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.
Sixty one patients with myelin oligodendrocyte glycoprotein antibody‐associated disease were included, of whom 90.2% experienced at least one episode of optic neuritis. At last visit (median range follow‐up of 177 98–657 months), 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 15.7% had visual acuity (VA) ≤0.1. Bilateral blindness (VA ≤0.1) was present in 5.9% of patients. No factor was associated significantly with a final EDSS ≥3 or with final VA ≤0.1. Overall long‐term favourable outcomes were achieved in a majority of patients, but severe impairment, in particular visual damage, was not uncommon.
L’IRM cérébrale dans l’encéphalite à anticorps anti-NMDAr (E-NMDAR) est habituellement normale ou montre des hypersignaux limbiques. Les hypersignaux extra-limbiques (25–35 % des patients) sont ...considérés comme atypiques.
Cette étude vise à déterminer si les hypersignaux extra-limbiques sont associés à un pronostic particulier de l’E-NMDAR, à décrire les particularités cliniques de ces patients et à identifier les sous-groupes radiologiques.
Au total, 249 patients ayant un suivi supérieur à 1 an ont été inclus rétrospectivement. Les données cliniques, paracliniques et thérapeutiques des patients, présentant des hypersignaux extra-limbiques (cas), ont été comparées à celles des patients avec une IRM cérébrale normale ou retrouvant des anomalies limbiques isolées (contrôles) (Fig. 1). Un pronostic défavorable était défini par un score de Rankin modifié (mRS) supérieur à 2 à 2 ans de suivi. Une double relecture en aveugle était réalisée pour toutes les imageries disponibles.
Nous identifions 66 cas (26,5 %), dont 51 IRM disponibles pour relecture. Quatre patterns d’atteinte extra-limbique sont identifiés : lésions inflammatoires (parfois étendue, Fig. 1), aspécifiques, associées à une maladie démyélinisante et autres. Comparativement aux contrôles, les cas étaient plus âgés, présentaient davantage de symptômes atypiques, avaient un pronostic plus souvent défavorable (19/66, 28,8 % vs 25/183, 13,7 %, p=0,001), et une mortalité plus élevée (5/66, 7,6 % vs 4/183, 2,2 % ; p=0,035).
L’analyse rétrospective de cette cohorte nationale d’E-NMDAR montre que la présence d’anomalies radiologiques extra-limbiques s’accompagne d’atypies cliniques et d’un pronostic défavorable, suggérant que le traitement et le suivi doivent être modulés ou adaptés en fonction de l’IRM. L’analyse des sous-groupes radiologiques et la recherche d’autres auto-anticorps associés (MOG, AQP4) permettront d’identifier la population la plus à risque.
L’atteinte radiologique extra-limbique dans l’E-NMDAR est associée à un pronostic défavorable justifiant d’une surveillance plus étroite de ces patients et posant la question d’un traitement immunosuppresseur plus agressif.
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•11/464 (2.4%) patients presenting with non-traumatic neurological injury had evidence of current/recent HEV infection.•In 7/11 cases HEV RNA was found in the serum.•Three cases were ...neuralgic amyotrophy with bilateral symptoms, which is the HEV-associated phenotype.•The relationship between HEV and neuralgic amyotrophy is causal.•The relationship between HEV and other neurological syndromes requires further study.
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.
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.
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.
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.
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.
We present a cohort of 15 patients with neuromyelitis optica and associated disorders who had Coronavirus disease 2019 (COVID‐19). COVID‐19 outcome was overall favorable, 5 patients, all on Rituximab, needed hospitalization, and one patient needed mechanical ventilation.
To evaluate the effectiveness of plasma exchange (PLEX) for optic neuritis (ON).
We conducted an international multicenter retrospective study evaluating the outcomes of ON following PLEX. Outcomes ...were compared to raw data from the Optic Neuritis Treatment Trial (ONTT) using a matched subset.
A total of 395 ON attack treated with PLEX from 317 patients were evaluated. The median age was 37 years (range 9-75), and 71% were female. Causes of ON included multiple sclerosis (108), myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) (92), aquaporin-4-IgG–positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (75), seronegative-NMOSD (34), idiopathic (83), and other (3). Median time from onset of vision loss to PLEX was 2.6 weeks (interquartile range IQR, 1.4-4.0). Median visual acuity (VA) at the time of PLEX was count fingers (IQR, 20/200-hand motion), and median final VA was 20/25 (IQR, 20/20-20/60) with no differences among etiologies except MOGAD-ON, which had better outcomes. In 81 (20.5%) ON attacks, the final VA was 20/200 or worse. Patients with poor outcomes were older (P = .002), had worse VA at the time of PLEX (P < .001), and longer delay to PLEX (P < .001). In comparison with the ONTT subset with severe corticosteroid-unresponsive ON, a final VA of worse than 20/40 occurred in 6 of 50 (12%) PLEX-treated ON vs 7 of 19 (37%) from the ONTT treated with intravenous methylprednisolone without PLEX (P = .04).
Most ON attacks improved with PLEX, and outcomes were better than attacks with similar severity in the ONTT. The presence of severe vision loss at nadir, older age, and longer delay to PLEX predicted a worse outcome whereas MOGAD-ON had a more favorable prognosis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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.
To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013.
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.
Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation.
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).
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.
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.
Introduction:
Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if ...COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry.
Case series:
We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild.
Discussion:
These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.
Background:
Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk ...may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk.
Objective:
To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS).
Methods:
The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal.
Results:
Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations.
Conclusion:
These recommendations propose a strategic approach to managing cancer risk in PwMS.
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