Abstract
The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive–compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing–remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of post-streptococcal OCD and tic disorders. The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea. The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen. The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.
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References
Osler W . On Chorea and Choreiform Affections. P. Blakiston, Sons & Co.: Philidelphia, 1894.
Stollerman GH . Rheumatic fever in the 21st Century. Clin Infect Dis 200; 33: 806–814.
Chapman AH, Pilkey L, Gibbons MJ . A psychosomatic study of eight children with Sydenham's chorea. Pediatrics 1958; 21: 582–595.
Freeman JM, Aron AM, Collard JE, MacKay MC . The emotional correlates of Sydenham's chorea. Pediatrics 1965; 35: 42–49.
Grimshaw L . Obsessional disorder and neurological illness. J Neurol Neurosurg Psychiatry 1964; 27: 229–231.
Swedo SE, Rapoport JL, Cheslow DL . High prevalence of obsessive–compulsive symptoms in patients with Sydenham's chorea. Am J Psychiatry 1989; 146: 246–249.
Swedo SE, Leonard HL, Schapiro MB, Casey BJ, Mannheim GB, Lenane MC et al. Sydenham's chorea: physical and psychological symptoms of St. Vitus dance. Pediatrics 1993; 91: 706–713.
Allen AJ, Leonard HL, Swedo SE . Case study: a new infection-triggered autoimmune subtype of pediatric OCD and Tourette's Syndrome. J Am Acad Child Adolesc Psychiatry 1995; 34: 307–311.
Swedo SE, Leonard HL, Kiessling LS . Speculations on antineuronal antibody-mediated neuropsychiatric disorders of childhood. Pediatrics 1994; 93: 323–326.
Kurlan R . Tourette's syndrome and ‘PANDAS’: will the relation bear out? Neurology 1998; 50: 1530–1534.
Singer HS, Loiselle C . PANDAS: a commentary. J Psychosom Res 2003; 55: 31–39.
Kurlan R, Kaplan EL . 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 2004; 113: 883–886.
Swedo SE, Leonard HL, Rapoport JL . The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics 2004; 113: 907–911.
Swedo SE . Sydenham's chorea (SC): a model for childhood autoimmune neuropsychiatric disorders. J Am Med Assoc 1994; 272: 1788–1791.
Garvey MA, Giedd JN, Swedo SE . PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. J Child Neurol 1998; 13: 413–423.
Giedd JN, Rapoport JL, Kruesi MJP, Parker C, Schapiro MB, Allen AJ et al. Sydenham's chorea: magnetic resonance imaging of the basal ganglia. Neurology 1995; 45: 2199–2202.
Colony HS, Malamud N . Sydenham's chorea: a clinicopathologic study. Neurology 1956; 6: 672–676.
Greenfield JG, Wolfsohn JM . The pathology of Sydenham's chorea. Lancet 1922; 32: 603–606.
Saxena S, Rauch SL . Functional neuroimaging and the neuroanatomy of obsessive–compulsive disorder. Psychiatr Clin North Am 2000; 23: 563–586.
Demirkol A, Erdem H, Inan L, Yigit A, Guney M . Bilateral globus pallidus lesions in a patient with Tourette syndrome related disorders. Biol Psychiatry 1999; 46: 863–867.
Hahm DS, Kang Y, Cheong SS, Na DL . A compulsive collecting behavior following an A-com aneurysmal rupture. Neurology 2001; 56: 398–400.
Max JE, Smith Jr WL, Lindgren SD, Robin DA, Mattheis P, Stierwalt J et al. Case study: obsessive–compulsive disorder after severe traumatic brain injury in an adolescent. J Am Acad Child Adolesc Psychiatry 1995; 34: 45–49.
Mordecai D, Shaw RJ, Fisher PG, Mittelstadt PA, Guterman T, Donaldson SS . Case study: suprasellar germinoma presenting with psychotic and obsessive–compulsive symptoms. J Am Acad Child Adolesc Psychiatry 2000; 39: 116–119.
Peterson BS, Bronen RA, Duncan CC . Three cases of symptom change in Tourette's syndrome and obsessive–compulsive disorder associated with paediatric cerebral malignancies. J Neurol Neurosurg Psychiatry 1996; 61: 497–505.
Mindus P, Nyman H . Normalization of personality characteristics in patients with incapacitating anxiety disorders after capsulotomy. Acta Psychiatr Scand 1991; 83: 283–291.
Dougherty DD, Baer L, Cosgrove GR, Cassem EH, Price BH, Nierenberg AA et al. Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive–compulsive disorder. Am J Psychiatry 2002; 159: 269–275.
Rauch SL . Neuroimaging and neurocircuitry models pertaining to the neurosurgical treatment of psychiatric disorders. Neurosurg Clin N Am 2003; 14: 213–223, vii–viii. Review.
Greenberg BD, Murphy DL, Rasmussen SA . Neuroanatomically based approaches to obsessive–compulsive disorder. Neurosurgery transcranial magnetic stimulation. Psychiatr Clin North Am 2000; 23: 671–686, xii. Review.
Swedo SE, Rapoport JL, Leonard HL, Lenane M, Cheslow D . Obsessive–compulsive disorder in children and adolescents: clinical phenomenology of 70 consecutive cases. Arch Gen Psychiatry 1989; 46: 335–341.
Leonard HL, Swedo SE, Lenane M, Rettew DC, Hamburger SD, Bartko J et al. Tics and Tourette's disorder: a 2- to 7-year follow-up of 54 obsessive–compulsive children. Am J Psychiatry 1992; 149: 1244–1251.
Leckman JF, Peterson BS, Pauls DL, Cohen DJ . Tic disorders. Psychiatr Clin North Am 1997; 20: 839–861.
Cardona F, Orefici G . Group A streptococcal infections and tic disorders in an Italian pediatric population. J Pediatr 2001; 138: 71–75.
Kiessling LS, Marcotte AC, Benson M, Kuhn C, Wrenn D . Relationship between GABHS and childhood movement disorders. Pediatric Res 1993; 33: 12A.
Taranta A, Stollerman GH . The relationship of Sydenham's chorea to infection with group A streptococci. Am J Med 1956; 20: 170–175.
Stollerman GH . Rheumatic Fever and Streptococcal Infection. Grune & Stratton: New York, 1975.
Coburn AF . The Factor of Infection in the Rheumatic State. Williams and Wilkins: Baltimore, 1931.
Collis WRF . Acute rheumatism and haemolytic streptococci. Lancet 1931; 1: 1341–1345.
Paul J . Epidemiology of Rheumatic Fever. American Heart Association: New York, 1957.
Hill AB . The environment and disease: association or causation? Proc R Soc Med 1965; 58: 295–300.
Husby G, van de Rijn I, Zabriskie JB, Abdin ZH, Williams RC . Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J Exp Med 1976; 144: 1094–1110.
Bronze MS, Dale JB . Epitopes of streptococcal M proteins that evoke antibodies that cross-react with human brain. J Immunol 1993; 151: 2820–2828.
Moore DP . Neuropsychiatric aspects of Sydenham's chorea: a comprehensive review. J Clin Psychiatry 1996; 57: 407–414.
Church AJ, Cardoso F, Dale RC, Lees AJ, Thompson EJ, Giovannoni G . Anti-basal ganglia antibodies in acute and persistent Sydenham's chorea. Neurology 2002; 59: 227–231.
Church AJ, Dale RC, Cardoso F, Candler PM, Chapman MD, Allen ML et al. CSF serum immune parameters in Sydenham's chorea: evidence of an autoimmune syndrome? J Neuroimmunol 2003; 136: 149–153.
Kirvan CA, Swedo SE, Heuser JS, Cunningham MW . Mimicry autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med 2003; 9: 914–920.
Hamilton CS, Garvey MA, Swedo SE . Therapeutic implications of immunology for tics and obsessive–compulsive disorder. Adv Neurol 2001; 85: 311–318.
Benoist C, Mathis D . Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? Nat Immunol 2001; 2: 797–801.
Snider LA, Swedo SE . Post-streptococcal autoimmune disorders of the central nervous system. Curr Opin Neurol 2003; 16: 359–365.
Levin MC, Lee SM, Kalume F, Morcos Y, Dohan Jr FC, Hasty KA et al. Autoimmunity due to molecular mimicry as a cause of neurological disease. Nat Med 2002; 8: 509–513.
Lougee L, Perlmutter SJ, Nicolson R, Garvey MA, Swedo SE . Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). J Am Acad Child Adolesc Psychiatry 2000; 39: 1120–1126.
Kiessling LS, Marcotte AC, Culpepper L . Antineuronal antibodies: tics and obsessive–compulsive symptoms. J Dev Behav Pediatr 1994; 15: 421–425.
Singer HS, Giuliano JD, Hansen BH, Hallett JJ, Laurino JP, Benson M et al. Antibodies against human putamen in children with Tourette syndrome. Neurology 1998; 50: 1618–1624.
Morshed SA, Parveen S, Leckman JF, Mercadante MT, Bittencourt Kiss MH, Miguel EC et al. Antibodies against neural nuclear cytoskeletal, and streptococcal epitopes in children adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders. Biol Psychiatry 2001; 50: 566–577.
Wendlandt JT, Grus FH, Hansen BH, Singer HS . Striatal antibodies in children with Tourette's syndrome: multivariate discriminant analysis of IgG repertoires. J Neuroimmunol 2001; 119: 106–113.
Loiselle CR, Wendlandt JT, Rohde CA, Singer HS . Antistreptococcal, neuronal, and nuclear antibodies in Tourette syndrome. Pediatr Neurol 2003; 28: 119–125.
Hoffman KL, Hornig M, Yaddanapudi K, Jabado O, Lipkin WI . A murine model for neuropsychiatric disorders associated with group A beta-hemolytic streptococcal infection. J Neurosci 2004; 24: 1780–1791.
Taylor JR, Morshed SA, Parveen S, Mercadante MT, Scahill L, Peterson BS et al. An animal model of Tourette's syndrome. Am J Psychiatry 2002; 159: 657–660.
Mima T, Matsuoka T, Hallett M . Functional coupling of human right and left cortical motor areas demonstrated with partial coherence analysis. Neurosci Lett 2000; 287: 93–96.
Loiselle CR, Lee O, Moran TH, Singer HS . Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes. Mov Disord 2004; 19: 390–396.
Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive–compulsive disorder tic disorders in childhood. Lancet 1999; 354: 1153–1158.
Giedd JN, Rapoport JL, Leonard HL, Richter D, Swedo SE . Case study: acute basal ganglia enlargement and obsessive–compulsive symptoms in an adolescent boy. J Am Acad Child Adolesc Psychiatry 1996; 35: 913–915.
Giedd JN, Rapoport JL, Garvey MA, Perlmutter S, Swedo SE . MRI assessment of children with obsessive–compulsive disorder or tics associated with streptococcal infection. Am J Psychiatry 2000; 157: 281–283.
Church AJ, Dale RC, Lees AJ, Giovannoni G, Robertson MM . Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry 2003; 74: 602–607.
Flament MF, Whitaker A, Rapoport JL, Davies M, Berg CZ, Kalikow K et al. Obsessive compulsive disorder in adolescence: an epidemiological study. J Am Acad Child Adolesc Psychiatry 1988; 27: 764–771.
Snider LA, Seligman LD, Ketchen BR, Levitt SJ, Bates LR, Garvey MA et al. Tics and problem behaviors in schoolchildren: prevalence characterization, and associations. Pediatrics 2002; 110: 331–336.
Shulman ST . Streptococcal pharyngitis: clinical and epidemiologic factors. Pediatr Infect Dis J 1989; 8: 816–819.
Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998; 155: 264–271.
Perlmutter SJ, Garvey M, Castellanos X, Mittleman BB, Giedd J, Rapoport JL et al. A case of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (clinical conference). Am J Psychiatry 1998; 155: 1592–1598.
Murphy TK, Petitto JM, Voeller KK, Goodman WK . Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function? Semin Clin Neuropsychiatry 2001; 6: 266–276.
Veasy LG . Rheumatic fever: T. Duckett Jones and the rest of the story. Cardiol Young 1995; 5: 293–301.
Asbahr FR, Ramos RT, Negrao AB, Gentil V . Case series: increased vulnerability to obsessive–compulsive symptoms with repeated episodes of Sydenham chorea. J Am Acad Child Adolesc Psychiatry 1999; 38: 1522–1525.
Mercadante MT, Busatto GF, Lombroso PJ, Prado L, Rosario-Campos MC, do Valle R et al. The psychiatric symptoms of rheumatic fever. Am J Psychiatry 2000; 157: 2036–2038.
Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL et al. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry 1999; 45: 1564–1571.
Snider LA, Swedo SE . Antibiotic prophylaxis against group A beta-hemolytic streptococci with azithromycin and penicillin for childhood-onset neuropsychiatric disorders. Pediatric Research: Pediatric Academic Societies’ Annual Meeting. Vol. 55 (4), 2004, p 69A.
Pavone P, Bianchini R, Parano E, Incorpora G, Rizzo R, Mazzone L et al. Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection. Pediatr Neurol 2004; 30: 107–110.
Singer HS, Loiselle CR, Lee O, Minzer K, Swedo S, Grus FH . Anti-basal ganglia antibodies in PANDAS. Mov Disord 2004; 19: 406–415.
Tucker DM, Leckman JF, Scahill L . A putative post-streptococcal case of OCD with chronic tic disorder, not otherwise specified. J Am Acad Child Adolesc Psychiatry 1996; 35: 1684–1691.
Trifiletti RR, Packard AM . Immune mechanisms in pediatric neuropsychiatric disordersTourette's syndrome OCD, and PANDAS. Child Adolesc Psychiatr Clin N Am 1999; 8: 767–775.
Murphy ML, Pichichero ME . Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med 2002; 156: 356–361.
Thomsen PH . Obsessive–compulsive disorder in children adolescents: predictors in childhood for long-term phenomenological course. Acta Psychiatr Scand 1995; 92: 255–259.
Leonard HL, Swedo SE, Lenane MC, Rettew DC, Hamburger SD, Bartko JJ et al. A 2- to 7-year follow-up study of 54 obsessive compulsive children and adolescents. Arch Gen Psychiatry 1993; 50: 429–439.
Denckla MB . Revised neurological examination for subtle signs. Psychopharmacol Bull 1985; 21: 773–800.
Snider LA, Swedo SE . Pediatric obsessive–compulsive disorder. JAMA 2000; 284: 3104–3106.
Goldman S, Amrom D, Szliwowski HB . Reversible striatal hypermetabolism in a case of Sydenham's chorea. Movement Disord 1993; 8: 355–358.
Weindl A, Kuwert T, Leenders KL, Poremba M, Grafin von Einsiedel H, Antonini A et al. Increased striatal glucose consumption in Sydenham's chorea. Movement Disord 1993; 8: 437–444.
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Snider, L., Swedo, S. PANDAS: current status and directions for research. Mol Psychiatry 9, 900–907 (2004). https://doi.org/10.1038/sj.mp.4001542
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DOI: https://doi.org/10.1038/sj.mp.4001542
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