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

Obsessive-compulsive Disorder Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02190292
• Other study ID #: 523-2011-3646_1
• Status: Completed
• Start date: June 2014

Study information

• Verified date: October 2020
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. primary completion date: June 30, 2017
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Childhood Acute Neuropsychiatric Symptoms (CANS)
• Disease
• Obsessive-Compulsive Disorder
• Obsessive-compulsive Disorder With Acute Onset
• PANDAS
• Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)
• Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
• Streptococcal Infections

Locations

Country	Name	City	State
Sweden	Northern Stockholm psychiatry	Stockholm	Sverige

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska Institutet	The Swedish Research Council

Country where clinical trial is conducted

Sweden, 

References & Publications (22)

Bejerot S, Bruno K, Gerland G, Lindquist L, Nordin V, Pelling H, Humble MB. [Suspect PANDAS in children with acute neuropsychiatric symptoms. Infection behind the disease - long-term antibiotic therapy should be considered]. Lakartidningen. 2013 Oct 9-15;110(41):1803-6. Review. Swedish. — View Citation

Bernstein GA, Victor AM, Pipal AJ, Williams KA. Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2010 Aug;20(4):333-40. doi: 10.1089/cap.2010.0034. — View Citation

Brimberg L, Benhar I, Mascaro-Blanco A, Alvarez K, Lotan D, Winter C, Klein J, Moses AE, Somnier FE, Leckman JF, Swedo SE, Cunningham MW, Joel D. Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders. Neuropsychopharmacology. 2012 Aug;37(9):2076-87. doi: 10.1038/npp.2012.56. Epub 2012 Apr 25. — View Citation

Demiroren K, Yavuz H, Cam L, Oran B, Karaaslan S, Demiroren S. Sydenham's chorea: a clinical follow-up of 65 patients. J Child Neurol. 2007 May;22(5):550-4. — View Citation

Hachiya Y, Miyata R, Tanuma N, Hongou K, Tanaka K, Shimoda K, Kanda S, Hoshino A, Hanafusa Y, Kumada S, Kurihara E, Hayashi M. Autoimmune neurological disorders associated with group-A beta-hemolytic streptococcal infection. Brain Dev. 2013 Aug;35(7):670-4. doi: 10.1016/j.braindev.2012.10.003. Epub 2012 Nov 9. — View Citation

Kirvan CA, Swedo SE, Heuser JS, Cunningham MW. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med. 2003 Jul;9(7):914-20. — View Citation

Kirvan CA, Swedo SE, Snider LA, Cunningham MW. Antibody-mediated neuronal cell signaling in behavior and movement disorders. J Neuroimmunol. 2006 Oct;179(1-2):173-9. Epub 2006 Jul 27. — View Citation

Kurlan R, Johnson D, Kaplan EL; Tourette Syndrome Study Group. Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study. Pediatrics. 2008 Jun;121(6):1188-97. doi: 10.1542/peds.2007-2657. — View Citation

Leckman JF, King RA, Gilbert DL, Coffey BJ, Singer HS, Dure LS 4th, Grantz H, Katsovich L, Lin H, Lombroso PJ, Kawikova I, Johnson DR, Kurlan RM, Kaplan EL. Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2011 Feb;50(2):108-118.e3. doi: 10.1016/j.jaac.2010.10.011. Epub 2010 Dec 31. — View Citation

Leonard HL, Swedo SE. Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Int J Neuropsychopharmacol. 2001 Jun;4(2):191-8. doi: 10.1017/S1461145701002371. — View Citation

Mabrouk AA, Eapen V. Challenges in the identification and treatment of PANDAS: a case series. J Trop Pediatr. 2009 Feb;55(1):46-8. doi: 10.1093/tropej/fmn039. Epub 2008 May 22. — View Citation

Morris-Berry CM, Pollard M, Gao S, Thompson C; Tourette Syndrome Study Group, Singer HS. Anti-streptococcal, tubulin, and dopamine receptor 2 antibodies in children with PANDAS and Tourette syndrome: single-point and longitudinal assessments. J Neuroimmunol. 2013 Nov 15;264(1-2):106-13. doi: 10.1016/j.jneuroim.2013.09.010. Epub 2013 Sep 18. — View Citation

Murphy TK, Goodman WK, Fudge MW, Williams RC Jr, Ayoub EM, Dalal M, Lewis MH, Zabriskie JB. B lymphocyte antigen D8/17: a peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette's syndrome? Am J Psychiatry. 1997 Mar;154(3):402-7. — View Citation

Murphy TK, Kurlan R, Leckman J. The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol. 2010 Aug;20(4):317-31. doi: 10.1089/cap.2010.0043. Review. — View Citation

Murphy TK, Sajid M, Soto O, Shapira N, Edge P, Yang M, Lewis MH, Goodman WK. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biol Psychiatry. 2004 Jan 1;55(1):61-8. — View Citation

Nicholson TR, Ferdinando S, Krishnaiah RB, Anhoury S, Lennox BR, Mataix-Cols D, Cleare A, Veale DM, Drummond LM, Fineberg NA, Church AJ, Giovannoni G, Heyman I. Prevalence of anti-basal ganglia antibodies in adult obsessive-compulsive disorder: cross-sectional study. Br J Psychiatry. 2012 May;200(5):381-6. doi: 10.1192/bjp.bp.111.092007. Epub 2012 Jan 26. — View Citation

Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999 Oct 2;354(9185):1153-8. — View Citation

Singer HS, Gilbert DL, Wolf DS, Mink JW, Kurlan R. Moving from PANDAS to CANS. J Pediatr. 2012 May;160(5):725-31. doi: 10.1016/j.jpeds.2011.11.040. Epub 2011 Dec 22. Review. Erratum in: J Pediatr. 2012 May;160(5):888. — View Citation

Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998 Feb;155(2):264-71. Erratum in: Am J Psychiatry 1998 Apr;155(4):578. — View Citation

Swedo SE, Leonard HL, Mittleman BB, Allen AJ, Rapoport JL, Dow SP, Kanter ME, Chapman F, Zabriskie J. Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. Am J Psychiatry. 1997 Jan;154(1):110-2. — View Citation

Tan J, Smith CH, Goldman RD. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Can Fam Physician. 2012 Sep;58(9):957-9. — View Citation

Vincenzi B, O'Toole J, Lask B. PANDAS and anorexia nervosa--a spotters' guide: suggestions for medical assessment. Eur Eat Disord Rev. 2010 Mar;18(2):116-23. doi: 10.1002/erv.977. Review. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Psychiatric health of individuals assessed with the Cunningham Panel of PANS-biomarkers		up to 4 years
Secondary	Sensitivity and Specificity of the Cuningham-Panel of PANS biomarkers as a diagnostic tool for PANS		up to 4 years