Publications by authors named "Julie Pique"

7 Publications

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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

Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders.

Eur J Neurol 2020 Oct 26. Epub 2020 Oct 26.

Service de Neurologie and CIC INSERM 1434, CHU de Strasbourg, Strasbourg, France.

Background: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown.

Methods: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death).

Results: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]).

Conclusions: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.
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http://dx.doi.org/10.1111/ene.14612DOI 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.
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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

Progressive Multifocal Leukoencephalopathy Incidence and Risk Stratification Among Natalizumab Users in France.

JAMA Neurol 2020 01;77(1):94-102

CHU de Nantes, Service de Neurologie, CIC015 INSERM, Nantes, France.

Importance: Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated.

Objective: To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013.

Design, Setting, And Participants: This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018.

Exposures: Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation.

Main Outcomes And Measures: Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016).

Results: In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016.

Conclusions And Relevance: The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.
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http://dx.doi.org/10.1001/jamaneurol.2019.2670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724170PMC
January 2020

Acute hepatitis E in French patients and neurological manifestations.

J Infect 2018 09 10;77(3):220-226. Epub 2018 Jul 10.

UMR Inserm, U1043; UMR CNRS, U5282, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, F-31300, France; CHU Toulouse, Hôpital Purpan, Laboratoire de virologie, Centre national de référence du virus de l'hépatite E, Toulouse, F-31300 France.

Objectives: Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. However, our understanding of the source of contamination is incomplete and the frequency of neurological manifestations in still unknown.

Methods: 200 eligible cases reported to the French National Reference Center from January 2015 to December 2015 were prospectively included in this case-control study (1 case: 1 control, matched for sex, age and area of living) to investigate the risk of infection. We documented the factors associated with their HEV infection and clinical manifestations.

Results: The 200 HEV-infected patients included 137 who were immunocompetent and 63 immunocompromised. The factors associated with an HEV infection were contact with farm animals, eating pork liver sausage and eating unpeeled fruit. The 33 patients (16.5%) who reported neurological symptoms included 14 with neuropathic pain suggesting small fiber neuropathy, 9 with painless sensory disorders, 6 with Parsonage-Turner syndrome, one Guillain-Barre syndrome, one meningitis, one encephalitis and one diplopia. Neurological manifestations were more frequent in immunocompetent patients (22.6% vs 3.2%, p < 0.001).

Conclusions: This study highlights the risk of HEV transmission by the environment in industrialized countries. The higher frequency of neurological disorders in immunocompetent patients suggests pathophysiological mechanisms involving the immune system.
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http://dx.doi.org/10.1016/j.jinf.2018.06.007DOI Listing
September 2018

Hepatitis E virus infection and acute non-traumatic neurological injury: A prospective multicentre study.

J Hepatol 2017 11 20;67(5):925-932. Epub 2017 Jul 20.

Department of Neurology and Immunology, Erasmus MC, University Medical Centre Rotterdam, The Netherlands.

Background & Aims: Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury.

Methods: Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands.

Results: Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus.

Conclusions: In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.
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http://dx.doi.org/10.1016/j.jhep.2017.07.010DOI Listing
November 2017

Multiple sclerosis broke my heart.

Ann Neurol 2017 May 9;81(5):754-758. Epub 2017 May 9.

Neurology, Multiple Sclerosis, Myelin Disorders and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Lyon/Bron.

We report 5 cases of acute heart failure (AHF) related to multiple sclerosis (MS) relapses. AHF was inaugural in 3 patients, always preceded or accompanied by signs of brainstem dysfunction; it was severe, requiring intensive care management. Echocardiography showed left ventricular hypokinesis. No other cause of AHF has been found. All patients showed a new medullary lesion on brain magnetic resonance imaging. All had rapid and complete recovery of ventricular function after intravenous corticosteroids. We concluded that the cases represent a takotsubo phenomenon. Physicians should be aware of rare cases of takotsubo cardiomyopathy in MS relapses. Ann Neurol 2017;81:754-758.
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http://dx.doi.org/10.1002/ana.24935DOI Listing
May 2017