Dr_Rosario_Trifiletti

I've heard reports of this in a number of my patients. I make it a point to prescribe a full 10 days of clindamycin to sterile the tonsils prior to tonsillectomy. Other antibiotics could be used, but those that treat a strep carrier state must be used. Amoxicillin was not sufficient. I always explain to patients that the tonsils are lymphatic tissue and are a little like filters on air purifiers. Have you ever changed a dirty one - the room is full of dust. In the same way, a surgeon manipulating infected tonsils is sure to seed the blood with strep and in the PANDAS patient this can be disastrous. I'm thinking of submitting a little article to an ENT journal on this to try to try to encourage a practice of pre-op tonsillar sterilization in PANDAS patients .... Dr. Trifiletti

Dear Ginger, I'd be happy to speak to you and advise your pediatrician if you would like. No charge. Please feel free e-mail me at trifmd@gmail.com with contact info. Dr. T

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus or Mycoplasma? PANDASM sounds a little X-rated. Might catch on a little TOO well. Pediatric Autoimmune Neuropsychiatric Disorders associated with EBV, Mycoplasma, and other Infectious agents but most Commonly Strep PANDEMICS never will catch on but probably the most descriptive

This is a paper on Toll-Like Receptors, the overactivation of which, in my opinion, is the root cause of PANDAS http://www.nature.com/msb/journal/v2/n1/pdf/msb4100057.pdf The idea is this - 1. You have this basic system called TLR, a component of innate immunity - present and primed to go as part of your immune system even before encountering organisms 2. Different organisms use different TLR's (for example p41 flagellin signals through TLR5) but converge on the same, inflammatory like signaling pathway - this explains the phenomenon of co-infection. Let's say organism 1 signals through TLR1 and organism 2 through TLR2. Then getting them both together is particularly bad. 3. Organisms that tend to be persistent, i.e. develop carrier states like strep, mycoplasma and Lyme are particularly bad actors in this as they can chronically activate TLR's 4. Something about the TLR signaling pathway activation leads to a common neurochemical change resulting in tics, OCD or a rage-like syndrome. This will ultimately link to CaM-dependent signaling, i.e. CaMII kinase (see Fig.2) - so it all fits This idea is testable as there are tests for TLR activation. If I am right, the proper immunosuppressive treatment for PANDAS will be TLR-specific drugs (already in the drug company pipelines for other reasons). P.S. I am a nerd and this is what I do in my spare time ... Dr. T

Sorry, this is utter silliness .... Suppose you were able to sterilize your home 100% .... Now your child goes to school - the first strep he or she encounters - kaboom ... The clorox baths will damage your skin. And your skin is a key barrier to infection. I frankly cannot believe that a medical professional told you to do this! Dr. T

Dear Smartyjones, Of course neurology and psychiatry are interrelated. Our certification board is the American Board of Psychiatry and Neurology. Sigmund Freud was a well-respected neurologist for many years before founding psychoanalysis. And Hans Berger, a psychiatrist, did most of the important early work on EEG tests. I think most psychiatrists today will admit that major psychiatric illness are medically-based. For example, there are 150+ genes associated with autism. Pure psychiatric illnesses are by-and-large, neurological illnesses in which all neurological testing (MRI, EEG, spinal taps) are normal. Of course, many medical diseases have prominent psychiatric manifestations, for example neurosyphilis and Wilson's disease. As time goes on, and the true mechanisms of psychiatric illnesses are discovered it would appear that they will be subsumed into medical science. And yet the great psychiatrists I have met have skills which no neurologists have - ability to see a holistic cause of problems. Therefore, psychiatry will still be a major area in the year 3000. God knows, it may be the biggest area of medicine if present trends of increases in mental illnesses continue. I just wish that psychiatrists and neurologists talked to each other more. PANDAS is one of the areas where this actually occurs to some extent. Dr. T

Hello, As many of you know, I like to perform a battery of tests early on in the treatment of PANDAS to try to identify the triggering agent. These tests include: ASO, Anti-DNAase B, Streptozyme, Mycoplasma IgG + IgM and EBV panel, at a minimum, perhaps others depending on the patient's history. I also test for Lyme. True Lyme-associated OCD has been reported, but it is a very rare condition (I think I've seen it 2 times in 15 years), and one wonders how carefully other more common triggers were excluded. However, there is a curious finding I'm noting in many (> 80%) of patients with PANDAS: Whether or not Lyme titers are elevated - a postive 41kd IgG and (almost always) 41kd IgM band. Nothing else. The 41kd protein is called flagellin, and is known to immunologically cross-react with other flagellar proteins of spirochetes. This curious pattern is NOT diagnostic of Lyme disease. What if anything could it mean? I think the pattern is too uncommon to simply be an association. These proteins are also seen in oral treponeme infections, a major cause of peridontitis. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC130738/ My hypothesis is that there is a non-Borellia spirochete that is either an important cause or unindicted co-conspirator in some cases of PANDAS. If so, this patient would have an "idiopathic antibiotic responsive neuropsychiatric syndrome". Does anyone out there have any thoughts on this? Dental procedures and PANDAS? Peridontitis and PANDAS? Other patients who have had Western blot testing for Lyme?

Back in Black. I mean Black and White. Like a Panda Bear. Sorry for the confusion. I'll continue to post here ... as well as on the new forum. Dr. T

I found this nice like page to quickly find "equivalent" doses of corticosteroids. http://www.globalrph.com/corticocalc.htm This may be helpful to those of you currently taking or thinking of taking corticosteroids. Dr. T

For nerds only ... Here is a very recent review article which covers the connection between infection and autoimmunity. This is highly relevant to PANDAS and related disorders. http://www.jleukbio.org/cgi/rapidpdf/jlb.0709517v1 Leave the page alone for a few moments and the PDF should appear .... Dr. T

Somebody recently asked what the "Exorcist Syndrome" was At the 2008 Child Neurology Society meeting in San Jose, California, I presented six children with a unique syndrome I called "exorcist syndrome" 1. Hyperacute onset - parents point to hour of change 2. Ballistic tics - forceful, unrestrained, violent - can put holes in walls, etc. 3. Disinhibition - expletives, capable of serious physical harm to self or others 4. "Falsetto" vocal change - voice is clear, no aphasia but change in quality of voice - gruff/demonic, Bugs Bunny, infantile 5. Symptoms seem to turn on and off like a switch. At times appear completely normal, then symptoms above suddenly rage. These previously normal children acquire this illness suddenly and appear to be demonically possessed. It is not an encephalitis or encephalopathy as the sensorium remains clear, there is no significant cognitive dysfunction. Every one of these children was fully alert, could recall the episode entirely. Video EEG normal in all. MRI was not done in all, but where done show significant reversible basal ganglia swelling LP was not done in all, but where done was normal. No antibiotics or meds (such as neuroleptics) helped significantly. IVIG works - but loses effect in 2-3 weeks. Only PEX produces lasting changes So the lowdown is don't putz around with antibiotics or drugs, go straight to the big immunosuppressive guns. What causes it? You guessed it .... Every one of these kids have SKY HIGH strep markers, ASO 800-1000 range, anti-DNAase B >1:2720. In my view, this is the most severe PANDAS variant and is a neuropsychiatric quasi-emergency due to the risk of violence. It's a central catecholaminergic storm ... We never measured Cunnigham panel on these kids, but I'll bet they show anti-neurotransmitter receptor antibodies. If left alone, it resolves spontaneously in months-years. Resolution is often sudden. Amazingly, outcome is excellent. Cognitive ability is preserved. This is one of the reasons why I believe the outcome in PANDAS, long-term, is good. Has anyone's child had anything like this ??? Dr. T

CDH2 interacts with IQGAP1 which interacts with calmodulin which interacts with CaM2Kinase Mutations in CDH2 produce OCD in dogs and antibodies against CaM2Kinase are associated with PANDAS. My hypothesis: alteration of calmodulin-target protein interacts are critical in OCD. The aberrant immune response to strep somehow distorts this process. Dr. T

I will be happy to give you a free second opinion by phone anytime you wish Dr. T

The book I mentioned was about Streptococcus itself. I'm sad to say there is no medical textbook on PANDAS, something written by doctors for doctors. I want to write or edit one. Long overdue. Does anyone want to help me? Work in the publishing field? Dr. T

So far about 20 people have asked for the form. I'm going to try to put it on a file server so that all can get by http or ftp download. Any comments are appreciated. It's probably best to post comments here so that we can share ideas. Is it too cumbersome to be useful? My idea is that you could look at the whole thing and see correlations that would otherwise be missed in history taking. It is also nice to have it as an excel file, as you could simply e-mail it to your doctor to update them on progress ... This might be good stuff to discuss at the "think tank"! But you guys are the REAL think tank! Dr. T

Streptozyme

Hello all, I think it's important to try to develop a uniform method of tracking onset and treatment of children with PANDAS, to see the big picture. This will be key to serious clinical research. Towards this end, I have developed a PANDAS treatment log in the form of an Excel spreadsheet. It is a first try and I would appreciate your comments. Only problem, I don't know how to send an attachment. If you would like the file, please e-mail me at trifmd@gmail.com and I will send it to you. If there is lots of interest, I will try to make it available from my website as a download .... also learning how to do this .... Dr. T

This is what I am reading these days. It's the best book on Strep that I have been able to find. I bought a used copy (that looks brand new) for about $65. What a bargain! http://www.amazon.com/Gram-Positive-Pathog...8284&sr=8-1 Dr. T

Also this http://www.ncbi.nlm.nih.gov/pubmed/1971852...mp;ordinalpos=4 There is a suggestion that Mycoplasma may be joining strep with the "infection inducing immune response inducing neurotransmitter system dysfunction" category. I look for it routinely now. NMDAR encephalitis is a very hot topic in the neurology literature currently. Maybe it will help give PANDAS more credibility, win some converts ... P.S. I spend three years of my life doing my Ph.D. in the same room as the next to last author of this paper. Dr. Lynch. He's a good friend and I will be speaking to him regarding NMDAR encephalitis to try to learn more information on the spectrum of this condition. Seizures are not an essential part of this condition; some, but certainly the minority, of PANDAS patients have documented.

Bravo Laura! Wonderful article! Dr. T

Vickie, I think you hit an important point. From the vantage point of a doctor who is seeing about 100 PANDAS or PANDAS-like cases a month nowadays, I'm learning a whole lot about this disease very quickly. I'm learning something new every day. This is what makes this fun; playing some part in curing a child in need is also very gratifying and keeps you going. The sad thing is that, although I have tried really hard in academic settings to get med students and colleagues interested in this disease, I haven't been very successful. So at times you feel like a lonely quack. But then another "zithromax miracle cure" comes along and it keeps you going. Awe and wonder at the complexity of the human body and disease. How little we really know. Parents are far more interested in this disease than the doctors. I always bum out when I hear that a parent is told by a doctor that it can't be PANDAS if a throat culture is negative. The parents observations on this board are so much more sophisticated and accurate than 99.99%. You guys are the experts. You learn medicine from patients, not books or papers, but you still have to use the books and papers. Mostly, you have to think - who does this patient in front of me remind me of? Where have I seen this before? How did we get that previous child better? So you creep your way to an optimal protocol. So if we had to make a movie about PANDAS, one story would be parents empowering and educating themselves, using modern technology, to challenge and educate their doctors. In a sense, it's a shame it has to be this way! But in another, doctors should be ever open to be educated by their patients. Dr. T

Dear Parents, I have just encountered two cases of acute sneezing tics in which there was acute (markedly elevated IgM) Mycoplasma infection plus possible strep co-infection. Mycoplasma responds to zithromax specifically and not other antibiotics ...as well as IVIG. So I'm certainly considering this in the differential diagnosis of PANDAS-like illnesses. I wonder if there is some sort of interaction between Mycoplasma and Strep at the immunological level .... Have any of your children been tested for this .... Sorry for the short post --- very very busy today Dr. T

Dear parents, Below please find a summary of my current thinking on the subject of PANDAS and related illness. This is an outline of a paper I hope to submit for publication soon which summarizes our understanding at of the dawn of the '10 decade This is somewhat dense. Any comments appreciated (especially any from Buster!) Post-infectious Neuropsychopathy of Childhood Basic problem: Selective immunopathy to streptococcus (or less commonly other infectious agents) that incite an dysimmune process leading to a functional catecholaminergic neurotransmitter imbalance in basal ganglia circuits and perhaps other part of the brain, Resulting in some combination tics, OCD and affective symptoms Classic (Swedo) presentation: 1. Age 3-11 2. Acute onset OCD and/or Tics, often remitting/recurring 3. Temporally associated with infection (if GABHS = PANDAS) Variants (see my Pavone 2006 paper): 1. < 3yrs old at onset 2. > 11 yrs old at onset 3. Subacute or chronic temporal features 4. Atypical symptoms 5. Severe symptoms a. Exorcist syndrome 6. PANDAS in children with other conditions a. PDD-PANDAS Immune subgroups: Type 1 PANDAS – Overactive immune system 1. Markedly elevated ASLO, Anti-DNAase B and/or streptozyme 2. Intermittent culture positive for GABHS 3. (?) Immunocompetent on pneumococcal serotype testing 4. Anti-CaM2K positive in PANDAS range – possibly higher end 5. Immunoglobulin levels fall with effective strep treatment (?) 6. ASLO, Anti-DNAase B and streptozyme fall with effective strep treatment Type 2 PANDAS – Underactive immune system 1. Non- or minimally elevated ASLO, Anti-DNAase B and/or streptozyme. May show serial changes (though feeble) with streptococcal infection 2. Can be culture positive for strep, don’t develop expected titer rise afterward 3. (?) Immunodeficient on pneumococcal serotype testing 4. Anti-CaM2K positive in PANDAS range – possibly lower end 5. Immunoglobulin levels don’t change much with effective treatment 6. ASLO, Anti-DNAase B and streptozyme fall with effective strep treatment Type 1 PANDAS is easier for the medical community to digest since there is evidence of streptococcal infection, similar to Sydenham Chorea, etc. Type 2 PANDAS is harder for the medical community to understand since there is little evidence of streptococcal infection, similar to Sydenham Chorea, etc. Non-PANDAS 1. Not GABHS (i.e. non-GABHS PANDAS) GABHS=group A beta-hemolytic streptococcus A. Alpha-hemolytic B. Non- group A Beta-hemolytic C. Gamma-hemolytic 2. Not strep at all (i.e. non-PANDAS PITANDS) A. Lyme and related illnesses 1. Borrelia 2. Babesia 3. Erlichia 4. Other tick-bornes B. Viruses a. EBV b. Others 3. Idiopathic antibiotic-responsive neuropsychiatric disorder (no cause identified but amazingly good response to antibiotics) 4. Not infectious at all A. Medication-related a. Tics with stimulant medication use b. Others B. Metabolic disease a. Wilson’s disease b. Others C. Other known causes (very rare) a. Structural brain lesions 5. Idiopathic According to medical thinking circa 1985, this is the ONLY group. For PANDAS non-believers, this is STILL the only group INITIAL WORKUP Basic workup in everybody with clinically suggestive picture should be: Initial screen: 1. ASLO, Anti-DNAase B, streptozyme (GABHS marker enzymes = GABHS-ME) 2. Lyme titers (especially if from endemic region, suggestive symptoms, others infected) If GABHS-ME panel positive, then diagnosis of probable Type 1 PANDAS made. This diagnosis is strengthened by longitudinal temporal correlation of clinical symptoms with repeated infection. If 3 or more such episodes (rarely fully documented) – definite Type 1 PANDAS If GABHS-ME panel negative, then diagnosis is likely Type 2 PANDAS or non-PANDAS To further workup in these patients: 1. Repeat GABHS-ME when convalescent ( to compare acute vs. convalescent titers) 2. Throat culture – helpful if positive; supports Type 2 PANDAS. Not helpful if negative. 3. If Prevnar has been received, anti-pneumococcal panel (14 serotypes). If panel abnormal, supports Type 2 PANDAS. Probably not helpful if Prevnar not received. If Prevnar received and normal, probably non-PANDAS. 4. Further investigation of immune status if anti-Prevnar deficient.   FURTHER PATIENT CLASSIFICATION At this point, one should be able to classify patient with a working diagnosis: A. PANDAS TYPE 1 B. PANDAS TYPE 2 C. NON-PANDAS Treatment of all but most severe Type 1 or all Type 2 PANDAS , ANTIBIOTIC TREATMENT PHASE can begin at this point. For NON-PANDAS patients, further “trigger search” should be attempted, but not too exhaustively, in most cases. In SEVERE (i.e. Exorcist-syndrome) Type 1 PANDAS, consider proceeding directly to STRONG IMMUNOSUPPRESSION PROTOCOL. This will almost always be done in the hospital setting. In Type 2 PANDAS patients, a PANDAS IMMUNOPATHY WORKUP should be done before considering STRONG IMMUNOSUPPRESSION PROTOCOL All NON-PANDAS patients should be further investigated with the NON-PANDAS WORKUP . While this workup is in progress, and if there are no contraindications, treatment with ANTIBIOTIC PHASE should be considered. If patient initially felt to have NON-PANDAS does in fact respond very well to antibiotics, patient should be labeled IDIOPATHIC ANTIBIOTIC-RESPONSIVE NEUROPSYCHIATRIC DISORDER. So we now have 5 categories: A. PANDAS TYPE 1 (HYPERIMMUNE TYPE) B. PANDAS TYPE 2 (IMMUNODEFICIENT TYPE) C. NEUROPSYCHIATRIC DISORDER WITH NON-STREPTOCOCCAL TRIGGER D. IDIOPATHIC ANTIBIOTIC-RESPONSIVE NEUROPSYCHIATRIC DISORDER E. IDIOPATHIC ANTIBIOTIC-RESISTANT NEUROPSYCHIATRIC DISORDER (AKA PLAIN OLD OCD AND/OR TICS)   BASICS OF TREATMENT - DIFFERENT, DEPENDING ON GROUP PANDAS TYPE 1 (HYPER-IMMUNE) Not very severe: 1. ACUTE ANTIBIOTIC PHASE (consider adjunctive steroids or Advil) 2. ANTIBIOTIC PROPHYLAXIS 3. Consider tonsillectomy 4. Adjunctive psychotherapy ( if indicated) 5. Consider adjunctive psychotropics 6. IF NECESSARY, IMMUNOSUPPRESSION Steroid burst IVIG PLASMA EXCHANGE Severe: 1. Antibiotics and psychotropics can be tried, but are usually ineffective at this stage, so consider proceeding quickly A. IV CORTICOSTEROIDS B. IVIG C. PLASMA EXCHANGE Strep STILL HAS TO BE AGGRESSSIVELY ELIMINATED once immune cool-down completed PANDAS TYPE 2 (IMMUNODEFICIENT) 1. ACUTE ANTIBIOTIC PHASE (consider adjunctive Advil) 2. ANTIBIOTIC PROPHYLAXIS (with good probiotic regimen) 3. Consider tonsillectomy 4. Adjunctive psychotherapy (if indicated) 5. Consider adjunctive psychotropics 6. ATTEMPT TO BOOST IMMUNE SYSTEM – a. CONSIDER IVIG CAUTIOUSLY. b. KEFIR c. AVOID CORTICOSTEROIDS, PEX d. IF EVER AVAILABLE, STREP HYPER-IMMUNE GLOBULIN ideal here – A GOOD SOURCE WOULD BE PANDAS TYPE 1 KIDS! IDIOPATHIC ANTIBIOTIC-RESPONSIVE NEUROPSYCHIATRIC SYNDROME 1. ACUTE ANTIBIOTIC PHASE (consider adjunctive Advil) 2. ANTIBIOTIC PROPHYLAXIS (with good probiotic regimen) 3. Consider tonsillectomy 4. Adjunctive psychotherapy (if indicated) 5. Consider adjunctive psychotropics NON-PANDAS 1. WAIT AND WATCH – RE-EVAL IN 6-12 MOS 2. Adjunctive psychotherapy (if indicated) 3. Consider adjunctive psychotropics SPECIAL SITUATIONS 1. SYDENHAM CHOREA CONCERNS a. CaM2 kinase essential (needed to distinguish SC vs. PANDAS groups) b. PEDIATRIC CARDIOLOGY EVALUATION 2. UNUSUALLY STRONG FAMILY HISTORY a. CONSIDER CGH MICROARRAY Hopefully this framework can guide workup and treatment protocols. I think the Cunningham and ant-pneumococcal tests may be the most specific we have, and the most helpful. Obviously, there is a lot to verify here. Happy new year to all with a wish of hope and recovery in 2010, Dr. Rosario Trifiletti ( Dr. T)

I intended this to be tongue in cheek ... I acutally like the PANDAS acronym - it's easy to remember and although long does describe the condition fairly accurately. The SINS idea was meant to be a bit of a joke; of course that's a horrible name for the innocent children who get this horrible disease. The idea of streptococcal immunopathy, however is important. In many patients, there is either an over- or under-reaction to streptococcal infection; so one often sees a tendency in the personal or family history of "handling strep infections poorly". I really think there is a frequent abnormality in the anti-pneumococcal antibodies acquired after immunization in these patients that is very telling. In most cases, it's a selective immunopathy, not due to a detectable global problem in immunity. We know surprisingly little regarding the immune response to streptococcal infection and knowing more is the key to understanding PANDAS. So we need an "S-I" We could drop the "pediatric part". It's very clear that this syndrome is more common in children than adults. However, we know that ADD is seen more commonly in kids than adults and we don't call the condition "pediatric attentional problem". Drop the "P". I also sense that the medical community takes adult diseases as more organic than children's diseases. Another striking feature of "textbook" PANDAS is the sudden onset, i.e. Acute nature of the illness. Not every case has this, but this is part of the original Swedo criteria. So one might go with ANSI - Acute Neuropsychopathy with Streptococcal Immunopathy. These kids are ANTSY, can't relax, etc. but this is not a pejorative connotation. We've removed the autoimmune business which many non-believers criticize. Anyway, everybody enjoy your holidays! Dr. Trifiletti