How I solved my neuroinflammation

[stefanosstef]

I am posting this because I have a strong feeling that it can help many others.For me neuroinflammation was/is the worst symptom.
The manifestation is happening in many ways:

• Heavy feeling on head, similar to the feeling I have when I'm sick (which is very rare for the past years).A little more of this is like the feeling of the migraine that is just outside the door.A little more and the peak is a migraine
• Heavy eyelids and red eyes
• Fatigue and mental fatigue (difficult concentrating and processing, delays, memory recall issues)
• Light and sound sensitivity
• Tinnitus
• Dizzyness

There is much information on my journal on how I dealt with this.But I have ommited one very important aspect, mainly because I hadn't realized it.
My big improvement was last year when I was taking pramipexole along with LDN.At that point I hadn't realized that pramipexole has antiinflammatory action on the brain, I attributed all improvement on LDN, which should have this action in theory through endorphins and the opioid receptors upregulation.

When I quit pramipexole the benefit was lost, so I attributed it all to pramipexole and after researching it a bit, I verified that it has antiinflammatory action.This is widely unknown even to neurologists and the studies that have found this are few and small.But the effect to me is clear, I know what neuroinflammation is and I certainly know when I don't have it because I am a totally different person.

After starting pramipexole again I improved, but not to the extend of last year.After a few on/off tests with the addition of LDN I am quite certain now that it is the combination that gives the magnitute of the improvement I'm experiencing.Pramipexole solo would give me a 40-50% reduction.LDN solo would give me a 10% reduction.Together I'm over 80% and I only have short deteriorations when I overexert myself and don't take breaks.

Those 2 drugs target neuroinflammation via different pathways.I have also found that ibudilast, which also uses a different pathway than the other 2, TLR-4 antagonism, is also very effective and acts very quickly.So if I need a bit more antiinflammation or I'm having PEM-induced neuroinflammation, which is quite worse, I would add ibudilast and feel the effect in 2-3 hours.

These things clearly work for me and have turned the game.I have tried numerous supplements and drugs and placebo was always weak on me.Things I believed they would work would fail, and things I had almost zero faith in turned out to be helpful.

I wish more people had tried this so I wouldn't be the only one, then maybe this thread would get sticky because I really believe in this combo.The pramipexole protocol is in my journal but I'll give the dosages here to have a reference:

Pramipexole: 2mg at night after slowly building up in the span of 4 weeks
LDN:1.5-2.5MG at night
Ibudilast: I take it as needed, only on some occasions and the dosage would be 10-15mg.20mg is the upper limit because it causes nausea.

Some other things that had very small but positive impact on neuroinflammation were ALCAR (500-1000mg) and turmeric (1 heaped teaspoon) or curcumin (Longvida).

The other benefit is less fatigue, due to pramipexole's dopamine agonism but also due to lifted neuroinflammation.And a great reduction in the frequency and severity of migraines.I used to have 3-4 per week which were dealt with paracetamol (500mg), aspirin (500mg) and caffeine (65-150mg).

Pramipexole also has neuroprotective effect on the brain, which I very much feel.My brain was in a constant "light storm" which I felt was doing minor damage but long term it would have consequences.Now my head feels like a sunny day most of the week.

Pramipexole is a long term commitment.You need 4 weeks to reach therapeutic dosage and start getting the benefits, until then you are increasing the dosage and that leads to an increase in fatigue.It needs patience.

Also, for Parkinson's patients, there is around 15% risk that it causes DAWS, which means you will not be able to quit it and have to take it for life, or until science finds a solution to this.My situation was such that it wasn't even a dilemma for me, I took the chance.Due to the neurodegenerative nature of PD I believe that this risk might be lower for non PD patients, but in reality I don't know.

If someone wants to quit it should be done very very slowly, slower than the increases of the dosage when he/she started this drug.25% reduction every 2 weeks was my recommendation by an ominous psychiatrist that was very against this drug.I've asked 3 neurologists and all agreed that there is no issue of long term damage from pramipexole, they have worked with this a lot, given it to patients for decades and have never seen the theoretic danger he described (check my journal).

There may be also side effects that are related to inhibitions control.Many PD patients turned hypersexual, addicted to porn or gambling, and ruined their lives.I find that risk low too and never took it seriously, but that might not have been the right approach.Luckily I've had none of this.

I post some studies at the end of the thread.The most interesting are Fawcett's studies for anhedonia (which in my opinion may very well be neuroinflammation and not real depression, since the patients on the study had an average of 6 antidepressants that failed for them, yet pramipexole cured almost all of them).

Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143506/ (Fawcett)
https://pubmed.ncbi.nlm.nih.gov/26844792/ (Fawcett)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143506/
https://pubmed.ncbi.nlm.nih.gov/27825895/
researchgate.net/publication/309724812_Antidepressant-like_effect_of_pramipexole_in_an_inflammatory_model_of_depression
https://www.researchgate.net/public...he_experimental_animal_models_of_inflammation

A recent review of pramipexole in psychiatry:
https://psychscenehub.com/psychinsights/pramipexole-treatment-resistant-depression/

 

[YippeeKi YOW !!]

I have a lot of thoughts, but corralling them right now is waaaaaay beyond me.

Will be back either later today or tomorrow, but in the meantime, thank you for sharing this. I know it has the potential to help a lot of people .

 

[stefanosstef]

A new study that may explain my results with pramipexole:

https://www.healthrising.org/blog/2...erosis-fibromyalgia-chronic-fatigue-syndrome/

 

[stefanosstef]

Another coincidence.A member here also reports LDN working synergistically with low dose Abilify (also dopamine agonist in a way):
https://forums.phoenixrising.me/threads/abilify-stanford-clinic-patients.62807/page-15#post-2302268

I will say again that I think I'm onto something here and have a feeling that it will work on many patients.

Aripiprazole was next to my list if pramipexole failed, but I'm glad it didn't.Aripiprazole has a negative impact on male hormones, even at low doses.It lowers testosterone and increases prolactin.Pramipexole on the other hand decreases prolactin and doesn't affect other hormones.Something to take into consideration.

 

[leokitten]

@stefanosstef could you give us more quantitative information as to how significantly your severity level and symptoms have improved? Can you exert a lot more without crashing? How about PEM? How about sleep and cognitive issues?

I think it’s always important to detail this so others can do a cost-benefit eval of trialing something like this. For example, depending on one’s severity level, they might be more or less open risk, even if the effects aren’t astounding, because e.g. more severe ME even small improvements can be huge for QOL.

But for those who are moderate or mild-to-moderate, sometimes we are looking for treatments that can have a more significant improvement, otherwise it’s not worth the risk. If a treatment only lets me do 10-15% more, it’s not going to change my QOL much.

Also, many of us who aren’t severe are looking for treatments that give enough improvement that we can get back to working more. We are looking to have a bigger exertional envelope and resiliency required to handle working more with more manageable PEM, far fewer crashes, and little to no long-term deterioration.

 

[stefanosstef]

My situation about neuroinflammation is what I described in my first post.Mornings were the worst late night I would be quite better.I could somewhat function, definitely not bed bound and I could work for 4 hours a day with impaired focus.3-4 migraines per week.I could fall asleep and remain asleep but the quality was bad, I would wake up like I was hit by a car.I believe my sympathetic system stayed overly active and my hrv values were indicating that, not normal at all (hrv steady at 45 +-2).

Now when I wake up I am still at my worst but it's incomparable.80% improvement and I feel much more rested when I wake up.

I can push myself quite harder without breaks.But breaks are still important because PEM is unavoidable even now, but it is also reduced by, say, 80% in severity and duration.I am much much more functional and I can go without rests, which is wrong, with very minor consequences.

My ibs-d is also very improved and I rarely need resistant starch+glutamine anymore.Migraines are now maximum 1 per week and quite less intense.

I will measure hrv for the next few weeks and post the results here.

 

[leokitten]

My situation about neuroinflammation is what I described in my first post.Mornings were the worst late night I would be quite better.I could somewhat function, definitely not bed bound and I could work for 4 hours a day with impaired focus.3-4 migraines per week.I could fall asleep and remain asleep but the quality was bad, I would wake up like I was hit by a car.I believe my sympathetic system stayed overly active and my hrv values were indicating that, not normal at all (hrv steady at 45 +-2).

Now when I wake up I am still at my worst but it's incomparable.80% improvement and I feel much more rested when I wake up.

I can push myself quite harder without breaks.But breaks are still important because PEM is unavoidable even now, but it is also reduced by, say, 80% in severity and duration.I am much much more functional and I can go without tests, which is wrong, with very minor consequences.

My ibs-d is also very improved and I rarely need resistant starch+glutamine anymore.Migraines are now maximum 1 per week and quite less intense.

I will measure hrv for the next few weeks and post the results here.

thank you and nice to read!

 

[jaybee00]

Where is this journal? Thanks.

There is much information on my journal

 

[stefanosstef]

Where is this journal? Thanks.

Here:
https://forums.phoenixrising.me/threads/stefanosstefs-journal.78344/