Glutamate Study background and hyperarousal

[skn0412]

I saw a couple posts about insomnia, and I felt compelled to share Dr. Allen's write-up in the Study he is doing "Glutamate, hyperarousal and RLS" at John Hopkins that I participated in, Dr. Allen writes:

"This research is the second of two phases of a research project designed to evaluate a new cause for RLS. This research is being done to evaluate a possible new basic biological basis for the RLS. It had been thought that RLS was mainly a disorder involving the dopamine system. This was largely because medications increasing dopamine activity provided dramatic benefit. We now realize that while dopamine medications remove the motor and sensory systems of RLS, they fail to adequately correct the sleep and excessive arousal problems of RLS patients. With long-term use, they may also make the RLS worse."

"In our recent preliminary studies we noted that people with RLS had elevated glutamate levels in the thalamus. Glutamate is major brain chemical that generally increases brain activity. The thalamus is a major relay center in the brain that regulates wake and sleep. During waking the thalamus opens the gate for sensory stimulation. During sleep it largely closes that gate allowing sleep to continue without frequent arousals. That gateway involves glutamate and increased glutamate may occur with a failure to adequately close the sensory gate during sleep and also during resting. Thus this may be the primary source of the RLS symptoms for both the drive to move when awake and also the arousals disrupting sleep. Dopamine may have a secondary role compensating for this abnormality. If so, this changes entirely our concepts about RLS and the directions for developing treatments and even prevention of RLS."

I had a conversation with Dr. Earley about the hyperarousal during my visit with him; I was obviously tired as hell, and he knew that !! But, I wasn't "sleepy" .... that is the difference. My body was tired, but once I lay down to sleep, I wasn't sleepy, I was wired !!! That is the hyperarousal that they are trying to figure out. After being so darn tired from no sleep, I totally understood the reasoning behind this study ....... I sure hope they can figure it out because as Dr. Allen says, this could totally change the way they treat RLS.

[Polar Bear]

Sue, thank you for this. It is pretty exciting information.
And it explains 'me and my sleep/lack of sleep' exactly.

[Rustsmith]

Sue, I agree with PB, thanks for sharing this. In my case, it could very well explain why I have always been a very light sleeper, even pre-WED.

Out of curiosity, did Dr Allen give you any indication that they might have an idea of how to treat this if the current project indicates that glutamate is a major factor? Or is that a topic for the next series of studies?

[badnights]

The study itself has I think another year to run, then analysis of the data and write-up, so I wouldn't be surprised if it's 2 years or even more before it's published. In my little pea-brain, I see the process as a long and tedious one. Once it's published - or perhaps even now, since the preliminary study has been out for a while - there will be a focus for further research, but it's still pretty fuzzy. What is it in the thalamus that's failing to block sensory input? What is the cause of the increased glutamate? The JH study might be enough to get a pharamceutical company with real money researching the glutamate connection, but even with that kind of money, a treatment will likely take years to arise out of this line of inquiry. That said, I keep hoping that a miraculous breakthrough in understanding will circumvent the whole process. And anyway, what do I know - maybe Dr A has something up his sleeve.

I'm just bloody happy that he's checking out this aspect of the disease. And that he has retained an interest in WED over the years, and in different aspects of it too, from being one of the first to recognize and describe augmentation, and devise methods of dealing with it, to his intensive investigations with Earley on the importance of iron and their clinical experiments with iron infusion that have given us a useful protocol for that form of treatment, and now this focus on insomnia. He doesn't just do research, he follows it through to a useful conclusion. All his research is people-based - he is not working in isolation from us but with us. He has stimulated and taught a whole team of people to think about WED. He is a truly remarkable person and we're lucky it was WED he became interested in.

[peanut1]

I also am excited about this study and can totally relate to being wired vs. sleepy when getting NOTHING for sleep. I can feel sick like I have the flu when going for days with so little sleep, but I'm never tired or sleepy. I can totally relate! I guess the first thing is for us to NOT take any thing with glutamate in it.

[Revelle]

Yes, I too read this new article about Glutamate. I think we have a lot
Of new discoveries that will be unveiled about RLS and that its
Not just about leg moving impulse. I think this discovery
Is also for the Insomnia's out there w/o RLS.
Its a grapevine of medical mysteries. And just one
Path is not the only road anymore
Gina

[badnights]

I guess the first thing is for us to NOT take any thing with glutamate in it.

That doesn't follow, peanut. Glutamate is manufactured in the brain cells, I don't think there's any evidence that it will increase if we eat more glutamate.

But - that said - I think there are other good reasons for avoiding MSG (monosodium glutamate) in food.

[peanut1]

Oops--didn't know that However, I will say that if I eat MSG my WED really acts up. However, I realize that could be a food allergy or something. I would love to know what causes the additional glutamte in the brain and if there is a way it can get decreased somehow. Probably will be years before we get any type of remote answer on that but at least we are heading in the right direction

[badnights]

Yup!

[Chipmunk]

I guess the first thing is for us to NOT take any thing with glutamate in it.

That doesn't follow, peanut. Glutamate is manufactured in the brain cells, I don't think there's any evidence that it will increase if we eat more glutamate.

But - that said - I think there are other good reasons for avoiding MSG (monosodium glutamate) in food.

Yes, it's like how eating less cholesterol doesn't lower your cholesterol levels and eating fat doesn't make you fat - for both, there is a long chain of cause and effect which triggers certain hormones in your body to activate or deactivate and a similar thing is likely going on with glutamate levels in the brains of people with WED. If we can find that root cause...wow...that would be amazing!