PANDAS is a hypothesized condition where symptoms of obsessive compulsive disorder (OCD) or tic disorders are exacerbated by group A streptococcal (GAS) infections in children. It is characterized by: 1) Abrupt onset and episodic course of OCD and/or tic symptoms, 2) Pediatric onset between ages 3-puberty, 3) Temporal association between GAS infection and symptom onset/exacerbation. Treatment involves antibiotics for GAS infections combined with standard neuropsychiatric treatments for OCD/tics. However, the association between PANDAS and GAS is controversial and more research is still needed.

1. Pediatric Autoimmune Neuropsychiatric
Disorders Associated with
Streptococcal infection (PANDAS)
Dr Prashant Makhija

2. INTRODUCTION
 Group of neuropsychiatric disorders that are proposed to have an
autoimmune basis and to be related to infection with group A
beta-hemolytic streptococci (GAS)
 Neuropsychiatric disorders- obsessive–compulsive disorder
(OCD) and tic disorder or Tourette’s syndrome
 Susan E. Swedo et.al - Clinical Description of the 50 Cases
 Epidemiology- true incidence/prevalance not known, rare
disorder, 10 cases were identified among 30,000 throat
cultures positive for GAS
1.http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci
2. Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases.
Susan E. Swedo et.al. Am J Psychiatry 1998; 155:264–271
3. Perrin EM. Et.al. Arch Pediatr Adolesc Med 2004; 158:848

3. PATHOGENESIS

4. EVIDENCE
 Presence of antineuronal antibodies among patients with
childhood-onset OCD and/or tic disorders
 Animal studies suggest these antineuronal antibodies may play
an etiologic role in these neuropsychiatric disorders
 Striking effectiveness of immunomodulatory therapies, such
as therapeutic plasma exchange and intravenous immunoglobulin
(IVIG) in the PANDAS subgroup
LA Snider and SE Swedo. PANDAS: current status and directions for research. Molecular Psychiatry (2004) 9, 900–907

5.  Genetic predisposition- rates of tic disorders and OCD in firstdegree relatives of children in the PANDAS subgroup are higher
than those in the general population
 MRI scans- enlargements of the caudate, putamen, and globus
pallidus, which points to regional inflammatory changes
LA Snider and SE Swedo. PANDAS: current status and directions for research. Molecular Psychiatry (2004) 9, 900–907

6. CLINICAL FEATURES
 Clinical Description of the 50 Cases[Susan E. Swedo.et.al(1998) ]
 Age
 Prepubertal (3-11), 6.3 years for tics and 7.4 years for obsessivecompulsive symptoms, 3 years younger than that from other
childhood-onset OCD and tic disorders
 Sex
 M:F= 2.6:1
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases.
Susan E. Swedo et.al. Am J Psychiatry 1998; 155:264–271

7.  Symptoms
 primary diagnosis of OCD (N=24, 48%) and those with primary
tic disorder(N=26, 52%)
 43 (86%) of the children reported obsessive-compulsive
symptoms, and 40 (80%) of the children were found to have
motor tics
 severity of the obsessive-compulsive symptoms as well as motor
and vocal tics was moderate, on average

8.  Symptoms of OCD varied by primary diagnosis - Children with
primary OCD reported more washing and checking behaviors
than did children with a primary diagnosis of tic disorder
 Psychiatric comorbidity was common for the children with
PANDAS- ADHD, affective disorders, and anxiety disorders
were most prevalent (40%,42%, and 32%, respectively)
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases. Susan
E. Swedo et.al. Am J Psychiatry 1998; 155:264–271

10. COMORBID DIAGNOSES

11. Symptoms Associated With Exacerbations of PANDAS

12. DIAGNOSTIC CRITERIA
 Presence of OCD and/or a tic disorder
 Pediatric onset: Symptoms of the disorder first become evident
between 3 years of age and the beginning of puberty
 Episodic course of symptom severity: Clinical course is
characterized by the abrupt onset of symptoms or by dramatic
symptom exacerbations
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases. Susan E.
Swedo et.al. Am J Psychiatry 1998; 155:264–271

13. DIAGNOSTIC CRITERIA(contd..)
 Association with GABHS infection: Symptom exacerbations
must be temporally related to GABHS infection, i.e., associated
with positive throat culture and/or elevated anti-GABHS antibody
titers
 Association with neurological abnormalities- During symptom
exacerbations, patients will have abnormal results on neurological
examination. Motoric hyperactivity and adventitious movements
(including choreiform movements or tics) are particularly common
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases. Susan E. Swedo
et.al. Am J Psychiatry 1998; 155:264–271

14. Sydenham Chorea Versus PANDAS
Feature
Sydenham chorea
PANDAS
Age at onset (yr)
5–15
6–9 years
Male:female
Close to 1:1 most studies
2.6:1
Typical duration
1–6 mths
Relapsing-remitting course
Time lag between inciting
infection/symptom
Longer
Shorter
Association with rheumatic fever
Characteristic. A ‘‘major’’ Jones
criterion
Rare
Association with carditis
Common (25–80%)
Rare
Association with arthritis
Common
Rare
Presence of chorea
Obligatory
Rare; mild if present
Presence of tics
Uncommon
Characteristic
Presence of OCD
Frequent
Characteristic
Clinical signs of motor
impairment (milkmaid’s
grisp, darting tongue)
Present
Present in 30–40% of cases
Antineuronal antibodies
Common; usually anti–basal
ganglia
Common; usually anti–basal
ganglia
Putative GABHS M-protein
subtypes involved
M6, lesser extent M5, M19
M12, lesser extent M3, 13, 11, 1

15.  Evidence against
 negative reports from investigators who were not able to induce
behavioral changes through an infusion
 isolated group A b-hemolytic streptococcal infection is common
in children-GAS accounts for 15 to 30 percent of all cases of
pharyngitis in children between the ages of 5 and 15 years
Prospective surveillance identified GAS carriage in 2.5 percent
of well children and 4.4 percent of children with URI (including
a sore throat)
1.http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci
2. Piero Pavone et.al. J Child Neurol 2006;21:727–736

16.  OCD occurs in 1 to 2 percent of school-age children and
transient motor tics in as many as 25 percent
 Occurrence of OCD/Tics with GAS- coincidental
1.http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci
2. Piero Pavone et.al. J Child Neurol 2006;21:727–736

17. MANAGEMENT
 Therapy for GAS infection
 Therapy for OCD/Tic disorder
 Immunomodulatory therapy ?
 Prophylactic therapy ?

18.  GAS infection
 Children with positive culture or rapid antigen detection test for
GAS - antistreptococcal therapy ↓ incidence suppurative
complications, ↓ nonsuppurative complications, ↓ the risk of
transmission
 no randomized controlled trials of antibiotic treatment of
children suspected of having PANDAS syndrome
http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci

19.  Prospective study(Murphy. et.al., 2002)
 Children with abrupt onset of neuropsychiatric symptoms and
evidence of recent GAS infection, antistreptococcal (penicillin or
cephalosporin) therapy was associated with prompt symptom
resolution in all cases
 Antistreptococcal therapy also was associated with prompt
resolution of symptoms in patients who developed recurrent
symptoms associated with GAS infection
 mean time to resolution of symptoms was shorter among
children treated with cephalosporin than with penicillin (14
versus 5 to 6 days)
Murphy ML et.al. 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.

20.  Neuropsychiatric therapy
 Manifestations respond to treatment with standard
pharmacologic and behaviour therapies
 Evidence-based treatment for OCD
 Pharmacological- SSRIs first-line pharmacological treatment,
 Nonpharmacological interventions - cognitive behavioral
therapy (ie, exposure and response prevention) is considered
first- line nonpharmacological treatment
1.http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci
2. Vilma Gabbay et.al . Pediatrics 2008;122;273

21. 



Treatment of Tic disorder/Tourette’s syndrome
α adrenergic agonists - clonidine and guanfacine
atypical neuroleptic agents - risperidone
typical neuroleptic agents- haloperidol or pimozide
1.http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci
2. Vilma Gabbay et.al . Pediatrics 2008;122;273

22.  Immune modulating therapy
 Glucocorticoids, plasma exchange, and intravenous
immunoglobulin (IVIG)
 Treatment of PANDAS with immune modulating therapies-not
recommended outside of the research setting
 May be considered an alternative for severely ill patients who
have not responded to standard therapies
1.http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci

23.  Prophylactic therapy
 Prophylactic antibiotics to prevent recurrences of PANDAS- not
recommended
 Prospective case-control study (Shulman ST et.al, 2009) continuous prophylaxis against GAS might prevent an average of
0.06 exacerbations per patient-year
Shulman ST et. al. Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS): update. Curr Opin Pediatr
2009; 21:127

24. PROGNOSIS
 Long-term outcome of children who meet criteria for PANDAS
is not known
 Unrecognized PANDAS and untreated PANDAS may result in
an increased risk of progression to lifelong OCD and tic
disorders
1.
2.
Dale RC, Heyman I, Giovannoni G, Church AW. Incidence of anti-brain antibodies in children with obsessive-compulsive disorder. Br J
Psychiatry 2005; 187:314
http://www.uptodate.com/contents/pandas-pediatric-autoimmune-neuropsychiatric-disorder-associated-with-group-a-streptococci

25. SUMMARY AND CONCLUSION
 Subset of children whose symptoms of obsessive compulsive
disorder (OCD) or tic disorders are exacerbated by group A
streptococcal (GAS) infection- hypothesized association
between PANDAS and GAS is controversial
 PANDAS, five working criteria
 OCD and/or tic disorder
 Pediatric onset (between three years and onset of puberty)
 Abrupt onset and episodic course of symptoms
 Temporal relation between GAS infection and onset and/or
exacerbation
 Neurologic abnormalities or tics during exacerbations

26.  Children who present with abrupt onset of OCD/tic disorder be
evaluated for GAS infection
 Children with abrupt onset OCD and/or tic disorders and evidence
of GAS infection - be treated with antistreptococcal therapy
along with standard neuropsychiatric treatment for OCD/tic
disorder
 Treatment with immune-modulating therapies outside of the
research setting not recommended
 Use of prophylactic antibiotics to prevent recurrences of
PANDAS not recommended

27. THANK YOU