What are the diagnostic criteria and methods for diagnosing Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal (PANDAS) infections?

Diagnosing PANDAS

PANDAS diagnosis is based on five clinical criteria that must all be met: presence of OCD and/or tic disorder, prepubertal onset, abrupt symptom onset or episodic course, temporal association with Group A Streptococcal (GAS) infection, and associated neurological abnormalities such as choreiform movements or motor hyperactivity. 1, 2

Essential Diagnostic Criteria

The diagnosis requires meeting all five of the following criteria simultaneously:

• Presence of obsessive-compulsive disorder (OCD) and/or tic disorder - specifically looking for recurrent intrusive thoughts with compulsive behaviors (hand washing, germ preoccupation) or new motor/vocal tics that were not previously present 3, 1

• Prepubertal age at symptom onset - typically presenting around age 7 years (range 5-11 years in prospective studies) 1, 2

• Abrupt onset and/or episodic course - the hallmark is sudden, dramatic appearance of severe symptoms rather than gradual development 1, 2

• Temporal association with GAS infection - symptoms must appear in close temporal relationship to documented streptococcal infection 3, 1

• Associated neurological abnormalities - specifically motor hyperactivity, adventitious movements, choreiform movements, or tics 1, 2

Key Clinical Features to Identify

Beyond the core criteria, look for these distinctive presentations:

• Daytime urinary urgency and frequency without dysuria, fever, or incontinence - this was the most notable symptom in 58% of prospectively identified cases, with symptoms disappearing at night and negative urinalysis 1

• Behavioral symptoms that are more specific than general moodiness - irritability, aggressivity, and food restriction are common, particularly in the broader PANS category 4

• Choreiform movements - these are key distinguishing neurological features that help differentiate PANDAS from normal developmental behavioral variations 5

Laboratory Testing Approach

Important caveat: The American Heart Association explicitly states that PANDAS "should be considered only as a yet-unproven hypothesis" and does not recommend routine laboratory testing for GAS solely to diagnose PANDAS. 3, 5 However, when clinical suspicion is high based on meeting the clinical criteria above, the following tests can support the diagnosis:

Primary Antibody Tests

• Antistreptolysin O (ASO) titer - obtained first to detect recent GAS infection, with titers rising approximately 1 week after infection and peaking at 3-6 weeks 3

• Anti-DNase B titer - particularly important if ASO is negative, as it may remain elevated longer, rising 1-2 weeks after infection and peaking at 6-8 weeks 3

Critical Interpretation Points

• Age-specific reference ranges are essential - normal streptococcal antibody levels are higher in school-age children than adults, which commonly leads to misinterpretation 3

• Antibodies reflect past immunologic events - a positive result requires careful interpretation in the context of clinical symptoms and temporal relationship, not as standalone diagnostic proof 3

• Very high anti-DNase B titers (10-fold elevation) are more characteristic of PANDAS compared to PANS 4

Acute Infection Documentation

• Throat culture or rapid antigen detection test - indicated if the patient has any throat symptoms to document active GAS infection 5, 1

• Post-treatment cultures - only indicated for patients who remain symptomatic, experience symptom recurrence, or have history of rheumatic fever 3, 6

Diagnostic Algorithm

1. Screen for all five clinical criteria - if any criterion is missing, PANDAS diagnosis cannot be made 1, 2

2. Document temporal relationship - establish clear timeline between GAS infection (or symptoms) and neuropsychiatric symptom onset 1

3. Obtain streptococcal antibody titers (ASO and anti-DNase B) - interpret using age-appropriate reference ranges and clinical context 3

4. Perform throat culture if symptomatic - to document active infection 5

5. Exclude other causes - behavioral changes alone are too nonspecific and could represent normal developmental variation, especially in children with baseline mood issues 5

Common Diagnostic Pitfalls

• Overdiagnosis based on antibody titers alone - elevated titers are common in school-age children and do not confirm PANDAS without meeting all clinical criteria 3

• Misinterpreting nonspecific behavioral symptoms - screaming, crying, and tantrums without the specific neuropsychiatric features (OCD, tics) and neurological abnormalities are insufficient for diagnosis 5

• Ignoring the episodic nature - true PANDAS cases show recurrence of symptoms with subsequent GAS infections, which can help confirm the diagnosis retrospectively 1

• Using newer assay methods without proper standardization - latex agglutination or nephelometric assays may not be well standardized against traditional neutralization assays 3

Relationship to Broader PANS Category

Research has shifted from PANDAS to the broader concept of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), which encompasses sudden-onset obsessive-compulsive symptoms triggered by various infections and insults beyond streptococcal infection 7. PANS patients show more irritability, aggressivity, and food restriction compared to PANDAS, while PANDAS patients demonstrate higher streptococcal antibody titers 4.