Inflammatory and Infectious Diseases of the Nervous System

Objective:

The objective of this study is to examine the natural course of infectious and inflammatory
diseases of the nervous system, to identify causative or associated pathogens when unknown,
and generally to better understand the underlying immunological, genetic and pathophysiologic
mechanisms that cause and contribute to these diseases and their ultimate neurological
outcomes.

Study Population:

The study population will be patients at least 2 years old with known or suspected infection
or inflammation of the nervous system. Subjects will be recruited through referrals to the
NIH.

Design:

This is a longitudinal case series with standardized research data collection at predefined
time points. Subjects will have scheduled visits at the NIH either as an outpatient or an
inpatient. The core research evaluations include: a comprehensive history and neurological
examination; blood, urine, and saliva collection; neuroimaging; and lumbar puncture. All
subjects who are willing and able will be asked to return for at least a 1-year follow up
visit. Subjects will be eligible for longitudinal follow up until the clinical phenotype has
been fully characterized or the subject is too ill to participate in further evaluations.

Additionally, we will also enroll subjects with known or suspected infections or inflammation
of the nervous system from whom only biological samples collected by outside clinicians will
be processed and retained for research analyses. In cases were samples remain from those
collected for clinical reasons and the samples are deidentified and coded, the samples may be
obtained with a waiver of informed consent.

Outcome Measures:

The study outcomes will primarily be the characterizations of varied inflammatory and
infectious nervous system diseases. These characterizations will include: the clinical
phenotype and biomarkers.

- INCLUSION CRITERIA:

At the time of enrollment, subjects will:

1. Have a known or suspected infection or inflammation of the nervous system based on
clinical or imaging data provided by the referral facility. For the purpose of this
study, neuroinfectious disease or neuroinflammation is defined as any of the
following:

1. fever with nervous system signs or symptoms (excluding delirium)

2. any neurological symptoms accompanied by cerebrospinal fluid (CSF) with evidence
of inflammation (which may include pleocytosis, hypoglycorrachia, elevated
protein, or other evidence of intrathecal immune activation including IgG index
or presence of oligoclonal bands)

3. systemic infection or inflammatory disease with neurological involvement

4. neuroimaging suggestive of infection or inflammation (for example, presence of
contrast-enhancing lesions on CT or MRI)

5. clinical presentation suggestive of infection or inflammatory process of the
nervous system without better explanation

2. Be willing to participate in the protocol s procedures, unless clinically
contraindicated

3. Be willing to provide informed consent, either directly or via appointed legally
authorized representative

4. Be willing to consent for collection of clinical data or biological samples or their
cryopreservation

5. Be at least 2 years old

INCLUSION CRITERIA FOR PROCESSING OF BIOLOGICAL SAMPLES ONLY:

At the time of enrollment, subjects will:

1. Have a known or suspected infection or inflammation of the nervous system based on
clinical or imaging data provided by the referral facility. For the purpose of this
study, neuroinfectious disease or neuroinflammation is defined as any of the
following:

1. fever with nervous system signs or symptoms (excluding delirium)

2. any neurological symptoms accompanied by cerebrospinal fluid (CSF) with evidence
of inflammation (which may include pleocytosis, hypoglycorrachia, elevated
protein, or other evidence of intrathecal immune activation including IgG index
or presence of oligoclonal bands)

3. systemic infection or inflammatory disease with neurological involvement

4. neuroimaging suggestive of infection or inflammation (for example, presence of
contrast-enhancing lesions on CT or MRI)

5. clinical presentation suggestive of infection or inflammatory process of the
nervous system without better explanation

2. Be willing to provide informed consent, either directly or via appointed legally
authorized representative

3. Be willing to consent for collection of clinical data or biological samples or their
cryopreservation

4. Be at least 2 years old

EXCLUSION CRITERIA:

At the time of enrollment, subjects will:

1. Not have a clinically significant medical condition that, in the best judgment of the
investigators, may expose the patient to undue risk of harm or prevent the patient
from completing the study (examples include, but are not limited to, ischemic
cardiomyopathy, clotting disorder, brittle diabetes)

2. Not have an acute or unstable medical condition that, in the best judgement of the
investigator, would be difficult to handle at the NIH Clinical Center

3. Not have a clearly-established diagnosis of well-characterized disease entity with
validated treatment algorithms for which proposed resource investment, in the opinion
of the investigators, would not contribute to further advancement of knowledge

EXCLUSION CRITERIA FOR PROCESSING OF BIOLOGICAL SAMPLES ONLY:

At the time of enrollment, subjects will not have:

1. A clearly-established diagnosis of well-characterized disease entity with validated
treatment algorithms for which proposed resource investment, in the opinion of the
investigators, would not contribute to further advancement of knowledge