PANDAS

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

## Contents

* 1 Background
* 2 Identification
* 3 Proposed mechanism
* 4 Experimental treatments
* 5 See also
* 6 References

## Background

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File:Streptococcus pyogenes 01.jpgStreptococcus pyogenes (stained red), a common group A streptococcal pathogen.

PANDAS is an abbreviation for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. This diagnosis is used to describe a set of children who are thought to have developed obsessive-compulsive disorder (OCD) and/or tic disorders such as Tourette syndrome following group A beta-hemolytic streptococcal (GABHS) infections such as "strep throat" and scarlet fever.[1] Whether this condition exists is controversial and has been disputed, as some scientists think this sub-set of patients do not differ in any significant way from the remainder of the patient population and that infections do not increase the risk of Tourette syndrome. Consequently, the PANDAS model is a complex and rapidly-moving area of medical research. PANDAS is currently not listed as a diagnosis in the ICD or DSM.

## Identification

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Children with PANDAS are clinically identified by dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions,[1] although this has not been consistent in all studies. Indeed some studies have shown no acute motor exacerbations among clinically defined PANDAS subjects[2][3] whilst others have shown a profound one.

In addition to the motor symptoms, it is also thought that children may have psychiatric manifestations, becoming moody, irritable or show concerns about separating from parents or loved ones.[1] In the PANDAS model, this abrupt onset is thought to be preceded by a strep throat infection. As the clinical spectrum of PANDAS appears to resemble that of Tourette's syndrome, some researchers hypothesize that PANDAS and Tourette's may be associated. This idea is controversial and a focus for current research.

Concerns have been raised that PANDAS may be overdiagnosed, as nearly a third of patients diagnosed with PANDAS by community physicians did not meet the criteria when examined by specialists, suggesting that the PANDAS diagnosis is conferred by community physicians without scientific evidence.[4]

## Proposed mechanism

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At present, whether the group of patients diagnosed with PANDAS have developed tics and OCD through a different mechanism (pathophysiology) than seen in other people diagnosed with Tourette syndrome is unclear.[5][2] However, researchers at the NIMH are pursuing a hypothesis that the mechanism is similar to that of rheumatic fever, an autoimmune disorder triggered by streptococcal infections, where antibodies attack the brain and cause neuropsychiatric conditions.[1]

In every bacterial infection, the body produces antibodies against the invading bacteria, and the antibodies help eliminate the bacteria from the body. However in rheumatic fever, the antibodies mistakenly recognize and "attack" the heart valves, joints, and/or certain parts of the brain.[6] This phenomenon is called "molecular mimicry", which means that antigens on the cell wall of the strep. bacteria are similar in some way to the proteins of the heart valve, joints, or brain. Because the antibodies set off an immune reaction which damages those tissues, the child with rheumatic fever can get heart disease (especially mitral valve regurgitation), arthritis, and/or abnormal movements known as Sydenham's chorea or "St. Vitus Dance".[7] In PANDAS, it is believed that Tourette syndrome is produced in a similar manner. One part of the brain that may be affected in PANDAS is the basal ganglia, which is believed to be responsible for movement and behavior. Thus, the antibodies damage the brain to cause the tics and OCD that characterize Tourette syndrome, instead of Sydenham's chorea.[1][5] However, current data neither disprove nor support this hypothesis, indeed one recent study found no association between streptococcal infections and the risk of PANDAS symptoms.[8]

## Experimental treatments

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As both the PANDAS diagnosis and the hypothesis that symptoms in this subgroup of patients are caused by infection are controversial, anti-infective treatments for Tourette syndrome are experimental.[2][9] According to the Advisory Boards of the Tourette Syndrome Association and the NIH,[10] this diagnosis has engendered the use of dangerous and unproven treatment methodologies for children with tics and OCD, such as intravenous immunoglobulin (IVIG),[11] plasma exchange, and the use of prophylactic antibiotics for the prevention of streptococcal infections.

The results from these experimental treatments have been mixed, although an initial study with 37 children found no effect of antibiotic treatment on either infection rate or obsessive-compulsive or tic symptom severity,[12] a smaller study on twenty-three children later suggested that antibiotics were beneficial.[13] However, the methods in the latter study have been criticized.[14]

## See also

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* Tourette syndrome
* Neurology
* Microbiology

## References

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1. ↑ 1.0 1.1 1.2 1.3 1.4 NIH. PANDAS. Retrieved 25 November 2006.
2. ↑ 2.0 2.1 2.2 Luo F, Leckman J, Katsovich L, Findley D, Grantz H, Tucker D, Lombroso P, King R, Bessen D (2004). "Prospective longitudinal study of children with tic disorders and/or obsessive-compulsive disorder: relationship of symptom exacerbations to newly acquired streptococcal infections". Pediatrics. 113 (6): e578–85. PMID 15173540.CS1 maint: Multiple names: authors list (link)
3. ↑ Singer HS, Hong JJ, Yoon DY, Williams PN. Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls. Neurology. 2005 Dec 13;65(11):1701-7. PMID 16207842
* Loiselle CR, Wendlandt JT, Rohde CA, et al. Antistreptococcal, neuronal, and nuclear antibodies in Tourette syndrome. Pediatr Neurol. 2003 Feb;28(2):119-25. PMID 12699862
* Loiselle CR, Lee O, Moran TH, Singer HS. Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes. Mov Disord. 2004 Apr;19(4):390-6. PMID 15077236
4. ↑ Moyer, Paula. PANDAS May Be Overdiagnosed, Contributing to Overuse of Antibiotics. Medscape Medical News, from AACAP 53rd Annual Meeting: Abstract C21. Presented October 26 2006. Retrieved March 13 2007
5. ↑ 5.0 5.1 Swedo S. "Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)" (PDF). Mol Psychiatry. 7 Suppl 2: S24–5. PMID 12142939.
6. ↑ Rullan E, Sigal L (2001). "Rheumatic fever". Curr Rheumatol Rep. 3 (5): 445–52. PMID 11564377.
7. ↑ Bonthius D, Karacay B (2003). "Sydenham's chorea: not gone and not forgotten". Semin Pediatr Neurol. 10 (1): 11–9. PMID 12785743.
8. ↑ Perrin E, Murphy M, Casey J, Pichichero M, Runyan D, Miller W, Snider L, Swedo S (2004). "Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children?". Arch Pediatr Adolesc Med. 158 (9): 848–56. PMID 15351749.CS1 maint: Multiple names: authors list (link)
9. ↑ Singer HS, Loiselle C. PANDAS: a commentary. J Psychosom Res. 2003 Jul;55(1):31-9. PMID 12842229
* Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004 Apr;113(4):883-6. PMID 15060240 Full-text, Retrieved March 14 2007
* Dale RC. Post-streptococcal autoimmune disorders of the central nervous system. Dev Med Child Neurol. 2005 Nov;47(11):785-91. Review. PMID 16225745
* Johns Hopkins Medicine. A Strep - Tourette Connection? Brain Waves Fall 2004 Volume 16, Number 4. Retrieved 25 November 2006
10. ↑ Franklin, Deeanna. Warning About Two Therapies for Tourette's, OCD - obsessive-compulsive disorder. Family Practice News, September 15 2000. Retrieved 25 November 2006.
11. ↑ Hoekstra PJ, Minderaa RB, Kallenberg CG. Lack of effect of intravenous immunoglobulins on tics: a double-blind placebo-controlled study. J Clin Psychiatry. 2004 Apr;65(4):537-42. PMID 15119917
12. ↑ Garvey M, Perlmutter S, Allen A, Hamburger S, Lougee L, Leonard H, Witowski M, Dubbert B, Swedo S (1999). "A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections". Biol Psychiatry. 45 (12): 1564–71. PMID 10376116.CS1 maint: Multiple names: authors list (link)
13. ↑ Snider L, Lougee L, Slattery M, Grant P, Swedo S (2005). "Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders". Biol Psychiatry. 57 (7): 788–92. PMID 15820236.CS1 maint: Multiple names: authors list (link)
14. ↑ Gilbert D, Gerber M (2005). "Regarding "antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders"". Biol Psychiatry. 58 (11): 916. PMID 16242119.

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