Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)
Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)
Background:

 PANS is an illness that comes on suddenly in children. The full name is Pediatric Acute-Onset
 Neuropsychiatric Syndrome. It can cause sudden obsessive-compulsive behaviors. It can also
 cause children to suddenly restricte their food intake. Researchers want to learn more about
 children with PANS. They also want to learn more about the illness.

 Objective:

 To study some disorders of behavior and emotion that start in childhood.

 Eligibility:

 Children 3 14 years old who have had severe obsessive-compulsive symptoms or food restriction
 start quickly

 Design:

 Parents will answer questions. The topics include:

 Their child s medical history

 Their child s physical and mental health

 Their family history. The focus will be on neurodevelopmental and psychiatric conditions. A
 family tree will be drawn.

 Participants will have a physical exam.

 Participants may take tests on paper or computer. These will focus on thinking, memory, and
 behavior.

 Participants and parents will give a blood sample.

 Participants will have magnetic resonance imaging (MRI). A strong magnetic field and radio
 waves take pictures of the brain. Participants will lie on a table that slides in and out of
 a metal scanner.

 Participants may have photos or videos taken.

 Participants may have other tests. These may include heart tests, sleep tests, and lumbar
 puncture.

 Sponsoring Institute: National Institute of Mental Health
This multi-site study is intended to collect data and samples from a nationwide cohort of
 children with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is defined by
 three clinical criteria:

 1. Abrupt, dramatic onset of obsessive-compulsive disorder (OCD) or severely restricted

 food intake AND

 2. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and
 acute onset, from at least two of the following seven categories:

 -  Anxiety (particularly separation anxiety)

 -  Emotional lability and depression

 -  Irritability, aggression, and/or severely oppositional behaviors

 -  Behavioral (developmental) regression

 -  Deterioration in school performance (due to inattention, concentration
 difficulties, memory deficits, or others)

 -  Sensory or motor abnormalities

 -  Somatic signs and symptoms, including sleep disturbances, enuresis, or urinary
 frequency

 3. Symptoms are not better explained by a known neurologic or medical disorder, such as
 Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others.

 As a clinical syndrome, PANS likely represents a number of different disorders with unique
 symptom constellations, disease mechanisms, and etiologies. The purpose of this investigation
 is to identify these distinctive disorders by carefully documenting, archiving, and analyzing
 the clinical features of each case of PANS, including not only details of the onset and
 course of symptoms, but also results of physical examination, laboratory assays, and
 paraclinical assessments, such as electroencephalography (EEG), polysomnography (PSG), brain
 imaging (e.g., magnetic resonance imaging [MRI] scans), and others. In addition to defining
 the unique clinical features associated with a specific disorder, we also hope to identify
 biomarkers of risk and disease severity, including not only determinant genes, but also
 environmental triggers, such as those producing post-infectious autoimmunity (e.g., Pediatric
 Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection, or PANDAS). To
 accomplish this, we propose to collect and archive clinical information and biospecimens at
 different stages of the illness (e.g., initial onset, first exacerbation, following known
 environmental triggers, during convalescence, etc.) and also to compare these results against
 data and specimens obtained from healthy controls and children with non-PANDAS OCD, tics,
 anxiety disorders, or eating disorder. Clinical, laboratory, and biomedical data will be
 stored in the NIMH database (housed on the Clinical Trials Database [CTDB] of NICHD) and
 blood, genetic material, and other biospecimens, including microbial cultures, stored in the
 NIMH Genetics/Biological Repository. There are two types of baseline evaluations within this
 protocol. The first is limited to participants with acute-onset neuropsychiatric symptoms
 (PANS subjects) and will be conducted in the NIH Clinical Center by investigators from the
 NIMH Section on Behavioral Pediatrics (Drs. Swedo, Grant, and Hommer.) These in-depth
 phenotyping evaluations will include medical and psychiatric history, family history,
 completion of standardized questionnaires, physical and neurological examinations,
 neuropsychological testing, MRI scan, throat swab (for microbiologic testing), cheek swab (to
 obtain genetic samples), and phlebotomy to obtain blood for laboratory assays and genetic
 testing. Children with undiagnosed acute-onset neuropsychiatric symptoms may undergo
 additional testing as part of the diagnostic evaluation; these assessments might include
 (among others), electroencephalography (EEG), echocardiogram/electrocardiogram (ECHO/ECG)
 and/or polysomnography (PSG). If the child s clinical presentation warrants a lumbar puncture
 as part of the diagnostic evaluation, (e.g. abnormal findings on neurologic exam, EEG or PSG,
 or lab abnormalities suggestive of systemic autoimmunity or neuroinflammation), a sample of
 cerebrospinal fluid will be collected for research, as well as for clinical testing. Sedation
 will not be used for these lumbar punctures, nor will it be used for any research purposes in
 this protocol.

 The second type of baseline evaluation will be used at NIMH for subjects with non-PANDAS
 psychiatric disorders and healthy volunteers. At participating extramural institutions, this
 is the evaluation that will be used for all participants (PANS, non-PANS, healthy volunteers)
 evaluated. These evaluations will include standardized questionnaires, medical and
 psychiatric history, family history, physical examination, throat swab (for microbiologic
 testing), cheek swab (to obtain genetic samples), and phlebotomy to obtain blood for clinical
 assays and research, including genetic studies. The assessments will generally be completed
 in an outpatient clinic at the participating site, but also might be performed on
 hospitalized children, if their medical condition permits research participation. Family
 members of PANS probands will have a medical and psychiatric history and physical exam and
 provide a blood sample (or cheek swab) for genetic research.

 The Affected Probands, Healthy Volunteers, and Subjects with Non-PANS Psychiatric Disorders
 will have follow-up evaluations annually, as well as on Ad Hoc basis. The Annual check-ups
 will include an interim clinical history and relevant symptom ratings (tailored to the
 subject s clinical profile). These follow-up evaluations may be done by phone or
 videoconference. Ad hoc evaluations will occur during periods of health (if not healthy at
 baseline) and during an episode of acute illness (either infectious illness or
 neuropsychiatric symptom exacerbations) and convalescence (at least 8 weeks after recovery).
 These in-person evaluations will include an interim clinical history, relevant symptom
 ratings, phlebotomy to obtain research bloods, and in some cases, acquisition of microbial
 samples (oral, nasal, nasopharyngeal and/or pharyngeal swabs, and feces). To identify
 biomarkers of disease and recovery, children with PANS may be followed until their 18th
 birthday, even if fully recovered from their acute illness. Healthy volunteers and
 psychiatric controls will be followed no longer than 3 years from study entry.

 This is a natural history study, with the primary goal of collecting clinical data and
 biospecimens in order to identify subgroups of patients sharing a common disease mechanism
 and thus provide opportunities for development of new treatment and prevention strategies.
 The wealth of clinical information and the large number of biologic and genetic samples
 acquired in this prospective, longitudinal investigation also permits us to address four
 specific aims:

 1. Identify unique and distinctive clinical, paraclinical, and laboratory features of
 acuteonset neuropsychiatric disorders among patients meeting criteria for PANS.

 2. Determine the role of environmental pathogens, such as Group A streptococci, in the
 etiopathogenesis of acute-onset neuropsychiatric disorders.

 3. Investigate factors influencing host susceptibility and resistance.

 4. Elucidate the role of immune dysfunction in PANS or a subgroup of its patients.

 5. Provide clinical diagnostic assessments to children with undiagnosed acute-onset
 neuropsychiatric symptoms.
-  INCLUSION CRITERIA:

 Affected Probands (Children with PANS) will be eligible if they:

 1. Are 3 to 14 years of age (initial enrollment must occur prior

 2. Have a history of abrupt onset (less than 24-48 hours) of impairing OCD and/or eating
 restrictions.

 3. Are able to travel safely to the regional medical center where the evaluations will be
 conducted and are able to be examined safely over a period of one or more days.

 4. Assent to participate (if they are at least seven years old and have capacity to do
 so) and have legal guardians who consent to their minor child s participation.

 5. Are under the care of a primary physician in their home community.

 First-degree Relatives will be eligible if they:

 1. Are a biologic parent or sibling of an affected proband.

 2. Consent (or assent) to undergo study evaluations and to provide blood, microbial and
 genetic samples.

 Children with Non-PANS Neuropsychiatric Symptoms may be enrolled if they:

 1. Are 3 to 14 years of age (initial enrollment must occur prior to the participant s
 15th birthday to permit prospective longitudinal evaluations)

 2. Have OCD, tics, anxiety disorders, or other psychiatric symptoms, but do NOT have a
 history of acute symptom onset.

 3. Are willing to participate in medical, psychiatric, and behavioral assessments and to
 provide bio-specimens including blood, urine, and microbial flora (mouth, oropharynx,
 and/or stool).

 4. Assent to participate (if they are at least seven years old and have capacity to do
 so) and have legal guardians who consent to their minor child s participation.

 5. Are under the care of a primary physician in their home community.

 Healthy Pediatric Volunteers may be enrolled if they:

 1. Are 3 to 14 years of age (initial enrollment must occur prior to the participant s
 15th birthday to permit prospective longitudinal evaluations).

 2. Are physically healthy and do not have psychiatric symptoms.

 3. Are willing to participate in medical, psychiatric, and behavioral assessments and to
 provide bio-specimens including blood, urine, and microbial flora (mouth, oropharynx,
 and/or stool).

 4. Assent to participate (if they are at least seven years old and have capacity to do
 so) and have legal guardians who consent to their minor child s participation.

 EXCLUSION CRITERIA:

 Participants will not be eligible if they:

 1. Appear to the investigators to be too unstable psychiatrically or medically to
 participate safely in the protocol.

 2. Are unwilling or unable to be evaluated and followed prospectively.

 3. Have a parent/guardian who is not willing to participate at a distance through
 web-based or phone-based data collection.