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New eBook: Your Child Has Changed; Should You Consider PANDAS?


Have you seen the ACN Latitudes PANDAS eBookOur helpful book is a 37-page primer in a friendly question & answer format.  This eBook contains useful information to understand the symptoms of PANDAS, how it is diagnosed (including lab tests), the different types of treatments, approaches for prevention, and how to find the help and support that you need. Learn more

 






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PANDAS Fact Sheet


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#1 buster

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Posted 13 December 2009 - 02:12 AM

What is PANDAS?

PANDAS is a pediatric autoimmune disorder characterized by the dramatic onset of neuropsychiatric symptoms such as obsessions, compulsions, motor or vocal tics [Swedo1997]. PANDAS is thought to be similar to Sydenham Chorea where there is dramatic symptom exacerbation following a strep infection[Kirvan2006].

Signs and Symptoms:

Children with PANDAS must be initially diagnosed with Obsessive Compulsive disorder or a tic disorder [Swedo2004]. These children may have some of the following symptoms that accompany the OCD or tic disorder [Swedo1998][Moretti2006]:

  • Obsessions (e.g., preoccupation with a fixed idea or an unwanted feeling, often accompanied by symptoms of anxiety)
  • Compulsions (e.g., an irresistible impulse to act, regardless of the rationality of the motivation)
  • Choreiform movements (e.g., milk-maid grip, fine finger playing movements in stressed stance)
  • Emotional lability (e.g.,irritability, sudden unexplainable rages, fight or flight behaviors) (66%)
  • Personality changes (54%)
  • Age inappropriate behaviors particularly regressive bedtime fears/rituals (50%)
  • Separation anxiety (46%)
  • Oppositional defiant disorder (40%)
  • Tactile/sensory defensiveness (40%)
  • Hyperactivity, impulsivity, fidgetiness, or inability to focus (40%)
  • Major Depression (36%)
  • Marked deterioration in handwriting or math skills. (26%)
  • Daytime urinary frequency/enuresis (12%)
  • Anorexia (particularly fear of choking, being poisoned, contamination fears, fear of throwing up)
PANDAS/OCD is a clinical diagnosis, often marked by the sudden onset and extreme symptom exacerbations (such as an increase of +18 points on the OCD CY-BOCS score during an exacerbation [Murphy2004]). The abrupt onset and remission after eradication of streptococcal infection separates the child from non-PANDAS OCD[Swedo2004]. Many parents can pinpoint a day or a week when behaviors changed [Çengel-Kültür2009]

When a child has primarily vocal and motor tics, the symptoms may appear to overlap with symptoms of Tourettes Syndrome; however, the children can be differentiated by observing symptom exacerbations over time [Pavone2006]. In PANDAS children, a streptococcal infection precedes symptom exacerbation and once treated, initial exacerbations generally remit. The rapid onset with significant remission is characteristic of PANDAS.

Researchers have described chronic PANDAS [Pavone2006] where the tics and/or obsessive-compulsive disorder have a much more gradual course. These cases are difficult to separate from non-PANDAS tics or OCD. Some researchers have found other immunologic markers (anti-neuronal and anti-basal-ganglia antibodies) that help separate PANDAS and non-PANDAS children[Kirvan2006].

Diagnostic tests:

At this time, there are no commerically available tests for diagnosing PANDAS. There are ongoing research trials that indicate there are differences in specific antibodies that can be tested in blood serum. [Kirvan2006] [Church2006][Martono2007]. These are recent findings and the accuracy, repeatability and specificity of the results are not known. Additional research funding is needed to repeat the experiments at independent laboratories and confirm the diagnostic effectiveness.

A throat culture for Group A Beta-Hemolytic streptococcus (GABHS) at time of exacerbation onset is recommended to diagnose a pharyngeal streptococcal infection [Swedo2004]. If the culture is negative, a blood test may be able to test for streptococcal exotoxins. A common blood test is Anti-Streptolycin O. While this test can confirm a previous strep infection, it cannot exclude a prior infection or a diagnosis of PANDAS. This test is affected by many factors and in one study over 46% of children did not have a rising ASO titer despite having colonized strep [Shet2003].

For children affected by PANDAS, a GABHS infection is considered to be the triggering event that causes an initial episode. However, as is the case with Sydenham's Chorea, subsequent PANDAS exacerbations may be triggered by recurrent GABHS, or by other bacterial or viral infections (ear infections, sinusitis, pneumonia, meningitis, impetigo) further complicating diagnosis [Swedo1998].


Treatment:


Streptococcal infections are treated with antibiotics.

Cognitive Behavioral Therapy (CBT) has been shown to be effective in some children with PANDAS and to provide families with coping strategies during a PANDAS flare [Storch2006]. Caution is recommended for using SSRI's with PANDAS/OCD as there are reports of higher activation rates in such cases [Murphy2006]. In addition, there is a lack of controlled studies showing safety and efficacy of anti-tic or anti-OCD medications (e.g., SSRI and anti-psychotics) for children in the PANDAS subgroup.

Several reports have shown effectiveness of immunomodulating therapy (IVIG and PEX) in combination with longer term prophylactic antibiotics[Perlmutter1999]. In addition, several studies have shown efficacy of longer term prophylactic antibiotics alone [Snider2005]. These treatments are still considered experimental and have several risks. Some physicians will use a prednisone steroid burst for a short period of time to assist in diagnosis of an auto-immune disorder. Immunomodulating therapies are not effective for Tourettes Syndrome or other non-PANDAS OCD cases, again separating the child with PANDAS [Nicolson2000].

Getting Help:

PANDAS was only identified in 1998 and as such is a recent disease [Swedo1998]. Additional research is needed to identify the most effective treatment protocols. Taking copies of recent studies to your doctor may help them diagnose and treat your child. You may need to interview pediatricians, neurologists and immunologists. For referrals to local doctors with experience, one source is a parent's support group at http://www.latitudes...?showtopic=3928.

Research:

PANDAS is thought to be caused by the following sequence of events in this order:

  • The production by the immune system of an antibody that can interact with neuronal tissue [Kirvan2006][Kirvan2003]
  • A failure of the immune system to suppress this antibody [Kawikova2007]
  • A breach of the blood brain barrier such that the antibody reaches neuronal tissue [Yaddanapudi2009]
All three areas have active research results and require duplication of experiments to help reach consensus in the research community.
For those interested in a brief history of PANDAS research, please see http://www.latitudes...amp;#entry36300

Other considerations:

Other autoimmune illnesses that may cause sudden onset OCD and other neuropsychiatric disorders include: Lyme Disease, Thyroid Disease, Celiac Disease, Lupus, Sydenham Chorea, Kawasaki's disease, and acute Rheumatic Fever [Schneider2002]. Some children have been found to have Immunology challenges such as IgG subclass deficiencies [Kawikova2009]. Children will need to be evaluated for this issue by an immunologist. In addition, while there is good evidence of anti-neuronal antibodies in PANDAS, the diagnosis remains controversial primarily due to the observations by Johns Hopkins researchers who have not been able to detect such antibodies in their research subjects [Martono2007].

References

[Swedo1997] S Swedo et al, "Identification of Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections by a Marker Associated With Rheumatic Fever", Am J Psychiatry 154:1, January 1997 http://ajp.psychiatr...t/154/1/110.pdf

[Kirvan2003] Kirvan CA, Swedo SE, Heuser JS, Cunningham MW, "Mimicry and Auto-antibody mediated neuronal Signaling Cells in Sydenham Chorea", Nature Medicine 9, 914 - 920 (2003) http://www.pandasnet....NMpaper[1].pdf

[Kirvan2006] Kirvan CA, Swedo SE, Kurahara D, Cunningham MW, "Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea". 2006 Autoimmunity 39 (1): 21–9. http://www.pandasnet...NICaMKinase.pdf

[Swedo2004] Swedo SE, Leonard HL, Rapoport JL." The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction", Pediatrics. 2004 Apr;113(4):907-11. http://pediatrics.aa...print/113/4/907

[Moretti2008] Moretti G, Pasquini M, Mandarelli G, Tarsitani L, Biondi M (2008). "What every psychiatrist should know about PANDAS: a review". Clin Pract Epidemol Ment Health 4: 13. http://www.ncbi.nlm....5-0179-4-13.pdf

[Swedo1998] Swedo SE et al., "Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases", Am J Psychiatry 155:2, February 1998. http://ajp.psychiatr...print/155/2/264

[Çengel-Kültür2009]Çengel-Kültür2009, et al. "The relationship between group A beta hemolytic streptococcal infection and psychiatric symptoms: a pilot study", The Turkish Journal of Pediatrics 2009; 51: 317-324, http://www.turkishjo...pdf_TJP_674.pdf

[Murphy2004] Murphy TK, Muhammad S, Soto O, et al. "Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics", Biological Psychiatry, Volume 55, Issue 1, Pages 61-68, January 2004 http://www.journals....0704-2/abstract

[Pavone2006] Pavone P, Parano E, Rizzo R, Trifiletti RR (2006). "Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants". J Child Neurol 21 (9): 727-36. http://jcn.sagepub.c...stract/21/9/727

[Shet2003]Shet A, Kaplan EL, Johnson DR, Cleary PP, "Immune response to group A streptococcal C5a peptidase in children: implications for vaccine development", J Infect Dis. 2003 Sep 15;188(6):809-17. http://www.journals..../10.1086/377700

[Storch2006]Storch EA, Murphy TK, Geffken, G et al, "Cognitive-Behavioral Therapy for PANDAS-Related Obsessive-Compulsive Disorder: Findings From a Preliminary Waitlist Controlled Open Trial", Journal of the American Academy of Child & Adolescent Psychiatry: October 2006 - Volume 45 - Issue 10 - pp 1171-1178 http://www.ncbi.nlm....pubmed/17003662

[Murphy2006]Murphy TK, Storch EA, Strawser MS, "Selective serotonin reuptake inhibitor-induce behavioral activation in the PANDAS subtype", Primary Psychiatry, 2006;13(8):87-89, http://mbldownloads....06PP_Murphy.pdf

[Perlmutter1999]Perlmutter SJ, Leitman SF, Garvey MA, "Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood", Lancet 1999; 354 : 1153 – 58 http://intramural.ni.../pubs/pub-5.pdf

[Snider2005]Snider L, Lougee L, Slattery M, Grant P, Swedo S. "Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders". Biol Psychiatry 57 (7): 788–92. 2005 http://intramural.ni.../pubs/pub-9.pdf

[Nicolson2000]Nicolson et al, "An Open Trial of Plasma Exchange in Childhood Onset Obsessive-compulsive Disorder Without Poststreptococcal Exacerbations. " J Am Acad Child Adolesc Psychiatry 2000, 39[10]: 1313-1315 http://www.ncbi.nlm....pubmed/11026187

[Yaddanapudi2009] K Yaddanapudi, M Hornig, R Serge, J De Miranda, A Baghban, G Villar, W I Lipkin Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Molecular Psychiatry August 11, 2009 doi:10.1038/mp.2009.77 http://www.nature.co.../mp200977a.html

[Schneider2002]Schneider R., Robinson M., Levenson J., "Psychiatric presentations of non-HIV infectious diseases: Neurocysticercosis, lyme disease, and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection",
Psychiatric Clinics of North America, Volume 25, Issue 1, Pages 1-16 http://www.ncbi.nlm....pubmed/11912935

[Martono2007]Martono D, Church A, Giovannoni G, "Are antibasal ganglia antibodies important and clinically useful?", Practical Neurology, 2007; 7: 32-41 http://pn.bmj.com/co.../7/1/32.extract

[Kawikova2007]Kawikova I, Leckman J, Kronig H, et al. "Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study", Biol Psychiatry. 2007 Feb 1;61(3):273-8. http://www.journals....0804-3/abstract

[Kawikova2009]Kawikova I, Grady BP, Tobiasova Z, et al., "Children with Tourette's Syndrome May Suffer Immunoglobulin A Dysgammaglobulinemia: Preliminary Report", Biological Psychiatry, Sept 2009. http://www.ncbi.nlm....pubmed/20006327




#2 buster

buster

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Posted 11 March 2010 - 09:12 PM

Hi folks, I got several emails asking if I was okay with material from this post (and others) being posted on other web sites. Yes, however, people should create a link back to this post for the latest material as that means I don't have to try to keep multiple sites up to date :-) My goal in writing this stuff is to get good summaries of the scientific literature out there in a way that is hopefully easy to understand.

Buster




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