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

CLINICAL PROJECT 2: Project Summary Neuroinflammatory diseases, such as autoimmune encephalitis (AE), new onset refractory status epilepticus (NORSE), and Rasmussen syndrome, can present with abrupt onset of severe neurological symptoms such as cognitive, psychiatric, and epilepsy. These diseases are included in our registry entitled ARISEN (Autoimmunity, Rasmussen’s, Inflammation & Status Epilepticus research Network) as AE overlaps with NORSE and Rasmussens. These diseases also have presumed inflammatory causes. Clinical course, recovery, and treatment response is variable in these diseases, high mortality and >90% have residual neurocognitive symptoms. Thus, patients are impaired from their disease, and as an extension, their caregivers are also affected, but very few studies have explored patient and caregiver reported outcomes. Moreover, the common outcome measure reported in these patients do not adequately capture the clinical course or outcomes in these patients, and thus, improved outcome measures are needed in these diseases in a larger cohort. In ARISEN, we will obtain patient and caregiver reported outcomes to further understand their experience, as this is critical to clinical trial study design, since the goal of clinical trials is to improve outcomes. Since ARISEN includes patients with anti-NMDARE not included in the U01 NeuroNext ExTINGUISH clinical trial, we include outcome measures from the ExTINGUISH trial to harmonize both patient datasets for comparison studies. Other assessments include the CASE (Clinical Assessment Scale in Autoimmune Encephalitis), a 27-point scale that includes a score of 0-3 in 9 categories affected in autoimmune encephalitis. For patient reported outcomes (PROs), we include Quality of Life (QoL) Measure and the validated NIH toolbox measure Patient-Reported Outcomes Measurement Information System (PROMIS). For caregivers, we include the Caregiver Global Impression (CaGI) Scales and the Quality of Life Disability (QI-Disability), validated in caregivers of children with intellectual impairment. We also include the Cognitive and Linguistic Scale (CALS), as we have data that the CALS is a complementary measure to the mRS and CASE in children with anti- NMDARE. We will assess these scales in children and adults, a strength of this registry since children are understudied. We have partnered with patient advocacy groups (PAGs) for identify improved outcome measures. Aim 1 will measure and compare patient and caregiver reported outcomes within autoimmune encephalitis, NORSE, and Rasmussen syndrome. Aim 2 will Identify factors that impact patient and caregiver reported outcomes in autoimmune encephalitis, NORSE, and Rasmussen syndrome. Aim 3 is to identify optimal cognitive screening measures that are short, without practice effect, and capture the neurocognitive sequelae are needed for future clinical trials. The goals of this project are to identify optimal outcome assessments that are more sensitive to clinical changes, more accurately reflect outcomes and could be validated in future studies to prepare for clinical trial design, including in children. Project Number: 1U54HD122209-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: GRACE GOMBOLAY | Institution: EMORY UNIVERSITY, ATLANTA, GA | Award Amount: $109,239 | Activity Code: U54 | Study Section: Special Emphasis Panel[ZTR1 RD-4 (02)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1U54HD12220901