Pediatric Acute-Onset Neuropsychiatric Syndrome: Current Perspectives

Abstract

Pediatric acute-onset neuropsychiatric syndrome (PANS) features a heterogeneous constellation of acute obsessive-compulsive disorder (OCD), eating restriction, cognitive, behavioral and/or affective symptoms, often followed by a chronic course with cognitive deterioration. An immune-mediated etiology is advocated in which the CNS is hit by different pathogen-driven (auto)immune responses. This narrative review focused on recent clinical (ie, diagnostic criteria, pre-existing neurodevelopmental disorders, neuroimaging) and pathophysiological (ie, CSF, serum, genetic and autoimmune findings) aspects of PANS. We also summarized recent points to facilitate practitioners with the disease management. Relevant literature was obtained from PubMed database which included only English-written, full-text clinical studies, case reports, and reviews. Among a total of 1005 articles, 205 were pertinent to study inclusion. Expert opinions are converging on PANS as the effect of post-infectious events or stressors leading to “brain inflammation”, as it is well-established for anti-neuronal psychosis. Interestingly, differentiating PANS from either autoimmune encephalitides and Sydenham’s chorea or from alleged “pure” psychiatric disorders (OCD, tics, Tourette’s syndrome), reveals several overlaps and more analogies than differences. Our review highlights the need for a comprehensive algorithm to help both patients during their acute distressing phase and physicians during their treatment decision. A full agreement on the hierarchy of each therapeutical intervention is missing owing to the limited number of randomized controlled trials. The current approach to PANS treatment emphasizes immunomodulation/anti-inflammatory treatments in association with both psychotropic and cognitive-behavioral therapies, while antibiotics are suggested when an active bacterial infection is established. A dimensional view, taking into account the multifactorial origin of psychiatric disorders, should suggest neuro-inflammation as a possible shared substrate of different psychiatric phenotypes. Hence, PANS and PANS-related disorders should be considered as a conceptual framework describing the etiological and phenotypical complexity of many psychiatric disorders.

Clinicolaboratory characteristics of pediatric autoimmune neuropsychiatric disorders associated with Streptococcal infections: A cross-sectional study

“…Similarly, children and adolescents with Tourette syndrome may be more likely to have GABHS infections and exhibit more antibacterial and antineuronal antibodies with a stronger immune response to GABHS [24,39]. Notably, Snider et al [38] concluded that antibiotic therapy with azithromycin and penicillin in children with PANDAS is effective in preventing GABHS infections and GABHS-related psychiatric exacerbations.…”

Inflammation in obsessive–compulsive disorder: A literature review and hypothesis‐based potential of transcranial photobiomodulation

“…We did not include animal studies in our analysis, as they replicate OCD models and are predominantly based on serotonergic and dopaminergic systems (Alonso et al, 2015;Grados et al, 2016). This topic of inflammation in OCD and associated disorders has also been the subject of recent reviews (Bhatt et al, 2023;Gagliano et al, 2023;Kamble & Dandekar, 2023;Marazziti et al, 2023;Vreeland et al, 2023), underscoring its relevance and the ongoing discourse in the scientific community.…”

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

“…Some authors advocate for PANDAS belonging to the complex Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) spectrum, assuming that not only GAS may induce neuropsychiatric symptoms in children. However, this point is also debatable, and different classification criteria have been provided for PANS patients, making this aspect even more complex [13]. According to the latest accredited evidence, after a GAS infection, antibodies produced against GAS epitopes presumably cross-react against self-tissue, such as proteins expressed in the neurons of basal ganglia, through a molecular mimicry mechanism, suggesting an autoimmune pathogenesis similar to SC [14].…”