PANDAS

[Guest mommy007]

Hello,

 

My DS has been diagnosed with PANDAS by a neurologist a A. I. Dupont for children. He is 11years old The diagnosis was made in February, we have our second appointment on Tuesday.

 

My son has been treated will every stimulant, it helps focus, but the side effects are terrible, His tics increase 10 fold and he has signs of OCD.

 

With Pandas he has frequent urination, hyperactivity, lack of concentration, and recently night terrors. In december he had the flu, 103 fever and the night terrors started. His ASO is at 573 and his antiDNase B is at 480.

 

I was a child of rhamatic fever and syndems chorea with a titer of 1400. I know there may be a genetic factor involved. My sons handwriting is unreadable and the school has been tough. He is a B average, but since the Flu his grades are droping.

The Nuro put him on 250mgs of Penn. and now he needs to take clonizapam for the night terrors.

 

My concern is that he has had symptoms since the age of 4, they have only increased with time. Knowing how bad my illness was and my tics and OCS, I wonder how he will progress. I was lucky, I am in complete remission of all symptoms.

I have no heart damage. I was bed ridden for 3 years and experenced a complete central nervous system shut down during my illness for 6 months.

 

What have you all tried? what has worked or caused additional problems?

[Guest Guest]

Mommy,

 

Welcome to the Latitudes.

 

My suggestion to you would be to read through the various threads on this site for Tourettes over the last few months. It would be very repetitive for everyone who posts here to start replying in detail as there are numerous threads where most have provided details of the supplements that their children take and the purpose for taking them.

 

You will see from reading here that there is much negativity with respect to medical prescriptions in controlling tics, etc. and you will also see the great success that many of us have had with the natural supplements.

 

Chemar had drastic results with her son taking medical drugs just as you have already seen with your son. Her posts are very detailed and helpful.

 

good luck

 

Heather

[Chemar]

Hi Mommy and welcome

as Heather has mentioned, we had a nightmare year with prescription meds, but have been med-free for almost 3 years now with remarkable improvement coming from using alternative therapy.

 

Ronna is our "expert" on PANDAs and has just returned from a trip abroad, so I am sure she will be checking in soon and be able to give you lots of good info....

 

If you start back reading the threads here you will gain enormously from the experiences that have been shared with regard to allergies, heavy metal detox, Candida)yeast) elimination, supplement treatments, biofeedback, accupuncture and careful diet, avoiding artificial stuff that have so helped.

 

My son's OCD was always more troubling than his tics, but thankfully is now almost negligible thanks to corrective supplements like 5HTP, St John's Wort and Inositol.....

 

again, welcome to the Latitudes Community

[mommy007]

Thanks for the response, I have been reading throught posts, and wanted to make myself known.

 

This is the first board to discuss PANDAS that I have found active. I am very much interested in treatment and will continue to read the older posts.

 

Did any of your children get a diagnosis after years of symptoms? We have been struggling for 7 years.

 

My goal right now is to bring down the titers - what have you found effective?

 

I was speaking to a women in indiana who used the ivig (?) method with success, but it sounds extream.

 

It's nice to find an active group.

[Ronnas]

Hi All,

 

Welcome Mommy 007! Over the last year I have learned alot about PANDAS. A thread you may want to read on BrainTalk's old board would be:

 

http://neuro-mancer.mgh.harvard.edu/ubb/Fo...TML/005700.html

 

If you go to the Tourette Syndrome Board at BrainTalk you will find parents who actively post about PANDAS as well. As well BrainTalk has a PANDAS board as well as does Yahoo.

 

As a start it is best to read as much as you can find. My son was on prophylactic antibiotics for a year and since January has been on no meds. My son is also another example of a child who has been helped tremendously by supplements, changes in diet (eliminating dairy, corn, eggs and chocolate) treating yeast and building his immune system up.

 

In my experience from reading these boards I have found that the greatest success has been found from parents who are guided by expereinced naturopathic doctors. In our case we have a very supportive pediatrician and a naturopath doctor who guides me and wtih whom I can discuss different options. Initially, all of this can be so overwhelming but with time it becomes easier and a path forms.

 

Below is a recent article about PANDAS which I thought you might find interesting. I am not sure if I have posted it before...I have the worst case of jet lag right now and my brain is very muddled!

 

Let me know if you have any questions.

 

Ronna

 

 

--------------------------------------------------------------------------------

 

COMMENTARY

 

The Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection (PANDAS) Subgroup: Separating Fact From Fiction

Abbreviations: OCD, obsessive-compulsive disorder • PANDAS, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection • NIMH, National Institute of Mental Health

 

Over a century ago, Sir William Osler wrote, "To carefully observe the phenomena of life in all its phases ... to call to aid the science of experimentation, to cultivate the reasoning faculty, so as to be able to know the true from the false—these are our methods."1

 

These were also the methods that led to the discovery of poststreptococcal obsessive-compulsive disorder (OCD) and tic disorders and a decade of observations and research resulting in the description of a novel cohort of patients, the pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup.2,3 In this issue of Pediatrics, Kurlan and Kaplan raise questions about the veracity of these data.4 To respond, we will provide a brief literature review and clarification of the guidelines for management of a patient in the PANDAS subgroup.

 

The discovery of the PANDAS subgroup was the result of 2 parallel lines of clinical research conducted at the National Institute of Mental Health (NIMH): studies of children with OCD and investigations of children with Sydenham’s chorea, the neurologic manifestation of rheumatic fever. Systematic observations of children with OCD revealed that, although the majority of children had a gradual onset of symptoms over several weeks to months, a subgroup of the patients experienced an explosive "overnight" onset of obsessions and compulsions followed by a relapsing-remitting symptom course.5 Closer observation revealed that the neuropsychiatric symptom relapses frequently occurred after episodes of streptococcal pharyngitis or scarlet fever. These findings in OCD closely paralleled those from a series of investigations of Sydenham’s chorea.6 In those studies, 65% to 100% of children with Sydenham’s chorea were noted to have obsessive-compulsive symptoms, typically presenting 2 to 4 weeks before the onset of the adventitious movements and peaking in severity simultaneously with the chorea.6,7 Longitudinal observations of the OCD subgroup and the patients with Sydenham’s chorea clearly demonstrated a temporal association between streptococcal infections and obsessive-compulsive symptoms. This relationship was not only observed consistently among patients presenting to the NIMH but also noted by several independent groups.8–11 The nature of the association was unknown, and the observations could not elucidate whether the streptococcal infections played an etiologic role, but these issues would be addressed through subsequent scientific experimentation.

 

The title of the article by Kurlan and Kaplan4 provides a provocative starting point for discussion of the scientific hypotheses that derive from the clinical observations of the PANDAS subgroup. However, the authors subsequently blur the distinction between clinical observation and scientific investigation, leading them to dismiss the well-documented observations that neuropsychiatric symptoms are associated with streptococcal infections in the PANDAS subgroup because the etiology of PANDAS "remains a yet-unproven hypothesis."4 The authors thus recommend against obtaining throat cultures or serial titers in patients with abrupt-onset OCD and tics "until more definitive scientific proof is forthcoming." We strongly disagree with this recommendation. The continued threat of rheumatic fever mandates the detection and appropriate treatment of streptococcal infections, including asymptomatic infections, the leading cause of rheumatic carditis in the United States.12 If one argues that OCD and tics are a manifestation of streptococcal infection for children in the PANDAS subgroup, then the infections aren’t really "silent" or "asymptomatic." In either case, a conservative treatment course would include administration of antibiotics for culture-proven streptococcal infections. In addition, Murphy and Pichichero11 have documented that prompt treatment of streptococcal infections is associated with a rapid diminution of obsessive-compulsive symptom severity for some children in the PANDAS subgroup. Thus, the potential benefits of appropriate diagnosis and treatment of an occult streptococcal infection far outweigh the modest cost of obtaining a throat swab and culture. Of course, when throat cultures are obtained, there is a risk of falsely identifying a "carrier" as an asymptomatic infection, but this risk is small. Systematic studies typically report the frequency of carriers to be <5% to 10%.13 Thus, the vast majority of positive throat cultures represent true streptococcal infections, for which antibiotics administration is the accepted standard of care.

 

 

CLINICAL CRITERIA

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Kurlan and Kaplan contend that the 5 criteria defining the PANDAS subgroup are not "particularly useful in distinguishing patients suspected of PANDAS from children with more typical cases of TS [Tourette’s syndrome] or OCD."4 In actuality, the criteria have been used successfully by a variety of clinical groups to define cohorts of patients with common clinical characteristics and a predictable clinical course.3,9–11,14 This had been the original purpose of describing the PANDAS subgroup: to enable investigators to identify a clinically homogeneous group of patients for inclusion in research studies at the NIMH and elsewhere. Subsequent investigations have demonstrated that the criteria have clinical utility as well, in that they define a distinct cohort of patients who are uniquely responsive to novel therapeutic interventions and prevention strategies. The following is a clarification of the criteria.

 

The Presence of a Tic Disorder and/or OCD

The symptom characteristics and severity required for diagnosis are defined in the Diagnostic and Statistical Manual of Mental Disorders.15 The neuropsychiatric symptoms of the PANDAS subgroup were intentionally limited to tics and obsessive-compulsive symptoms because of our interest in establishing a homogeneous patient cohort for research studies. Subsequent interest in the PANDAS subgroup has sparked a number of authors to speculate that the criteria should be expanded to include other related disorders such as attention-deficit/hyperactivity disorder16 and anorexia.17 However, such a change requires systematic evidence documenting that the association between streptococcal infections and symptom onset in these disorders is not merely a chance finding; to date, such systematic studies have not been done.

 

Prepubertal Age at Onset, Usually Between 3 and 12 Years of Age

This criterion was based on historical data demonstrating that rheumatic fever and other poststreptococcal sequelae are uncommon before the age of 3 years and after the age of 12 years.18 Fischetti19 provides a possible explanation for the rarity of postpubertal sequelae of streptococcal infections and demonstrated the presence of serum antibodies conferring protection against streptococcal infections in 98% of healthy 12-year-old controls, making it unlikely that poststreptococcal neuropsychiatric symptoms would have their initial presentation after this age. Thus, we set the age range for the PANDAS subgroup at a point that had biological relevance and would include 98% of the cases.

 

Abrupt Symptom Onset and/or Episodic Course of Symptom Severity

Prospective longitudinal investigations have demonstrated that this criterion is the most useful in identifying children in the PANDAS subgroup.2,3,9–11 Contrary to the concerns expressed by Kurlan and Kaplan,4 the abrupt onset of tics in the PANDAS subgroup is clearly different from the typical onset of an isolated, intermittent, simple motor or vocal tic, because children in the PANDAS subgroup experience the simultaneous onset of several different motor and vocal tics of such intensity and frequency that emergency treatment is often sought.14 PANDAS-related OCD is also easily distinguished from non-PANDAS OCD, because the latter patients have a slow, gradual symptom onset, whereas children in the PANDAS subgroup have an overnight "explosion" of obsessive-compulsive symptoms, reaching maximal, clinically significant impairment in 24 to 48 hours.3,20

 

The episodic, relapsing-remitting course of the PANDAS subgroup is distinctly different from the undulating, waxing-waning course seen in other patients with OCD or tic disorders.20,21 When the symptoms of a child in the PANDAS subgroup are graphed against time, a "saw-toothed" pattern emerges, in which periods of symptom quiescence are interrupted abruptly by severe symptom exacerbations; these relapses typically take several weeks to months to resolve. Prospective, longitudinal evaluation of these patients allows for documentation of the relationship between the symptom exacerbations and streptococcal infections: throat cultures obtained at the beginning of a symptom relapse will be positive, and titers obtained at baseline and 4 to 6 weeks later will demonstrate a clinically significant rise.

 

Temporal Association Between Symptom Exacerbations and Streptococcal Infections

Although it was postulated initially that there could be a significant time lag between the inciting streptococcal infection and the presentation of the neuropsychiatric sequelae (such as that seen in Sydenham’s chorea),6 clinical observations of the PANDAS subgroup revealed that the window is actually much narrower. Exacerbations of neuropsychiatric symptoms begin within 7 to 14 days after the streptococcal infection and usually occur simultaneously (ie, a throat culture obtained because of the recent onset of OCD and/or tics is positive).3,11,20,21

 

One caveat in evaluating the relationship between streptococcal infections and neuropsychiatric symptoms is that the disorders are so common that co-occurrence can be a random coincidence rather than a clinically significant finding. OCD occurs in 1% to 2% of school-aged children, and transient motor tics occur in as many as 10% to 25% of early elementary students.22,23 Furthermore, during regional streptococcal epidemics, the majority of children will be infected at least once during the outbreak.13 Thus, as discussed in our original report,3 a single positive throat culture or elevated antistreptococcal antibody titer is not sufficient to determine that a child’s neuropsychiatric symptoms are associated with streptococcal infections.3,20 Instead, the determination that a child fits the PANDAS profile is made through prospective evaluation and documentation of the presence of streptococcal infections in conjunction with at least 2 episodes of neuropsychiatric symptoms, as well as demonstrating negative throat culture or stable titers during times of neuropsychiatric symptom remission.3 A child who has multiple symptom exacerbations without evidence of streptococcal infection would not be considered part of the PANDAS subgroup, nor would a child who has numerous streptococcal infections without subsequent symptom exacerbations.

 

Presence of Neurologic Abnormalities During Periods of Symptom Exacerbation

Neurologic examination of acutely ill children in the PANDAS subgroup reveals that 95% have choreiform movements.3 These fine piano-playing movements of the fingers are not easily confused with the writhing adventitious movements of Sydenham’s chorea.24 Choreiform movements are not present at rest and must be elicited through stressed postures, whereas choreatic movements are present continuously and increase with unrelated voluntary movements. In addition, choreiform movements are an isolated finding, whereas the choreatic movements of Sydenham’s chorea are accompanied by a failure to sustain tetanic contractions (milk-maid’s grip, snake-like tongue) and muscle weakness.6,18 Choreiform movements and chorea may share a common pathophysiology (related to dysfunction of the basal ganglia), but the clinical manifestations are quite distinct, and children in the PANDAS subgroup do not represent missed cases of Sydenham’s chorea. In fact, rheumatic fever, including Sydenham’s chorea, is a strict exclusionary criterion for the PANDAS subgroup.3

 

 

SCIENTIFIC HYPOTHESES

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CLINICAL CRITERIA

SCIENTIFIC HYPOTHESES

CLINICAL RECOMMENDATIONS

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Clinical observations of the PANDAS subgroup led to a number of scientific hypotheses including the postulate that the tics and OCD represent sequelae of group A streptococcal infections. This etiologic hypothesis involves a series of factors including pathologic strains of group A streptococcal bacteria, host susceptibility (genetic, developmental, or other), and abnormal immune responsivity (Fig 1). The working model of pathogenesis not only provides a framework for understanding the etiology of OCD and tic disorders but also allows for the development of novel intervention and prevention strategies. A recent review provides a detailed description of the model as well as ongoing research efforts directed at understanding the pathologic mechanisms involved in the PANDAS subgroup.25

 

 

 

 

 

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Fig 1. Model of pathogenesis for PANDAS.

 

 

 

 

 

CLINICAL RECOMMENDATIONS

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CLINICAL CRITERIA

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These guidelines are drawn from our clinical and research experience as well as the practice parameters of the American Academy of Child and Adolescent Psychiatry.26

Laboratory testing: Children with an abrupt onset or exacerbation of OCD or tic disorder should have a throat culture obtained. If the symptoms have been present for >1 week, serial antistreptococcal titers may be indicated to document a preceding streptococcal infection. (Titers should be timed to catch the rise at 4–6 weeks.)

 

Use of antibiotics: Antibiotics are indicated only for the treatment of acute streptococcal infections as diagnosed by a positive throat culture or rapid streptococcal test. Clinical trials are underway to determine whether prophylactic antibiotics will be useful in the management of children in the PANDAS subgroup, but at present, they are not indicated. In the only placebo-controlled trial reported to date, penicillin administration failed to prevent streptococcal infections (14 of 35 infections occurred during the penicillin phase of the crossover trial), and thus there were no between-group differences in neuropsychiatric symptom severity.27

 

Management of neuropsychiatric symptoms: Children in the PANDAS subgroup respond to treatment with standard pharmacologic and behavioral therapies. Obsessive-compulsive symptoms are treated best with a combination of medication (typically, a serotonin reuptake-blocking drug) and cognitive-behavior therapy, and motor and vocal tics respond to a variety of pharmacologic agents.

 

Immunomodulatory therapies: A randomized, placebo-controlled trial of intravenous immunoglobulin and therapeutic plasma exchange demonstrated significant and persistent improvements for a group of 29 severely affected children meeting criteria for the PANDAS subgroup.28 The specificity of their response was demonstrated through a subsequent open-label trial of plasma exchange, which failed to produce benefits among children not meeting the PANDAS criteria.29 After the publication of these reports, the American Society for Apheresis ranked therapeutic plasma exchange for poststreptococcal OCD and tic disorders "acceptable as second-line therapy or as an adjunct to primary therapy based on controlled trials."30 Thus, immunomodulatory therapy may be a consideration for acutely and severely affected children in the PANDAS subgroup. Clinicians considering such an intervention are invited to contact the PANDAS research group at the NIMH for consultation.

 

 

CONCLUSIONS

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CLINICAL CRITERIA

SCIENTIFIC HYPOTHESES

CLINICAL RECOMMENDATIONS

CONCLUSIONS

REFERENCES

 

 

The PANDAS subgroup is both a clinical entity and the subject of scientific experimentation. Systematic, longitudinal observations have demonstrated that the PANDAS subgroup has a distinct clinical presentation and an identifiable course of symptoms and that, for these children, there is a clear relationship between streptococcal infections and neuropsychiatric symptom exacerbations. Additional research is required to determine the nature of that relationship as well as to determine the etiopathogenesis of the poststreptococcal obsessive-compulsive symptoms and tics. Additional studies are required also to determine the role of immunomodulatory therapies and antibiotics prophylaxis for this group of patients. Meanwhile, it is time to end the debate about the existence of the PANDAS subgroup and begin to "call to aid the science of experimentation ... so as to be able to know the true from the false."

 

 

Susan E. Swedo, MD, Henrietta L. Leonard, MD and Judith L. Rapoport, MD

 

 

Pediatrics and Developmental Neuropsychiatry Branch

Intramural Research Program

National Institute of Mental Health

Bethesda, MD 20892

Division of Child Psychiatry

Brown University

Providence, RI 02912

Child Psychiatry Branch

Intramural Research Program

National Institute of Mental Health

Bethesda, MD 20892

 

 

FOOTNOTES

 

Received for publication Aug 27, 2003; accepted Aug 27, 2003.

 

Address correspondence to Susan E. Swedo, MD, Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health, 10 Center Dr, MSC 1255, Bethesda, MD 20892-1255. E-mail: swedos@mail.nih.gov

 

 

REFERENCES

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Osler W. Aphorisms From His Bedside Teachings and Writings. Bean WB, ed. Springfield, IL: Charles C. Thomas, 1968

Allen AJ, Leonard HL, Swedo SE. Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry.1995; 34 :307 –311[iSI][Medline]

Swedo SE, Leonard HL, Garvey MA, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry.1998; 155 :264 –271[Abstract/Free Full Text]

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Swedo SE, Rapoport JL, Leonard H, Lenane M, Cheslow D. Obsessive-compulsive disorder in children and adolescents: clinical phenomenology of 70 consecutive cases. Arch Gen Psychiatry.1989; 46 :335 –341[Abstract]

Swedo SE. Sydenham’s chorea: a model for childhood autoimmune neuropsychiatric disorders. JAMA.1994; 272 :1788 –1791[iSI][Medline]

Asbahr FR, Negrao AB, Gentil V, et al. Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study. Am J Psychiatry.1998; 155 :1122 –1124[Abstract/Free Full Text]

Murphy TK, Petitto JM, Voeller KK, Goodman WK. Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function? Semin Clin Neuropsychiatry.2001; 6 :266 –276[Medline]

Tucker DM, Leckman JF, Scahill L, et al. A putative poststreptococcal case of OCD with chronic tic disorder, not otherwise specified. J Am Acad Child Adolesc Psychiatry.1996; 35 :1684 –1691[iSI][Medline]

Giulino L, Gammon P, Sullivan K, et al. Is parental report of upper respiratory infection at the onset of obsessive-compulsive disorder suggestive of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection? J Child Adolesc Psychopharmacol.2002; 12 :157 –164[iSI][Medline]

Murphy ML, Pichichero ME. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Arch Pediatr Adolesc Med.2002; 156 :356 –361[Abstract/Free Full Text]

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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth ed. Washington, DC: American Psychiatric Association; 1994

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Sokol MS. Infection-triggered anorexia nervosa in children: clinical description of four cases. J Child Adolesc Psychopharmacol.2000; 10 :133 –145[iSI][Medline]

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Perlmutter SJ, Garvey MA, Castellanos X, et al. A case of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Am J Psychiatry.1998; 155 :1592 –1598[Free Full Text]

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[Claire]

Hi Ronna,

 

Welcome back from your trip!

 

When you have a chance, could you update me on the amount of non-LCD TV/Computer that you have your son watch in one week these days? (I remember your saying that you had an LCD screen or laptop). Does he seem to tolerate it well?

 

How is he doing in general? I think by now you would have treated his suspected yeast or leaky gut that your naturopath suspected from the antibiotics?

 

Claire

[Ronnas]

Hi Claire,

 

My son is doing very well. He is tolerating watching TV again. I think his not tolerating TV was a part of his "threshold" being lowered given his food sensitivities and yeast from being on long term antibiotics. Now that his diet is well controlled and he is on the supplements he is tolerating alot of things that use to be a trigger for him such as stress, fatigue and TV etc.

 

As well, he has made it through a winter of colds, flu etc quite well and he "looks" alot healthier than he has in years. Stopping all of his meds has been the biggest blessing and I feel like I have my son back.

 

I hope all is ok for you and it sounds like you are working too hard. Try and take time to catch your breath.

 

Ronna

[guligirl]

Is it possible to have the PANDAS test come back incorrect? I was so sure my son's tics and OCD were a result of it since he'd had so many strep infections as a child but the Doc says "no."