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Introduction: Progressive Multifocal Leukoencephalopathy (PML) is a rare and deadly demyelinating disease caused by JC virus (JCV) replication in the central nervous system. PML occurs exclusively in patients with severe underlying immune deficiencies, including AIDS and hematological malignancies. PML has also emerged as a significant threat to patients on potent new immunosuppressive biologics, including natalizumab in multiple sclerosis. Methods: Here, we developed an IFN-g release assay (IGRA) that mainly detects JCV-specific effector memory T cells and effectors T cells in the blood. Results: This assay was frequently positive in patients with active PML (with a positive JCV PCR in CSF) of various underlying immunosuppression causes (84% sensitivity). Only 3% of healthy donors had a positive response (97% specificity). The frequency of positivity also increased in multiple sclerosis patients according to the time on natalizumab (up to 36% in patients treated for more than 48 months, who are considered at a higher risk of PML). Discussion: The results show this assay's frequent or increased positivity in patients with PML or an increased risk of PML, respectively. The assay may help to stratify the risk of PML. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. Methods: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea–hypopnea index ⩾ 15. Results: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. Conclusion: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Journal of Neurology discussing the humoral response to an accelerated schedule of hepatitis B virus (HBV) vaccination in patients with multiple sclerosis (MS) before receiving anti-CD20 therapy. The study was conducted in France and aimed to evaluate the efficacy and safety of the accelerated vaccination schedule. The results showed that 58.8% of MS patients achieved seroconversion after the first three injections of the vaccine, which is lower than the reported seroconversion rate for a standard vaccination schedule. The study also highlighted the need for long-term monitoring of immune responses and education on the risks of HBV transmission in MS patients. [Extracted from the article]

Background: Fungal infections of the central nervous system usually affect immunocompromised patients. Primary Aspergillus myelitis has never been described. Report: A 45-year-old immunocompetent male with subacute paraplegia was treated for inflammatory myelitis before clinical deterioration requiring mechanical ventilation. Purulent meningitis preceded the formation of a paraspinal nodule biopsied by neurosurgery. Histopathological analysis revealed the presence of fungal hyphae, and polymerase chain reaction was positive for Aspergillus fumigatus. No cause of immunodeficiency was identified in this patient. Discussion: Primary Aspergillus myelitis may be confused with inflammatory myelitis and should be considered even in the absence of apparent immunosuppression. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021. Objectives: We aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022. Methods: This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity. Results: Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave (p < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = [1.25–1.64] per 10 years), male sex (OR = 2.01, 95% CI = [1.51–2.67]), obesity (OR = 2.36, 95% CI = [1.52–3.68]), cardiac comorbidities (OR = 2.36, 95% CI = [1.46–3.83]), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = [1.43–3.06] for EDSS 3–5.5 and OR = 4.53, 95% CI = [3.04–6.75] for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = [1.85–3.87]) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = [0.60–0.69]) or off (RR = 0.32, 95% CI = [0.30–0.33]) anti-CD20. Discussion: In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status. [ABSTRACT FROM AUTHOR]

Background: Counseling on pregnancy is still challenging, particularly regarding the use of disease-modifying treatments (DMTs). We are lacking long-term outcomes in children exposed to DMTs. Objectives: This study aimed to set up a French pregnancy registry for women with multiple sclerosis (MS) and related disorders nested within the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Methods: Prospective, observational, multicentric, epidemiological study in France. Neurological visits are organized according to routine practice. Data are collected on the OFSEP minimal datasheet. Auto-questionnaires on pregnancy are completed by patients at Months 5–6 and 8 during pregnancy, and Months 3, 6, and 12 postpartum. A specific survey on analgesia is completed by anesthesiologists. Pediatric data are collected from the child's health book, where visits on Day 8, Month 9, and 24 are mandatory. Parents complete neurodevelopmental questionnaires at Year 1, Years 2 and 6. Results: The RESPONSE study started in August 2019. On 7 April 2023, 515 women were included. Baseline demographics are presented. Conclusions: RESPONSE will provide rich information on the global management of pregnancy in France and prospective data on children until the age of 6 years, exposed or not to a DMT, including data on neurodevelopment that can be compared to the general population. Study funding: EDMUS and ARSEP Foundation, Biogen, Roche. [ABSTRACT FROM AUTHOR]

Recent studies in adults suggested that extended-interval dosing of rituximab/ocrelizumab (RTX/OCR) larger than 12 months was safe and could improve safety. This was an observational cohort study of very active pediatric-onset multiple sclerosis (PoMS) (median (range) age, 16 (12–17) years) treated with RTX/OCR with 6 month standard-interval dosing (n = 9) or early extended-interval dosing (n = 12, median (range) interval 18 months (12–25)). Within a median (range) follow-up of 31 (12–63) months after RTX/OCR onset, one patient (standard-interval) experienced relapse and no patient showed disability worsening or new T2-weighted lesions. This study suggests that the effectiveness of RTX/OCR is maintained with a median extended-interval dosing of 18 months in patients with very active PoMS. [ABSTRACT FROM AUTHOR]

Background: Aquaporin-4 immunoglobulin G Neuro Myelitis Optica spectrum disorders attacks (NMOSD-AQP4-IgG+ attacks) can cause respiratory failure requiring orotracheal intubation (OTI), but the risk factors and outcomes of OTI during attacks remain unclear. Our primary objective was to identify the clinical and radiological risk factors for OTI in NMOSD-AQP4-IgG+ attacks. As a secondary objective, we aimed to evaluate the prognosis of OTI-attacks. Methods: We retrospectively analyzed NMOSD-AQP4-IgG+ attacks at the Pitié-Salpêtrière Hospital (Jan 2010–Jan 2021), excluding isolated optic neuritis. The primary outcome was the need for OTI due to neurological dysfunction an attack (OTI-attack). The secondary outcome was attack's poor recovery after 12 months, defined as a modified Rankin score (mRS) > 2 in patients with an initial mRS ≤ 2, or an increase ≥ 1 point in mRS in other patients. Analyses were performed using a binomial generalized linear mixed model, with a random intercept for the patient ID to account for within-patient correlations. Results: Seventy-three attacks in 44 patients NMOSD-AQP4-IgG+ were analyzed. Of 73 attacks, 8 (11%) required OTI during the attack, related to acute restrictive respiratory failure (n = 7) and/or severe swallowing disorder (n = 2). None of the OTI-attacks occurred in patients previously treated with active disease-modifying treatment (DMT), while 36 (55.4%) of the non-OTI-attacks occurred in patients who were already on active DMT. On admission, OTI-attacks were more likely to have upper limbs motor paresis of (75.0% versus 29.2%, p = 0.366) and dyspnea (3 [50.0%] versus 4 [6.6%], p = 0.002) compared to non-OTI-attacks. MRI analysis showed that OTI-attacks had edematous lesions in the cervical spinal cord, mainly at levels C1 (75% versus 0% in non-OTI-attacks), C2 (75% versus 1.9%), C3 (62.5% versus 1.9%), and C4 and C5 levels (50% versus to 3.9%). One OTI-attack resulted in the death of one patient. Five patients with OTI-attack had mRS ≤ 2 one year after OTI-attack. Two (25%) OTI-attacks had poor recovery compared to 15 (24.2%) non-OTI-attacks (p = 0.468). Conclusion: OTI-attacks occurred in untreated NMOSD-AQP4-IgG+ patients and were associated with edematous upper cervical lesions. The prognosis of these attacks may be favorable, and warrant maximal medical and supportive treatment. Trial registration This was a retrospective observational monocentric cohort study nested in the NOMADMUS cohort (ClinicalTrials.gov Identifier: NCT02850705) [ABSTRACT FROM AUTHOR]

Background: Late-onset neutropenia (LON), defined as an absolute neutrophil count (ANC) < 1500/mm3 that develops between 4 weeks and 6 months after the last drug administration, is a rare side effect of anti-CD20 drugs including ocrelizumab. Although continuation of ocrelizumab after LON is not contraindicated, the risk of LON recurrence is not well known. Cases: We report three cases of recurrent symptomatic agranulocytosis (ANC < 500/mm3) occurring under ocrelizumab. Conclusion: Given the risk of recurrence of symptomatic agranulocytosis and the availability of other treatments, a therapeutic switch may be discussed after the first episode of LON. [ABSTRACT FROM AUTHOR]