Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System
Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System
Inflammatory or degenerative diseases of the brain and spinal cord, such as multiple
 sclerosis, may be related to problems with an individual s immune system. However, more
 information is needed on the ways in which the cells of the immune system interact with the
 central nervous system (CNS). This study will compare tests performed on both healthy
 volunteers and individuals who have signs or symptoms of immune-related damage to their CNS.

 This study will include two groups of subjects at least 12 years old. Subjects will either
 have symptoms of immune-related CNS damage, or will be healthy volunteers selected for
 comparison purposes.

 Study participants will visit the NIH Clinical Center on an outpatient basis for an initial
 evaluation visit. During the visit, patients will provide a comprehensive medical history and
 undergo a neurological examination, and will provide blood samples for research purposes. The
 healthy volunteers will be asked to schedule a return visit for a magnetic resonance imaging
 (MRI) procedure, and may be asked to undergo other tests requested by the study researchers
 on an as-needed basis. The group of patients with symptoms of immune-related CNS damage will
 be asked to undergo a series of tests, including the following:

 -  MRI procedures, with a minimum of three brain MRIs and one spinal cord MRI taken
 approximately 4 weeks apart

 -  A diagnostic lumbar puncture, performed on an outpatient basis

 -  Tests of brain and vision activity

 -  Additional blood and tissue samples

 All study participants will return for a followup visit 1 year after the initial evaluation
 visit. Patients with symptoms of immune-related CNS damage may be offered the opportunity to
 participate in additional followup tests with NIH researchers.
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.

 The 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 and 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 immunemediated

 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
 year 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 will provide sex and age-matched (to adult patients) normative values.

 "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.

 Outcome Measures:

 MRI and immunological outcomes are outlined in section 8. However, no pre-defined research
 questions will be addressed other than to establish the diagnosis, determine the level of
 disease activity, and monitor the natural history.
-  PATIENT INCLUSION CRITERIA (for participation in the whole protocol):

 1. Presentation with a clinical syndrome consistent with immune-mediated CNS
 disorder and/or

 2. Neuroimaging evidence of inflammatory and/or demyelinating/ dysmyelinating CNS
 disease

 3. At least 12 years old at the time of enrollment

 4. Adults: Able to give informed consent on their own or via a Legally Authorized
 Representative (LAR) or Durable Power of attorney (DPA), or Minors: parent or
 legal guardian able to give consent, with child willing to give assent, if
 reasonable based on their age and assent capacity, able to give assent with
 consent given by their parent or legal guardian

 5. Able to undergo the required procedures, including LP, MRI and
 clinical/functional evalautions.

 HEALTHY VOLUNTEER INCLUSION CRITERIA:

 1. At least 18 years old at the time of enrollment

 2. Vital signs are found within normal range at the time of the screening visit

 3. Able to give informed consent

 4. Able to undergo related research procedures, such as blood draw, LP

 PATIENT INCLUSION CRITERIA for processing of collected biological samples:

 1. Presentation with a clinical syndrome consistent with immune-mediated CNS disorder
 and/or

 2. Neuroimaging evidence of inflammatory and/or demyelinating/ dysmyelinating CNS disease

 3. Ability to obtain either direct or surrogate informed consent for sample processing
 and storage

 PATIENT EXCLUSION CRITERIA (for participation in the whole protocol):

 1. Significant medical condition that would make participation in diagnostic and research
 part of evaluation impossible or risky

 2. Medical contraindications for MRI (ie- any non-organic implant or other device such as
 a cardiac pacemaker or infusion pump or other metallic implants, objects or body
 piercings that cannot be removed)

 3. Unable to provide informed consent

 4. Unwilling to consent for collection of biological samples or their cryopreservation

 HEALTHY VOLUNTEER EXCLUSION CRITERIA:

 1. Systemic inflammatory disorder or inflammatory or non-inflammatory nurological
 diseases.

 2. Previous or current history of alcohol and substance abuse

 3. Medical contraindications for MRI (i.e. any non-organic implant or other device such
 as a cardiac pacemaker or infusion pump or other metallic implants, objects or body
 piercings that cannot be removed)

 4. Medical contraindication for LP

 5. Psychological contraindications for MRI (i.e. claustrophobia). This will be assessed
 at the time the medical history is collected.

 6. Pregnancy or current breastfeeding

 7. Any contraindications to having study procedures done<TAB>

 8. History of auditory disorder (i.e. hearing impairment, known impaired acoustic reflex,
 tinnitus)

 HEALTHY VOLUNTEER SUB STUDY TO OBTAIN NORMATIVE DATA FOR THE SMARTPHONE APPS:

 1. Because this sub study collects no personal identifiable information (PII), there are
 no inclusion/exclusion criteria.

 2. Participating subjects are self-declared as not having any neurological deficit, which
 would be the same population that would provide normative data if the apps were freely
 available via App store.