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

NCT02190292 | Completed

• 1 other identifier: 523-2011-3646_1
• Study Type: observational
• Target: 185
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Psychiatric health of individuals assessed with the Cunningham Panel of PANS-biomarkers

  up to 4 years

Secondary Outcomes (1)

• Sensitivity and Specificity of the Cuningham-Panel of PANS biomarkers as a diagnostic tool for PANS

  up to 4 years

Study Arms (3)

PANS group

All current Swedish cases investigated with the Cunningham panel (approximately 150 individuals) will be invited to participate in the study. 50 of these will be re-assessed with the Cunningham panel.

Psychiatric controls

60 individuals with psychiatric disorder (eg. ADHD, autism spectrum disorder, psychosis, major depression, obsessive-compulsive disorder) will be recruited.

Healthy controls

25 age and sex matched children to the PANS group will be recruited.

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Consecutive cases that have been assumed to have PANS and have been assessed with the Cunningham panel in Scandinavia.

You may qualify if:

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

You may not qualify if:

• intellectual disability, non-Swedish speaking
• diagnosed with a psychiatric disorder
• age \<40 years
• intellectual disability, non-Swedish speaking
• age and sex matched to the PANS-group
• intellectual disability, non-Swedish speaking

Sponsors & Collaborators

• Karolinska Institutet: lead
• The Swedish Research Council: collaborator

Study Sites (1)

Northern Stockholm psychiatry

Stockholm, Sverige, SE-112 81, Sweden

Location

Related Publications (23)

• 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. No abstract available. Swedish.

  PMID: 24187894 BACKGROUND

• 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.

  PMID: 20807071 BACKGROUND

• 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.

  PMID: 22534626 BACKGROUND

• 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. doi: 10.1177/0883073807302614.

  PMID: 17690060 BACKGROUND

• 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.

  PMID: 23142103 BACKGROUND

• 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. doi: 10.1038/nm892.

  PMID: 12819778 BACKGROUND

• 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. doi: 10.1016/j.jneuroim.2006.06.017. Epub 2006 Jul 27.

  PMID: 16875742 BACKGROUND

• 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.

  PMID: 18519489 BACKGROUND

• 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.

  PMID: 21241948 BACKGROUND

• 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.

  PMID: 11466169 BACKGROUND

• 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.

  PMID: 18499734 BACKGROUND

• 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.

  PMID: 24080310 BACKGROUND

• 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. doi: 10.1176/ajp.154.3.402.

  PMID: 9054790 BACKGROUND

• 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.

  PMID: 20807070 BACKGROUND

• 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. doi: 10.1016/s0006-3223(03)00704-2.

  PMID: 14706426 BACKGROUND

• 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.

  PMID: 22282431 BACKGROUND

• 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. doi: 10.1016/S0140-6736(98)12297-3.

  PMID: 10513708 BACKGROUND

• 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. No abstract available.

  PMID: 22197466 BACKGROUND

• 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. doi: 10.1176/ajp.155.2.264.

  PMID: 9464208 BACKGROUND

• 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. doi: 10.1176/ajp.154.1.110.

  PMID: 8988969 BACKGROUND

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

  PMID: 22972724 BACKGROUND

• 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.

  PMID: 20148396 BACKGROUND

• Hesselmark E, Bejerot S. Patient Satisfaction and Treatments Offered to Swedish Patients with Suspected Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. J Child Adolesc Psychopharmacol. 2019 Oct;29(8):634-641. doi: 10.1089/cap.2018.0141. Epub 2019 Apr 19.

  PMID: 31009235 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood (whole blood and serum)

MeSH Terms

Conditions

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections; Pediatric acute-onset neuropsychiatric syndrome; Obsessive-Compulsive Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: July 15, 2014
• Study Start: June 1, 2014
• Primary Completion: June 30, 2017
• Last Updated: October 22, 2020

Record last verified: 2020-10

Locations

SE (1)