BACKGROUND: The pediatric autoimmune neuropsychiatric disorders associated with 
streptococcal infection (PANDAS) hypothesis suggests an association between 
group A beta-hemolytic streptococcus (GABHS) infections and subsequent onset or 
exacerbation of neuropsychiatric symptoms, such as obsessive-compulsive disorder 
or tic disorders.
METHODS: We performed a systematic review and meta-analysis including 
longitudinal, prospective studies on exacerbations of neuropsychiatric symptoms 
associated with GABHS infections in children with PANDAS. We searched PubMed and 
EMBASE through August 14, 2017. Two independent reviewers extracted data and we 
used random-effects analysis to calculate rate ratios (RR).
RESULTS: Three studies were included with a total of 82 PANDAS cases and 127 
control children with obsessive-compulsive disorder or chronic tic disorder. 
PANDAS cases had a nonsignificantly increased RR of 2.33 [95% confidence 
interval [CI]: 0.63-8.70, P = 0.21, I = 28.3%] for exacerbations of 
neuropsychiatric symptoms in temporal proximity to a GABHS infection and no 
increased risk of GABHS infections (RR = 0.99, 95% CI: 0.56-1.73, P = 0.97, I = 
45%) compared with the control children. However, PANDAS cases had an increased 
risk of neuropsychiatric exacerbations in general with a RR of 1.54 (95% CI: 
1.12-2.11, P = 0.008, I = 0%) compared with the control children. The studies 
had methodologic heterogeneity, high risk of selection bias and differed 
concerning case definition and infection measures.
CONCLUSIONS: Our findings did not show significant evidence concerning higher 
rates of temporally associated GABHS infections and exacerbations of 
neuropsychiatric symptoms in children with PANDAS. The included studies were 
small and limited by low GABHS rates and exacerbations. Future studies with 
large population sizes and routine evaluations are needed to thoroughly examine 
the PANDAS hypothesis.