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

Patients with symptoms of immune-related CNS damage may be offered the opportunity to participate in additional followup tests with NIH researchers.

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.

Eligibility Criteria:
* PATIENT INCLUSION CRITERIA (for in-person and telemedicine sub-cohorts):

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

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

At least 12 years old at the time of enrollment

Willing to share medical records (including past MRI results) with the study team.

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

For in-person sub-cohort: Able to undergo the required procedures, including LP, MRI and clinical/functional evalautions.

HEALTHY VOLUNTEER (in person) INCLUSION CRITERIA:

At least 18 years old at the time of enrollment

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

Able to give informed consent

Able and willing to undergo related research procedures, such as blood draw, LP

PATIENT INCLUSION CRITERIA for processing of collected biological samples:

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

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

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

Aged 0+ years

PATIENT EXCLUSION CRITERIA (for in-person and telemedicine subcohorts):

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

For in-person sub-cohort: 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)

Unable to provide informed consent

Unwilling to consent for collection of biological samples or their cryopreservation

HEALTHY VOLUNTEER (in person) EXCLUSION CRITERIA:

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

Previous or current history of alcohol and substance abuse

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)

Medical contraindication for LP

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

Pregnancy or current breastfeeding

Any contraindications to having study procedures done\<TAB\>

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:

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

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.