Allergies and Anticonvulsants worsening RLS

[Rustsmith]

I have had WED/RLS for more than 15 yrs, but was always able to control my symptoms with iron supplements.

I also have had very severe respiratory allergies all my life and I am only able to "live" with a combination of antihistamines (Zyrtec), nasal steroids and a leukotriene inhibitor.

About 5 yrs ago, I started seeing a neurologist for help with treating my migraine headaches. She put me on Topiramate, which went well until the start of the next seasonal allergy season. At that point, I started getting what I now know were severe WED issues in my arms and body at bedtime. This was causing severe insomnia and sleep deprivation, so she also gave me Lunesta.

Once the pollen levels subsided, so did my WED symptoms. However it took another year before I was able to convince myself that the two were linked. I discussed my WED symptoms with my neurologist, my allergist and my GP and none of them made the connection to WED.

This year, even the Lunesta wasn't able to allow me to sleep, so I knew something else had to be done. It was only when I sent myself to a sleep doctor for testing that they sort of made the connection. I was diagnosed with PLMD and treated with a DA. With the first dose, my afternoon and evening WED problems in my arms disappeared.

I have seen a number of comments about how some antihistamines can trigger RLS, but can anyone give me an idea why my more severe issues seem to be triggered by the anticonvulsant and the higher histamine loads during allergy season? During the summer and winter, these same drugs rarely trigger any problems.

And before anyone asks, I am still waiting on the results of the test with my ferritin level.

Steve

[ViewsAskew]

Steve - not a clue.

Dr Buchfuhrer is a researcher and has written one book about WED and co written a few others. He answers patient's questions - email him at somno@verizon.net. Let us know what he says.

[Rustsmith]

Ann, thanks for the suggestion to contact Dr B.

Unfortunately, he was not able to provide any additional insight into my problem. The majority of his response was:

"It is difficult to figure out why the allergies worsen your RLS as that is not a common problem. It is possible that any stress (such as being bothered
by allergies) might increase RLS in a non-specific manner. The anticonvulsants typically do not worsen RLS so that should not be an issue."

I doubt that stress is the issue since I have only known life with hayfever and my condition does not change much day-to-day. I also have far fewer other
sources of stress in my life these days than I did before I retired, which six months before all this got started.

So I guess that I just have to chalk this up as an odd reaction that cannot be explained by the current understandings of neurochemistry.

Steve

[Polar Bear]

Yes, there are sometimes just reactions that have no explanation.

Regarding retirement, I agree with you on every level, life is so much calmer as a retiree.

[Rustsmith]

Since I originally posted this inquiry, I have found four papers from Europe that talk about either topriamate induced RLS or zonisamide induced RLS. All four papers are very limited case studies rather than the results of large scale research. There are also papers that talk about the successful use of either topiramte or zonisamide as analogs of gabapentin for the treatment of WED. Therefore, one set of doctors says that these drugs trigger WED by reducing the release of dopamine and another group claims they use these drugs to successfully treat it.

Most of the papers are behind walls requiring payment and do not even have abstracts available. Fortunately I was able to use my university access get all four, if anyone is interested in the specifics please let me know by PM.

Here are the four papers where the drugs induced WED:
http://www.neurology.org/content/60/1/147.extract - Zonisamide induced RLS
Bermejo, et al., in Movement Disorders, Vol 22(10), pp 1517-1518, Jul 30 2007, "Restless legs syndrome induced by zonisamide"
Romigi, et al., Journal of Neurology, Vol 254(8), pp 1120-1121, Aug 2007, "Topiramate-induced restless legs syndrome"
Bermejo, Journal of Neurology, Vol 256(4), pp 662-663, Apr 2009, "Restless legs syndrome induced by topiramate: Two more cases"

Here is an example of a paper where topiramate was used to treat WED:
http://www.ncbi.nlm.nih.gov/pubmed/15168262

[badnights]

But - why would your WED only worsen in allergy season? You're taking the topiramate all the time, aren't you?
This is still a bit of a mystery.

[Rustsmith]

My theory at this point is that the levels of histamine that normally circulate in my body are far above what is normal for most people due to my allergic reactions to everything in the air that isn't gaseous. To illustrate how abnormal my reactions are, I have never been able to use benedryl and the reason has nothing to do with the WED reaction. Benedryl is simply ineffective and didn't even work when I was just four years old. It is like a placebo pill to me, it does nothing even now. As a young child, I would take an antihistamine and it would only reduce my allergy symptoms a bit. My father tried taking one of my pills once when he was having problems and it knocked him out via the sedation effect. The same pills keep me awake.

I therefore suspect that during allergy season, the histamine levels in my brain are elevated enough that they are providing a secondary stimulus effect to the glutamate. I have seen articles that indicate that histamines in the blood are not supposed to cross the barrier. But I am enough of a chemist to know that very high concentrations of a chemical on one side of a diffusion barrier will cause some diffusion to occur to the other side. So, normal levels of histamine in the blood may not cause changes in the concentrations in the brain, but my blood levels are probably quite elevated, even compared to my "normal", during allergy season and in spite of all the non-sedating allergy medications that I take.

[badnights]

Re the effect of benadryl. I know you know that substances that are supposedly sedative for others are symptom aggravators for us because sedation/relaxation triggers symptoms. If we consider hyper-alertness as one of the symptoms of WED, the arousing effect of benadryl on you (and me) is in line with that.

But I still don't understand the role of histamines and anti-histamines. Having excess histamines worsen your WED makes sense from the point of view of their being excitatory neurotransmitters, but seems backwards when considered against the fact that excess anti-histamines worsen WED - implying that histamines are good for it. It's obviously more complicated than my simple view of it.

[Rustsmith]

I am going to start this by admitting that there is still a lot that I do not understand. But here goes:

Antihistamines are properly described as histamine antagonists or inverse agonists. They work by attaching to the same receptor sites as histamines, but block the channel rather than triggering it. Histamine in the brain also plays a key role in the sleep regulation. Antihistamines that block the H1 receptor sites (like bendryl) trigger sleep while antihistamines that trigger the H3 sites trigger wakefullness. Histamine also plays a role in dopamine and glutamine regulation via the H3 receptors.

I also know that I have atypical reactions to many drugs in the allergy treatment family. As stated earlier, bendryl has no effect on me as an allergy treatment, as a sedative or a WED trigger and chlorphenamine is only useful as a secondary short term add-on. Pseudoephedrine (Sudafed) and all the other decongestants act like amphetamine for me, possibly via sudden releases of dopamine that are a side effect of the substituted amphetamines. Finally, Fexofenadine (Allegra) is a second generation drug that isn't supposed to cross the blood-brain barrier at all or have any antidopaminergic effects. But the one (and only time) I took it I was up for 24 hours with none of the normal insomnia signs. It wasn't that I couldn't go to sleep, I didn't need to and that was really scary.