Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

doi:10.1016/j.jaac.2010.10.011

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 50, Issue 2, February 2011, Pages 108-118.e3

https://doi.org/10.1016/j.jaac.2010.10.011 Get rights and content

Objective

The objective of this blinded, prospective, longitudinal study was to determine whether new group A β hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or OC disorder without a PANDAS history served as the comparison (non-PANDAS) group.

Method

Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25-month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results.

Results

No group differences were observed in the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions of a total of 51 (12%), a newly diagnosed GABHS infection was followed, within 2 months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group.

Conclusions

This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria.

Section snippets

Subjects

All subjects were sequentially enrolled at one of six clinical settings (Yale University, Cincinnati Children's Hospital Medical Center, New York University Child Study Center, Johns Hopkins University School of Medicine, University of Alabama at Birmingham, and University of Rochester School of Medicine) during a 4-year 6-month period from July 2002 to December 2006. Approval by the institutional review boards was obtained at all sites.

Case subjects met all five of the published diagnostic

Description of Study Cohort

Apart from age, the PANDAS cases and the non-PANDAS comparison group had similar demographic and clinical characteristics (Table 1). As a consequence, all case and control comparisons included age as a covariate.

Exacerbations

The PANDAS cases and the non-PANDAS cases had very similar rates of tic and/or OC symptom exacerbations (PANDAS: 0.45 per person per year; non-PANDAS: 0.42 per person per year; Table 2). The relative risk for PANDAS versus non-PANDAS after controlling for age was 1.27 (95% confidence

Discussion

In this prospective, blinded, case-control study of children who met published diagnostic criteria for PANDAS, there was no temporal association between clinical exacerbations and antecedent GABHS infections documented by microbiologic and/or immunologic criteria. The number of hits was larger in the non-PANDAS cases than in the PANDAS cases, although this difference was not statistically significant. Our findings support those from earlier previous prospective, blinded, case-control study in

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At the population level, and after adjusting for parental psychiatric history and autoimmune diseases, a significantly increased risk of OCD and TS/CTD was found in individuals exposed to prenatal maternal (but not paternal) infections (OCD: HR, 1.33; 95% CI, 1.12–1.57; TS/CTD: HR, 1.60; 95% CI, 1.23–2.09) and early childhood infections (OCD: HR, 1.19; 95% CI, 1.14–1.25; TS/CTD: HR, 1.34; 95% CI, 1.24–1.44). However, these associations were no longer significant in the sibling analyses.
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Although exposure-based cognitive behavior therapy (CBT) and pharmacotherapy have demonstrated efficacy for obsessive-compulsive disorder (OCD), the lack of clinicians effectively trained in these treatments significantly limit effective intervention options for affected youth. This is very unfortunate since child onset is reported by 50% of adults with OCD. To ameliorate this serious global issue the 14 nation International Obsessive-Compulsive Disorders Accreditation Task Force (ATF) of The Canadian Institute for Obsessive Compulsive Disorders (CIOCD) has developed knowledge and competency standards recommended for specialized treatments for OCD through the lifespan. Currently available guidelines are considered by experts to be essential but insufficient because there are not enough clinicians with requisite knowledge and competencies to effectively treat OCD. This manuscript presents knowledge and competency standards recommended for specialized cognitive behavior therapy (CBT) for pediatric OCD, derived from comprehensive literature review and expert synthesis. In addition to standards covering the elements of individual CBT-based assessment and treatment, family and school interventions are addressed given the critical role these domains play in the psychosocial development of youths. The ATF standards presented in these phase two papers will be foundational to the upcoming development of certification (individuals) and accreditation (sites) for specialized treatments in OCD through the lifespan.
Deep slow nasal respiration with tight lip closure for immediate attenuation of severe tics
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Citation Excerpt :
The correlation between the pathophysiology of TS/CTD and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) remains unclear [40,41]. However, a prospective longitudinal study reported no evidence for a temporal association between group A β hemolytic streptococcal infections and tic symptom exacerbations in children [42]. A possible confounder of the relationship between TS/CTD and PANDAS could be oral respiration, which is associated with both tics and upper respiratory infection [43].
Severe intractable tics, which are associated with Tourette syndrome and chronic tic disorder (TS/CTD), severely affect the quality of life. Common less-invasive treatments are often unable to attenuate tics with deep brain stimulation currently being the only effective treatment. We aimed to assess the anti-tic effect of deep slow nasal respiration with tight lip closure using patients with TS/CTD.
We retrospectively analyzed 10 consecutive patients (9 men, 1 woman; 23–41 years old). We instructed the patients to perform the procedure for 120 s and to obtain a video recording of before and during the procedure. The videos were used to count tics and determine lip competency or incompetency. The counted tics were rated using the modified Rush Video Rating Scale.
Compared with before the procedure, there were significantly lower frequencies of motor and phonic tics, as well as video scored, during the procedure. Eight patients presented with lip incompetency before the procedure and none after the procedure (P = 0.041). There were no side effects associated with the procedure.
Our findings indicate that deep slow nasal respiration with tight lip closure ameliorates tics in patients with TS/CTD. In accordance with our results, lip opening and oral breathing could be causes of tics, in addition to heritability. Therefore, this novel procedure could improve tics. Furthermore, our findings could contribute toward the development of tic treatments and elucidate their pathophysiology regarding the reward system, hypersensitivity, autonomic nerves, and nasal airway.
Tourette syndrome
2020, Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease: Volume 2
Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by compulsive, habitual motor, and vocal tics and holds one of the highest familial recurrence rates indicated by a heritability of 0.77, affecting 1 in 150 children. To date, genome-wide association analyses reveal few significant loci or biomarkers, leading to the hypothesis that the disorder results from both genetic alterations and environmental risk factors. Neuroimaging studies describe abnormalities in the cortico-striatal-thalamo-cortical circuitry, including striatal volume loss and metabolic hypofunction. In addition, analysis of human postmortem brain tissue of adult TS patients has demonstrated cellular and molecular abnormalities, including a decrease in several classes of striatal interneurons. These findings have driven efforts to develop animal models that display tic-like stereotypies following genetic or cellular disruptions of basal ganglia interneuron circuitry. Biobehavioral and pharmacological strategies aim to ameliorate symptoms via action at dopaminergic receptors and other potential target sites within the basal ganglia and cortical-striatal-thalamic-cortical circuitry.

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: This article was reviewed under and accepted by Ad Hoc Editor Daniel S. Pine, M.D.

: This research was funded in part by the Tourette Syndrome Association and the National Institutes of Health, grants (R01MH061940 (J.F.L.); K05 MH076273 (J.F.L.); K02 MH01527 (P.J.L.); M01RR006022; and RR00125).

: Disclosure: Dr. Leckman has received research support from the National Institutes of Health and the Tourette Syndrome Association. He has received salary support from the National Institutes of Health. He has received support from the Klingenstein Third Generation Foundation from the medical student fellowship program. He has received royalties from John Wiley and Sons, McGraw Hill, and Oxford University Press. Dr. Coffey receives research support from Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Co., the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Tourette Syndrome Association. She has served on the advisory board for Jazz Pharmaceuticals, Eli Lilly and Co., Novartis, and the Tourette Syndrome Association. She has served on the speakers' bureau for the Tourette Syndrome Association. Dr. Singer has received research and salary support from the National Institutes of Health. He has received royalties from Elsevier and has served as an editor for the journal Neurolograd. Dr. Gilbert has received honoraria from the American Academy of Pediatrics, the Tourette Syndrome Association/Center for Disease Control, the Movement Disorder Society, and the American Academy of Neurology. He has served on the advisory board for the Tourette Syndrome Association. He has received research support from the National Institutes of Health, Cincinnati Children's Hospital Research Foundation, the University of Cincinnati, and the Tourette Syndrome Association. He will receive salary support for clinical research from the Genzyme Corporation, Otsuka Pharmaceuticals, and Psyadon Pharmaceuticals. Dr. Kurlan has received research support from the National Institutes of Health, the Centers for Disease Control, the Michael J. Fox Foundation, Neurologix, Boehringer Ingelheim, and Kyowa. He has received salary support from the National Institutes of Health, Neurologix, Boehringer Ingelheim, and Kyowa. Dr. Lombroso has received research and salary support from the National Institute of Mental Health, the Institute for the Study of Aging, the American Health Assistant Foundation, and the Fragile X Foundation. Drs. King, Dure, Lin, Kawikova, and Kaplan, Ms. Grantz, Mr. Johnson, and Ms. Katsovich report no biomedical financial interests or potential conflicts of interest.

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New researchStreptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

Objective

Method

Results

Conclusions

Section snippets

Subjects

Description of Study Cohort

Exacerbations

Discussion

Psychiatr Clin North Am

Biol Psychiatry

Pediatr Neurol

J Neuroimmunol

J Neuroimmunol

J Neuroimmunol

J Neuroimmunol

J Neurol Sci

J Am Acad Child Adolesc Psychiatry

Lancet

J Psychiatr Res

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Brain Behav Immun

Am J Child Adolesc Psychiatry

Am J Child Adolesc Psychiatry

Am J Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Psychiatry Res

Brain Dev

Prevalence of the tic disorders and Tourette syndrome in a Swedish school population

Dev Med Child Neurol

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases

Am J Psychiatry

Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS): update

Curr Opin Pediatr

Prospective longitudinal study of children with tic disorders and/or obsessive-compulsive disorder: Relationship of symptom exacerbations to newly acquired streptococcal infections

Pediatrics

Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children?

Arch Pediatr Adolesc Med

Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study

Pediatrics

Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea

Nat Med

New research
Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study