PANS - A Detailed Study of the Patients, Their Symptoms, Biomarkers and Treatment Offered in a Scandinavian Cohort

Background: Obsessive-compulsive disorder (OCD) is considered one of the most debilitating of the psychiatric illnesses, yet much remains unclear regarding causes and cures. A diagnostic subgroup with acute onset of obsessive-compulsive symptoms (and sometimes tics or anorexia nervosa) possibly due to an autoimmune response, has been entitled Pediatric Acute onset Neuropsychiatric Syndrome (PANS). PANS is sometimes treated with immunomodulatory therapy or antibiotics, with a variable outcome. A diagnosis of PANS is supported by elevated levels of auto-antibodies and antibody-enzyme activity measured with the Cunningham panel, but the relationship between these biomarkers and the patients' symptoms remains unclear. A clinician rated symptom scale for PANS (the PANS scale) has been developed, but needs to be further evaluated regarding sensitivity and specificity.

Aims:

• To assess a Swedish cohort of patients diagnosed with PANS and compile their psychiatric health status, biomarkers, psychiatric symptoms, soft neurological signs and treatment outcomes in a systematic way
• To compare psychiatric health status, biomarkers and psychiatric, neurologic and motor symptoms in this PANS cohort with a control group of psychiatric patients and with healthy children.
• To evaluate the Cunningham panel as a diagnostic tool for PANS.
• To evaluate a clinician rated symptom scale (the PANS scale) as a diagnostic tool for PANS.

Method: Observational study Participants: Patients (n≈150) who have been tested with the Cunningham panel of PANS biomarkers in Sweden (or Swedish patients tested in Denmark) will be asked to participate.

Procedure: Assessment of current symptoms, psychiatric health, neurological and motor symptoms and possible biomarkers for PANS will be collected for all patients. Retrospective assessment through interview and medical records, including results from the first assessment with the Cunningham panel of PANS-biomarkers is made with all patients. 50 out of the total PANS cohort of 150 patients will be re-tested with the Cunningham panel. A control group consisting of psychiatric patients (n=60) and healthy children (n=25) will be examined with a similar test battery and signs and symptoms will be compared with the PANS group.

Significance:

Previous and current symptoms of PANS, levels of PANS biomarkers and treatment outcome will be investigated, thus knowledge regarding long-term outcome and evidence for the use of clinical assessment tools and biomarkers for diagnosing PANS will be gained.

Data collected comprises:

Retrospective data

• Interview
• Medical records
• Five to Fifteen (FTF)
• Cunningham panel of PANS biomarkers result prior to inclusion (at time point 1)
• Change in Clinical Global Impression-Improvement (CGI-I) since the first assessment of the Cunningham panel

Current data

Current levels of Cunningham panel of PANS biomarkers

• Cunningham panel of PANS biomarkers at time point 2

Current neuropsychiatric status

• Psychiatric interview
• PANS symptom scale

Standardized assessment for children:

• Child behavior checklist (CBCL)
• The Autism spectrum Quotient: Children's version (AQ-Child)
• Brief Obsessive-Compulsive Scale (BOCS)
• Mini international Neuropsychiatric Interview - KID (M.I.N.I. KID)
• Five to Fifteen (FTF)

Standardized assessment for adults:

• Schizotypal Personality Disorder Questionnaire (SPQ)
• Liebowitz social anxiety scale (LSAS)
• The Autism spectrum Quotient (AQ)
• Adult ADHD Self-Report Scale (ASRS)
• Brown Attention-Deficit Disorder Scales (Brown ADD Scales)
• Quality of Life Inventory (QOLI)
• Brief obsessive-compulsive scale (BOCS)
• Mini international Neuropsychiatric Interview (M.I.N.I.)
• FTF retrospective data

Current soft neurological signs

• Alternating skips
• Romberg's balance test
• Diadochokinesia
• Involuntary finger movements

Current neuropsychological status

• Drawing exercises
• Writing exercises
• WAIS/WISC Block design
• WAIS/WISC Digit Span
• WAIS/WISC Letter Number Sequencing
• WAIS/WISC Digit Symbol Coding

Current biomarkers in blood/serum

• D8/17 antigen expression
• Human leukocyte antigen (HLA)
• C-reactive protein (CRP)
• T-cell activation
• Human proteome serum analysis

Inclusion Criteria the PANS-group:

• Scandinavian patients assessed with the Cunningham panel through Wieslab, Lund, Sweden or Statens Serum Institut (SSI), Copenhagen, Denmark.

Exclusion Criteria PANS-group:

• intellectual disability, non-Swedish speaking

Inclusion Criteria Psychiatric Controls:

• diagnosed with a psychiatric disorder
• age <40 years

Exclusion Criteria Psychiatric Controls:

• intellectual disability, non-Swedish speaking

Inclusion Criteria Healthy Controls:

• age and sex matched to the PANS-group

Exclusion Criteria Healthy controls:

• intellectual disability, non-Swedish speaking