Buster and Others of Scientific Persuasion

[MomWithOCDSon]

I posted a topic a few days ago regarding a link between narcolepsy and strep, and had read that a Stanford University study had found a link, though I couldn't find a copy of the actual study at that point.

 

Meanwhile, DS13 fell asleep in class again today, despite a full 10-hour night's uninterrupted sleep and, when questioned, seems to literally fit the narcoleptic classification of "Excessive Daytime Sleepiness."

 

Here's a link to a copy of the Stanford study. In addition to the potential narcoleptic/strep link, I'm wondering if there's anything here that might inform the PANDAS research, but I don't have enough science at my disposal to discern that, really. There is discussion here, however, about blood brain barrier permeability. Is there anything new to be learned from this information? Does hypocretin, for example, figure into PANDAS at all?

 

Stanford University Strep and Narcolepsy Study

 

Thanks in advance!

Edited April 7, 2010 by MomWithOCDSon

[kimballot]

Very interesting ... and my son (also 13) just informed me that he went to the nurse's office to sleep today and then he fell asleep after dinner at his cousin's house... My daughter is just finishing up a 5-day Z-pack for strep and my husband is just finishing a course of biaxin for the same... I am hoping Buster chimes in on this one - I need the reader's digest version!

Edited April 7, 2010 by kimballot

[Buster]

Wow, fascinating study. There are several great comments in the paper. The authors list 3 basic hypothesies:

1. that streptococcal infections (or their exotoxins) cause superantigen interactions Tcell receptors and lead to the destruction of hypocretin neurons
   
2. or perhaps the exotoxins open the BBB allowing other specific blood factors to trigger narcolepsy
   
3. or perhaps the bacteria/exotoxins just reactivate the immune system nonspecifically causing inflammation triggering narcolepsy
   

What was also fascinating was the incredible correlation found to long-lived ASO titers. They noted "In uncomplicated infections, antistreptococcal antibodies are reported to increase after 2 weeks, to peak at 2–4 months, and decrease thereafter.19 The long-lasting antibody response in narcolepsy may thus reflect the special genetic

background of these subjects and/or a sustained narcolepsy-

related immune reaction."

 

They further go on to quote Machado's 2001 paper where "A similar pattern of slow ASO titer decrease lasting several years, with moderately increased titers up to 3 years from diagnosis, was found in acute rheumatic fever."

 

Finally, they noted a difference in the HLA-DQB1*0602 which is an allele (or specific gene transformation) that has been found in 90% of nacolepsy patients and interestingly in many patients suffering from migraines and interestingly in MS patients. This might (might) be a marker for a BBB susceptibility. There's a nice paper on this here http://www.jimmunol.org/cgi/content/abstract/183/5/3531

 

Nacrolepsy is thought to be an insufficiency of dopamine (or a blocking/interference with dopamine receptors) so curiously these all might be related. Great paper.

[kimballot]

Finally, they noted a difference in the HLA-DQB1*0602 which is an allele (or specific gene transformation) that has been found in 90% of nacolepsy patients and interestingly in many patients suffering from migraines and interestingly in MS patients. This might (might) be a marker for a BBB susceptibility. There's a nice paper on this here http://www.jimmunol.org/cgi/content/abstract/183/5/3531

 

Nacrolepsy is thought to be an insufficiency of dopamine (or a blocking/interference with dopamine receptors) so curiously these all might be related. Great paper.

 

OK... my son and I both have mild cateplexy (mild loss of hand strength when emotional (laughing) or when first waking up in the morning. My son is the only other person I've ever known to have it besides myself. Is this something I should be looking into? (and who would I look into it with - Dr. T??) We have no other signs of narcolepsy that I know of... but maybe I've not been looking for it...

[MomWithOCDSon]

Nacrolepsy is thought to be an insufficiency of dopamine (or a blocking/interference with dopamine receptors) so curiously these all might be related. Great paper.

But isn't OCD thought to be related to too much or unregulated dopamine in the brain? "Hyperfunction" of dopamine is the term I keep seeing in the literature. So how could a person like my DS display both OCD and narcoleptic-like behaviors?!?!

 

Color me confused!

[Buster]

These are slightly different posts with similar components. If we take PANDAS, the current theory is one of interference with Dopamine 2 receptors -- not having too much or too little but rather that the dopamine becomes unregulated. Dopamine works with a rather funny thing called a feedback cycle. A way to think about it is like listening to a show and then a commercial comes on really loud so you turn down the TV then your show comes back on and now you can't hear it. Now have that happen all the time.

 

That's what is thought to be going on in PANDAS. It isn't having too much or too little volume it's that the volume is changing or not regulated correctly. The antibodies are like the very loud commercials interferring with the volume setting. Poor analogy but close.

 

Now what was interesting about the narcolepsy paper was that they were finding some other breach of the blood-brain barrier and another interference pattern. It's very possible that the narcolepsy is an interference with Dopamine receptor 1 whereas PANDAS is an interference with dopamine receptor 2 -- we don't really know --

 

Actually that's probably way more than you wanted to know too :-)

 

The point I should have said was that the narcolepsy paper was interesting because it was finding a genetic predisposition to slow ASO recovery and found an apparent BBB breach. The genetic marker was also one found in ARF/SC and in MS patients. The hypothesis is beyond the findings, but it was interesting.

 

Buster

 

 

Nacrolepsy is thought to be an insufficiency of dopamine (or a blocking/interference with dopamine receptors) so curiously these all might be related. Great paper.

But isn't OCD thought to be related to too much or unregulated dopamine in the brain? "Hyperfunction" of dopamine is the term I keep seeing in the literature. So how could a person like my DS display both OCD and narcoleptic-like behaviors?!?!

 

Color me confused!