Enuresis

[LNN]

Pandas aside, DS continues to struggle with primary enuresis. Has never been dry and is now at the age where friends are having sleep overs. In my research, there seem to be three main reasons for enuresis - 1. you don't produce enough vasopressin/ADH (antidiruetic hormone (so your body doesn't know to make less urine while you sleep) 2. your bladder contracts, causing urges even when the bladder isn't full (i.e. over-active bladder - same condition that makes older men wake up frequently at night to pee) or 3. the child sleeps too heavily and ignores signals to wake up before succumbing to a filled bladder.

 

We tested ADH and while not super high, it's in the normal range (a 4 in a range of 0-12). When researching overactive bladder, I came across this explanation and it made a lot of sense Pandas-wise (similar to the explanation Dr L gives):

 

The bladder is a membrane sac that serves as a temporary collection reservoir for urine to be held before it is released from the body by urination. The bladder is capable of shrinking or expanding depending on the amount of urine that it contains. The outside wall of the bladder is covered with the detrusor muscle, a muscle that automatically contracts or relaxes depending upon the amount of fluid inside the bladder. The nervous system is also involved in the urination process. It is able to sense when the bladder is full, send a signal for the detrusor muscle to contract and also helps control the sphincter that allows the person to initiate urination. (5)

 

For unknown reasons, in OAB the body inappropriately senses the volume of urine contained within the bladder and the detrusor muscle tends to contract and relax in an uncontrolled, sporadic manner. The increased frequency is likely a combined result of the decreased function of the bladder as well as a way in which the person adapts to try to avoid leaking urine. Urgency is the uncontrolled contraction of the detrusor muscle leading to an increased urge to urinate. The urinary incontinence occurs when the contraction of the detrusor muscle cannot be overcome.

 

There are multiple causes for bladder incontinence. With OAB the person is limited by the symptoms and generally the bladder or urinary tract does not deteriorate any further. Other causes for urinary incontinence include problems with the sphincter on the urethra, birth defects, blockages in the bladder or urinary tract infections. A condition known as neurogenic bladder has the same symptoms as OAB and can be classified as OAB, but generally results from a disease of the nervous system such as multiple sclerosis, Parkinson’s disease or even a spinal cord injury. (6) It is important to have a healthcare professional determine why the urine incontinence exists so that the proper treatment can be given.

 

So the notion of excessive contractions seemed like a reasonable thing to look into. Because methylation is my "thing", I looked at the various cycles, particularly the urea cycle. One semi-essential amino acid that's involved in this cycle is l-arginine. ADH is known as arginine vasopressin. Now I realize they are different but I can't seem to find a good explanation of how different. Still, the shared name is enough to intrigue me. One of l-arginine's main functions is as a vaso-dialator. (I think arginine vasopressin has the opposite effect as a mild vaso-constrictor but not sure). Arginine as a vaso-dialator means it makes blood vessels relax (it therefore has some effect in lowering blood pressure and it is also used to help men with erectile dysfunction). So maybe, if DS's issue is over-active bladder, l-arginine could help.

 

I've found mixed info so far. Some sites that advocate natural supplements say it can help. More mainstream sites say it doesn't help. But that's not uncommon. Some sites also warn against long term supplementation, saying not enough research has been done, no upper limits have been established...other sites say no long term effects. Some sites point to abuse in the body building world because high dose l-arginine can release growth hormones, but they're talking about 10 grams. I'm only talking about a 500mg pill.

 

Anyway, out of frustration (DS's and mine), I've given him 500mg l-arginine for 5 days now. The first 3 nights, I think he was dry at 6am when I checked on him but he woke up wet. He confessed that he's now in the lazy habit of peeing in a pull-up before he gets out of bed because it's "easier" than getting up to go to the bathroom and interrupting his weekend lounging-in-bed time (men!). The past two days, after a "do you really want this?" talk and the benefits of having to get up earlier for school days, he's woken dry. So I'm kinda semi-optimistic.

 

I'm fairly comfortable that at 500mg I don't need to be worried about growth hormone and probably not even blood pressure. Also, some reading suggests arginine quickly dissipates. But...some of you are amazing in your research skills and I was wondering if anyone had info - pro or con - that I was missing. It would certainly be awesome to put this issue behind us, but not at the price of introducing any risks. Any thoughts? (He is almost 10 - "growing out of it" is wearing thin).

Edited May 22, 2012 by LLM

[coco]

Laura, I appreciate this research, as we are in the same wet boat. I keep thinking that once she is clear of underlying infection this will clear up as well, but the lazy comfort factor surely must be a player in this. So many things have improved for our dd, I am encouraged this will as well. But I think I gotta nudge this along more. When she was first put on biaxin for mycop she was dry 9 out of ten nights for a stretch, but that was short-lived. We are still pursing lexafloxicin once Dr T gives the high sign. Right now I am in wait and push mode with him. Thanks again for sharing this.

[dut]

Have you looked at mast cells.. not sure how relevant but those with mastocytosis (and I assume those at the low end of the spectrum like ds who hasn't got mastocytosis but seems to have abberant enough mast cells to cause perma itching) can get interstitial cystitis.

 

here's an anecdotal loink (blog post)

 

https://www.inspire.com/groups/rare-disease/discussion/systemic-mastocytosis-and-the-bladder/

 

here's a more formal one.

 

http://mastcellmaster.com/documents/Interstitial-Cystitis/Mast-cells-IC-Urol-2007.pdf

 

dunno, probably no link but just wondering. Also saw another artciel where IC is mor ecommon in those with autoimmune. The pain bit of IC seems to be missing for most kids but I dunno maybe there are variants.

 

[AmySLP]

Reading with interest as my 5 yr old (likely PANDAS dx by Dr. B some time ago) has nighttime incontinence and he's tied it to the PaNDAS. I never quite understood the connection.

 

Thanks for your findings.

 

Amy

[Mayzoo]

I found this so far:

 

"Nowadays Desmopressin, a synthetic analogue of Vasopressin, available since 1980, is used. Desmopressin, or dDAVP, is created by de-aminating the cysteine residue (which prolongs its activity) at one end of Vasopressin and replacing L-arginine with D-arginine (which reduces the vasopressor activity). In so doing this renders dDAVP a potent antidiuretic with reduced vasopressor activity and a prolonged half-life of 1.5-3.5 hours compared to about 12 mins for Vasopressin (60). The time to maximal biological activity following ingestion is approximately 60 mins (61). Its rapid onset of action means that it is often recommended where a quick response (such as going on overnight camps, sleepovers etc) is needed."

 

My link

 

Will keep digging since yup, we are in this boat too.

[lfran]

I posted earlier today that a few days after starting methylfolate supplementation, my DS10 pretty much ended nighttime wetting, which has been a continual problem since he was very little. Now he is completely dry most mornings, with an occasional very very tiny spot. He is MTHFR C677T homozygous, so we know he has methylation and folate issues, but here's this article, titled Decreased Vitamin B12 Levels in Children with Nocturnal Enuresis, that I thought was quite interesting. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302062/

 

I posted about this earlier, in the MTHFR post. It seems that several of our kiddos are turning up with MTHFR issues. Since so many of our kids also have enuresis, and since there may be a link between the two, I am hoping that as more of us take the MTHFR test, we may uncover an underlying metabolic issue that is behind some of our kids' symptoms. My DS10 also dropped all of his anxieties and debilitating fears shortly after we started this supplementation a couple of months ago.

 

When I posted earlier, others reminded me that this supplementation should only be done after testing and under a doctor's care. I agree completely, although finding a doctor that has experience with this is not easy, so I still want to post about our good experience in the hopes that it may help others.

 

 

I found this so far:

 

"Nowadays Desmopressin, a synthetic analogue of Vasopressin, available since 1980, is used. Desmopressin, or dDAVP, is created by de-aminating the cysteine residue (which prolongs its activity) at one end of Vasopressin and replacing L-arginine with D-arginine (which reduces the vasopressor activity). In so doing this renders dDAVP a potent antidiuretic with reduced vasopressor activity and a prolonged half-life of 1.5-3.5 hours compared to about 12 mins for Vasopressin (60). The time to maximal biological activity following ingestion is approximately 60 mins (61). Its rapid onset of action means that it is often recommended where a quick response (such as going on overnight camps, sleepovers etc) is needed."

 

My link

 

Will keep digging since yup, we are in this boat too.

[LNN]

Thanks for the link Mayzoo. It was good background!

 

lfran - my DS has no MTHFR mutations, so methylfolate/methylB12 won't be his answer. Ironically, it's my daughter who has the mutation and she's been dry since she was 2. But I will try to research B-12 and take a closer look at his intake. Because he has no mutation, it hasn't been a focus on mine before.

 

Coco - you sound like me. I keep telling myself that once we tackle the most recent issue, the enuresis will resolve. I feel like I'm trapped in the song "The Bear went over the Mountain" - every time we climb one mountain, we find yet another friggin mountain and the grocery cart continues to get filled with pull-ups. It's the one symptom we haven't made a dent in. And unfortunately, this morning he wasn't dry, breaking the 3 day streak (tho he was dry until daybreak). I know that of all the symptoms, this one if by far the last one to complain about. I just hate to see him beat himself up.

 

Will keep trying the arginine for awhile longer and keep digging.

[trggirl]

I vaguely remember a connection between Vasopressin and CamKII. Maybe researching that angle will turn up something???