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Review
. 2023 Oct 13;11(10):2549.
doi: 10.3390/microorganisms11102549.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease

Saverio La Bella  1 , Giovanna Scorrano  1 , Marta Rinaldi  2 , Armando Di Ludovico  1 , Francesca Mainieri  1 , Marina Attanasi  1 , Alberto Spalice  3 , Francesco Chiarelli  1 , Luciana Breda  1
Affiliations
Review

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease

Saverio La Bella et al. Microorganisms. .

Abstract

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is one of the most controversial diseases in pediatric rheumatology. Despite first being described more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine release in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

Keywords: CaM kinase; PANDAS; PANDAS syndrome; Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections; molecular mimicry; neuropsychiatric disorder; obsessive–compulsive disorder; streptococcal infection; streptococci; striatal cholinergic interneurons.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The pathophysiology of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome involves an autoimmune response triggered by a streptococcus infection. The presence of neuroinflammation in the dorsal striatum can result in the disruption of cholinergic activity. This disruption can lead to an imbalance between the direct and indirect pathways within the basal ganglia. Consequently, off-target behaviors such as tics, obsessions, and compulsions may be disinhibited. Notably, the hyperactivity of the direct pathway in relation to motor and limbic domains has been linked to these behaviors (created with BioRender.com). Abbreviations. Ach: acetylcholine, MSNs: medium-sized spiny neurons.
Figure 2
Figure 2
The IgG antibodies derived from pediatric patients diagnosed with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) exhibit affinity towards cholinergic interneurons (CINs) located within the striatum. The deficiency of CINs has been found to be independently linked to the presence of tics in people and the manifestation of repeated behavioral disease in mice. This suggests that CIN deficiency could potentially serve as a viable pathological factor (created with BioRender.com).
See this image and copyright information in PMC

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