Research

Cytokine Correlations in Youth with Tic Disorders

E. Carla Parker-Athill, Jared Ehrhart, Jun Tan, Tanya K. Murphy
JCAP-2015

These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders.

Antineuronal Antibodies in a Heterogeneous Group of Youth and Young Adults with Tics and Obsessive-Compulsive Disorder

Carol J. Cox, Amir J. Zuccolo, Erica V. Edwards, Adita Mascaro-Blanco, Kathy Alvarez, Julie Stoner, Kiki Chang, Madeleine W. Cunningham
JCAP-2015

Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology.

Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections

Miro Kovacevic, Paul Grant, Susan E. Swedo
JCAP-2015
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This case series demonstrates the benefits of IVIG therapy for youths with PANDAS/PANS, including those who had been symptomatic for several years prior to treatment. Although the generalizability of this retrospective report is limited, the selected cases represent the breadth of symptom presentations in PANDAS/PANS and provide additional evidence that IVIG may be useful in the management of children with moderate-severe symptoms.

Therapeutic Plasma Apheresis as a Treatment for 35 Severely Ill Children and Adolescents with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections

M. Elizabeth Latimer, Nathan L’Etoile, Jakob Seidlitz, Susan E. Swedo
JCAP-2015

Therapeutic plasma apheresis is an invasive medical intervention that should be reserved for treatment of children and adolescents who are severely affected by PANDAS. In such patients, it appears to be a safe, well-tolerated, and beneficial treatment option.

Basal ganglia inflammation in children with neuropsychiatric symptoms

Ajay Kumar, Mitchel Williams, Otto Muzik and Harry Chugani
Journal of Nuclear Medicine–2015

Our findings suggest increased activated microglial cells, suggesting underlying neuroinflammation, in bilateral caudate nuclei in children with PANDAS and TS and in bilateral lentiform nuclei in PANDAS patients only. These differences in the pattern and extent of neuroinflammation signify a possible difference in pathophysiological etiology between PANDAS and TS.

Sydenham Chorea and PANDAS in South Africa: Review of Evidence and Recommendations for Management in Resource-Poor Countries

Kathleen G. Walker, Petrus J. de Vries, Dan J. Stein, and Jo M. Wilmshurst
Journal of Child Neurology-2015

In South Africa, and worldwide, rheumatic fever represents a public health problem. Improved diagnosis and management of Sydenham chorea, a major manifestation of acute rheumatic fever is key to prevention of rheumatic heart disease. This article reviews Sydenham chorea from its original description to current opinions.

The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness

Hornig M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol. 2013 Jul;25(4):488-795. doi: 10.1097/BOR.0b013e32836208de. PMID: 23656715.

Summary: Microbes, both pathogenic and commensal, can induce autoantibodies that bind to brain and affect behavior in susceptible hosts. Interventions that correct the microbial balance or diminish autoantibody binding may be effective in diverse neuropsychiatric conditions mediated by autoimmunity.

Immune-mediated animal models of Tourette syndrome

Hornig M, Lipkin WI. Immune-mediated animal models of Tourette syndrome. Neurosci Biobehav Rev. 2013 Jul;37(6):1120-38. doi: 10.1016/j.neubiorev.2013.01.007.

“Demonstration of the ability to recreate these abnormalities through passive transfer of serum IgG from GAS-immunized mice into naïve mice and abrogation of this activity through depletion of IgG has provided compelling evidence in support of the autoimmune hypothesis. Immunologically-based animal models of TS are a potent tool for dissecting the pathogenesis of this serious neuropsychiatric syndrome.”

Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview

Rhee H, Cameron D. Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview. Int J Gen Med. 2012;5:163-174
https://doi.org/10.2147/IJGM.S24212

B. burgdorferi and GAβHS are very different microorganisms that evade the immune system and invade a wide variety of tissues, including the central nervous system (CNS). Lyme and PANS can have periods of active disease and periods of remission. Both infections cause physical, neurological, and cognitive symptoms.

Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection

Yaddanapudi K, Hornig M, Serge R, De Miranda J, Baghban A, Villar G, Lipkin WI. Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Mol Psychiatry. 2010 Jul;15(7):712-26. doi: 10.1038/mp.2009.77.

Executive and Attention Functioning Among Children in the PANDAS Subgroup

Matthew E. Hirschtritt, Christopher J. Hammond, David Luckenbaugh, Jason Buhle, Audrey E. Thurm, B. J. Casey & Susan E. Swedo (2009) Executive and Attention Functioning Among Children in the PANDAS Subgroup, Child Neuropsychology, 15:2, 179-194, DOI: 10.1080/09297040802186899

Evidence from past studies indicates that adults and children with Obsessive-Compulsive Disorder (OCD) and Tourette syndrome (TS) experience subtle neuropsychological deficits. Less is known about neuropsychological functioning of children and adolescents with a symptom course consistent with the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) subgroup of OCD and tics. T

Administered three tests of attention control and two of executive function to 67 children and adolescents (ages 5–16) diagnosed with OCD and/or tics and a symptom course consistent with the PANDAS subgroup and 98 healthy volunteers (HV) matched by age, sex, and IQ.
The PANDAS subjects were less accurate than HV in a test of response suppression.
In a two-step linear regression analysis of the PANDAS group in which clinical variables were added stepwise into the model and in the second step matching variables (age, sex, and IQ) were added, IQ emerged as a predictor of performance on this task.
ADHD diagnosis and age emerged as predictors of response time in a continuous performance task.
Subdividing the PANDAS group by primary psychiatric diagnosis revealed that subjects with TS or OCD with tics exhibited a longer response time compared to controls than subjects with OCD only
Children with PANDAS exhibit neuropsychological profiles similar to those of their primary psychiatric diagnosis.

Case Study: A New Infection-Triggered, Autoimmune Subtype of Pediatric OCD and Tourette’s Syndrome

Albert J. Allen MD, PhD, Henrietta L. Leonard, MD, Susan E. Swedo, MD
Journal of the American Academy of Child & Adolescent Psychiatry-1995

A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham’s chorea, infections with group A β-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette’s syndrome).