RLS Patient Symposium

For everything and anything else not covered in the other RLS/WED sections.
Polar Bear
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Re: RLS Patient Symposium

Postby Polar Bear » Fri Oct 05, 2018 5:07 pm

Quote from Views ""I have often said that if only the researchers would read the posts here, they'd get a whole 'nother perspective. I also think they'd be surprised by what lengths we go to - hoarding medications, trying crazy things, and potentially doing things that could cause harm, all because we are so desperate.""

Views.... Just picking up on your comment above.

Last month I attended my GP, there are several new and ongoing issues that need attention. This GP is not my usual GP who was pretty helpful in as far as he acknowledged what information I would provide for him. Circumstances a few months ago led me to attend a young lady doctor who is now permanently with the Medical Practice and I feel that it was a welcome change. She made comment that she would never prescribe a DA as first line treatment for RLS and several other comments that led me to believe she was not totally ignorant of the issues with RLS.

Anyways..... whilst attending with her a couple of weeks ago with regard to burning and slight numbness in my lower legs since starting a blood pressure medication we got onto the subject of my general intake of medication. My meds included Cocodamol 30/500 plus Tramadol ER 50mg x 2 daily. Doctor said she would like me to consider coming off the Tramadol. Indeed my feeling rightly or wrongly was that it didn't do a lot for me and so I was really quite happy to consider this. So, no more Tramadol ER and I started right away to wean myself off it, haven't had any Tramadol for the last 5 or 6 days.

I also brought up the issue of the Cocodamol 30/500. It has always concerned me about the intake of the 500 of paracaetamol as it does nothing for RLS but does affect the organs. (I think it is supposed to make the codeine work more efficiently??). She agreed to change me over to Codeine Phosphate and I've been taking it at the same time as coming off the Tramadol. I have 10 pills of 15mg codeine per day with her hoping that I can get away with 8 or 9 pills. (plus ropinerole)

To date I'm minus the paracaetamol and the Tramadol.
I do think there has been a little more breakthrough of symptoms but I'm getting by .... Just about. To be expected really with the Tramadol gone and no increase in the Codeine to cover it. And I do feel emotionally good to have reduced my meds intake by two that were on the list.

Sorry, this post has become longer than I intended but I felt the background is useful information and relevant to Views' comment above when I say - Doctor told me to hand into a pharmacy any Cocoamol 30/500 that I might still have in my possession. Yes, like that's gonna happen! It is so useful to have a few extra when certain circumstances arise, an air journey, the movies, a social setting where we really need to be able to sit at peace. It's called trying to achieve some 'quality of life.'

There also was a time very recently when I ran out of a couple of days Co-Cod and my dear friend had some Co-Co 10/500 because hers made her puke. We have spoken at times here on the discussion board about the security of having a stash, my stash had been depleted completely.
I now have a stash and don't feel so vulnerable.
I don't advocate that any other person should do this regarding a stash, but it is what I did.

As Views states above..... ""hoarding medications, trying crazy things, and potentially doing things that could cause harm, all because we are so desperate"" ----- I hold my hands up.
Betty
http://www.willis-ekbom.org/about-rls-wed/publications
Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation

Rustsmith
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Re: RLS Patient Symposium

Postby Rustsmith » Fri Oct 05, 2018 6:05 pm

Betty, my recent experience is somewhat similar. When I changed from methadone to Tramadol ER, my methadone stash was now much less useful and I didn't have any extra Tramadol. But I quickly found that I needed a higher dose of Tramadol, so my GP was willing to write another prescription for the higher dose. I had not finished the first batch, so now I have a few extra of the lower dose Tramadol as backups. As for my methadone stash, that stays inside my safe because my neurologist has already said that she intended to switch me back to it when I see her in January.
Steve

Augmentation Evaluation http://bb.rls.org/viewtopic.php?f=4&t=9005

Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation, and are not medical advice.

Polar Bear
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Re: RLS Patient Symposium

Postby Polar Bear » Fri Oct 05, 2018 8:32 pm

Steve, our meds are so precious to us. They are what lets us retain some notion of sanity.

The last time I acquired a stash was under similar circumstances. Long may there be occasional circumstances.
Betty
http://www.willis-ekbom.org/about-rls-wed/publications
Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation

2BassetMom
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Re: RLS Patient Symposium

Postby 2BassetMom » Sat Oct 06, 2018 8:19 am

I was without a stash until recently. I am on oxycodone 7.5/3.25 that I take midday. I found that I often was taking it also at 4:00am because of pain and rls. My PA prescribed enough for me to take 2 a day if needed so now I am building up a small stash. I feel better having that. I helped me through a painful period with an infected tooth that I am having extracted on Monday, eek! I agree that our meds give us some sense of sanity in this crazy syndrome.

badnights
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Re: RLS Patient Symposium

Postby badnights » Thu Oct 11, 2018 8:17 am

Well, here are my notes, such as they are. They are organized by talk, but I have lumped similar talks together (there were a number on iron, for example). Very important: I didn't make notes on everything, I didn’t try to summarize the talks, in fact I only made notes on things that tweaked my interest. I didn't write down things I already knew. So these notes may not be useful to you.

CONNOR - iron and the bbb
Connor talked about iron and the bbb (blood-brain barrier). (The bbb is the layer of cells that comprises the walls of capillaries in the brain, and which separates blood from cerebrospinal fluid (CSF)). The old thinking on how iron crossed the bbb was overly simple. Experiments show that iron-deficient CSF somehow signals the cells of the bbb to send more iron across the cell membrane into the CSF – but this signalling does not happen in WED/RLS. Big question Dr. Connor wants to answer is WHAT is that signal, which is missing in WED/RLS

Also, what can be used as a predictor of response to iron infusions in WED patients? Serum (blood) ferritin levels don’t reflect CSF (brain) ferritin levels, and don’t predict how well you will respond to infusions. But hemoglobin levels in the blood might be a predictor of brain iron uptake.

ONDO – iron infusions & new meds in development
Infusions
About 5 different compounds can be used, all are equally effective for anemia, but not for uptake into the brain; only two work for that: ferric carboxymaltose and LMW iron dextran (has to be LMW = low molecular weight). Most studies have been done on the former; evidence of the latter working is mostly anecdotal.
Ferric carboxymaltose: 2/3 of patients saw a benefit at 4-6 weeks, 1/3 later (I assume that’s 2/3 of the patients who benefitted). 500 mg was not effective, 1000-1500 was. There was no correlation between beginning serum ferritin levels and derived benefit. About $1000 per treatment. More than one treatment is usually necessary, spaced months apart.
LMW iron dextran: 1000 mg dose is used.
New drugs in the pipeline:
  • ecopipam, a D1-receptor antagonist (our cells have 5 different types of receptor for dopamine, called D1 to D5), the thinking is that the number of D1 receptors increase in augmentation so blocking them might stop augmentation; there are very few D1 antagonist drugs, ecopipam is one; currently being tested for Tourette’s (Ondo is involved in this study, which finished last week but results not analyzed yet). From Wikipedia, it has been shown to reduce gambling behaviors in subjects with pathological gambling, and to be an effective treatment for obesity but not useful because of side effects of depression and anxiety.
  • dipyridamole – an ENT1 inhibitor which indirectly reduces adenosine; adenosine might be elevated in WED causing a cascade in which glutamate gets elevated which messes with dopamine etc; 100-400 mg; a very small human trial was done, not blinded so not as reliable; this is the med that stjohn and legsbestill are trying
  • a partial D3 agonist (sort of like the existing dopamine agonists)
  • an inhaled L-dopa
  • pitolisant, a histamine-3 inverse agonist, sort of does the opposite of an antihistamine, increases the release of histamine, being used for narcolepsy in Europe and in trials for treatment of hypersomnia.

MORE ON IRON FROM SATURDAY Q&A
Oral iron: there is no danger in taking it unless you are susceptible to hemochromatosis.
IV iron in WED: has never been associated with iron overload. Ondo’s cutoff: serum ferritin of 250 or less. Earley has no worries giving IV iron to people with serum ferritin up to 500. Over 1000 is not good. Ferritin can be falsely elevated but is never falsely low. An infusion of 1000 mg will raise someone’s serum ferritin by about 150 mg, and the goal is to place someone into upper 300’s, so he will easily give infusion to someone whose ferritin is 200 or even more.

ALLEN - iron
Goals of iron treatment are to increase brain iron and reduce WED symptoms
Test your iron status after a 12-hour fast, if there is no inflammatory disease present, and repeat after any change in symptoms.

Iron numbers in a WED patient who might benefit from infusion (I think this is what they were talking about):
- serum ferritin 75-300 (different people have different opinions)
- iron 30-160
- Transferrin saturation 20-45 (must be less than 45 or 50 otherwise danger of iron overload)
- TIBC 210-450
- hemoglobin less than 13.5 in males, less than 12 in females
The consensus guidelines say ferritin should be below 100 before initial infusion, but this was a compromise among those like Earley and Allen who think it can be as high as 300 (6 people received infusions at ferritin of 300 with no problem), and some who wanted it even lower than 100. Earley and Allen are confident that the guidelines will be changed in the future once more testing has been done, to say ferritin should be less than 300, instead of less than 100.

Repeated treatments work, but ferritin should drop below 300 for a repeat treatment. Earley says (in Q&A session) he feels there is no chance of hemochromatosis in WED patients with ferritin up to 500.

Response to IV iron for WED patients is only 60%

WED people lose iron in the brain but not the periphery (blood, etc). A mouse model of this shows that giving IV iron raises iron ONLY in the parts of the brain that were deficient, thus no iron overload.

MY PERSONAL CONVERSATION with Earley and Allen – Iron
If I stop taking iron pills for 1-2 days, my transferrin saturation will drop below its current 45. If I stop for (unknown amount of time), my ferritin will drop below 100 (it is currently about 120). These changes will put me within the limits acceptable for iron transfusions as per guidelines for RLS.

Q&A SUNDAY - Iron
You can be severely iron deficient but not anemic. Red blood cells will suck iron out of everywhere else to ensure they have enough - - thus they are the last thing to be missing iron
The diagnostic code for iron disorder is E83.10, which is what your doctor should write so insurance will cover an infusion (in USA).

Any divalent metal will compete with iron to be absorbed, so don’t take iron with zinc or calcium or magnesium bearing foods.

Iron will help excema, alopecia, immune system (less colds, ear infections, etc); in kids with WED who have been deficient, iron can cause a growth spurt.

ONDO - Genetics
there is a strong genetic component to WED but it is not entirely genetic – 50-60% genetic, the rest is environmental factors (i.e. (my addition) even if you have the genes, you’re not doomed to have the disease).

Types of genetic studies:
Linkage studies: commonly done 20 yrs ago. Take one family, separate genetic material, and look for areas of chromosome that correlate with presence of WED. Effective, but each area contains hundreds of genes. A number of areas have been identified, but no one has identified a specific gene from any of these studies.

Genome-wide association studies (GWAS): done today. Requires thousands of people. They identify genes that increase risk by a small amount. They look at specific SNPs (single-nucleotide polymorphisms, ie, mutations). Huge study identified 19 specific genes including the well-known MEIS1 and PTPRD which are risk factors for WED. (– Mice without normal MEIS1 lose their circadian pattern. ) Most of these genes are known to be active when the fetal brain is developing, the rest are involved in repair of DNA.

Exome-wide sequencing: Newer. Sample from a single person. Separate out all the genes that encode for proteins (this set of genes is the exome, as opposed to the entire set of genes which is the genome). Map out all the millions of base pairs and look for mutations. Very few studies have been done but this method has lots of promise.

EARLEY – Genetics
5 genes correlate with WED symptoms – key questions to solve are What is the relationship among thse genes, what do they have in common with WED?
From Q&A SUNDAY: BTDB9 is now reported by 23 & me.

BAINBRIDGE – Alternative therapies
Things that have helped in some trials:
- acupuncture
- aerobic exercise with leg resistance
- transcutaneous DC stimulation of thespine
- pneumatic compression devices on the legs
- repetitive transcranial magnetic brain stimulation
( Her slides will be better than my notes)
There is promise in studies of the brain-gut interaction

Cannabis: industrial hemp has (by definition) less than 0.3 % THC but can have high CBD which has the medicinal effect (THC causes the high ) – but some amount of THC may be necessary to enable the medicinal effect of the CBD and no one knows how much
- epidolex is a cannabidiol newly classified by FDA as Schedule 5 drug (easy to get at)
- Dosing for inhaled THC: 7-18 mg is a medium dose.
- Although THC and CBD can be absorbed thru the skin and might therefore be effective for topical pain, it is unlikely they will reach the central nervous system by this route therefore unlikely to affect WED or sleep this way.
From Q&A SUNDAY: Inhaled cannabis works in 5 minutes but only lasts half an hour. CBD oil is good.

DURMER – TECHNOLOGY
Apps that make your screen go orange in the evening are not very effective
Orange/amber glasses that remove blue and green light ARE effective
There is an app for conductive auditory stimulation that might help you sleep

PARUTHI – kids, pregnancy, renal
- Most WED kids (80% in her practice) respond well to oral iron. The rest respond to 25-50 mg gabapentin.,
- Instead of Relaxis, try an office-chair vibrating pad.
- MEds to use in pregnancy are iron, L-dopa, low-dose clonazepam, and "opioids”. After delivery, the above plus gabapentin.
- 4-6% of renal transplant patients still have WED after transplant (my note: this is comparable to incidence in the general population)
- kidney failure causes iron deficiency

KOO – PLMS
gabapentin and iron can work with PLMs as well as with WED

Q & A SESSION, Saturday
Brains can’t be donated to RLS Brain BAnk because each brain costs $8000 to store, and Foundation cant afford that. Instead, donate your brain to Neuro Brain Bank of NIH and designate your disease as RLS/WED, but there is unfortunately no assurance that it will be used for WED/RLS research. Complete the paperwork before you die. 1 800 BRAINBANK

People with WED generally estimate the amount of sleep they’re getting accurately, whereas people with insomnia routinely underestimate it.

BUCHFUHRER – DAs, Augmentation ,ICD, α2δ’s
Augmentation and DAs
depressed people on DAs are more likely to get impulse control disorder (ICD). Moore(2014) suggested that DAs need a black box warning for ICD.
Instructions to all doctors: Whenever a patient requests a dose increase who has been on a stable dose for 6 months or more, consider it to be augmentation unless it can be proven otherwise. (Other things it might be: medications, low iron, comorbid conditions, change in lifestyle, increased stress/anxiety/depression.)
Augmentation might happen because dopamine binding to D3 receptors cause upregulation (increasing numbers of) D1 receptors.
Augmentation happens at a rate of about 7-8% of DA patients per year, so a 10 years, 70-80% will have augmented.
There is some indication (unpublished) that once a patient has been on DAs, she/he will not respond as well to α2δ’s.
Treatment of augmentation: some doctors recommend a 10 or 12-day washout, then see if any medications are needed. The amount of opioids needed will probably be less than if no washout had been done.

Alpha-2-delta anti-convulsant meds:
Initial dose of gabapentin for people less than 55 is 300 mg
55-70 yr olds is 200 mg
over 70 is 100 mg

Transporters that take gabapentin from gut to blood exist only in one small section of the small intestine, so they fill up fast, so taking a higher dose at the same time might be a waste.

Horizant uses high-capacity transporters available throughout the bowel so it is absorbed better. It is best absorbed with fat. It is not the same as gabapentin – the peak effectiveness takes longer to arrive and lasts longer. FDA says 600, but 1200 and even 1800 can be prescribed.

Lyrica 300 mg worked as well as Mirapex in some studies. Starting dose 75 mg for people up to 70 yr old, 50 mg for over 70. Increase by the initial dose every 5-7 days until an effective dose is found. Max 300-450 mg in the evening, 600 mg daily. If patient has renal impairment, adjust the dose or split in two.

EARLEY opioids
Opioids are effective on both the sensory and akathisia portions of WED as well as the involuntary motor movements (PLMs).
WED/RLS does not have the same underlying pathophysiology as pain! There are opioid receptors throughout the body and not all of them have to do with pain! – some are involved with motor functions, learning, reward.
There are four parts of the brain involved with pain that have less opioid receptors in WED than in normal brains.

The terms high and low potency opioids refer to the effectiveness of an opioid in dealing with pain, and are absolutely irrelevant to how they deal with WED sensations

Pentazocine 50 mg pill works black and white – really well in some people and not at all in others. Only one company makes it anymore. (In Canada, my doctor tells me, it is only available as an injection.)
Beth - Wishing you a restful sleep tonight
Click for info on WED/RLS AUGMENTATION & IRON
I am a volunteer moderator. My posts are not medical advice. My posts do not reflect RLS Foundation opinion.

Polar Bear
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Re: RLS Patient Symposium

Postby Polar Bear » Thu Oct 11, 2018 4:22 pm

Beth, thanks for this. I will come back on it to read it properly. Already, with just a glance at Earley's opioids I have learned....
The terms high and low potency opioids refer to the effectiveness of an opioid in dealing with pain, and are absolutely irrelevant to how they deal with WED sensations
Betty
http://www.willis-ekbom.org/about-rls-wed/publications
Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation


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