Serial Immune Markers Do Not Correlate With Clinical Exacerbations in Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

Singer, Harvey S.; Gause, Colin D.; Morris, Cynthia Taft; López, Pablo H.H.

doi:10.1542/peds.2007-2658

Cited by 87 publications

(61 citation statements)

References 34 publications

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“…However, these combined cytokine clinical fluctuations were more frequent in the non-PANDAS than in PANDAS cases. In contrast, Singer et al (2008) found no association between clinical exacerbations (associated or not with GAS infection) and several effector molecules including both TNF-a and IL-12 (Singer et al 2008).…”

Section: Serologic and Prospective Studiesmentioning

confidence: 85%

“…They also found that antibodies to pyruvate kinase reacted strongly with surface antigens of infectious strains of Streptococcus, and antibodies to streptococcal M proteins reacted with pyruvate kinase. However, increases in antibodies to aldolase C, enolase, and pyruvate kinase were not detected in serial serum specimens obtained during one of the prospective longitudinal studies described above (Kurlan et al 2008;Singer et al 2008). Methodological differences in the laboratory procedures and patient selection may account for some of the inconsistencies across studies (Martino et al 2009).…”

Section: Serologic and Prospective Studiesmentioning

confidence: 92%

“…The binding of autoantibodies to neuronal cell surface antigens may promote signal transduction, leading to the release of excitatory neurotransmitters, and may explain mechanistically the symptoms of SC and PANDAS. In contrast, not all studies conducted have shown that antibrain antibodies correlate with clinical exacerbations in PANDAS and are a topic of continued debate (Morer et al 2008;Singer et al 2008;Gause et al 2009). …”

Section: Serologic and Prospective Studiesmentioning

confidence: 99%

See 2 more Smart Citations

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

Murphy

Kurlan

Leckman

2010

Journal of Child and Adolescent Psychopharmacology

143

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Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas-the basal ganglia of the brain and the related cortical and thalamic sites-adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS.

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Section: Serologic and Prospective Studiesmentioning

confidence: 85%

Section: Serologic and Prospective Studiesmentioning

confidence: 92%

Section: Serologic and Prospective Studiesmentioning

confidence: 99%

See 1 more Smart Citation

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

Murphy

Kurlan

Leckman

2010

Journal of Child and Adolescent Psychopharmacology

143

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“…Indirect support of such a theory includes a significantly higher incidence of autoimmune disease in the mothers of children with tics (Murphy et al, 2010). Nevertheless, the existence of this etiological entity is extremely controversial based on both epidemiological and autoimmune studies (Kurlan, 1998(Kurlan, , 2004Singer and Loiselle, 2003;Kurlan and Kaplan, 2004;Singer et al, 2005b;Kurlan et al, 2008;Singer et al, 2008;Morris et al, 2009;Leckman et al, 2011).…”

Section: Etiologymentioning

confidence: 99%

Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.

Felling¹,

Singer²

2011

J. Neurosci.

199

116

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Tourette syndrome (TS) is a common, chronic neuropsychiatric disorder characterized by the presence of fluctuating motor and phonic tics. The typical age of onset is ϳ5-7 years, and the majority of children improve by their late teens or early adulthood. Affected individuals are at increased risk for the development of various comorbid conditions, such as obsessive-compulsive disorder, attention deficit hyperactivity disorder, school problems, depression, and anxiety. There is no cure for tics, and symptomatic therapy includes behavioral and pharmacological approaches. Evidence supports TS being an inherited disorder; however, the precise genetic abnormality remains unknown. Pathologic involvement of cortico-striatal-thalamo-cortical (CSTC) pathways is supported by neurophysiological, brain imaging, and postmortem studies, but results are often confounded by small numbers, age differences, severity of symptoms, comorbidity, use of pharmacotherapy, and other factors. The primary site of abnormality remains controversial. Although numerous neurotransmitters participate in the transmission of messages through CSTC circuits, a dopaminergic dysfunction is considered a leading candidate. Several animal models have been used to study behaviors similar to tics as well as to pursue potential pathophysiological deficits. TS is a complex disorder with features overlapping a variety of scientific fields. Despite description of this syndrome in the late 19th century, there remain numerous unanswered neurobiological questions.In the 1880's, Georges Gilles de la Tourette published a two-part article in which he emphasized differences between tics and chorea. Although many of the descriptions about the disorder, which now bears his name [Tourette syndrome (TS)], have been revised, his belief that tics are a neurological movement disorder and not a psychiatric condition persists to the present (Goetz and Klawans, 1982). Nevertheless, despite multiple advances and widespread acceptance of TS being a biological disorder, the precise etiology and underlying pathophysiological mechanisms remain unknown. The goals of the present review are to briefly describe the clinical phenomenology of TS and related tic disorders, to review current information on genetic and neurobiological mechanisms, and to identify areas in need of further investigation.

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“…Early reports demonstrated that the unique clinical presentation of the PANDAS subgroup was useful in determining which children would benefit from treatment with antibiotics (Murphy and Pichichero 2002) or immunomodulatory therapies Perlmutter et al 1999;Snider et al 2005), such as intravenous immunoglobulin (IVIG) and plasmapheresis (interventions that are not helpful for non-PANDAS tic disorders and OCD, respectively) (Hoekstra 2004;Nicolson et al 2000). In addition, cross-reactive autoantibodies were found in sera of acutely ill PANDAS patients (Kirvan et al 2006(Kirvan et al , 2007Swedo 1994); these autoantibodies were not present in convalescent samples or in samples obtained from patients with non-PANDAS OCD or tic disorders (Singer et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections in Research and Community Settings

Swedo

Seidlitz

Kovacevic

et al. 2015

Journal of Child and Adolescent Psychopharmacology

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Background: The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described > 15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessivecompulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS. Methods: A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n = 52) and Bethesda, Maryland (n = 40). Results were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n = 48). Results: As described in the original PANDAS cohort, males outnumbered females (95:45) by * 2:1, and symptoms began in early childhood (7.3 -2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86-92%), school issues (75-81%), sleep disruptions (71%), tics (60-65%), urinary symptoms (42-81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections. Conclusions: The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may preclude a diagnosis of PANDAS in some children with acute-onset OCD, they do appear to meet criteria for pediatric acute-onset neuropsychiatric syndrome (PANS).

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Serial Immune Markers Do Not Correlate With Clinical Exacerbations in Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

Abstract: The failure of immune markers to correlate with clinical exacerbations in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections raises serious concerns about the viability of autoimmunity as a pathophysiological mechanism in this disorder.

Cited by 87 publications

References 34 publications

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.

Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections in Research and Community Settings

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