Beyond Avonex and Valtrex

[NHE]

I'm looking at dimethyl fumurate. What influence would that have on those tests?
The reason I picked that is it most similar in activity to my way of thinking? In particular it downregulates Th1, is antioxidant and not really an immune suppressant.

This is a myth. Dimethylfumarate is a strong oxidant that attacks thiols such as can be found on cysteine. Please see http://www.thisisms.com/forum/tecfidera ... ml#p210473 It also depletes glutathione. http://www.thisisms.com/forum/tecfidera ... ml#p215248 Lastly, the prescribing information indicates that lymphopenia is a common side effect. http://www.tecfidera.com/pdfs/full-pres ... mation.pdf

[Scott1]

OK! Quite a lot of mice and dogs but not a lot of humans.

How would you deal with this? I'm almost inclined to stay as I am and see what happens.
It looks as though the lymphocyte count at the start is a predetermining factor.
Regards

[NHE]

OK! Quite a lot of mice and dogs but not a lot of humans.

Fumiderm, which is a very similar drug, has been widely used in Germany for psoriasis. In 2010 Fumiderm grossed $51 million for Biogen. http://www.thisisms.com/forum/post19904 ... ny#p199045

In addition, it was reported that patients experiencing lymphopenia had better outcomes with respect to their psoriasis than patients that did not have lymphopenia. http://www.thisisms.com/forum/tecfidera ... ml#p198425

Reversible leucopenia, lymphopenia and transient eosinophilia are also frequently observed [2]. Leucopenia occurs in a quarter of patients [8,29]. A reduction in lymphocyte count occurs in around 70% of patients [6,8,25,29] and can exceed 50% in about 10% of patients [4]. The dose of Fumaderm® should be reduced if lymphocytes fall below 0.5x109/L or leucocytes fall below 3.0x109/L; if blood counts improve, treatment can continue at the reduced dose, but otherwise Fumaderm® should be stopped [9]. It has been reported that patients with lymphopenia are significantly more likely to show improvement in psoriasis than those whose lymphocyte count stays within the normal range [6,22,24].

[NHE]

How would you deal with this? I'm almost inclined to stay as I am and see what happens.

I have yet to formulate a position on Tecfidera at this time. Early on, it was thought that that dimethlyfumarate acted as an Nrf2 activator. However, I suspect that it's more complicated than that. Nrf2 activators are great though. There are plenty of natural Nrf2 activators and I'm sticking with those for now. Here's a free review paper discussing natural Nrf2 activators.
https://www.thieme-connect.com/products ... 088302.pdf

[Scott1]

Thanks,
It's like choosing a drink when you don't want one of any sort.
I am feeling better, albeit in waves. The prednisolone and beta blockers take a bit of adjusting to. I've concluded the steroidal part and I think Th1 is back in its box. The heart issues take longer but it looks like I didn't do any real damage in the long term. The AF greatly increases the chance of clotting so for a while I was a walking time bomb. I will need to take a very sedate wind back over some months but it looks like they think its the attack at work rather than a structural problem. Thank goodness.

Nrf2 has got me wondering. I can see positives in the fumurate but I think the lymphocyte count will be critical. I saw one Wikipedia note that said BCL2 was upregulated and that rang alarm bells big time with me. The Dimethyl fumurate almost looks best as a quick fix close to an attack and then roll off it and switch to the likes of curcumin or EGC from green tea etc. Does it look a bit like that to you?
I'll probably see the neuro tomorrow as I am still in rehab for the numbness (so boring!!) and ask him about the b12 stuff.
I still think I will make a full recovery but my hands and some hug effects are still quite evident.

Regards

[Anonymoose]

Sorry for the off topic but the curiosity is killing me. Did you have an MRI and if so, how did it look? Also, does rehab help numbness? I've always been doc-phobic so just muddle through exacerbations on my own but if rehab can help... What therapies are they doing?

[Scott1]

Hi,
They took a 45 minute MRI of my spine and spent 20mins on my brain. I haven't seen the reports but want to get the details. The neuro did say the numbness in my hands is consistent with one of the lesions.I want to be able to show my Osteo and Pilates people where the damage is so they can plan for it. This will be very important with Pilates as the girl I see really knows her stuff (Olympic medallists and major sports teams) and she is my friend so we can talk very openly which helps.
So far I have had only one rehab because I came in at the end of the week. It was very basic and wasn't even a proper assessment, more filling in time on a weekend. Today they will start me on a twice a day program including hydro in a pool.
The only interesting thing so far was making me lie on the hottest of hot towels as a muscle relaxant. It seemed to make a difference the next day but didn't last.
I hope the neuro comes in today. My body is screaming out to go back on the Q10 as my energy is starting to deplete. I'm not fatigued but my battery runs down too fast and I then need to sleep
Regards

[Anonymoose]

Thanks. It will be pretty neat if the only changes from your last MRI is a couple of new enhancing lesions. One can dream.

So let me get this straight. They hospitalize/rehab you for a relapse involving hand numbness and the hug? I'm beginning to feel quite the dunce. Who knew?!

Hope you can break out of there soon.

[Scott1]

They see it as left sided impairment for rehab which they are confident about. I think I have been in bed too long, the bowel gave me hell this morning! better now I hope.
What totally freaked them was the AF. The lesions on the MRI and the obvious numbness are the triggers that got me into rehab. I think I need the TLC at the moment. The physios love my Pilates background because I know what to do and what to discuss. Its like going on a camp without privileges.

Regards

[Scott1]

Hi Anonymoose
Just seen my MRI results-
Spine -"multifocal T2 hypertense lesions within the cord especially C2/3, C7, T8 vertebral levels. These findings are in keeping with primary demyelination. No expansion of the cord. Background minimal multilevel degenerative changes within the spine. plus a few bulges. Pretty good by the sound of it but I am still sore.
Brain - "Multiple periventricular, subcortical white matter T2 hypertense lesions with some of them showing central cavitation/necrosis. Some of the lesions in the periventricular region are orientated perpendiculary. The right posterior periventricular lesion shows minimal restricted diffusion. A few T2 hypertense lesions are also noted within the pons and the left middle cerebellar peduncle. No infacts or haemorrhage. No hydrocephalus.
Conclusion - Multiple T2 hypertense lesions within the cerebral white matter and supratentorially are likely due to primary demylination, Some of the lesions show central cystic change/tumefaction. These lesions have progressed when compared to the previous study from June 2011.
Pretty good seeing I have had a decent attack.
NHE
Getting B12 etc results soon. Even the professor in charge is interested.

Regards

[Scott1]

I've elected to try the dimethyl fumurate. I read the FDA review plus this clinical note. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972027/
It fits with my thinking. I will still take valacyclovir, green tea extract, curcumin Carrot juice,Q10, magnesium, zinc and probiotics but will think about L-arginine before deciding as I might be double loading.
The bottom line is I had an attack I didn't expect (although I was thoughtless) and I can see Th1 needs to be under control. I intend to post what happens so we improve our knowledge. I think the rest of my views are quite valid and stick by them. Whatever the reason our immune system does behave inappropriately at times and needs to be watched. My view is still hinged on the early problems as neonates with megalin but how can we prove it? The lack of vitamin A synthesis exposes the gut to be leaky and once we have pathogens we are locked and loaded on some pathway or other. My problems this time stemed from peptidoglycans and identifying the culprit will be hard. I'll continue Zinnat for some time to lower that load.
Peroxynitrite in my view is the cause of fatigue so it's still necessary to limit its production by lowering iNOS and superoxide from EBV infected B cells.
The Th1 activation is just bad news. You just don't want all the metabolic issues At work when Th1 is activated.
I did 10 years on Avonex and hated every dose so hopefully this is easier. We will see.

Regards

[Anonymoose]

Ugh. Aside from being useful and informative, I hate MRI results, don't you? Looks like you've had a doozy. I didn't realize you had been having mris all along. Were they stable prior to this recent attack (was your regimen working in that regard?)? I wonder if that even matters as I've heard of people with nightmare mris that don't seem to suffer much disability.

Best of luck with the tecfidera. Do you plan to keep an eye out for possible complications...things that might impact the aim of your protocol? The frustrating thing about bg12 is it's so new, not a lot of its effects have been studied.

Did they let you have your q10 back yet?

[Scott1]

I don't mind MRIs. Close my eyes and go to sleep is my usual tactic. As I can't influence them as may as well just chill out. My MRIs aren't that bad. Don't forget that's straight after an attack 20 years after the first episode. Over the years I had some that showed signs of improvement. The comments on my right sided pontial lesion are better than my original MRI result. I do think I'm on the right track but stuffed up because I didn't think about peptidoglycans.
I certainly will watch the tecfidera, particularly the lymphocyte count. In the Krebs cycle, fumurate is interesting; the oxidation of succinate to fumarate is the only Krebs reaction that takes place on the inner membrane itself. The other reactions are catalyzed by soluble enzymes. Fumurate links the citric acid cycle and the urea cycle. When argininosuccinate splits it forms arginine and fumurate. On that basis I should think about still taking L-arginine but I want to be sure.
They said ok to the Q10. The whole fumurate step really depends on it as a transport agent. (I don't think they know or remember that)
The BG12 was invented by a german scientist to deal with his psoriasis about 1958. I guess that's long enough to observe reactions in that population. The use in MS is accidental because it seemed to work with people who had both problems.
My wife brought me an empty container with the Q10. I sent her way to have another go. Hopefully I start that today.
Regards

[Scott1]

Looks like I was right on the psoas being affected. The physios say its really tight. I swear when they hit pressure points to release it!

[NHE]

Getting B12 etc results soon. Even the professor in charge is interested.

That's great! I look forward to hearing about your results. Are they testing folate as well, or just B12, homocysteine and methylmalonic acid? RBC folate has a range of 499-1504 ng/mL and mine was 400 ng/mL. Just another in a stack of problems. Note, I've been taking a sublingual B12 + folate supplement, but haven't had folate retested yet.