ARISEN (Autoimmunity, Rasmussen’s, Inflammation & Status Epilepticus research Network)

Emory University, Atlanta GA

Investigators

Abstract

CLINICAL PROJECT 1: Longitudinal Course in Autoimmune Encephalitis, Rasmussen Syndrome, and new onset refractory status epilepticus (NORSE) Project/Narrative This project aims to longitudinally study the clinical course and neurocognitive outcomes in rare neuroinflammatory diseases: autoimmune encephalitis (AE), Rasmussen Syndrome (RS), and new onset refractory status epilepticus (NORSE) by leveraging a novel multi-center patient registry, ARISEN (Autoimmunity, Rasmussen's, Inflammation & Status Epilepticus research Network). Patients can develop new onset seizures that are challenging to treat, which can be caused by AE, Rasmussen, or NORSE. These disorders can mimic each other, leading to diagnostic challenges. Furthermore, the risk of mortality is high in these diseases, and survivors can have severe neurological sequelae with >90% not returning to baseline, yet neurocognitive outcomes are not well-defined in these diseases. This lack of clinical phenotyping is a barrier to clinical trials, and current studies are mainly retrospective. ARISEN addresses this challenge by being the first multi-center prospective patient registry for AE, RS, and NORSE. A natural history study without intervention would be unethical as patients are at high risk for mortality and severe neurocognitive symptoms, including intensive care unit admission, and thus their symptoms require symptomatic treatment concurrently with immunomodulatory therapies. Here we propose a longitudinal clinical history study to assess longer term outcomes, as we identify more applicable outcome measures including patient/caregiver reported outcomes (Project 2) along with biomarker studies and novel antibody discovery (Project 3). This is not an interventional study as we will not control the treatments. Even within AE, there are different heterogeneous diseases, including multiple antibody-associated diseases that respond differently to treatment, and then patients who test negative to antibodies (seronegative AE). Seronegative AE patients likely have undiscovered anti-neuronal antibodies, and while a heterogeneous population, seronegative AE inclusion has been requested by our patient advocacy groups (PAGs). This heterogeneity in treatments and treatment response highlights the need for clinical trials. ARISEN is a synergistic effort that builds on the strengths of two consortia: CONNECT (CONquering Inflammation and Epilepsies ConsorTium), which is the first multi-center prospective U.S.-based registry for AE, and the NORSE Institute. CONNECT is unique in its pediatric focus, as children are understudied. This project aims to understand the longitudinal disease course and long-term outcomes in these diseases. Aim 1 will focus longitudinal studies in AE, including the different antibody subtypes and seronegative AE. Aim 2 will focus on the longitudinal course in Rasmussens including the difference in those patients who undergo hemispherectomy versus those who do not. Aim 3 will assess longitudinal and long-term outcomes in patients with NORSE. ARISEN can be the prospective study on the longitudinal course and longterm outcomes to help us understand how patients currently affected by their diseases to better assess treatment efficacy for clinical trial readiness. Project Summary/Abstract