MRI Assessment of Children With Obsessive-Compulsive Disorder or Tics Associated With Streptococcal Infection

Giedd, Jay N.; Rapoport, Judith L.; Garvey, Marjorie A.; Perlmutter, Susan J.; Swedo, Susan E.

doi:10.1176/appi.ajp.157.2.281

Cited by 265 publications

(162 citation statements)

References 6 publications

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“…Potential mechanisms by which these autoantibodies cause clinical manifestations in central nervous system (CNS) diseases include direct stimulation or blockade of receptors in the basal ganglia, or immune complexes promoting inflammation of these brain regions (Giedd et al 1996(Giedd et al , 2000. Antineuronal antibody binding to basal ganglia tissue was found in both patients with PANDAS (Pavone et al 2004) and patients with ADHD (Sanchez-Carpintero et al 2009), whereas in SC patients, increased antineuronal antibody binding to basal ganglia tissue correlates with symptom severity (Church et al 2002;Husby et al 1976;Kotby et al 1998).…”

Section: Serologic and Prospective Studiesmentioning

confidence: 99%

“…In addition to two case reports (Giedd et al 1996;Tucker et al 1996), Giedd et al (2000) assessed selective basal ganglia involvement in a subgroup of 34 children with OCD and/or tics believed to be associated with GAS infections, compared with 82 healthy children. The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the PANDAS cases compared with controls and were similar in magnitude to those seen in children with SC.…”

Section: Neurological and Cardiac Concernsmentioning

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

144

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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: 99%

Section: Neurological and Cardiac Concernsmentioning

confidence: 99%

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

144

View full text Add to dashboard Cite

show abstract

“…Only 2-4% of the control groups (children with an uncomplicated GAS infection, children with other neurologic disorders, adults with other neurologic disease, and adult healthy controls) were found to have these antibodies. 62 Using similar methodologies, anti-basal ganglia antibodies crossreactive with GAS were demonstrated in 42% (n ¼ 21) of children with childhood-onset OCD compared to 2-10% of the pediatric control groups: autoimmune disorders, other neurologic disorders, and uncomplicated GAS infection. (Dale, 2003 personal communication.)…”

Section: Pathogenesis Of Pandasmentioning

confidence: 98%

“…59 The striking effectiveness of immunomodulatory therapies, such as therapeutic plasma exchange and intravenous immunoglobulin (IVIG) in the PANDAS subgroup, suggests that there is systemic involvement, at least in severely affected individuals.61 Magnetic resonance imaging scans reveal enlargements of the caudate, putamen, and globus pallidus, which points to regional inflammatory changes, 60,61 while local autoimmune reactions are suggested by the presence of serum antibodies which cross-react with neurons of the caudate, putamen, and globus pallidus. 51,62 The pathobiology of the neuropsychiatric symptoms in the PANDAS subgroup is postulated to be similar to that of SC. The etiopathogenesis is hypothesized to occur when GAS bacteria infect a susceptible host and induce an abnormal immune response.…”

Section: Pathogenesis Of Pandasmentioning

confidence: 99%

PANDAS: current status and directions for research

2004

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The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive-compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing-remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of poststreptococcal OCD and tic disorders. The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea. The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen. The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.

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“…MR imaging in patients with suspected PANDAS has demonstrated a lack of structural abnormality, though volumetric evaluations revealed enlargement of the basal ganglia. 4 This report describes a patient presenting with dystonia and basal ganglial imaging abnormalities following streptococcal infection. Because there is no specific test to confirm this diagnosis, poststreptococcal dystonia was presumptive.…”

mentioning

confidence: 98%

Poststreptococcal Dystonia with Bilateral Striatal Enlargement: MR Imaging and Spectroscopic Findings

Kendi

Krenzel

Ott

et al. 2008

AJNR Am J Neuroradiol

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SUMMARY: Isolated bilateral striatal necrosis is an abnormality of the basal ganglia associated with acute dystonia in children. This report describes the development of dystonic movements in a 7-year-old male patient 2 weeks after streptococcal pharyngitis. Dystonia with basal ganglial imaging abnormalities is usually related to structural, metabolic, toxic, traumatic, or vascular disorders.1,2 Swedo et al 3 coined the term "pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection" (PANDAS) to describe them. MR imaging in patients with suspected PANDAS has demonstrated a lack of structural abnormality, though volumetric evaluations revealed enlargement of the basal ganglia. 4This report describes a patient presenting with dystonia and basal ganglial imaging abnormalities following streptococcal infection. Because there is no specific test to confirm this diagnosis, poststreptococcal dystonia was presumptive. To our knowledge, this is the first case report addressing the findings on diffusion-weighted MR imaging and on MR spectroscopy in a patient with poststreptococcal dystonia and striatal enlargement. Case ReportA 7-year-old boy presented with rigidity and difficulty breathing. Diagnosis of streptococcal pharyngitis was made, and he was treated with an aminopenicillin. Two days later, he was unable to get out of bed, and persistent drooling was noted. Dexamethasone was begun, but his condition deteriorated with increasing rigidity, dystonia, drooling, and tremor of the hands. Rigidity and dystonia rapidly progressed, and he developed mutism, dysphagia, and incontinence. Laboratory testing demonstrated borderline high antistreptolysin O titer and a high level of antideoxyribonuclease antibody.Cranial MR imaging demonstrated bilateral T2 hyperintensity in the heads of the caudate nuclei, the putamina, and the external/ extreme capsules. The heads of the caudate nuclei and the putamina were enlarged (Fig 1) and demonstrated minimal restricted diffusion on diffusion-weighted images (Fig 2). Single-voxel MR spectroscopy of the left lentiform nucleus demonstrated elevation of the lipid/lactate peak and a decreased N-acetylaspartate (NAA) peak (Fig 3A).Follow-up MR imaging 1 month later showed no significant change. MR spectroscopy demonstrated continued depression of the NAA peak with interval increase in the choline/creatine ratio compared with the initial MR spectroscopy (Fig 3B).

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MRI Assessment of Children With Obsessive-Compulsive Disorder or Tics Associated With Streptococcal Infection

Abstract: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.

Cited by 265 publications

References 6 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

PANDAS: current status and directions for research

Poststreptococcal Dystonia with Bilateral Striatal Enlargement: MR Imaging and Spectroscopic Findings

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