computed for each metric.

Results: Hub disruption indexes of degree and betweenness centrality were negative at baseline in patients ( < 0.05), suggesting brain reorganization. After 1 year, hub disruption indexes for degree and betweenness centrality were still negative ( < 0.00001), but such reorganization appeared more pronounced than at baseline. Different brain regions were driving these alterations. No global efficiency differences were observed between PwCIS and HCs either at baseline or at 1 year.

Conclusion: Dynamic changes in functional brain networks appear at the early stages of MS and are associated with the maintenance of normal global efficiency in the brain, suggesting a compensatory effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458518813108DOI Listing
February 2020

Differential Gray Matter Vulnerability in the 1 Year Following a Clinically Isolated Syndrome.

Front Neurol 2018 11;9:824. Epub 2018 Oct 11.

Univ. Bordeaux, Bordeaux, France.

Whether some gray matter (GM) regions are differentially vulnerable at the early stages of MS is still unknown. The objective of this study is to investigate whether deep and cortical GM are differentially vulnerable after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Fifty-six patients with CIS (PwCIS) and 38 healthy controls (HC) had conventional and diffusion tensor imaging (DTI) at baseline and 46 PwCIS and 20 HC were rescanned after 1 year. Deep GM (DGM) volumes, cortical thickness (CTh), and DTI metrics (FA: fractional anisotropy; MD: mean diffusivity) within these structures were calculated for each participant at each time-point and compared between PwCIS and HC. Linear regression models were used to investigate whether baseline DTI parameters could predict GM volume loss over time. At baseline, GM volumes did not differ between PwCIS and HC, but hippocampal MD was higher in PwCIS than HC ( < 0.01). Over 1 year, GM alterations became more widespread with putamen and hippocampus volumes decreasing in PwCIS ( < 0.01), and cortical thinning in different parts of the cortex along with a significant increase of MD. Hippocampus MD at baseline could predict its volume loss ( = 0.159; < 0.05) and cortical thinning was associated to microstructural damage (Spearman's rho ranging from -0.424 to -0.603 with < 0.003). Along with MS being a diffuse inflammatory disease, GM showed a differential vulnerability at the early stage spreading from hippocampus to the cortex. Hippocampus volume loss could be predicted by its MD at baseline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2018.00824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193084PMC
October 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000005560DOI Listing
May 2018

Social cognition according to cognitive impairment in different clinical phenotypes of multiple sclerosis.

J Neurol 2017 Apr 20;264(4):740-748. Epub 2017 Feb 20.

CHU de Bordeaux, INSERM-CHU CIC-P 1401 & Service de Neurologie, 33076, Bordeaux, France.

The objective of this study is to evaluate the relationship between social cognition (SC) and cognitive impairment in persons with multiple sclerosis (PwMS). A prospective study was conducted in 60 PwMS, 30 with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS) and 15 with primary progressive MS (PPMS), and in healthy subjects (HS). All subjects were assessed by the Bordeaux Social Cognition Evaluation Protocol (PECS-B) (facial emotion recognition, theory of mind, emotional awareness and cognitive and affective alexithymia), by a large neuropsychological battery and by questionnaires (depression and anxiety). 43.3% of PwMS were impaired for at least one SC test. The proportion of PwMS with at least two impaired SC tests was similar in all three phenotypes (20%). Mean scores differed significantly between PwMS and HS only for the Reading the Mind in the Eyes Test, a test of Theory of Mind (ToM). ANOVA analyses showed an effect of phenotype on emotional awareness scores with lower scores in PPMS as compared to RRMS. ToM performance was significantly correlated (r  = 0.56) with executive functions, working memory and episodic memory scores. SC impairment was found in all phenotypes and was more prominent in cognitively impaired MS patients. Executive functions, and working and episodic memory performance accounts for approximately 50% of ToM performance. Emotional awareness is more impaired in progressive MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-017-8417-zDOI Listing
April 2017