Clinical Research Directory

High-throughput Omic Technology for Identification of Biomarkers of Relapsing Acute Disseminated Encephalomyelitis in Immune Cell Network

Acute disseminated encephalomyelitis (ADEM) is a neuroinflammatory disorder of the central nervous system, manifesting itself as impaired consciousness, even to the point of coma, and multifocal neurological deficits. ADEM is the most common encephalitis in children. Moreover, 50-65% of ADEM in children is associated with the presence of anti-MOG antibodies (MOGAD). In fact, ADEM is the most frequent clinical presentation of MOGAD in children, 50-75% before the age of 10. The risk of recurrence is higher in pediatric MOGAD of ADEM manifestation, up to 30%, compared to myelitis or optic neuritis. Multiphasic MOGAD are more frequently associated with sequelae in 50-69% of cases, versus 4-32% for monophasic forms. In ADEM, cognitive and epileptic sequelae predominate. The 2020 European consortium and the 2022 national diagnosis and care protocol recommend the introduction of disease-modifying therapies as early as the second attack of the disease, or in the event of distant sequelae, in order to limit relapses and sequelae. However, these treatments take several months to take effect. There is currently no reliable predictive factor for MOGAD recurrence other than the persistence of an elevated blood anti-MOG antibody level (≥1:1280) at 1 year. The aim of this study is therefore to identify biomarkers associated with MOGAD recurrence from the first attack. To this end, we will study the transcriptome of circulating blood mononuclear cells by single-cell next-generation RNA sequencing in children with anti-MOGAD neuroinflammatory relapses. Anticipating the multiphasic trajectory of the disease would enable the introduction of early disease-modifying therapy to prevent recurrences and long-term sequelae. Furthermore, the discovery of a molecular and/or cellular signature would provide a better understanding of the pathophysiology of ADEM and MOGAD.

Neural Autoantibody Prevalence in New-onset Focal Seizures of Unknown Etiology

Seizure is one of the most common symptoms in autoimmune encephalitis with neuronal surface-mediated antibodies. Interestingly, some patients may exhibit new-onset seizures as the initial manifestation without fulminant sign of encephalitis, particularly in the early stage. It is essential to recognize these patients early and to perform antibody testing, as studies have reported early immunotherapy can improve their clinical outcomes. At the same time, it is important to limit the number of patients who require testing, for the sake of specificity and cost effectiveness. Thus, this prospective, multicenter study aims to identify neural antibodies in patients with focal seizures of unknown etiology, and to create a score to preselect patients requiring autoantibody testing.