The Proposed Neuroimmune Basis of PANDAS: How Infection-Triggered Immune Responses May Affect Basal Ganglia Circuits

A narrative literature review. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) refers to the abrupt onset of obsessive-compulsive behaviors and tics associated with other neuropsychiatric signs in pre-pubertal children following an infection with Group A Streptococcus. PANDAS was first described in 1998 and since then has fallen under the more general diagnosis of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). This review poses the question about the way infection-induced immune processes act on basal ganglia circuits leading to sudden onset of neuropsychiatric signs in children. This narrative review examines primary case series, prospective cohorts, case-control and imaging studies, clinical guidance, and reviews selected for their relevance to the proposed mechanism and its competing evidence. There are three strands of evidence pointing to basal ganglia. First, the specific symptom cluster that is characteristic of suspected PANDAS and differentiates it from pediatric OCD, including urge to urinate, increased physical activity, deterioration in handwriting skills and impulsive actions reflects known basal ganglia functions. Second, the diffusion-weighted imaging of children suffering from PANS reveals an increase in diffusivity in various brain regions which is especially high in the deep grey matter, including the thalamus, basal ganglia and amygdala. Third, the proposed molecular mimicry involving neuronal targets offers a reasonable explanation of why a single immune event may lead to both behavioral and motor abnormalities. However, no prospective blinded study has established a consistent association between GAS infection and symptom flares, and no biomarker can identify a patient with PANDAS.