Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System

OBJECTIVE The goal of this study is to define the pathophysiological mechanisms underlying the development of disability in immune-mediated disorders of the central nervous system (CNS) and to distinguish these from beneficial responses of the human immune system to CNS injury. The protocol serves as a screening tool for Neuroimmunological Diseases Section (NDS) of the National Institute of Allergy and Infectious Diseases (NIAID) clinical trials and enables development of clinically-useful tools such as diagnostic tests and new, sensitive scales of neurological disability, disease severity and CNS tissue destruction. This protocol also serves as a repository to enable prospective institutional review board (IRB) review of research using human samples and data collected under other NDS protocols. STUDY POPULATION Patients with evidence, or suspicion of immune-mediated CNS injury. Healthy volunteers (HV) are included as controls for immunological and imaging biomarkers and to obtain normative data for development of new clinical scales and smartphone apps. DESIGN Collection of multimodal data (standardized clinical/functional, neuroimaging and molecular/immunological data) during the diagnostic work-up of patients with varied disorders of the CNS in which immune-mediated processes are expected to play a pathophysiological role. For the patient cohort, a comprehensive evaluation establishes a definitive diagnosis or confirms diagnosis and subtype of multiple sclerosis (MS) as a pre-requisite for enrollment into NDS clinical trials. Adult patients have a mandatory follow-up visit approximately 1-2 years from protocol enrollment. Depending on the diagnosis and clinical/research needs, patients may be offered additional follow-up visits. The maximum frequency of the follow-up visits and research samples to be collected is specified to ensure patient safety. Patients age 12-17 years are included in the patient cohort to establish a definitive diagnosis, or to provide non-standard assays to help with diagnostic and therapeutic decisions as part of extraordinary clinical care. The HV provide sex and age-matched (to adult patients) normative values. A "telemedicine" patient sub-cohort enrolls patients who cannot (for any reason, but usually advanced disability) come to NIH for in-person evaluation. From these telemedicine patients, we will estimate neurological disability by Combinatorial MRI Scale (COMRIS) models derived from outside brain and spinal cord MRIs, and by NeuFun-TS smartphone application. Telemedicine patients will contribute capillary blood from at-home collection kits for research applications. Telemedicine patients with confirmed diagnosis of neuroimmunological disorder may be referred to NIAID Centralized Sequencing protocol (17-I-0122) for genetic testing. A "sample processing only" patient subcohort enrolls patients from whom only biological samples and data collected by outside clinicians are processed and evaluated to provide non-standard assays. A collaboration was in place until December 26, 2022, with the U.S. Food \& Drug Administration that included collection of clinical and normative data for diagnostic and research purposes. The FDA Principal Investigator Dr. Wenyu Sun will assist with the needs of the protocol by performing minimal protocol related procedures. Such procedures are discussed throughout Study Design and Methods. OUTCOME MEASURES Clinical, MRI, and immunological outcomes are outlined in this section. However, no pre-defined research questions will be addressed other than to establish the diagnosis, determine the level of disability, provide prognostic information, and monitor the natural history.