Studies Of The Relationship of GAS to Tic Disorders (Including Episodic Tic Disorders Labeled as PANDAS)
|[Kurlan2008]||Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study
Findings: (N=40, C=40) Compared TS/long-term tic patients who met PANDAS criteria to TS patients who did not (controls). Forty children with tics (95%), or comorbid tics+OCD (56%) or OCD-only(5%) were followed for 2 years to determine whether their exacerbations were temporally correlated with GABHS infections. Authors note that while their subjects met the criteria for PANDAS, they had a different clinical presentation than reported in the literature. Course and severity at exacerbations were similar between subjects and control with almost no change in OCD symptoms over a 2 year period. There was a surprisingly low number of GABHS infections in subjects and controls with subjects being twice as likely to have a positive culture for GABHS and three times as likely to have a probable GAS infection. Authors concluded that children meeting the PANDAS criteria seem more likely to get GAS infection and there was no statistical difference in exacerbations due to strep between TS patients meeting the PANDAS criteria & TS controls.
|[Singer2008]||Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections
Findings: (N=12) Serum was drawn from twelve patients in the [Kurlan2008] longitudinal study to determine if antibodies against human postmortem caudate, putamen and prefrontal cortex were correlated with exacerbations. No correlation was found.
|[Morer2008]||Antineuronal antibodies in a group of children with obsessive-compulsive disorder and Tourette syndrome
Findings: (N=53, C=19) Antibodies were assayed by immunohistochemistry and immunoblot. No anti-basal ganglia antibodies were detected by immunohistochemistry. Two proteins with weights of 86kDa and 55 kDa were found in sera from 7 patients. Though the study supports the hypothesis of an autoimmune process underlying OCD or TS in some patients, further research is needed.
|[Gause2009]||Antineuronal antibodies in OCD: comparison in children with OCD-only, OCD+chronic tics, and OCD+“PANDAS”
Findings: (N=13,20,23, C=29). ELISA and immunohistochemistry showed no differences amongst groups of OCD-only, OCD+PANDAS, OCD+Chronic Tic Disoder. Immunoblot showed that a greater percentage of individuals in the OCD+PANDAS cohort had reactive bands at 27 kDa (caudate, cingulate gyrus, dorsolateral prefrontal cortex), 36 kDA (caudate), 100 kDa (orbitofrontal, caudate) and increased peak height at 67 kDa (all regions). Immunoblotting studies using the Stu antigens (pyruvate kinase M1, aldolase C, alpha- and gamma-enolase) did not differ among groups. ASO titers were similar in all groups and did not correlate with immunoassays.
|[Morris2009]||Serum autoantibodies measured by immunofluorescence confirm a failure to differentiate PANDAS and Tourette syndrome from controls
Findings: (N=30 TS,30 PANDAS, C=30)
No significant differences in immunofluorescence or localization were identified in patients with PANDAS (n=30) and TS (n=30) as compared to controls (n=30). Further comparisons showed no correlation between autoreactivity determined by immunofluorescence and the presence of previously measured immunoblot reactivity against human caudate or putative antigens (pyruvate kinase M1 and aldolase C). These results confirm an inability to distinguish patient populations by antibody measurements and raise further concerns about the presence of an autoimmune mechanism in PANDAS and TS.
|[Bombaci2009]||Protein array profiling of tic patients sera reveals a broad range of enhanced immune response against Group A Streptococcus antigens.
Findings: (n=61, c=35, n=239) 61 kids had tics and neurological issues, 35 kids had no strep and no tics, and 239 kids had strep. Their blood was exposed to 102 proteins of Group A Strep. 33% of the tic patients reacted very intensely to 30% of the strep proteins while only 12% of strep kids & 1% of control kids reacted similarly. 21 antigens solicited a stronger response in tic patients than strep only patients and 5 of the strep proteins solicited a response from the tic only group, even they did not have a strep infection. This study provides evidence that tic patient sera from kids who did not have an active strep infection exhibits immunological profiles similar to and in some cases more robust than individuals who have a current strep infection.
|[Schrag2010]||Streptococcal infection, Tourette syndrome and OCD: Is there a connection?
Findings: (N=255, C=4519) Authors retrospectively sampled a large medical database in the UK to see whether a preceding infection led to a higher likelihood of a diagnosis of OCD or TS. Incident rates of OCD and TS matched preceding literature. Laboratory data in support of GABHS infection was largely missing with only 67 throat swabs and 6 ASO titers in the entire database. The authors used a wide set of diagnostic codes to look for a possible correlation. Conclusion was that subjects did not differ strongly from controls when seeking whether a preceding infection was correlated with a diagnosis of OCD or TS.
|[Leckman2011]||Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: a prospective longitudinal study.
Findings: (N=31, C=53). Children were monitored on monthly basis for 25 months to determine if there was a correlation between a positive GABHS infection (rise of titers and positive throat culture) and symptom exacerbation. Subjects and controls had very similar rates of tic and/or OCsymptom exacerbations. Rates of GABHS infection were likewise similar between subjects and controls.
|[Singer2015]||Neuronal Antibody Biomarkers for Sydenham’s Chorea Identify a New Group of Children with Chronic Recurrent Episodic Acute Exacerbations of Tic and Obsessive Compulsive Symptoms Following a Streptococcal InfectionFindings: (N=8, C=70) Study of serum anti-neuronal antibodies during exacerbations in 8 subjects with chronic tics with/without OCD who are asserted as meeting the 2004 definition of PANDAS. Key finding in paper is that controls differ between research institutes. One group used siblings of children with autism as controls. This group differed substantially from other controls (particularly in D1 and anti-Lysoganglioside GM1). Patients did have elevated CaM Kinase II activation compared to controls. Critique: Core teaching of paper is the need for better controls. One organization (Johns Hopkins) used children with known anti-neuronal antibodies (siblings of children with Autism) as their controls. Subjects appear to be drawn from 2008 Tourettes Study group longitudinal study that used different criteria raising whether selection criteria used in this paper is accurate. Paper has small sample size (n=8), focuses on children with chronic tics, and there remains a question whether subjects had clinical presentation similar to NIMH study (e.g., OCD exacerbations).|