PANDAS AND SYDENHAM’S CHOREA

PANDAS is not the first neuropsychiatric disorder to be associated with Group A streptococcal infections and autoimmunity. Sydenham’s chorea, a neurologic manifestation of an autoimmune response to a streptococcal infection, was first identified in the 1800s as well as the relationship to rheumatic fever and choreiform movements also known as Saint Vitus’s dance.* Sydenham’s chorea is believed to be a medical model for PANDAS as they both share considerable overlap in their clinical presentation and immunology.

* Vale, T. C. and F. Cardoso (2015). “Chorea: A Journey through History.” Tremor Other Hyperkinet Mov (N Y) 5.

WATCH VIDEO: SYDENHAM’S CHOREA

This 7-year-old girl was diagnosed with acute rheumatic fever and Sydenham’s chorea. This video was recorded one month after her diagnosis.

In the 1990s, the NIH identified a subgroup of children who presented with a sudden onset of OCD and/or tics in association with a recent Group A streptococcal infection. However, these patients did not meet the criteria for Sydenham’s chorea 1 and were subsequently classified as PANDAS – Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections.

“PANDAS may be thought of as ‘rheumatic fever’ of the brain. And just as Sydenham’s chorea gives you abnormal movements, PANDAS gives you abnormal thoughts and behaviors.” 2

PANDAS vs. non-PANDAS patients

Some MRI studies have shown that children with PANDAS have neuroanatomical differences when compared to non-PANDAS patients. They have significantly larger basal ganglia structures on MRI than healthy age-matched controls. 5 And, there is evidence that the basal ganglia, in particular dopamine receptors, are targeted by autoantibodies triggered by Group A streptococcal infections. 6,7,8,9,10

The basal ganglia is responsible for a variety of biological functions including: control of voluntary motor movements, procedural learning, eye movements, cognition, emotion and routine behaviors.

Immunological mechanism of Sydenham’s chorea

Sydenham chorea is a neuropsychiatric consequence of a group-A streptococcal infection, and is associated with autoantibodies directed against the basal ganglia of the brain. 19

Studies show children who meet the PANDAS criteria have higher levels of circulating antibodies targeting the caudate and putamen (parts of the basal ganglia) neuronal surface antigens in the midbrain, compared to children with Tourette’s syndrome or other tic disorders. 7,8

The increase in the size of the caudate and putamen suggests there’s autoimmune inflammation in these areas.

Studies show children who meet the PANDAS criteria have higher levels of circulating antibodies targeting the caudate and putamen neuronal surface antigens in the midbrain, compared to children with Tourette’s syndrome or other tic disorders. 7,8

The increase in the size of the caudate and putamen suggests there’s an ongoing autoimmune inflammation in these areas.

PANDAS has also been reported in children with an existing tic disorder or Tourette’s syndrome. In this scenario, the baseline frequency of the child’s tics may markedly increase when the child has a strep infection and return to baseline rates after antibiotic treatment. 11-16

Specific antibodies against neuronal surface glycolytic enzymes, lysoganglioside and N-acetyl-β-D-glucosamine, are found to be in higher concentrations and more active in children with tics compared to those children with only Group A streptococcal pharyngitis and without tics. 17,18


Cunningham Panel™ antibody tests successfully identify acute illness in Sydenham chorea and PANDAS patients.

Antineuronal biomarkers help diagnose encephalitis in children

Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS)


Author’s Take:

Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS)

WATCH VIDEO: Dr. Madeleine Cunningham

In this study, Dr. Madeleine Cunningham and colleagues examine whether anti-neuronal biomarkers, when used as a group, confirm acute disease in Sydenham chorea (SC) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), a type of post-infectious encephalitis in children.19 The results strongly suggest that both PANDAS and Sydenham Chorea are provoked by cross reactive anti-neuronal antibodies.

  1. Swedo SE, Rapoport JL, Cheslow DL, et al. High prevalence of obsessive-compulsive symptoms in patients with Sydenham’s chorea. The American Journal of Psychiatry. Feb 1989;146(2):246-249.
  2. Swedo SE, Leonard HL, Kiessling LS. Speculations on antineuronal antibody-mediated neuropsychiatric disorders of childhood. Pediatrics. Feb 1994;93(2):323-326.
  3. Radio interview with Dr. Susan Swedo, magic983.com, 10/12/2014.
  4. Swedo SE, Leonard HL, Kiessling LS. Speculations on antineuronal antibody-mediated neuropsychiatric disorders of childhood. Pediatrics. Feb 1994;93(2):323-326.
  5. Giedd JN, Rapoport JL, Garvey MA, Perlmutter S, Swedo SE. MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection. The American Journal of Psychiatry. Feb 2000;157(2):281-283.
  6. Brimberg L, Benhar I, Mascaro-Blanco A, et al. Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Aug 2012;37(9):2076-2087.
  7. Pavone P, Bianchini R, Parano E, et al. Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection. Pediatric neurology. Feb 2004;30(2):107-110.
  8. Church AJ, Dale RC, Lees AJ, Giovannoni G, Robertson MM. Tourette’s syndrome: a cross sectional study to examine the PANDAS hypothesis. Journal of neurology, neurosurgery, and psychiatry. May 2003;74(5):602-607.
  9. Dale RC, Heyman I, Giovannoni G, Church AW. Incidence of anti-brain antibodies in children with obsessive-compulsive disorder. The British Journal of Psychiatry : the journal of mental science. Oct 2005;187:314-319.
  10. Dale RC, Merheb V, Pillai S, et al. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain : a journal of neurology. Nov 2012;135(Pt 11):3453-3468.
  11. Cohen DJ, Leckman JF. Developmental psychopathology and neurobiology of Tourette’s syndrome. Journal of the American Academy of Child and Adolescent Psychiatry. Jan 1994;33(1):2-15.
  12. Cohen DJ, Leckman JF, Pauls D. Neuropsychiatric disorders of childhood: Tourette’s syndrome as a model. Acta Paediatr Suppl. Jul 1997;422:106-111.
  13. Cohen DJ, Leckman JF. Tourette’s syndrome. JAMA : the Journal of the American Medical Association. Apr 3 1991;265(13):1738.
  14. Findley DB, Leckman JF, Katsovich L, et al. Development of the Yale Children’s Global Stress Index (YCGSI) and its application in children and adolescents with Tourette’s syndrome and obsessive-compulsive disorder. Journal of the American Academy of Child and Adolescent Psychiatry. Apr 2003;42(4):450-457.
  15. Murphy TK, Sajid M, Soto O, et al. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biological psychiatry. Jan 1 2004;55(1):61-68.
  16. Leslie DL, Kozma L, Martin A, et al. Neuropsychiatric disorders associated with streptococcal infection: a case-control study among privately insured children. Journal of the American Academy of Child and Adolescent Psychiatry. Oct 2008;47(10):1166-1172.
  17. Findley DB, Leckman JF, Katsovich L, et al. Development of the Yale Children’s Global Stress Index (YCGSI) and its application in children and adolescents with Tourette’s syndrome and obsessive-compulsive disorder. Journal of the American Academy of Child and Adolescent Psychiatry. Apr 2003;42(4):450-457.
  18. Murphy TK, Sajid M, Soto O, et al. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biological psychiatry. Jan 1 2004;55(1):61-68.
  19. Chain Jennifer L., Alvarez Kathy, Mascaro-Blanco Adita, Reim Sean, Bentley Rebecca, Hommer Rebecca, Grant Paul, Leckman James F., Kawikova Ivana, Williams Kyle, Stoner Julie A., Swedo Susan E., Cunningham Madeleine W. “Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections.” Frontiers In Psychiatry, vol. 11, 2020, p. 564., doi: https://www.frontiersin.org/article/10.3389/fpsyt.2020.00564
PANDAS rheumatic fever of the brain

PANDAS may be thought of as ‘rheumatic fever’ of the brain.

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    The Cunningham Panel™ – Antibody testing that helps determine whether an autoimmune response may be triggering neurologic and/or psychiatric symptoms.

B. Robert Mozayeni, MD

Medical and Clinical Advisor

B. Robert Mozayeni MD

Dr. B. Robert Mozayeni was trained in Internal Medicine and Rheumatology at Yale and at NIH. He has had pre- and post-doctoral Fellowships in Molecular Biophysics and Biochemistry at Yale, and also at NIH where he was a Howard Hughes Research Scholar at LMB/DCBD/NCI and later, Senior Staff Fellow at LMMB/NHLBI/NIH. Editorial board of Infectious Diseases – Surveillance, Prevention and Treatment. Past President of the International Lyme and Associated Diseases Society (ILADS).

He is an expert in Translational Medicine, the science and art of advancing medical science safely and efficiently. He is a Fellow of the non-profit Think Lead Innovate Foundation and is a co-founder of the Foundation for the Study of Inflammatory Diseases. He is a Founder of the Foundation for the Study of Inflammatory Diseases to crowd-source medical solutions for complex conditions using existing knowledge, diagnostic methods, and therapies to meet patient needs immediately. He is the Chief Medical Officer of Galaxy Diagnostics, LLC. He is a Board member of the Human-Kind Alliance. Dr. Mozayeni has held admitting privileges (since 1994) on the clinical staff of Suburban Hospital, a member of Johns Hopkins Medicine and an affiliate of the National Institutes of Health Clinical Center.

Safedin Sajo Beqaj, PhD, HCLD, CC (ABB)

Moleculera Labs, Clinical Laboratory Advisor
Medical Database, Inc., President and CEO

Sajo Baqaj, PhD

Dr. Sajo Beqaj is board certified in molecular pathology and genetics and licensed as a Bioanalyst and High Complexity Laboratory Director. He has been practicing as a laboratory director since 2005.

Dr. Beqaj served as a technical director and was part of the initial management team for several well-known laboratories in the clinical lab industry including PathGroup, Nashville, TN; DCL Medical Laboratories, Indianapolis, IN, and Pathology, Inc, Torrance, CA. He is currently serving as off-side CLIA laboratory director for BioCorp Clinical Laboratory, Whittier, CA and Health360 Labs, Garden Grove, CA.

Dr. Beqaj received his Ph.D. in Pathology from Wayne State University Medical School, Detroit, Michigan. He performed his post-doctoral fellowship at Abbott Laboratories from 2001-2003 and with Children’s Hospital and Northwestern University from 2003-2005.

Dr. Beqaj has taught in several academic institutions and has published numerous medical textbook chapters and journal articles. He has served as a principal investigator in clinical trials for several well-known pharmaceutical and diagnostic companies such as Roche HPV Athena, Merck HPV vaccine, BD vaginitis panel, Roche (Vantana) CINtec® Histology clinical trials, and has presented various scientific clinical abstracts and presentations.

He is a member of several medical and scientific associations including the Association of Molecular Pathology, American Association of Clinical Chemistry and the Pan Am Society for Clinical Virology. He has served on a number of clinical laboratory regulatory and scientific committees, and has assisted several laboratories and physicians as a Clinical Laboratory Consultant.

Rodney Cotton, MBA

Moleculera Labs Board Member

Rodney Cotton, MBA

Rodney Cotton, MBA is an entrepreneurial thought leader in the pharmaceutical/biotech industry who is known for his holistic perspective, bias for action in the face of challenges, and commitment to agile processes.

Rod is an independent director for Orchard Software, a private equity-backed health technology company owned by Francisco Partners; an advisory board member to Flo2 Ventures, a venture capital-backed healthcare and health equity accelerator; and a member of the board of directors and three board committees (Audit, Compliance & Finance; Governance & Equity; and Quality of Care) for Community Health Network.

He built a successful career at Roche spanning more than two decades and culminating in the role of SVP, Head of Strategy & Transformation, and Chief of Staff to the CEO for Roche Diagnostics, the North American headquarters of the world’s largest ($17B) diagnostics company.

While at Roche, Rod led key enterprise initiatives, such as milestone corporate communications, health equity coalitions, the US/Roche Group audit, and global/US acquisition integrations. With 40+ years of experience, he drove the financial turnaround and cultural transformation of four global healthcare companies, led teams of up to 280 total reports, managed P&L of more than $1 billion, and served as a key member of the senior leadership team executing the most significant restructuring of the company in two decades.

In the face of the COVID-19 pandemic, Rod and his team at Roche accelerated six ground breaking products in 11 months, including the first launch of the market’s most accurate and in demand molecular diagnostic test. He also solved extraordinary challenges of product scarcity, supply chain, product allocation, and logistics to achieve accelerated global sourcing and self manufacturing in line with testing guidelines.

A frequent public speaker on health equity and other topics, Rod was named one of the Most Influential Black Executives in Corporate America by Savoy Magazine and one of the Top Blacks in Healthcare by BlackDoctor.org. He also received The Sagamore of the Wabash Award, one of the highest Indiana State honors, bestowed by Indiana Governor Eric J. Holcomb.

Rod holds an M.B.A. from California State University, Dominguez Hills, an M.S. in Strategic Management from the University of Southern California, and a B.A. in Biological Sciences & Technology from the University of California at Santa Barbara.