Research

Hilario Blasco-Fontecilla, Victor del Rio-Peña, Ping Wang, Chao Li, Marina Martin-Moratinos, Marcos Bella-Fernández, Trastorno por tics y trastorno obsesivo compulsivo: Trastornos neuropsiquiátricos pediátricos autoinmunes asociados a infecciones por estreptococos (PANDAS) y enfermedades psiquiátricas en niños y adolescentes, Psiquiatría Biológica, Volume 31, Supplement 1, 2024,100554, ISSN 1134-5934,https://doi.org/10.1016/j.psiq.2024.100554.

• Study Overview: Compared 801 children with and without ASLO positivity (Antistreptolysin O, a marker of past strep infection).
• ASLO-positive kids are 7x more likely to have tics & OCD.
• More ER visits and higher trauma/fracture rates.
• No link to ADHD or academic performance.

Newby MJ, Lane SJ, Haracz K, et al. Occupational performance patterns in children with paediatric acute-onset neuropsychiatric syndrome. Australian Occupational Therapy Journal. 2024;72:e12995. doi:10.1111/1440-1630.12995

Read more in a deeper dive Occupational Performance Fluctuates With PANS Disease State

• Children with PANS show significant declines in occupational performance and socialisation during symptom exacerbations
• Adaptive Behaviour Composite and socialisation scores were significantly lower during exacerbation compared with remission
• During remission, occupational performance returned to age-typical ranges across all measured domains
• Findings highlight the episodic, relapsing–remitting nature of functional impairment in PANS
• Authors emphasize the importance of occupational therapy during flare-ups and caution against assessment-based misinterpretation during exacerbations

This large population-based study in Sweden investigated the potential link between severe infections and obsessive-compulsive disorder (OCD) through a familial co-aggregation approach. By analyzing data from over 4.9 million individuals born between 1960 and 2008, researchers explored the risk of OCD among relatives of those with severe infections, spanning varying degrees of genetic relatedness. The study found that the risk of OCD increased with closer genetic ties, with monozygotic twins showing the highest correlation. A dose-response relationship between the number of infections and the odds of OCD was also identified. These findings remained robust even after adjusting for comorbid autoimmune disorders and infections in relatives. The results suggest that genetic factors play a significant role in the observed association, pointing to shared genetic susceptibilities between infections and OCD. This supports the idea that genetic pleiotropy—where the same genes influence multiple traits—may contribute to both infection susceptibility and OCD risk. The study highlights the importance of considering both genetic and environmental factors in understanding OCD development.

Swedo S, Menendez CM, Cunningham MW. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) 2024 Jul 7 [Updated 2024 Sep 13]. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]. 2nd edition. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2022 Oct 8. Chapter 26. 

Read: Deeper Dive: Streptococcal Involvement in PANDAS

• Multiple different types of studies show abnormalities within the basal ganglia of those with OCD, tic disorders, ADHD, and PANDAS. 
• The relapsing-remitting symptom progression within PANS/PANDAS is distinctly different from the fluctuating course of OCD and tic disorders. 
• The diagnostic criteria for PANS emphasize the importance of the concomitant onset of symptoms in multiple neuropsychiatric domains. 
• Genetic predisposition, different strains of S. pyogenes, and the environmental influence of S. pyogenes on the host are all important in the development of PANDAS.
• Treatment recommendations for severe cases, particularly those at risk for self-harm, include therapeutic plasmapheresis and IVIG. For mild to moderately ill people, corticosteroids or NSAIDs can provide symptom relief. Symptom relief with standard psychiatric, behavioral interventions, and family supports should also be provided

Leonardi L, Perna C, Bernabei I, Fiore M, Ma M, Frankovich J, Tarani L, Spalice A. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities. Children. 2024; 11(9):1043. https://doi.org/10.3390/children11091043

This study found that about a quarter of patients meeting strict PANS criteria who underwent lumbar punctures (LP) had cerebrospinal fluid (CSF) abnormalities, with the most common being elevated CSF protein and albumin quotient. These patients also exhibited signs of inflammation and autoimmunity, such as low complement levels, high immune complexes, non-specific autoantibodies, vasculopathy, and arthritis.

Interestingly, the “other psychiatric deterioration” group—those referred for PANS but not meeting strict criteria—had an even higher frequency (45%) of CSF abnormalities. Many of these patients also showed systemic inflammation, with conditions like thyroiditis and arthritis, and had symptoms overlapping with PANS, including obsessive-compulsive behaviors and food restrictions.

Both groups demonstrated a notable prevalence of arthritis, emphasizing systemic inflammation’s potential role, possibly affecting the blood-brain barrier (BBB). While the study was not designed to assess the significance of these differences, it suggests an overlap in psychiatric symptoms and inflammatory features across the groups, which may involve complement activation and vascular inflammation, similar to what’s seen in Long Covid.

• Children with PANS had lower levels of IgG antibodies (a type of immune protein) in their plasma during a symptom flare compared to matched controls.
• PANS IgG drawn at flare shows elevated binding to CINs in both mouse and human brain.
• PANS IgG binding to CINs reduces their activity using p-rpS6 as a marker.
• Reduction of PANS IgG binding to CINs parallels symptom improvement during recovery.
• Elevated IgG binding to CINs is resolved in the same subject during symptom recovery.
• The study suggests that at least a subset of PANS cases have a neuroimmune pathogenesis.

Whelan JP. Strep Throat and the Backstory for PANS and PANDAS. JAMA Netw Open. 2024;7(7):e2421636. doi:10.1001/jamanetworkopen.2024.21636

• Longitudinal analysis (Ma et al.) of 193 children with PANS revealed that 28% developed arthritis over 4 years, showing unusual rheumatic profiles like Achilles enthesitis (56%), inflammatory back pain (64%), and sacroiliac joint tenderness (69%). Only 2% had typical childhood arthritis.
• Back pain is a common concern among Whelan’s 600 families, often challenging to differentiate true spondyloarthropathy from pain amplification due to poor sleep, which almost all PANS patients experience.
• Ultrasonography in 40 children found effusions or synovitis, suggesting real back arthritis in many.
• A high prevalence of antihistone antibodies (20%) may result from multiple medications. 55% of children with PANS also had a coincident eating disorder.
• Frequent infections in two-thirds of these children may explain elevated inflammatory markers and the abrupt onset of tics, OCD, and behavioral issues, possibly due to “PANDA-genic” bacterial strains in genetically susceptible hosts.