Abstract
The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been used to describe a syndrome characterized by various obsessions, compulsions, tics, hyperactivity, motor stereotypies, and paroxysmal movement disorders that are correlated with prior infection by group A beta-hemolytic Streptococcus pyogenes (GABHS) infections. Five clinical criteria can be used to diagnose PANDAS: (1) the presence of obsessive–compulsive disorder (OCD) and/or any other tic disorders; (2) prepuberal onset (between 3 years of age and the start of puberty); (3) abrupt onset and relapsing–remitting symptom course; (4) a distinct association with GABHS infection; and (5) association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity). The exact pathogenesis of PANDAS remains unclear, and several theories that focus on multiple etiologic or contributive factors have emerged. PANDAS appears to be a neurobiological disorder that potentially complicates GABHS infections in genetically susceptible individuals. The current standard of care for PANDAS patients remains symptomatic, and cognitive behavioral therapy, such as exposure and response prevention, combined with family counseling and psychoeducation, should be the first approach for treating PANDAS. This review examines current theories of PANDAS pathogenesis, identifies possible treatments for managing this complex condition, and highlights areas for future research. Moving forward, developing more standardized diagnostic criteria and identifying specific laboratory markers to facilitate PANDAS diagnoses are crucial.
Similar content being viewed by others
References
Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK (1998) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 155:264–271
Gabbay V, Coffey BJ, Babb JS, Meyer L, Wachtel C, Anam S, Rabinovitz B (2008) Pediatric autoimmune neuropsychiatric disorders associated with streptococcus: comparison of diagnosis and treatment in the community and at a specialty clinic. Pediatrics 122:273–278
Macerollo A, Martino D (2013) Pediatric autoimmune neuropsychiatric disorders associated with Streptococcal infections (PANDAS): an evolving concept. Tremor Other Hyperkinet Mov (N Y) 3. pii: tre-03-167-4158-7
Singer HS, Loiselle C (2003) PANDAS: a commentary. J Psychosom Res 55:31–39
Cardoso F (2004) Chorea: non-genetic causes. Curr Opin Neurol 17:433–436
Garvey MA, Swedo SE (1997) Sydenham’s chorea. Clinical and therapeutic update. Adv Exp Med Biol 418:115–120
Garvey MA, Giedd J, Swedo SE (1998) PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. J Child Neurol 13:413–423
Kurlan R, Kaplan EL (2004) The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive–compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics 113:883–886
Wolf DS, Singer HS (2008) Pediatric movement disorders: an update. Curr Opin Neurol 21:491–496
Hoffman KL, Hornig M, Yaddanapudi K, Jabado O, Lipkin WI (2004) A murine model for neuropsychiatric disorders associated with group A beta-hemolytic streptococcal infection. J Neurosci 24:1780–1791
Yaddanapudi K, Hornig M, Serge R, De Miranda J, Baghban A, Villar G, Lipkin WI (2010) Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Mol Psychiatry 15:712–726
Lotan D, Benhar I, Alvarez K, Mascaro-Blanco A, Brimberg L, Frenkel D, Cunningham MW, Joel D (2014) Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats. Brain Behav Immun 38:249–262
Walker KG, Lawrenson J, Wilmshurst JM (2005) Neuropsychiatric movement disorders following streptococcal infection. Dev Med Child Neurol 47:771–775
Mell LK, Davis RL, Owens D (2005) Association between streptococcal infection and obsessive–compulsive disorder, Tourette’s syndrome, and tic disorder. Pediatrics 116:56–60
Falcini F, Lepri G, Rigante D, Bertini F, Matucci Cerinic M (2013) Descriptive analysis of pediatric autoimmune neuropsychiatric disorder associated with Streptococcus infection (PANDAS) in a cohort of 65 Italian patients. Pediatr Rheumatol 11(Suppl 2):P242
Schrag A, Gilbert R, Giovannoni G, Robertson MM, Metcalfe C, Ben-Shlomo Y (2009) Streptococcal infection, Tourette syndrome, and OCD: is there a connection? Neurology 73:1256–1263
Perrin EM, Murphy ML, Casey JR, Pichichero ME, Runyan DK, Miller WC, Snider LA, Swedo SE (2004) Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children? Arch Pediatr Adolesc Med 158:848–856
Kurlan R, Johnson D, Kaplan EL; Tourette Syndrome Study Group (2008) Streptococcal infection and exacerbations of childhood tics and obsessive–compulsive symptoms: a prospective blinded cohort study. Pediatrics 121:1188–1197
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 (2011) Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive–compulsive symptoms: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry 50:108–118.e3
Pavone P, Parano E, Rizzo R, Trifiletti RR (2006) Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants. J Child Neurol 21:727–736
Morris CM, Pardo-Villamizar C, Gause CD, Singer HS (2009) Serum autoantibodies measured by immunofluorescence confirm a failure to differentiate PANDAS and Tourette syndrome from controls. J Neurol Sci 276:45–48
Singer HS, Gause C, Morris C, Lopez P; Tourette Syndrome Study Group (2008) Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Pediatrics 121:1198–1205
Hachiya Y, Miyata R, Tanuma N, Hongou K, Tanaka K, Shimoda K, Kanda S, Hoshino A, Hanafusa Y, Kumada S, Kurihara E, Hayashi M (2013) Autoimmune neurological disorders associated with group-A beta-hemolytic streptococcal infection. Brain Dev 35:670–674
Singer HS, Gilbert DL, Wolf DS, Mink JW, Kurlan R (2012) Moving from PANDAS to CANS. J Pediatr 160:725–731
Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE (1999) Therapeutic plasma exchange and intravenous immunoglobulin for obsessive–compulsive disorder and tic disorders in childhood. Lancet 354:1153–1158
Walsh KH, McDougle CJ (2011) Psychotherapy and medication management strategies for obsessive–compulsive disorder. Neuropsychiatr Dis Treat 7:485–494
Singer HS, Walkup JT (1991) Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and treatment. Medicine (Baltimore) 70:15–32
Storch EA, Larson MJ, Shapira NA, Ward HE, Murphy TK, Geffken GR, Valerio H, Goodman WK (2006) Clinical predictors of early fluoxetine treatment response in obsessive–compulsive disorder. Depress Anxiety 23:429–433
Kleinsasser BJ, Misra LK, Bhatara VS, Sanchez JD (1999) Risperidone in the treatment of choreiform movements and aggressiveness in a child with “PANDAS”. S D J Med 52:345–347
Mancuso E, Faro A, Joshi G, Geller DA (2010) Treatment of pediatric obsessive–compulsive disorder: a review. J Child Adolesc Psychopharmacol 20:299–308
Bottas A, Richter MA (2002) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Pediatr Infect Dis J 21:67–71
Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, Witowski ME, Dubbert B, Swedo SE (1999) A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infection. Biol Psychiatry 45:1564–1571
Snider LA, Lougee L, Slattery M, Grant P, Swedo SE (2005) Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry 57:788–792
Murphy ML, Pichichero ME (2002) Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med 156:356–361
Acknowledgments
The authors are financially supported by Bando Giovani Ricercatori 2009 (Italian Ministry of Health).
Conflict of interest
The authors have no conflict of interest to declare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Esposito, S., Bianchini, S., Baggi, E. et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview. Eur J Clin Microbiol Infect Dis 33, 2105–2109 (2014). https://doi.org/10.1007/s10096-014-2185-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-014-2185-9