Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Multiple Sclerosis Inclusion Criteria

• Enrolled in the NINDS Natural History Study for MS (protocol 89-N-0045)

• Able to understand, and willing to sign, a written, informed consent document.

• Willing to comply with all study procedures and available for the duration of thestudy.

• Male or female, aged >=18.

• Diagnosis of MS according to the 2017 revision of the McDonald diagnostic criteria48 (in the presence or absence of a clinical relapse).

PML Inclusion Criteria

• Enrolled in the NINDS Natural History Study for PML (protocol 13-N-0017)

• Able to understand and willing to sign a written, informed consent document

• Willing to comply with all study procedures and available for the duration of thestudy.

• Male or female, aged >=18.

• Diagnosis of definite PML according to 2013 AAN Consensus Criteria49 or PML-IRISbased on clinical, radiological and laboratory evidence.

Patients with Known or Suspected Neuroinflammatory Diseases and Evidence of Open BBB Inclusion Criteria

• Clinical evaluation suggesting an inflammatory disorder of the central nervoussystem other than MS or PML.

• Recent brain MRI (within 1 month) with gadolinium enhancement indicating open BBB.

• Able to understand and willing to sign a written, informed consent document.

• Willing to comply with all study procedures and available for the duration of thestudy.

• Male or female, aged >=18.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnant or lactating.

• Contraindications for MRI gadolinium contrast administration or 3T MRI.

• History of, or current diagnosis with, concomitant medical or clinical conditionsthat would adversely affect participation in this study.

• Weighs > 350 lb (158 kg; weight limit for the scanner table) or is unable to fitwithin the MRI or PET imaging gantry.

• Severe claustrophobia unresponsive to oral anxiolytics.

• Has an alkaline phosphatase level greater than 2x ULN (unless known to havenon-liver related disorder) OR AST greater than 1.5 x ULN OR ALT greater than 1.5 xULN.

• Has a total bilirubin >1.5X ULN, unless known to have elevated bilirubin due tononliver related disorder or Gilbert s.

• Creatinine clearance < 60 mL/min as estimated by the Chronic Kidney DiseaseEpidemiology Collaboration (CKD-EPI)

• For females of reproductive potential: inability to use highly effectivecontraception for at least one month prior to screening and during studyparticipation.