Ellfindoe and LotteM please .... - Restless Legs Syn...

Restless Legs Syndrome

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Ellfindoe and LotteM please ....

67Waterman profile image
9 Replies

Thank you to Ellfindoe for being patient and explaining so well. I hope you don’t mind, but I have taken what you have said and put it in my own words to try to ensure that I understand what you have said. Here goes …..

The latest model of RLS is that there is a series of factors which lead to RLS. What seems to be the main differences between people with RLS and those who don't have it can be –

1. People with RLS have a failure in transporting iron from the blood into the brain across what is known as the Blood Brain Barrier (BBB). This can lead to a condition called Brain Iron Deficiency. BID in turn, causes a reduction in the activity of a neurotransmitter called "adenosine", which leads to two problems: (a) excessive levels of dopamine, a neurotransmitter and (b) excessive levels of glutamate, another transmitter. Excess glutamate can lead to "hyperarousal" and Periodic Limb Movement Disorder and, and excess dopamine can lead to “sensory-motor symptoms” and Periodic Limb Movement Disorder.

2. People with RLS have less Dopamine Receptors (otherwise known as D2, which are protein receptor sites which mediate the cognitive flexibility in humans) in their Dopaminergic Neurons. Dopaminergic Neurons, found in the midbrain, are the main source of dopamine in the central nervous system and their loss is associated with one of the most prominent human neurological disorders, Parkinson's disease. (Note from Lotte just received : “DAs seem to target the D3 receptors, thus not (so much) the D2 ones that are reduced in people with RLS.”)

* So in Case No 1, Brain Iron Deficiency leads to excessive levels of two transmitters, Dopamine (which enables neurons in your brain to communicate and control movement )and Glutamate (a brain chemical that either excites or inhibits the function of neurons), both of which cause RLS.

* And in Case 2, lack of Dopamine Receptors leads to the brain being unable to “process” the Dopamine (ie insufficient dopamine biosynthesis in the dopaminergic neurons) that is produced by the Dopaminergic Neurons, which also causes RLS.

Dopamine Receptor Agonists directly stimulate the Dopamine Receptors, and Gabapentinoids, Gabapentin and Pregabalin work by reducing Glutamate levels, i.e. the other aspect of RLS. Because these reduce "nerve sensitivity" they have a general calming effect on RLS, nerve pain and epilepsy.

So by taking Gabapentin, one is not “replacing” the Ropinirole, because the Ropinirole is a Dopamine Agonist, and the Gabapentin is targeting the Glutamate. By coming off Ropinirole, your Dopamine Receptors are back to square one again – ie not so many of them, not producing and not processing the dopamine in your brain. However, what you are doing by taking the Gabapentin is to concentrate on the over production of Glutamate caused by the failure in transporting iron from the blood into the brain the Blood Brain Barrier, which in turn leads to nerve sensitivity.

QUESTIONS PLEASE

If I have understood all this correctly, my first question now is “has it been proved beyond reasonable doubt that all RLS suffers do have Brain Iron Deficiency? Because if not, then those that do not have it, will not have excessive amounts of Glutamate”. My second question is “if there are no excessive amounts of Glutamate, what effect will taking Gabapentin have on the normal amounts of Glutamate found in a normal body”.

Please feel free to correct any of the above. I will be a lot happier when I get a true over view of my problem! Big thanks to all, Sally

And to complete the picture ... direct from Ellfindoe “Another approach to RLS is to correct the BID using iron therapy. A more recent development is the experimental use of dipyridamole, which increases adenosine.”

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9 Replies
LotteM profile image
LotteM

You have worked hard and git the main picture. Please realise, Sally, that even specialist scientists working on this problem do not fully understand what exactly is going on. So some of your questions cannot be answered with the current knowledge.

Brain Iron Deficiency is the main, widely accepted hypothesis as the cause of RLS. Scientists never know things for sure, they work with hypotheses that they try to disprove. So if you accept this, all people with primary RLS have BID but it is not known how this comes about. Up until now nothing has been researched about the transport of iron across the BBB on people with RLS. That is not strange, as it s not easy to do. Most likely you meed a living brain, but no-one wants to mess with living brains.

The effectivity for RLS symptoms of both dopamine agonists and gabapentinoids have been found coincidentally. It is not known exactly what they do, especially not in a 'RLS brain'.

It is easier to ask questions than to answer them .... But you're welcome. I always like to understand things fully too before I take action, but sometimes (often?) that is simply not possible.

67Waterman profile image
67Waterman in reply to LotteM

Thank you to both you and Ellfindoe for taking time to help explain what can be explained and what cannot be explained. Somehow, understanding always helps when suffering a medical condition. Thank you, thank you.

Elffindoe profile image
Elffindoe

A couple of slight corrections perhaps

67Waterman profile image
67Waterman in reply to Elffindoe

Correct away Ellfindoe ... I love learning.

Elffindoe profile image
Elffindoe in reply to 67Waterman

That's weird!

I did write some corrections and answered your questions, but it seems to have disappeared.

I'll try and answer your questions.

Hope it's not too technical.

Many things which vary, e.g. Iron levels in humans do in whats called a normal distribution. If you enter this into google images you'll see what I mean.

In this people vary about a central value, some people having less than this and some people more.

If you compared the distribution for non RLS to RLS people the central value level of iron will be lower for RLS than for non RLS. BUT, there may he some overlap.

In addition, the difference between central values will be "statistically significant". Meaning that it's more than due to chance.

There is then no absolute or fixed value you can associate with BID only a range of values.

Hence, long story short. BID may not account for everybody's RLS.

Second question. If somebody who has normal glutamate takes gabapentin then yes, it will reduce glutamate levels.

The effect of this will be to reduce nerve sensitivity. i.e. nerves react less to stimuli.

Hence gabapentin can be used to treat conditions where nerves could be said to be oversensitive. So, good treatment for nerve pain, epilepsy, fibromyalgia and migraines.

67Waterman profile image
67Waterman in reply to Elffindoe

Hi - thank you. Regarding Gabapentin, I think what I was trying to get at was "supposing my RLS was NOT caused by high levels of Glutamate, but ONLY a lack of Dopamine Receptors" ... would taking Gabapentin do anything for my RLS? Thank you for your patience.

Elffindoe profile image
Elffindoe in reply to 67Waterman

Sorry, I missed that point.

Answer

Statistically

In clinical trials, Gabapentin has been shown to have a statistically significant effect on the majority of users

I may be wrong, but I think the figure is 70%

However, you're an individual, not a statistic so the "chances" for you are 7 in 10.

You won't know 100% for sure until you try it.

67Waterman profile image
67Waterman in reply to Elffindoe

Great ... thank you. That manages my expectations! Warm regards, Sally

cicek profile image
cicek

Thanks for this. It makes it easier? to understand. I do realise that no-one is absolutely sure about the absolute cause of RLS but I can only thank any scientist/medic who is helping along the way to find the answers. One day we might have a one pill "cures" every sufferer of this debilitating syndrome.

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