Table 2.

Experimental models of PANDAS and TS.

Pandas and TS	Experimental models of pandas and TS	Future perspectives
Chronic tic disorders and/or OCD1	OCD-like behaviors: increased repetitive behaviors, stereotypies, perseverative behavior and fine motor coordination4−11	Extension of the behavioral phenotype to incorporate patterns analogous to tics
Association with streptococcal infections1	Association with streptococcal infections through active immunization7–11 or passive transfer of sera from TS patients4–6	Design of complex experimental protocols entailing a double hit hypothesis (e.g., stress during pregnancy x streptococcal immunization early in puberty)
Motor hyperactivity1	Motor hyperactivity	Prolongation of the analysis of motor behavior (e.g., continuous monitoring of behavior through automated systems)
Prepubertal onset1	Prepubertal onset	Earlier administration of streptococcal antigens
Relapsing and remitting course of the disease1	Relapsing and remitting course of the disease	–
Impaired PPI2	Impaired PPI9	–
Autoantibodies developed following streptococcal infections, cross the BBB and bind specific target at the level of BG, causing morphological alteration in CNS3	IgG deposits in cerebellum, striatum, hippocampus and paraventricular area7, 8 inflammation in rostral diencephalon9	Investigation of the role of microglia and astrocytes in the autoimmune sequelae in preclinical models12

Bold, Scientific evidence; Italics, hypothesis; Normal text, Clinical evidence not reproduced in animal models.

Numbers indicate the references in which the corresponding information has been described. (1) Swedo et al., 1998; (2) Swerdlow et al., 2001b; (3) Martino et al., 2009; (4) Hallett et al., 2000; (5) Taylor et al., 2002; (6) Yeh et al., 2012; (7) Hoffman et al., 2004; (8) Yaddanapudi et al., 2010; (9) Macrì et al., 2015; (10) Brimberg et al., 2012; (11) Lotan et al., 2014; (12) Benedek et al., 2016.