Dr_Rosario_Trifiletti Posted January 2, 2010 Report Share Posted January 2, 2010 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) GoodLuckIris 1 Link to comment Share on other sites More sharing options...
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