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.

Correlates of Perceived Health-Related Quality of Life in Post-Treatment Lyme Encephalopathy
Chandra AM, Keilp JG, Fallon BA. Correlates of perceived health-related quality of life in post-treatment Lyme encephalopathy. Psychosomatics. 2013 Nov-Dec;54(6):552-9. doi: 10.1016/j.psym.2013.04.003. Epub 2013 Jul 9. PMID: 23845316; PMCID: PMC5507690.

A significant portion of Lyme disease-treated patients experiences persistent symptoms for months or even years, including pain, fatigue, and neurocognitive issues, collectively referred to as post-treatment Lyme disease syndrome. Determining whether ongoing infection is present remains challenging with current technology, raising an open question. Alternatively, a post-infectious immune-mediated process could be responsible for sustained symptoms.

As fatigue and depression significantly impact the reported decline in both physical and mental functioning in patients with PTLDS, clinicians should thoroughly evaluate these symptoms. It is advisable to consider addressing these issues when selecting treatment interventions. Subsequent controlled studies should investigate the efficacy of such approaches for patients dealing with PTLDS.

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.”
Increased IFNα Activity and Differential Antibody Response in Patients with a History of Lyme Disease and Persistent Cognitive Deficits
Jacek E, Fallon BA, Chandra A, Crow MK, Wormser GP, Alaedini A. Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits. J Neuroimmunol. 2013 Feb 15;255(1-2):85-91. doi: 10.1016/j.jneuroim.2012.10.011. Epub 2012 Nov 8. PMID: 23141748; PMCID: PMC3557545.
The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.
Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease–endemic Region
Maggi RG, Mozayeni BR, Pultorak EL, Hegarty BC, Bradley JM, Correa M, Breitschwerdt EB. Bartonella spp. bacteremia and rheumatic symptoms in patients from Lyme disease-endemic region. Emerg Infect Dis. 2012 May;18(5):783-91. doi: 10.3201/eid1805.111366. PMID: 22516098; PMCID: PMC3358077.

  • Bartonella species infection associated with an expanding spectrum of symptoms and lesions
  • Study included 296 patients evaluated by a rheumatologist
  • High prevalence of Bartonella exposure: antibodies in 62%, bacteremia in 41.1%
  • Common prior diagnoses included Lyme disease (46.6%), arthralgia/arthritis (20.6%), chronic fatigue (19.6%), and fibromyalgia (6.1%)
  • B. henselae bacteremia associated with prior neurology referral and neurologic symptoms
  • B. koehlerae bacteremia associated with infectious disease referral
  • Cross-sectional design does not establish causality
  • Authors conclude Bartonella’s potential contribution to neurologic symptoms, joint pain, and progressive arthropathy warrants further study
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.

Lyme disease and the orthopaedic implications of lyme arthritis
Smith BG, Cruz AI Jr, Milewski MD, Shapiro ED. Lyme disease and the orthopaedic implications of lyme arthritis. J Am Acad Orthop Surg. 2011 Feb;19(2):91-100. doi: 10.5435/00124635-201102000-00004. PMID: 21292932; PMCID: PMC3656475.
  • Lyme disease is the most common tick-borne illness in the U.S. and Europe. Caused by Borrelia burgdorferi, affecting skin, nervous system, heart, and joints
  • Lyme arthritis is a common manifestation, especially in later disease stages
  • Typically presents as monoarticular or pauciarticular joint involvement
  • Should be considered in endemic regions when joint symptoms are present
  • Primary treatment is antibiotic eradication of the spirochete
  • Prognosis is generally excellent
  • Arthroscopic synovectomy reserved for antibiotic-refractory cases
Leah’s Story

Leah’s Story

In August of 2014 our daughter, Leah, was 6 years old.  We had just returned home from a month-long trip to Illinois to visit family.  When we arrived home in Arizona, she suddenly (overnight) developed a fear of vomit.