dut

Only study that I found that worried me was re men taking it.. small study too if I remember right and how some men experienced decreased sperm amounts and motility and how for some this continued despite cessation.... I'll go see if I can find it.... We have been told to rry 5htp if we are worried about it.. not tried it yet tho. We also were rec'd passiflora homeopathy but that super revved up my ds...

Just a quickie on the 'going to sleep battle'... I know just how soul destroying it is battling them to sleep for hours sometimes, after an exhausting day. Not sure if you know of it already but we use melatonin.. most folk produce enough towards evening to signal it's time to sleep but lots of PANDAS kids seem to have issues with this. We try to get away with the smallest amount possible but it gets them to sleep in 15 minutes or so rather than in hours. It keeps some asleep but not my two but I'll take not having to battle at bedtime. For us, if we give too high a dose (1mg or up), we can see some bad dreams creep in. The only long term side effect that I've read about that worried me with its use was lowered sperm motility and amount in men that didn't resolve for some with cessation. So I do try to use it, especially for ds, only when needed. Although, I suspect my needs creep into that equation more than they should

Hi our now 4 year old ds was 2 when he got his diagnosis. It is a little more blurry a diagnosis than his sister who is very obviously classic onset PANDAS (now PITAND) but if we were at all unsure, any doubts we had were blown out of the water when he upped his aggressiveness MAJORLY and our very savvy PANDAS ped swabbed him and he came back positive for strep with no symptoms whatsoever except the huge ramp in aggression. We have done limited testing on our ds due to age and getting blood drawn but have used antibiotics and used steroids once (as diagnostic test to see if we got improvement). He responded beautifully to abx last time with aggression dropping off totally 9 days after abx. The symptoms we have seen (with hindsight) started when he was 7 months, same time his sis got her 1st recognised PANDAS episode, are aggression, hitting/biting/kicking etc lowered interaction socially stammer that lasted a few weeks and also resolved well with abx sleep issues seperation anxiety hyperactivity impulsivity sensory issues - mainly tactile defensiveness and height fears there's been the odd ocdy type thing but not easy to tell with such a young kid A lot of what we got could have been explained away as normal little boy stuff if it weren't for the extreme intensity and sometimes non-stopness! Good news is that he seems to react well to abx treatment. He too has had c-diff and when we had to use abx since then we just make sure we really up his probiotics. We love florastor as it it a good yeast that backfills nicely when on abx and stops growth of nasties and we also use a probiotic by pharmax that su[pposedly is human type and takes reaaly well in the gut. Since we have used those we haven't had any gut issues. Luckily he also likes kefir. You may want to check other household members for strep. You'll find lots of good info on the pinned threads too. Sorry I can't offer more. You may need to look at other abx types (we use zith succesfully but it varies from child to child). You may also want to check other body areas for strep such as nasal swab and perianal area. We are currently supplementing our kids with B vitamins aimed at helping the methylation cycle as our dd came back with a couple of gene polymorphisms that impact that cycle. Our PANDAS ped who has 90+ PANDAS patients believes that this MTHFR gene is at the basis of this disorder. Researching it you can see how big of a problem it could be.... we'll see how the supplementation pans out.... and if it helps. Good luck....

peglem - sorry things aren't better than they are at the moment. Hoping that the thyroid treatment gets her some relief. Has your talked about Cytomel, the T3 replacement as well. I'm aware there is some controversy in the thyroid dr world re T4 or T4 and T3 replacement but I would be climbing the walls without my T3.. I'm only borderline low but the T3 bit is what scrapes me up off the ground emotionally...it knocked out my nail biting (trich?), postnatal "survivalist" type OCDishness (best not to ask) and also got me back to the now, rather than living in my head/living in the future/lots of planning type stuff. Hope you see some improvments soon...

peglem - just wondering how things are with your daughter at the moment?

LLM - we did our testing through an integrative dr who ordered the tests from Labcorp. The test name was 'MTHFR , DNA analysis' on the results sheet.

Hi - yes our dd is a compound heterozygote. She has one on A1298c and one on C1677T I believe. It puts her somewhere around 30% capacity or so. We are doing 5mthf, pyridoxyl B6 something and B12. We may also be adding TMG aka betaine.. not sure yet. I've also been giving it to ds and dh and I believe I am seeing the most drastic results in dh .. my dh's mood and overall demeanour has improved so much it is like living in a different house. He has also been taking/trying different blood pressure meds, so it's not totally clear what has been doing it but I'n sticking with the vitamins

Suzan - yep you're right, rather than being high itself, it is a hsitamine producer.. from the caseimorphs (sp) I beleive. Sorry, my bad Looking at histamine problem foods, I was interested to read azo dyes are troublesome. Our dd gets the upper cheek flush alot with yellow dyes. We had assumned it was cross reactivity with aspirin sensitivity as our immuno dr suggested but I'm wondering if it's the histamine issue. She also sometimes has upper cheek flush when eating other foods but we couldn't connect anything. Now I will watch and see if there is a histamine connection when this happens.

Here's a thread by some guy who I've seen mentioned lots rich van konyenburg.. anyways he's looking at yasko - he talks with relevance to CFS but it's all looking at meth block glutathione cycle.. some good stuff here but only scanned it for now... http://www.prohealth.com/me-cfs/blog/boardDetail.cfm?id=1092649

Thought this was an interesting discussion by ME/CFS sufferers re methylation block and why you could see increase in symptoms.. http://forums.phoenixrising.me/showthread.php?4240-Why-the-increase-in-excitotoxity-on-the-methylation-block-treatment

LLM - there is a lot of stuff that I came across and you probably saw too on Methylation Block as it's called... not got time now but can go find some later and will post.

sorry - one more off topic but following on from mthfr potentially inhibiting BH4 and this paper that cites BH4 deficiency and its effect on neurotransmission of dopamine and glutamate, specifically with relevance to schizophrenia but thought the glutamate bit interesting.... what I'm not understanding/getting/seeing is how an infection strep/bart/myco/an other could produce such a swift decline and sudden onset of symptoms if, as our ped thinks, mthfr is at the base of it all. Gotta love that acronym MTHFR. It does indeed appear to a right mthfr time for bed http://www.jbmb.or.kr/jbmb/pdf.php?data=MTExMDE4MTRAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0My05JTVEMTEwMTI3MjAwMl8lMjg1OTMtNTk4JTI5Qk1CMzgzJTI4OSVCRiVGOSVCOCVBRSVCQSVFNCUyOS5wZGY=

oooh - found this which to me was very interesting, as one of my dd's mthfr gene polymorphisms is the A1298C one. She also looks as though she would benefit from biopterin supplementaion from testing and this explains why.. I've italicised the bits I found super interesting and bolded the bit in one of the last sentences that could explain why mthfr means more infections. None of this is substantiated in any way but I intend to go look for some real research etc that might back this up.. found it on some ADHD forum... here it is anyway for what it's worth The A1298C mutation in the MTHFr enzyme affects the conversion of dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4). Less amounts of BH4 will therefore put a strain on the conversion of trytophan to serotonin and tyrosine to dopamine. This will lead to low levels of neurotransmitters such as dopamine, norepinephrine, serotonin and melatonin.In addition the activity level of the COMT enzyme will further affect the levels of dopamine and norepinephrine. COMT: Catechol-O-MethylTransferase is the enzyme involved in the metabolism of dopamine and norepinephrine into subsequent compounds such as HVA and VMA. The rate of activity of COMT will determine how fast these neurotransmitters will be broken down. Mutations in the COMT enzyme (COMT ++ or COMT +-) actually slow down the activity of the enzyme. Normal COMT activity (no mutations) is depicted as COMT -- Mutations in the COMT enzyme will slow down the breakdown of dopamine, therefore individuals who are COMT ++ or +- have higher (as in good) levels of dopamine compared to COMT -- individuals who are rapidly draining their dopamine stores. This condition is further exacerbated if the individual has the A1298C mutation (++ or +-) because their dopamine levels are low to begin with (remember these individuals have less BH4, so less dopamine gets made). Undermethylators: Dr.Amy categorizes individuals who are COMT -- as undermethylators. One of the ways the COMT enzyme breaks down dopamine is by using a methyl group donated by SAMe (remember it is the universal methyl donor). Therefore a COMT -- individual will be in constant need of methyl groups as they are rapidly metabolizing dopamine. This puts a strain on the Methylation cycle as the demand on SAMe for methyl groups is increased. Think of this as COMT constantly demanding methyl groups from SAMe. If there are issues in the Methylation cycle or Folate cycle that affect the levels of SAMe (which in turn is dependent on the levels of methionine), there will be less methyl groups to begin with and even less to go around. It is like a domino affect. A break or strain in one cycle has a ripple effect on the rest as they are all co-dependent. Less methyl groups -> less methylation -> less RNA/DNA/protein synthesis/heavier viral load due to lack of methylation etc. Overmethylators: These are the individuals who are COMT ++. Mutations make the COMT enzyme slower, so it will not break down dopamine as rapidly. Since it is slower in metabolizing dopamine, its demand for methyl groups is also reduced. Subsequently there is less of a strain on SAMe for methyl groups. So there will be relatively more methyl groups available for other biochemical reactions and to go around the various cycles. Remember these are just relative terms. An undermethylator is low in methyl groups and an overmethylator has a higher store of them, in comparison. Remember one of the reasons we are in this predicament with autism is because we have problems with methylation, regardless of the under or over status. In addition the strain on the BH4 cycle, the amount of BH4 will also affect the functioning of the Urea cycle. BH4 is the rate limiting factor for the Urea cycle. Two molecules of BH4 are necessary to drive the Urea cycle. One molecule will in turn generate peroxynitrite and if the individual has no BH4 left, super oxide is formed. Peroxynitrite and super oxide in combination cause damage to neurons when they accumulate in excess. . Peroxynitrite is a potent oxidant, which is capable of DNA strand scission (breaks open the bonds that keep the two DNA strands bound in a double-helix) , and nitrating tyrosine, all of which wreak havoc on the nervous system, especially a developing nervous system as in children. The ability to detoxify superoxide is facilitated by the enzyme superoxidedismutase (SOD). Urea Cycle: Urea is the chief nitrogenous waste of mammals. Most of our nitrogenous waste comes from the breakdown of amino acids. Breakdown of amino acids results in the production of ammonia (NH3). Ammonia is a toxic compound that is converted into its safer counterpart urea, by enzymes in the liver. Urea is then eliminated by our kidneys. Essentially the urea cycle involves the conversion of ammonia into urea with the help of the intermediates listed below. Arginine from our diet or from protein metabolism is converted to ornithine and urea by the enzyme Arginase. Ornithine is then converted to citrulline by ornithine transcabamoylase. This is the reaction on the far left side of the pathway diagram. Citrulline is converted back to arginine. This cycling of Arginine through the various intermediates is what converts ammonia to urea. Arginine is also required for the production of Nitric Oxide (NO) by the enzyme nitric oxide synthase (NOS or eNOS). This reaction is dependent on the levels of BH4 available from the BH4 cycle. Remember two molecules of BH4 are needed to generate Citrulline and NO. One molecule of BH4 will in turn generate peroxynitrite and if there is no BH4, super oxide is formed. If we do not have enough BH4 to go around because of the A1298C mutation, we are going to have trouble with ammonia. Because ammonia is dangerous to the body, any BH4 we have is going to be used to try to get rid of the ammonia rather than to be making neurotransmitters like serotonin and dopamine. Furthermore mutations in the NOS (eNOS) exacerbate the situation as they will affect the synthesis of NO. NO is needed for several functions including secretion of certain hormones, addressing inflammation, killing pathogens etc.In essence if the limited supply of BH4 puts a strain on the functioning of this pathway, excess ammonia will accumulate as there is not enough BH4 to help convert it to urea. In addition the lack of BH4 also creates damaging free radicals like peroxynitrite and super oxide (SOD is needed to detoxify superoxide). Read more: http://adhdldsupport.proboards.com/index.cgi?board=alt&action=display&thread=1126#ixzz1b6k6thkJ Sorry if this is off topic from the original question but didn't know what else to do with it....

Back to the original topic re histadelia - some foods are high in histamine and some are histamine promoters. Milk is one that is especially high and I've read that some people are histamine sensitive and that a proportion of those who believe they are lactose intolerant are in fact histamine sensitive. Not sure how this could or even would feed into PANDAS looking symptoms but thought it worth a mention....

I'm blushing

Hi - I'm awful at explaining and would probably cock it up anyway but this link is a fairly easy and visual explanation. http://www.ceu-usa.com/courses/WC001/test_drive/methylation_cycle.htm I don't get it totally but from what I've read it is important in very many body systems and it would seem to be important in neurotransmitter production (serotonin, dopamine, norepinephrine, melatonin too) and detoxing. it is also a step needed for methionine prodcution and consquently glutathione and is important for scavenging free radicals in oxidative damage. our dd who is compound heterozygote and so has one alelle wrong on two genes, has low metabolites for serotonin, dopa, norepin and is an awful sleeper without melatonin. She also is high histamine not tested but symptom wise would seem variably but always high It will be interesting to see how she does on this regimen... I'm trying to get a handle on the immune implications but am wondering if for some the increased histamine production alone (for the under methylators) is the initiating trigger for autoimmune, as is touted in some reasearch (increase H2 -> autoimmunity ...saw a paper where ranitidine aka zantac was used to decrease psoriasis symptoms). Sorry if this isn't clear but neither is my understanding Our PANDAS savvy ped says to especially consider mthfr if you have familial issues with heart/arteries/clots etc due to the increased homocysteine levels... We also have a family history of salicylate sensitivity and assume same in dd as she appears to have problems with yellow food colouring which cross reacts like aspirin according to our immunologist. I suspect she may have more than one impaired pathway methylation and possibly sulphation but I ain't even thought of opening that can yet :-)

I'm a google whore

Thought this was interesting - a study citing improved BBB function with B12 and B6.. http://content.karger.com/produktedb/produkte.asp?typ=pdf&file=DEM2003016003145

From wikipedia - The major step in the methylation cycle is the remethylation of homocysteine, which can occur via either of two pathways. The major pathway involves the enzyme methionine synthase, which requires vitamin B12 as a cofactor, and also depends indirectly on folate and various other B vitamins. The minor pathway involves betaine-homocysteine methyltransferase and requires TMG as a cofactor. Betaine is thus involved in the synthesis of many biologically important molecules, and may be even more important in situations where the major pathway for the regeneration of methionine from homocysteine has been compromised by genetic polymorphisms.

I'm wondering if the type of B12 is the important fact.. hydroxy or methyl?

Hi - it was the integrative dr that rec the following but dr keller says go with it and is also looking at using TMG (betaine) we are using 5 mthf (methylated folic acid), B6 with some some magnesium in it and B12. The integrative dr rec'd hydroxy B12 so as not to overmethylate but I'm not sure I get the reasoning and we are changing to methylcobalamin B12. dr keller reckons we should really be using B12 injections as most b12 cycles thru ur system in 4 hours or so whereas injectable lasts for 4 days. DD may not go for that so we are doing sublingual 4 times per day (when we remember). We may use TMG if she recs. it uses an alternate pathway to methylate. TMG is trimethylglycine and was wondering about it and that case study you posted about glycine being used to effectively treat the boy's symptoms... my chem is way too crap to work out the relationship.. could it be loading enough glycine into the system that even crap methylators can use it to rebalance. I'm probably way off mark and showing my scientific ingnorance I can see why adding normal folic acid or hydroxy B12 may cause issues as it may lead to more build up of un methylated products... I've found a couple of studies linking histamine and glutamate interations in the brain .. do you know anything in that area? you seem to be the glutamate guru

Momwith - yeh, dr Keller says she's seen a lot of PANDAS kids improve when addressing the under methylation issue (she currently sees 90 or so PANDAS kids). I didn't push for numbers etc last time we saw her but will do next time. I'm desperately trying to get my head round it all.. the under methylation thing has so many implication in so many systems....

Hi - I'm also interested as, from what I've been reading, too high or too low histamine levels can be as a result of over or under methylation. I got back on this track after reading a post about a mom seeing dr Keller in Redmond and being told by the dr that MTHFR gene may be to blame for the PANDAS symptoms. We also see Dr Keller. An integrative Dr tested our dd for the MTHFR gene polymorphisms. She came back as a compound heterozygote, putting her at about 30% of capacity of the wild type genes. So our dd doesn't methylate well. (So we're currently supplementing with 5MTHF- methylated folic acid, B6, and methylcobalamin B12 with dr Keller investigating the addition of TMG aka betaine). I don't totally get it all but there may be something to this MTHFR stuff and histamine being an issue for so many kids. Under methylators produce too much histamine and over methylators produce too little. So like Momof has said, maybe it's the dysregulation that is the issue and maybe it's the methylation cycle that is underlying that dysregulation. Dunno..more rabbit holes but there is loads out there to research. One of the most easily read,comprehensive articles I've read is here http://www.enzymestuff.com/methylation.htm would love folks ideas on this.. (not sure if it's been discussed before)

Hi - just my two cents on PANDAS looking like autism from our experience.. my dd closes down touch wise, especially with me during an episode. It isn't OCD based she just gets less cuddly and emotionally connected and way more aggro altogether. I know when things are looking better 'cos amongst other things, she wants to hug and be affectionate and will seek out these interactions. During an episode she will literally shy and pull away when touch is initiated. I don't believe it's OCD - she's very goodat telling me what's going on ocd wise, very open and aware. It's not sensory, we haven't had sensory involvement for her for a couple of years now. It looks very like very low level autistic stuff to my eyes but she's so not like that at her normal baseline. for my ds - when he was maybe 2 1/2, we tried a steroid burst to see if the symptoms we had witnessed were indeed PANDAS. The most "autistic" reversal response i saw was within 12 hours or so of the first dose (our dd's ocd diminished within a few hours of the first dose of steroids on both occasions that we've used them) my ds looked at me, really looked at me and said "i love you Mummy" - doesn't sound much but really was so noticeable 'cos although I wouldn't have said before that that he wasn't making a connection but suddenly the connection amped by 50% - much more intense eye contact than in many previous months and the I love you bit I hadn't heard for a very long time. I imagine that depending on severity, type of and age of presentation, PANDAS/PITANDS/PANS whatever may well look like autism or aspberger's

Hi - Dr B told me that both my kids PANDAS/PITANDS shouldn't be getting any shots as they will stimulate the immune system. Dr T felt we should be avoiding them too although if we felt we needed to we could give them (for us tetanus) as long as we give them when well and out of exacerbation and as uncombined as possible. Dd rides and so is round horses a lot.. possibly heightened risk of tetanus but we decided against it. Somebody mentioned that the viral load with vacs is lower than with the real disease which is true but for me it wouldn't be the viral load that would be the worry necessarily but rather the adjuvants that are added with the express intention of stimulating the immune system. Perhaps this may be more of an issue if you're PITANDS rather than pure PANDAS.. dunno but we're taking our risks with the real disease rather than shots for now.