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Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

Graziella Orefici, PhD, Francesco Cardona, MD, Carol J. Cox, PhD, and Madeleine W. Cunningham, PhD.
From the Book: Streptococcus pyogenes Basic Biology to Clinical Manifestations – University of Oklahoma Health Sciences Center-2016
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The inclusion of a chapter on pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (or PANDAS) is essential to provide a history of the disease and provide current information about its association with Streptococcus pyogenes (group A streptococci), tics, obsessive compulsive disorder (OCD) and its relationship to Sydenham chorea (SC), which is the neurologic manifestation of acute rheumatic fever.

N-Acetylcysteine in the Treatment of Excoriation Disorder – A Randomized Clinical Trial

Jon E. Grant, JD, MD, MPH; Samuel R. Chamberlain, MD, PhD; Sarah A. Redden, BA; Eric W. Leppink, BA; Brian L. Odlaug, PhD; Suck Won Kim, MD
JAMA Psychiatry-2016

This investigation suggests that N-acetylcysteine appears to be effective and well tolerated in the acute treatment of SPD. As effective treatments for skin picking emerge, it becomes increasingly important that physicians and other mental health care professionals screen for the disorder to provide timely treatment.

Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells

Thamotharampillai Dileepan, Erica D. Smith, Daniel Knowland, Martin Hsu, Maryann Platt, Peter Bittner-Eddy, Brenda Cohen, Peter Southern, Elizabeth Latimer, Earl Harley Dritan Agalliu. and P. Patrick Cleary
Journal of Clinical Investigation-2015
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Our results establish what we believe to be evidence of a novel crosstalk between the CNS and cellular immunity to infections, which may contribute to understanding the pathogenesis of many other CNS autoimmune diseases. Flare-ups associated with several chronic autoimmune conditions may be produced by the expansion of Th17 cells and the activation of cytokines induced by relatively common bacterial or viral infections. Aberrant cytokine expression could then disrupt the BBB to permit preexisting circulating autoantibodies to enter the brain, engage neural targets, and trigger the sudden onset of clinical symptoms.

Structural and functional features of central nervous system lymphatic vessels

Antoine Louveau, Igor Smirnov, Timothy J. Keyes, Jacob D. Eccles, Sherin J. Rouhani, J. David Peske, Noel C. Derecki, David Castle, James W. Mandell, Kevin S. Lee, Tajie H. Harris & Jonathan Kipnis
Nature-2015

The research findings reported in this study challenge the dogmas regarding the immune privilege status of the central nervous system (CNS) and its isolation from the immune system by the blood-brain barrier. Functional meningeal lymphatic vessels capable of carrying immune cells and interstitial fluids from the CNS are identified and characterized. Findings provide novel understanding on how autoimmune encephalopathies, like PANS/ PANDAS, can develop when these unique lymphatic vessels malfunction. Structural and functional features of central nervous system lymphatic vessels.

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus Immunology: A Pilot Study

Walls A, Cubangbang M, Wang H, Raiji M, Knight J, Steehler M, Latimer E, Harley EH Jr. 
Otolaryngol Head Neck Surg.-2015

Patients diagnosed with PANDAS appear to maintain significantly different concentrations of cytokines when compared with patients afflicted by chronic group A beta hemolytic streptococcus infections and obstructive sleep apnea. As a result, one could potentially use the described characterization of immunologic markers as a basis for future mechanistic and epidemiological studies.

N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review
Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, Sarris J. N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review. Clin Psychopharmacol Neurosci. 2015 Apr 30;13(1):12-24. doi: 10.9758/cpn.2015.13.1.12. PMID: 25912534; PMCID: PMC4423164.
    • 4 clinical trials, 5 case reports/series.
    • NAC (2,400-3,000 mg/day) showed symptom reduction and good tolerability.
    • 3 ongoing trials for OCD (2 adult, 1 pediatric) and 1 for excoriation.
  • Conclusions: Promising results from pilot studies, with potential for future research.
The Role of Tonsillectomy in the Treatment of Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS)

Daniel Demesh, MD; Jordan M. Virbalas, MD; John P. Bent, MD
JAMA Otolaryngol Head Neck Surg.-2015

Conclusions: Although current evidence is inconclusive, the data reported herein support previously described smaller case series and further strengthens the notion that tonsillectomy may benefit patients with PANDAS whose symptoms are not controlled with antibiotic therapy

Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders

Nicolini H, López Y, Genis-Mendoza AD, Manrique V, Lopez-Canovas L, Niubo E, Hernández L, Bobes MA, Riverón AM, López-Casamichana M, Flores J, Lanzagorta N, De la Fuente-Sandoval C, Santana D. 
Actas Esp Psiquiatr-2015

The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

Clinical Evaluation of Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference

Kiki Chang, Jennifer Frankovich, Michael Cooperstock, Madeleine W. Cunningham, M. Elizabeth Latimer, Tanya K. Murphy, Mark Pasternack, Margo Thienemann, Kyle Williams, Jolan Walter, and Susan E. Swedo, From the PANS Collaborative Consortium
Journal of Child and Adolescent Psychopharmacology-2015
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On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS.