My thoughts on PANDAS and related conditions

[Megs_Mom]

double post

[Megs_Mom]

Wow. Thanks so much for posting this. I think the implication here is that children that develops OCD or Tics should get a full work-up and perhaps an abx test. If nothing shows and no response to abx - then assume "standard OCD or TS". That is the complete opposite of the current recommendation. I love that - and think it would save a lot of kids and families from unnecessary suffering and expense.

 

This information was very timely for our family, as this has been a huge topic of conversation of late - we received back our immunology results last week. Happily, Meg does not have an immune deficiency – but as usual, this left us wondering why this happens to her – what the vulnerability is – and how to best prevent this for the rest of her life. Here is our situation in brief:

 

• Sudden severe onset of OCD at age 3.5, 6.8, 7.5 (dial up of 22-30 points on Y-Boc scale in 7-14 days). Complete remission between 3-6. Mild level between ages 6-7 with another severe exacerbation at 7.5.

• No strep test or titers run at 3. All negative at 6 and 7 – never a proven association with strep. Always associated with ear infection.

• Always ran high ANA levels at 1:1280. Also signs of inflammation in stomach – endoscope showed Peptic Ulcers, but no H. Pylori. After 5 months of abx treatment, ANA reduced down to 1:320.

• All immune numbers are fine – IgA, IgM, IgG, subclasses (except 4, but that is not supposed to show until 10), pneumococcal panel (14 serotypes) – showed only 4 with less than 1.0 – most are very high. All other responses to vaccine are high (good).

• WBC is low and remains low.

• Moderate Cunningham positive PANDAS score of 133 (or 136, now I have forgotten) at the end of an exacerbation.

 

She had an astonishing response to Prednisone, with 80% of OCD gone within 48 hours max - but returned immediately after 5 days. Antibiotics have been terrific – she had a small flare of about 6 days over this holiday, but it did not turn into an exacerbation. I would swear sometimes that she gets an episode from exposure to certain children (impetigo, strep), but does not seem to get it herself – we just see the OCD.

 

We use the term exorcist – but don’t feel that we are as bad as some we read about. It’s a nightmare each time – but we know there will be an end to it. With Prednisone & ABX, we are very hopeful for the future (we also use ERP therapy). Maybe IDIOPATHIC ANTIBIOTIC-RESPONSIVE NEUROPSYCHIATRIC DISORDER actually best describes our daughter? It’s such an interesting question for us, as we wonder if we have done enough for her, and why it is so hard to find proof. We are so thankful for Dr. Cunningham as those test results seem to keep our doctors interested and prescribing abx.

[Buster]

Meg's Mom, I just love your post. The switch of how to approach and the likely benefit for those who have PANDAS would be significant.

I think the implication here is that children that develops OCD or Tics should get a full work-up and perhaps an abx test. If nothing shows and no response to abx - then assume "standard OCD or TS". That is the complete opposite of the current recommendation. I love that - and think it would save a lot of kids and families from unnecessary suffering and expense.

[momto2pandas]

I like this thinking as well. As far as the clinical presentation, do you feel that the two posited types are different? What do you speculate to be the difference in underlying pathology? I have been thinking about, and would love to put together, a surveymonkey survey to get at some of this. I have a lot of experience in the design of these types of instruments in clinical research and I sure do think it would be useful for PANDAS.

 

I am having a hard time sorting out my family with respect to the two subtypes. I would have to put us into the hypo-immune subset, except that we seem to be hyper-immune when it comes to auto-immunity (like many immune deficiency types) - lots of autoantibodies, atopic symptoms, etc. Steroids have been very helpful clinically, though they have been used only sparingly.

 

One thought I have had: I believe that inflammatory cytokines are elevated both in hyperimmune states and in immune deficiency states (at least in AIDS) - and it's possible that at least a bunch of the process is mediated through those. There is certainly plenty of stuff in the literature about pro-inflammatory cytokines having direct neuromodulating effects that result in psychiatric symptomatology.

 

In my kids, sometimes I wonder if there are two distinct processes going on. There are the overall hypersensitivity (sensory and emotional) and affective lability/irritability/defiance that seem to wax and wane pretty frequently and to respond to a variety of immunological challenges (including allergens), and then there are the distinct, and considerably less frequent, real OCD/tic "flares" that start and stop quite suddenly only with/post infections and that seem to overlay the other symptoms (which also get worse at these times). I have wondered if the background sensory/lability stuff could be cytokine-mediated since it doesn't even seem to require the presence of an infection, and if the distinct OCD-tic episodes could result from a mechanism more similar to the SC model.

 

Has anyone else noticed this distinction?

 

 

 

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)

[dcmom]

Mom2pandas- most of your post went over my head- I will need to re read a few times.... but YES to everything you said! The sensory and emotional issues for both dds have been more on than off since original episode, but the true ocd has been more limited to clearcut exacerbations....

[sf_mom]

Love your comments on the switch too!!!

 

I'm sure you already know this but needed to add for others that might be reading. Ear infections 'Otitis media' is typically strep and some of the more resilient strains of strep.... currently most prevalent M1.

 

-Wendy

 

Wow. Thanks so much for posting this. I think the implication here is that children that develops OCD or Tics should get a full work-up and perhaps an abx test. If nothing shows and no response to abx - then assume "standard OCD or TS". That is the complete opposite of the current recommendation. I love that - and think it would save a lot of kids and families from unnecessary suffering and expense.

 

This information was very timely for our family, as this has been a huge topic of conversation of late - we received back our immunology results last week. Happily, Meg does not have an immune deficiency – but as usual, this left us wondering why this happens to her – what the vulnerability is – and how to best prevent this for the rest of her life. Here is our situation in brief:

 

• Sudden severe onset of OCD at age 3.5, 6.8, 7.5 (dial up of 22-30 points on Y-Boc scale in 7-14 days). Complete remission between 3-6. Mild level between ages 6-7 with another severe exacerbation at 7.5.

• No strep test or titers run at 3. All negative at 6 and 7 – never a proven association with strep. Always associated with ear infection.

• Always ran high ANA levels at 1:1280. Also signs of inflammation in stomach – endoscope showed Peptic Ulcers, but no H. Pylori. After 5 months of abx treatment, ANA reduced down to 1:320.

• All immune numbers are fine – IgA, IgM, IgG, subclasses (except 4, but that is not supposed to show until 10), pneumococcal panel (14 serotypes) – showed only 4 with less than 1.0 – most are very high. All other responses to vaccine are high (good).

• WBC is low and remains low.

• Moderate Cunningham positive PANDAS score of 133 (or 136, now I have forgotten) at the end of an exacerbation.

 

She had an astonishing response to Prednisone, with 80% of OCD gone within 48 hours max - but returned immediately after 5 days. Antibiotics have been terrific – she had a small flare of about 6 days over this holiday, but it did not turn into an exacerbation. I would swear sometimes that she gets an episode from exposure to certain children (impetigo, strep), but does not seem to get it herself – we just see the OCD.

 

We use the term exorcist – but don’t feel that we are as bad as some we read about. It’s a nightmare each time – but we know there will be an end to it. With Prednisone & ABX, we are very hopeful for the future (we also use ERP therapy). Maybe IDIOPATHIC ANTIBIOTIC-RESPONSIVE NEUROPSYCHIATRIC DISORDER actually best describes our daughter? It’s such an interesting question for us, as we wonder if we have done enough for her, and why it is so hard to find proof. We are so thankful for Dr. Cunningham as those test results seem to keep our doctors interested and prescribing abx.

[dcmom]

SF Mom- ear infections are many times caused by strep pneumonai. This is not the same as GABHS. I know you are trying to connect dots... have you been told by Dr Cunningham or others that strep pneumonai and GABHS are related? Is it possible that either of these can jumpstart pandas? I often see you use these two bacteria interchangeably- so I am wondering if there is a reason? Thanks!

[Buster]

I have wondered if the background sensory/lability stuff could be cytokine-mediated since it doesn't even seem to require the presence of an infection, and if the distinct OCD-tic episodes could result from a mechanism more similar to the SC model.

 

Has anyone else noticed this distinction?

 

My thought was that the two are related and that the pro-inflammatory cytokines increase ICAM-1 along the BBB enabling T-cells to cross. Once across, they get activated by fragments of neuronal tissue and release still more inflammatory cytokines creating a breach in the BBB. This then allows the anti-GM1 which trigger the interference with the basal ganglia signalling. All theory (i.e., 3 pieces of research stitched together without experiment), but seems to fit.

 

I keep having this feeling that once this crossing of the BBB is better understood, we'll have a significant improvement to the understanding and treatment of the Neuropsychiatric aspects of a set of disorders -- i.e., SC, PANDAS, potentially Autism, ....

 

Buster

[momto2pandas]

I have wondered if the background sensory/lability stuff could be cytokine-mediated since it doesn't even seem to require the presence of an infection, and if the distinct OCD-tic episodes could result from a mechanism more similar to the SC model.

 

Has anyone else noticed this distinction?

 

My thought was that the two are related and that the pro-inflammatory cytokines increase ICAM-1 along the BBB enabling T-cells to cross. Once across, they get activated by fragments of neuronal tissue and release still more inflammatory cytokines creating a breach in the BBB. This then allows the anti-GM1 which trigger the interference with the basal ganglia signalling. All theory (i.e., 3 pieces of research stitched together without experiment), but seems to fit.

 

I keep having this feeling that once this crossing of the BBB is better understood, we'll have a significant improvement to the understanding and treatment of the Neuropsychiatric aspects of a set of disorders -- i.e., SC, PANDAS, potentially Autism, ....

 

Buster

 

 

Yes, I have had this thought as well. The effects of cytokines could be both direct neuromodulating effects and "indirect" effects on the BBB that allow all kinds of things to happen. The thing that's making me think that there could be two distinct pathological processes, though, is the fact that we seem to have 2 distinct processes happening in our household as far as the clinical picture, and so far at least one other person is saying the same thing.

 

It seems that many of us science types have done a lot of research. I wonder if we should think about having a little informal mini scientific conference and really hash through ideas critically and brainstorm future directions in research. I'd love to put together slides with all of our ideas and have them critically examined. I'd also still love to do a really good survey to look, among other things, at clusters of symptoms/signs, etc. (e.g. do "hyperimmune" types "look different" than "hypoimmune" types? do different clinical types respond differently to different treatements?) so that we'd have at least that much "data" to work with. It'd be lovely to have the Dr T's, L's, K's, B's, S's, etc. involved. I imagine that there would be interest. The issue is funding, of course. I'd be more than happy to pay my own way and do the prep for free, but paying for everyone else would be something else!

[dut]

I feel that for our dd BBB integrity is key.

 

There is increasing evidence that Alzheimer's is a BBB disorder (my father had Alzheimer's and wonder if this is the weak spot for our family) and the following link introduces some recent research that looks at the role of infection and TNF in the progression of dementia in Alzheimer's patients. There is lots more in the literature about cytokines (eg IL-6) and the development of Alheimer's. Dr T told me that the girls he has seen have had some backsliding if given the contraceptive pill. There are also papers out there on the increase of IL-6 amongst those taking the pill.

 

Perhaps more out there on a limb.... night terros run in our family too. PANDAS dd will get these (only since the PANDAS started) at the first hint of a fever. I've heard other parents talk of their children's visual hallucinations often having a green/blue colouring to them. Night terror "creatures" are nearly always greenish. Is this another sign of proinflammatory cytokines leading to a breach in BBB?

 

I've read that the BBB matures at puberty. Is this why PANDAS remits/ends for so many at this time?

[dut]

My bad, forget the link....

 

http://www.timesonline.co.uk/tol/life_and_...icle6825457.ece

[sf_mom]

DCMom: If you've been reading my posts regarding S. Pyogenes (inclusive of M1, M3, M18 strain) can cause Otitis Media http://www.ncbi.nlm.nih.gov/pubmed/11688910 or AOM Acute Otitis Media http://cat.inist.fr/?aModele=afficheN&cpsidt=16960644. Yes, I have been in contact with at least three different strep experts and actually if there is no cross immunity to S. Pyogenes it is 'potentially' toxic to a child. S. Pyogenes can also cause strep throat, the kind with white puss in back of throat and also considered group A.

 

Perhaps you've read the summary from my Father-in-laws who is a Dr. I've included his comments again on several articles and one of the strep experts responses to his comments 'ALL CAPS'.

 

__________

 

In PANDAS when exposed to strep pyogenes early in life the humoral (antibody) portion of the immune response does not occur in affected children. The strep pyogenes antigens are not bound by the antibodies when infection occurs because PANDAS patients cannot produce the antibody due to AGE/state of immune system at time of exposure. Since this initial immunity to strep pyogenes infection is absent, the strep enters the PANDAS host and proliferates. This humoral response to the exposure to strep pyogenes is because it secretes protease enzymes that destroys antibodies measured by an ASO titers or Igg level.

 

IT IS TRUE THAT THE IMMUNE SYSTEM IN YOUNGER CHILDREN DOES NOT RESPOND AS WELL TO CARBOHYDRATES

 

This results in a 2nd immune response to components (polysaccharides) of the bacteria's cell walls producing an antibody (AB'). This second antibody cross reacts (also attacks) with nerve cell surfaces (brain) causing signaling activity (TICS, Chorea). Hence no raised titers unless additional exposures to more traditional strep strains occur.

 

REPEATED EXPOSURES TO STREP ARE BELIEVED TO BE IMPORTANT

 

__________

 

 

I've included another strep experts responses 'ALL CAPS' when discussing STREP PNEUMOCOCCAL ANTIBODY TITER and why they would be deficient in some children. READ CLOSELY as they would potentially go down if fighting an infection.

 

THE STREPT. PNEUMO TITERS ARE PROBABLY NOT INFORMATIVE. STREP. PNEUMO IS A DISTINCT PATHOGEN FROM GABHS (STREP. PYOGENES). STREP. PNEUMO CAUSES OTITIS MEDIA, SINUSITIS, AND SEVERE ACUTE INFECTIONS SUCH AS PNEUMONIA AND MENINGITIS. THERE IS A VACCINE AVAILABLE THAT MANY CHILDREN HAVE RECEIVED IN THE PAST FEW YEARS, AND VACCINATION AFFECTS THE ANTIBODY TITERS. I SUSPECT THESE CHILDREN WERE NOT VACCINATED BASED ON THE LOW TITERS. THERE ARE 90 DIFFERENT TYPES OF PNEUMO, SO EVEN IF EACH CHILD HAD ONE OR A FEW PAST PNEUMO INFECTIONS (EAR, SINUSES), IT MAY NOT BE SURPRISING THAT THEIR TITERS ARE LOW.

 

__________

 

 

Additional comments from my Father-in-law summary from another strep expert. ALL CAPS AGAIN.

 

This results in a 2nd immune response to components (polysaccharides) of the bacteria's cell walls producing an antibody (AB'). This second antibody cross reacts (also attacks) with nerve cell surfaces (brain) causing signaling activity (TICS, Chorea). Hence no raised titers unless additional exposures to more traditional strep strains occur. THAT IS A REASONABLE HYPOTHESIS

 

Treating with IGG binds with and lowers the levels of (AB') in conjunction with antibiotics (protects child from continued exposure) eventually cures child.THAT IS THE PROBABLE MECHANISM

 

 

__________

 

I've been hesitant to post these comments in fear of losing the trust I've gained.

 

 

SF Mom- ear infections are many times caused by strep pneumonai. This is not the same as GABHS. I know you are trying to connect dots... have you been told by Dr Cunningham or others that strep pneumonai and GABHS are related? Is it possible that either of these can jumpstart pandas? I often see you use these two bacteria interchangeably- so I am wondering if there is a reason? Thanks!

[sf_mom]

..

[Bat_Sheva_Myllys]

For the past 5 years I have been under the clear impression that PITANDS can and in Sandra's case is caused by Mycoplasma Pneomoniae antibodies.

Sent you her history in brief.

Sudden appearance with no history at age 15 following known MycopP and Influenza A. Symptoms are Super PANDAS, reactions to antibiotics, Prednison, IVIG, Medrol drip.

Have not noticed Mycoplasma Pneomoniae on your list.

Several published case reports in Germany, Turkey and France also support MycopP as one of the causes for PITANDS.

 

Bat-Sheva Myllys

 

 

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)

[brooke]

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)

Confused.

I think we are PANDAS 2 -- Low titers, possible Mycoplasma Pneumoniae -- but responded favorably to IVIG ,antibiotics and PEX, in that order. Dramatic improvements for three weeks post PEX, and then positive strep test. One week of regression, and now on and off. Still have Chorea and anxiety/OCD symptoms. No longer "Exorcist" symptoms, thank the Lord! Will pursue tonsilectomy, but continue to have concerns about the strep source being in the gut?

Thank you for the further clarification!