Evidence map›Paper›PMID 42196589›Full record

ReviewInternational journal of molecular sciences2026

PANDAS Syndrome: A Narrative Review of the Diagnostic Conundrum in Children with Acute Neuropsychiatric Symptoms.

Carlo Alberto Cesaroni, Giulia Pisanò, Susanna Rizzi, Agnese Pantani, Daniele Frattini, Carlo Fusco

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Carlo Alberto CesaroniChild Neurology and Psychiatry Unit, Mother and Child Department Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.ORCID 0000-0003-0092-5604
Giulia PisanòChild Neurology and Psychiatry Unit, Mother and Child Department Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.ORCID 0009-0005-2730-2791
Susanna RizziChild Neurology and Psychiatry Unit, Mother and Child Department Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.ORCID 0000-0002-8856-9722
Agnese PantaniChild Neurology and Psychiatry Unit, Mother and Child Department Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.ORCID 0009-0000-1501-0146
Daniele FrattiniChild Neurology and Psychiatry Unit, Mother and Child Department Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
Carlo FuscoChild Neurology and Psychiatry Unit, Mother and Child Department Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.ORCID 0000-0001-9321-0952

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The hypothesis that Group A beta-haemolytic Streptococcus (GAS) triggers an autoimmune cascade targeting basal ganglia dopaminergic circuits-producing obsessive-compulsive disorder (OCD), tic disorders, or chorea depending on the receptor subtype involved-is biologically compelling and supported by emerging molecular evidence. Yet PANDAS has remained a diagnostic conundrum since its original description in 1998, with ongoing uncertainty surrounding diagnostic criteria, the interpretation of streptococcal serology, and the distinction from primary neurodevelopmental disorders. This study aimed to review the diagnostic challenges of PANDAS, with focus on streptococcal serology interpretation, advances in dopamine receptor autoantibody biology, the genetic epidemiology of primary tic disorders, and the differential diagnosis of acute neuropsychiatric presentations in children. A structured narrative review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library for publications from 1998 to early 2025 addressing PANDAS, PANS, streptococcal antibodies, childhood movement disorders, autoimmune encephalitis, and the genetics of tic disorders. No currently available biomarker-including ASO, anti-DNase B, anti-basal-ganglia antibodies, or the Cunningham Panel-has demonstrated adequate individual-level diagnostic accuracy for PANDAS. Emerging molecular evidence identifies anti-D1R autoantibodies, acting via G protein-and beta-arrestin-mediated signalling, as candidate biomarkers for PANDAS/PANS neuropsychiatric phenotypes, and anti-D2R autoantibodies for Sydenham chorea movement phenotypes; independent replication in unselected populations is required. Primary tic disorders carry heritability estimates of 50-80% and first-degree familial risk ratios of approximately 18-fold in large population-based cohorts. Prospective blinded studies have not demonstrated a consistent population-level association between GAS infections and tic or OCD exacerbations: PANDAS and PANS remain diagnoses of exclusion. The high background prevalence of both GAS exposure and primary neurodevelopmental disorders in overlapping paediatric age ranges creates conditions for incidental temporal co-occurrence. In the absence of validated molecular biomarkers, diagnostic imprecision carries direct clinical consequences: children may be exposed to treatments with significant risk profiles-including IVIG, plasma exchange, and prolonged antibiotic prophylaxis-while evidence-based therapies are delayed. A stepwise diagnostic approach incorporating the full differential diagnosis is both an epistemological and a patient safety imperative.

Indexed as

Autoimmune DiseasesHashimoto DiseaseObsessive-Compulsive DisorderStreptococcal InfectionsTic DisordersAutoantibodiesBiomarkersChildChoreaDiagnosis, DifferentialHumansStreptococcus pyogenesAutoantibodiesBiomarkersanti-streptolysin Oautoimmune encephalitischoreadopamine receptor autoantibodiesheritabilitypaediatric movement disordersPANDASPANSSydenham choreatic disorderTourette syndrome

Identifiers

PMID42196589
PMCPMC13208071

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.