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Among the important scientific developments that have come out of the nineties, Paul Ewald's (Amherst College, Mass) evolutionary research deserves particular attention. By reinterpreting well known evolutionary theories, that somehow got "twisted" over the past century, Ewald has offered us a new prospective on the role of infectious agents in common diseases of modern man. A mere possibility that an infection can indeed be one of the major causes of diseases such as heart disease, atherosclerosis, mental illness, and cancer is very exciting and if his speculations are confirmed, new treatment opportunities will emerge soon.
Do you wish to learn more about the subjects from this page, or to learn more about the future path of medical sciences? Find it at our Reference page.
It must be pointed out that the original division of childhood autoimmune neuropsychiatric disorders into PANDAS and PITAND syndromes (depending on presence or absence of GABS) as initially proposed by Swedo et al. currently may be outdated and therefore ALL patients fulfilling the required criteria (as specified elsewhere) should be diagnosed with PANDAS.
Controversial and still highly contentious concepts of PANDAS (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococci) and PITAND (Paediatric Infection-triggered Autoimmune Neuropsychiatric Disorders) were introduced by A. J. Allen and Swedo et al. in the late nineties. The premise brought forward by these researchers, that certain mental illnesses (e.g. Obsessive-compulsive disorder, tic disorders including certain cases of Tourette's syndrome) can be caused by an infection with a common infectious agent (designated as "PANDAS": Group A beta-hemolytic Streptococcus - GABHS) and (possibly) by other infectious agents (designated as "PITAND": certain viruses, Mycoplasma pneumonie, etc.), severely challenges a century of Freudian "devotion" of the medical community. In a simple language, theories of Allen and Swedo are bringing the mental illness back to its biological roots and essentially define it as a physical illness with mental symptoms. Recent scientific evidences are widening the list of possible mental illnesses that could be included into PANDAS and PITAND group. Certain cases of Anorexia nervosa (see the footnote below), psychotic symptoms following the Lyme disease and at least some cases of Autistic Spectrum Disorders (PDD NOS) have all been linked to an infectious agent and their pathophysiology appears compatible with PANDAS and PITAND syndromes.
Sokol et al. (1997) reported a group of patients diagnosed with Anorexia nervosa who were classified as PANDAS. Our experiences bring to light new information on this particular group:
If you would like to learn more about PANDAS and PITAND syndromes, review PANDAS clinical cases page.
PANDAS clinical cases page also contains UPDATED PANDAS DIAGNOSTIC CRITERIA!
Updated PANDAS signs and symptoms
(1) Pediatric onset. The first symptoms of PANDAS are most likely to occur between 5 and 7 years of age. Symptoms can occur as early as 18 months of age or as late as 10 years of age. If the first clinically recognized episode is detected after the age of 10, it is unlikely true initial episode, but the recurrent one. Previous episode(s) were simply not recognized as such.
(2) Particular patient phenotype. PANDAS patient is frequently highly intelligent, very communicative child who is also a very good student. It is common that patient's past medical history contains information about occasional ("transient") tic(s), certain degree of obsession with order, cleanness, preciseness, etc. In addition, infantile problems with colic, poor sleeping habits are frequently reported in PANDAS patients.
(3) Presence and/or history of certain psychiatric symptoms.
OCD symptoms (intrusive thoughts, anxiety, different phobias, unfounded fears; repetitive physical and mental behaviors, behaviors or acts aimed at preventing or reduscing some dreaded event, coprolalia) are present in virtually ALL cases.
Sleep Disorder(s) (insomnia, inability to fall asleep, fright full sleep, nightmares) in some form is present in 84% of patients.
Behavioral regression (separation anxiety, insistence to remain at or close to home, "baby-talk", temper tantrums) in some form has been indentified in 98% of patients.
Aggressiveness (present in 62% of patients).
Hyperactivity and inattentiveness (present 71% of patients).
Learning disability particularly affecting mathematics' skills (present in 62% of patients).
Inability to concentrate (present in 87% of patients).
Hallucinations (9% of patients).
Eating disorders (17% of patients) are among the other less frequently present psychiatric symptoms of PANDAS.
(4) Presence and/or history of certain characteristic physical signs and symptoms.
Adventitious movements have been identified in 31% of patients.
Wide pupils (patient appears "terror stricken"; present 83% of patients).
Various and evolving tics (present in 72% of patients).
Deterioration in fine motor skills and handwriting (dysgraphia)(89% of patients).
Short-memory loss (62% of patients).
Enuresis and/or urinary frequency (88% of patients).
Increased sensory responses (increased sensitivity to light, and/or sound, and/or touch, and/or smell) reported in 39% of all patients.
Non-specific gastro-intestinal complaints are commonly reported.
(5) Characteristic clinical presentation.
- Sudden (sometimes overnight) onset of symptoms. Parents frequently recall the exact date and/or time of the day when symptoms appeared.
- Wax-and-wane pattern of symptoms. Symptoms exacerbation is frequently associated with or may occur following an infectious event and/or administration of certain vaccines. Even without the treatment there may be partial improvement in symptoms within 4 - 6 weeks. Unfortunately, certain symptoms (especially the separation anxiety) will persist even during these periods.
- The initial episode may be associated with GABHS infection, however subsequent episodes do not necessarily have to be related to GABHS. CAUTION: association of PANDAS and GABS appears to be more than casual, however firm evidences supporting the exclusive role of GABS in pathophysiology of PANDAS is currently lacking
(6) Significant elevation of GABS antibody titers (i.e., ASO titer, AntiDNase B titer) is common, but not necessarily present in every case. Negative GABS titers do not absolutely exclude the diagnosis of PANDAS.
(7) Measurable clinical improvement following the "Steroid Burst".

Suggested diagnostic criteria for PANDAS:
Absolute criteria
Sudden onset (applicable to patients >5 years of age).
Major criteria
Separation anxiety (type 1* or type 2**)
OCD symptoms present
Adventitious movements
Minor criteria group A (psychiatric symptoms)
Sleep disorders (insomnia, night terrors, refusal to sleep alone in the room)
Behavioral regression other than separation anxiety ("baby-talk", temper tantrums, behaviors unbecoming of actual chronological age)
Hyperactivity, inattentiveness, inability to concentrate
Significant deterioration in learning abilities (particularly in mathematics)
Minor criteria group B (physical symptoms)
"Puppet-like" spoken and body language; "hyper-alert" look or demeanor
Presence of wide pupils particularly during the acute stages of disease
Tics (motor, vocal, complex)
Urinary frequency and/or bed wetting and/or daytime accidents
Demonstrable short-memory loss
Fine motor skills deterioration including dysgraphia
Increased sensory responses (to smell, sound, light, touch)
* Separation anxiety Type 1 (person-dependent): patient's dependence on parents (most likely mother) that appears clearly inappropriate for patient's chronological age.
** Separation anxiety Type 2 (environment-dependent): patient severely dependent on certain (familiar) environment(s) (i.e., home). When offered any social interaction outside home (preferred environment) prefers to stay at home and not participate.

We are currently working out an acceptable diagnostic formula for PANDAS patients. Please consider this "work in progress" !
Diagnostic formula for patients >5 years of age:
Absolute criteria + TWO major criteria
TWO major criteria + FOUR minor criteria
Diagnostic formula for patients <5 years of age:
Absolute criteria + TWO major criteria
TWO major criteria + FOUR minor criteria
ONE major criteria + THREE minor criteria (group A) + TWO minor criteria (group B)

So, What is This All About?
The most exciting prospect of PANDAS and PITAND theory is realization that a biological agent(s) (in this case, an infectious vector) has been identified as a single cause of a mental illness. PANDAS and (possibly) PITAND do indeed represent a disease(s) that satisfies the McGovern and Troisi criteria (please refer to Autism page). Various descriptive terms so much abused in current scientific terminology of mental illnesses ("chemical imbalance", "abnormal brain chemistry", etc.) that have absolutely no scientific meaning nor diagnostic or therapeutic value, might be finally relegated to history. It is likely that following a century of unsuccessful search for the disease of the mind, the body will be where the answers shall be found.
Once the cause of an illness (in this case a mental illness) has been identified, search for an adequate treatment is the next logical step. In PANDAS and PITAND syndromes an adequate treatment already exists and has been proven successful. Use of antibiotics for GABHS infection (i.e. Penicillin) does not only "control" the symptoms but, in certain cases, may cure the patient. Once however, the damage to the nervous system has been demonstrated (both in PANDAS and PITAND) further treatments modalities may be necessary, and these are readily available as well (corticosteroids, Intravenous immunoglobulin, anti-inflammatory compounds other than steroids, etc.). It is also extremely important to mention that the resulting damage to the nervous system symptomatic of PANDAS and PITAND syndromes can be reversed in its early stages (please refer to our Bibliography page), and a complete cure can be expected. It is likely that with the passage of time and an increased acceptance of Allen's and Swedo's theories, a definite cause of a number of mental illnesses overwhelming the modern society will be defined and (possibly) true cures achieved.
Review of currently available treatments for PANDAS
Antibiotics have been the mainstay of PANDAS treatment (together with SSRIs). The idea behind use of antibiotics is the eradication of Group A beta hemolytic Streptococcus. Unfortunately, the results have been mixed at best what corresponds to our professional experiences with PANDAS patients as well. We have seen severely symptomatic patients who have had negative antibody titers for Strept and at the same we have seen at least one patient whose symptoms have disappeared completely following the antibiotic treatment despite of persistence of high Strept antibody titers. It is entirely possible and even likely that use of antibiotics in the early stages of PANDAS could result in a complete recovery. ADDENDUM: We have followed several patients in whom the initial antibiotic treatment resulted in a complete symptoms resolution for almost 6 years. Unfortunately, ALL of these patients eventually had a recurrence and had to be treated with the IVIG. Thus, it is our experience that eventually ALL patients with PANDAS will eventually become antibiotic non-responders and other therapeutic option must be considered. Thus, long-term full-dose antibiotic treatment for PANDAS does not appear to be a viable option!

ADDENDUM: Another possible explanation for the initial effectiveness of antibiotics in PANDAS may be the presumed neuroprotection as a result of an increased glutamate transporter expression (with use of beta-lactam antibiotics; Rothstein, J. D. et al, Letters to Nature, Nature Vol 433; 6 January 2005).

Just the fact that the "steroid burst" (used to test possible future effectiveness of IVIG) tend to control PANDAS symptoms effectively brings it into consideration as a possible treatment for PANDAS. Since the short-term steroid treatment only controls the symptoms temporarily (upon cessation of the treatment full return of symptoms is almost a rule!) and the prolonged use of it may have rather serious side effects, corticosteroids have not been (and should not be) used as a treatment in PANDAS.
Removal of adenoids and tonsils
At least one recent study reports symptom resolution in patients with PANDAS following a surgical removal of tonsils and/or adenoids. Since the fore said study had only limited time follow-up of these patients, the success (and the future failure) of this treatment is likely to parallel the results of antibiotic treatment(s).
Selective serotonin reuptake inhibitors (SSRIs)
SSRIs (i.e. Lexapro, Prozac, Luvox, Paxil, Zoloft) have been frequently and rather generously prescribed to children with PANDAS syndrome. Few parents understand that the use of these medications in children and particularly for symptoms of PANDAS is not recommended in manufacturers' brochures and is considered "off label" use. In addition, possible (sometimes very serious) side effects have recently prompted FDA to require so-called "black box" warning to be displayed on the packaging of these medications. Considering the fact, that clinical benefits of SSRIs have not been proven in patients with PANDAS, and the fact that these medications can have serious side effects, their frequent and prolonged use in PANDAS should be seriously questioned.
There are no true studies performed and/or reported on use of plasmapheresis in patients with PANDAS. There are however multiple case reports in the literature and the success rate of this treatment appears to be rather high. Unfortunately, relatively high incidence of (sometimes) serious side effects makes this therapeutic venue an unlikely treatment choice in PANDAS. Taking this into consideration and the fact that the effectiveness of this treatment equals the results of IVIG treatment, in our opinion plasmapheresis should not be a first choice of treatment for PANDAS. Important note: even if employed successfully, plasmapheresis (or its less invasive "cousin" plasma exchange), should be followed by at least one full-dose IVIG treatment!
In a carefully selected group of patients the effectiveness of the IVIG treatment in PANDAS patients appears excellent. It has been our experience that a complete and lasting recovery can and should be expected within days or weeks following the treatment (please check PANDAS clinical cases page) in 80%+ of patients. This, relatively safe procedure can be done in an outpatient setting thus avoiding additional trauma to the child and his/her parents. Unfortunately the serious drawback to this treatment is its cost and the fact that many insurance companies have not covered it until now. Recently however, several insurance carriers have started to cover the cost of the infusion. If you wish to learn more about this treatment please refer to our IVIG page!
You can review samples of PANDAS clinical cases seen and treated in our offices and learn tips on how to recognize signs and symptoms of PANDAS!
If you feel that your chid may have PANDAS, e-mail us your questions and Dr. Kovacevic will reply promptly. Please take a note: we will reply only to e-mails sent by parents or legal guardians of children suspected of having PANDAS. E-mail must contain full name and address of the sender and child's age.

IMPORTANT: Recently we have received a number of e-mails requesting information on other physicians specializing in PANDAS. Since we are NOT a referal service we cannot respond to such e-mails!

Copyright by WebPediatrics.com2003 * Modified Tuesday, March 27, 2012