title: Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis.
abstract: BACKGROUND
  The classical neurological disorder after group A beta haemolytic streptococcal infection is Sydenham's chorea. Recently a tic disorder occurring after group A streptococcal infection has been described and termed PANDAS (paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). It is proposed that antibodies induced after group A streptococcal infection react with basal ganglia neurones in Sydenham's chorea and PANDAS. Anti-basal ganglia antibodies (ABGA) are present in most cases of acute Sydenham's chorea, but rarely in controls.
  
  
  OBJECTIVE
  To investigate the hypothesis that Tourette's syndrome may be associated with group A streptococcal infection and ABGA.
  
  
  METHODS
  100 patients with Tourette's syndrome (DSM-IV-TR) were enrolled in a cross sectional study. Children with neurological disease (n = 50) and recent uncomplicated streptococcal infection (n = 40), adults with neurological disease (n = 50), and healthy adults (n = 50) were studied as controls. Recent group A streptococcal infection was defined using antistreptolysin O titre (ASOT). ABGA were detected using western immunoblotting and indirect immunofluorescence.
  
  
  RESULTS
  ASOT was raised in 64% of children with Tourette's syndrome compared with 15% of paediatric neurological disease controls (p < 0.0001), and in 68% of adults with Tourette's syndrome compared with 12% of adult neurological controls and 8% of adult healthy controls (p < 0.05). Western immunoblotting showed positive binding in 20% of children and 27% of adults with Tourette's syndrome, compared with 2-4% of control groups (p < 0.05). The most common basal ganglia binding was to a 60 kDa antigen, similar to the proposed antigen in Sydenham's chorea. Indirect immunofluorescence revealed autoantibody binding to basal ganglia neurones. Serological evidence of recent group A streptococcal infection, assessed by a raised ASOT, was detected in 91% (21/23) of Tourette's syndrome patients with positive ABGA compared with 57% (44/77) with negative ABGA (p < 0.01).
  
  
  CONCLUSIONS
  The results support a role of group A streptococcal infection and basal ganglia autoimmunity in a subgroup of patients with Tourette's syndrome and suggest a pathogenic similarity between Sydenham's chorea and some patients with Tourette's syndrome.
authors.affiliation: Neuroinflammation Department, Institute of Neurology, Queen Square, London, UK. a.church@ion.ucl.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Church
authors.forename: R C
authors.initials: RC
authors.lastname: Dale
authors.forename: A J
authors.initials: AJ
authors.lastname: Lees
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
authors.forename: M M
authors.initials: MM
authors.lastname: Robertson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D001479:Basal Ganglia / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D001523:Mental Disorders / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D008875:Middle Aged; D013290:Streptococcal Infections / Q000097:blood / Q000150:complications* / Q000276:immunology*; D005879:Tourette Syndrome / Q000097:blood / Q000209:etiology* / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic