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Background and Objectives: Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes., Methods: Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method., Results: We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%., Discussion: The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk., Classification of Evidence: This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Objectives: Compelling evidence indicates a significant involvement of cortical lesions in the progressive phase of multiple sclerosis (MS), significantly contributing to late-stage disability. Despite the promise of ultra-high-field magnetic resonance imaging (MRI) in detecting cortical lesions, current evidence falls short in providing insights into the existence of such lesions during the early stages of MS or their underlying cause. This study delineated, at the early stage of MS, (1) the prevalence and spatial distribution of cortical lesions identified by 7 T MRI, (2) their relationship with white matter lesions, and (3) their clinical implications., Materials and Methods: Twenty individuals with early-stage relapsing-remitting MS (disease duration <1 year) underwent a 7 T MRI session involving T1-weighted MP2RAGE, T2*-weighted multiGRE, and T2-weighted FLAIR sequences for cortical and white matter segmentation. Disability assessments included the Expanded Disability Status Scale, the Multiple Sclerosis Functional Composite, and an extensive evaluation of cognitive function., Results: Cortical lesions were detected in 15 of 20 patients (75%). MP2RAGE revealed a total of 190 intracortical lesions (median, 4 lesions/case [range, 0-44]) and 216 leukocortical lesions (median, 2 lesions/case [range, 0-75]). Although the number of white matter lesions correlated with the total number of leukocortical lesions (r = 0.91, P < 0.001), no correlation was observed between the number of white matter or leukocortical lesions and the number of intracortical lesions. Furthermore, the number of leukocortical lesions but not intracortical or white-matter lesions was significantly correlated with cognitive impairment (r = 0.63, P = 0.04, corrected for multiple comparisons)., Conclusions: This study highlights the notable prevalence of cortical lesions at the early stage of MS identified by 7 T MRI. There may be a potential divergence in the underlying pathophysiological mechanisms driving distinct lesion types, notably between intracortical lesions and white matter/leukocortical lesions. Moreover, during the early disease phase, leukocortical lesions more effectively accounted for cognitive deficits., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Exit strategies such as de-escalations have not been evaluated for rituximab in patients with neuromyelitis optica spectrum disorder (NMOSD). We hypothesized that they are associated with disease reactivations and aimed to estimate this risk., Methods: We describe a case series of real-world de-escalations from the French NMOSD registry (NOMADMUS). All patients met the 2015 International Panel for NMO Diagnosis (IPND) diagnostic criteria for NMOSD. A computerized screening of the registry extracted patients with rituximab de-escalations and at least 12 months of subsequent follow-up. We searched for 7 de-escalation regimens: scheduled discontinuations or switches to an oral treatment after single infusion cycles, scheduled discontinuations or switches to an oral treatment after periodic infusions, de-escalations before pregnancies, de-escalations after tolerance issues, and increased infusion intervals. Rituximab discontinuations motivated by inefficacy or for unknown purposes were excluded. The primary outcome was the absolute risk of NMOSD reactivation (one or more relapses) at 12 months. AQP4+ and AQP4- serotypes were analyzed separately., Results: We identified 137 rituximab de-escalations between 2006 and 2019 that corresponded to a predefined group: 13 discontinuations after a single infusion cycle, 6 switches to an oral treatment after a single infusion cycle, 9 discontinuations after periodic infusions, 5 switches to an oral treatment after periodic infusions, 4 de-escalations before pregnancies, 9 de-escalations after tolerance issues, and 91 increased infusion intervals. No group remained relapse-free over the whole de-escalation follow-up (mean: 3.2 years; range: 0.79-9.5), except pregnancies in AQP+ patients. In all groups combined and within 12 months, reactivations occurred after 11/119 de-escalations in patients with AQP4+ NMOSD (9.2%, 95% CI [4.7-15.9]), from 0.69 to 10.0 months, and in 5/18 de-escalations in patients with AQP4- NMOSD (27.8%, 95% CI [9.7-53.5]), from 1.1 to 9.9 months., Discussion: There is a risk of NMOSD reactivation whatever the rituximab de-escalation regimen., Trial Registration Information: Registered on ClinicalTrials.gov: NCT02850705., Classification of Evidence: This study provides Class IV evidence that de-escalation of rituximab increases the probability of disease reactivation., (© 2023 American Academy of Neurology.)

Objectives: Ultra-high field magnetic resonance imaging (MRI) (≥7 T) is a unique opportunity to improve the clinical diagnosis of brain pathologies, such as multiple sclerosis or focal epilepsy. However, several shortcomings of 7 T MRI, such as radiofrequency field inhomogeneities, could degrade image quality and hinder radiological interpretation. To address these challenges, an original synthetic MRI method based on T1 mapping achieved with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence was developed. The radiological quality of on-demand T1-based contrasts generated by this technique was evaluated in multiple sclerosis and focal epilepsy imaging at 7 T., Materials and Methods: This retrospective study was carried out from October 2017 to September 2019 and included 21 patients with different phenotypes of multiple sclerosis and 35 patients with focal epilepsy who underwent MRI brain examinations using a whole-body investigative 7 T magnetic resonance system. The quality of 2 proposed synthetic contrast images were assessed and compared with conventional images acquired at 7 T using the MP2RAGE sequence by 4 radiologists, evaluating 3 qualitative criteria: signal homogeneity, contrast intensity, and lesion visualization. Statistical analyses were performed on reported quality scores using Wilcoxon rank tests and further multiple comparisons tests. Intraobserver and interobserver reliabilities were calculated as well., Results: Radiological quality scores were reported higher for synthetic images when compared with original images, regardless of contrast, pathologies, or raters considered, with significant differences found for all 3 criteria (P < 0.0001, Wilcoxon rank test). None of the 4 radiologists ever rated a synthetic image "markedly worse" than an original image. Synthetic images were rated slightly less satisfying for only 3 epileptic patients, without precluding lesion identification., Conclusion: T1-based synthetic MRI with the MP2RAGE sequence provided on-demand contrasts and high-quality images to the radiologist, facilitating lesion visualization in multiple sclerosis and focal epilepsy, while reducing the magnetic resonance examination total duration by removing an additional sequence., Competing Interests: Conflicts of interest and sources of funding: This study was supported by the following funding sources: 7T-AMI ANR-11-EQPX-0001, A*MIDEX-EI-13-07-130115-08.38-7T-AMISTART, Fondation ARSEP (Fondation pour l'Aide à la recherche sur la Sclérose en Plaques), and CNRS (Centre National de la Recherche Scientifique). Dr Massire is an employee of Siemens Healthcare SAS since September 2019. Dr Troalen is currently an employee of Siemens Healthcare SAS. Dr Kober is a current employee and shareholder of Siemens Healthcare AG and holds patents filed by Siemens Healthcare. For the remaining authors, no relevant relationships are declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD)., Methods: We retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR)., Results: A total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; p = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; p = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF ( p = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA., Conclusions: The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status., Classification of Evidence: That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse., (© 2020 American Academy of Neurology.)

Objective: To perform a systematic analysis and scoring of brain MRI white matter hyperintensities (WMH) in adult-onset Krabbe disease., Methods: We retrospectively collected basic clinical data and the first available brain MRI from patients with confirmed Krabbe disease with first clinical manifestations beyond 10 years of age. Data were obtained from our reference center for lysosomal diseases (n = 6) and from contacted authors of published articles describing patients with adult-onset Krabbe disease (n = 15). T2-weighted fluid-attenuated inversion recovery images of each patient were analyzed and scored using a radiologic score of WMH in a single center., Results: The corticospinal tract was always affected by WMH (100% of patients), however, with some distinctions along the tract: the precentral gyrus (100%), corona radiata (95%), and posterior internal capsule (81%) were highly abnormal, whereas the mesencephalon (57%), pons (52%), and medulla oblongata (5%) were less affected. WMH were also frequently present in the posterior lateral periventricular white matter (95%), optic radiations (86%), postcentral gyrus (71%), medial lemniscus (62%), and corpus callosum, especially in the isthmus (71%), whereas the genu was always normal. A few patients did not have the classical MRI pattern but extensive hyperintensities (n = 3), or patchy distribution of hyperintensities mimicking an acquired etiology (n = 2), or very subtle hyperintensities of the corticospinal tract (n = 1)., Conclusions: We specified the main locations of WMH, which were observed in the earliest stages of the disease and were also present in patients with atypical MRI pattern, highlighting the importance of radiologic features to guide the diagnosis., (© 2019 American Academy of Neurology.)

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 ( p = 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., (© 2018 American Academy of Neurology.)

Objective: To investigate whether brain total sodium accumulation assessed by 23 Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS)., Methods: Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using 23 Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and 1 H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction)., Results: The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0-4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively., Conclusions: This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex., (© 2016 American Academy of Neurology.)

In recent years, evidence has accumulated regarding the ability of HAART to prevent HIV transmission. Early supportive evidence was derived from observational, ecological and population-based studies. More recently, a randomized clinical trial showed that immediate use of HAART led to a 96% decrease in HIV transmission events within HIV serodiscordant heterosexual couples. However, the generalizability of the effect of HAART, and the population-level impact on HIV transmission continues to generate substantial debate. We, therefore, conducted a review of the evidence regarding the preventive effect of HAART on HIV transmission within the context of the Bradford Hill criteria for causality. Taken together, we find the accumulated evidence supporting HIV treatment as prevention meets each of the Bradford Hill criteria for causality. We conclude that the opportunity cost of inaction while waiting for additional evidence on the generalizability of effect in other risk groups is too high. Efforts should be redoubled to mobilize the financial capital and political will to optimize implementation of HIV Treatment as Prevention strategies on a wide scale.