Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study.

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.

Mutation in the 3'untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy.

Aß-related cerebral amyloid angiopathy (CAA) is a major cause of primary non-traumatic brain hemorrhage. In families with an early onset of the disease, CAA can be due to amyloid precursor protein (APP) pathogenic variants or duplications. APP duplications lead to a ~1.5-fold increased APP expression, resulting in Aß overproduction and deposition in the walls of leptomeningeal vessels. We hypothesized that rare variants in the 3'untranslated region (UTR) of APP might lead to APP overexpression in patients with CAA and no APP pathogenic variant or duplication. We performed direct sequencing of the whole APP 3'UTR in 90 patients with CAA and explored the functional consequences of one previously unreported variant. We identified three sequence variants in four patients, of which a two-base pair deletion (c.*331_*332del) was previously unannotated and absent from 175 controls of same ethnicity. This latter variant was associated with increased APP expression in vivo and in vitro. Bioinformatics and functional assays showed that the APP c.*331_*332del variant affected APP messenger RNA (mRNA) structure and binding of two microRNAs (miR-582-3p and miR-892b), providing a mechanism for the observed effects on APP expression. These results identify APP 3'UTR sequence variants as genetic determinants of Aß-CAA.

[Atrial fibrillation in an acute stroke unit]. / La fibrillation atriale en unité de soins intensifs neuro- vasculaire (USINV).

Contrasting with the abundant literature dedicated to atrial fibrillation (AF) and to the use of new oral anticoagulants in this setting, very few recent studies have focused on patients with AF-associated stroke. From November 2010 to March 2011, we conducted a small prospective 4-month study in the stroke units of Lariboisière and Bicêtre hospitals. Fifty patients with FA and stroke were included (14% of all strokes), including 45 patients with cerebral infarcts (CI), 3 with transient ischemic attacks (TIA) and 2 with intracerebral hemorrhage (ICH). The results of this study, together with a review of the sparse relevant literature, underline the following points: these patients tend to be older and more frequently female than in recent clinical trials; TIAs are rare; these patients have numerous vascular risk factors and associated cerebrovascular diseases such as atheroma and leukoaraiosis; CI is often extensive and hemorrhagic; AF is discovered in a stroke unit in 40% of cases and is paroxystic in 33% of cases, with no consensus on the potential regulation; there is massive underuse of VKA in patients with known AF; rtPA intravenous thrombolysis is frequent; treatment difficulties arise in patients with AF-related CI and a history of ICH; the prognosis of VKA-related ICH is poor; the use of oral anticoagulants alone or combined with aspirin is controversial in case of AF associated with severe atheroma. Patients with AF seen in stroke units are therefore very different from those seen by cardiologists: they are older and have many vascular risk factors, stroke, and other cerebrovascular lesions, raising difficult treatment issues owing to the dual risk of embolic recurrence and symptomatic hemorrhagic transformation. In addition, contraindications to long-term VKA use are frequent. Many of these issues will again be raised with the arrival of new oral anticoagulants.