RW Yes, please send me anything you have regarding fevers and Tysabri. I am VERY curious.

Vic Sorry to hear it Vic. Are you going to do graphs with the Rebif? That would be interesting too.

Absolutely, Natalie.

I have had time to refine my analysis and collect the data necessary for a reasonable evaluation.

The graphs and analysis will be posted in a Rebif Log here at NT.

-Vic

# 20 DONE!

As usual, no problems, no concerns, scheduled infusions for the next 6 months.

Saw the doc afterwards and had a great discussion after my appt.

#1- my bloodwork showed elevated WBCs. He said this is normal with Tysabri due to the mechanism of action and that if you have inflammation, you will run a fever even if you don't notice it, and MS has inflammation associated with it (lesions!) and that it shows the Ty is doing it's work.
( For Natalie)

#2- ordered an MRI and had to have bloodwork because the MRI peeps are checking everyone before they will do a contrast study (NSF-nephrogenic systemic fibrosis associated with gadolinium). Also ordered the usual liver panel.

#3-talked about the new case (US) of PML and he says he is not prescribing Tysabri for anyone who has been on chemo, novantrone, cellcept, methotrexate, etc. Too big of a risk, drugs stay in system too long, thinks that there will be more neuros prescribing Ty as first line therapy because immune systems are intact and no exposure to strong immunosuppressants, etc.

#4-talked about the EU pts and specifically #2 pt who was in very bad shape with IRIS after the plasmapheresis treatments and mefloquine (antiviral used primarily for malaria)
http://en.wikipedia.org/wiki/Immune_...atory_syndrome


He'd had a look at the MRI from this pt and said the MRI of the PML was a walk in the park compared to the IRIS MRI and that we'd be hearing a lot more about IRIS in the future.

He said that there are studies going on right now with pre-treatment with Remeron http://www.drugs.com/remeron.html and Cyproheptadine http://www.drugs.com/pro/cyproheptadine.html because both of these drugs are 5HT2a blockers and inhibit the movement of JCV into the cells. In addition they are relatively cheap and very effective since they close the door on the JC virus.

All in all a very good (and informative!) appt, although long!

I'm off to bed! LONG LONG DAY!

RW
Thanks so much for all of this extremely useful information. It sounds like your neuro is really on top of things. So he was saying that inflammation in the brain from MS can cause fever? And that the Tysabri takes the inflammation away, along with fever? Very interesting.

What is NSF-nephrogenic systemic fibrosis?? What is the bloodwork test they are doing?

The treatment with Remeron would be given if you showed signs of the JVC virus?

Again, awesome information!! Sleep well!

That's the way I read it too . . . but you said that you are getting an increased fever only AFTER the infusion . . .

If that is what Tysabri is doing, why wouldn't the infusion reduce the inflammation/fever rather then increase it?

Cherie

I went into detail in your PM about the WBC and the BBB Natalie.

NSF is a disease that has been noted in some folks with kidney problems after use of gadolinium. You may see some commercials on TV from ambulance chaser lawyers about this. Evidently a lot of MRI companies are now testing for kidney problems before using gad now. I think the testing is like shutting the barn door after the fact for those of us who have had numerous MRIs with contrast.

The Remeron, cyproheptadine and mefloquine are very inexpensive antivirals or in the case of Remeron, used to treat depression but has anti viral qualities.

The BBB is supposed to be impermeable. Rogue T cells and WBCs are what gets by when the BBB loses that impermeability. Tysabri acts to block the T cells and the WBCs from crossing the BBB, restoring the BBB to impermeability. WBCs are the signal that there is inflammation. The body sends them out to fight it. That's why lesions are created, the WBCs are fighting the rogue T cell damage. We don't know why those T cells go rogue or why they are able to get into the brain or why the BBB opens. Tysabri doesn't block them all but it stops a lot of them. That is why some people still have relapses and lesions. There is still damage going on in many cases.

I am looking forward to seeing my new MRI when it's done. I had a really good one at 6 months. I am hoping that after 20 infusions I see more improvement. My last one showed no new lesions, no enhancing lesions and many of the large lesions were gone or greatly reduced in size.

I haven't had a relapse since I started and that for me, is the greatest benefit! I was cycling through every three months or so and to be able to see straight and clear, to be able to walk in a straight line without balance problems and dizziness, to be able to do most of what I did before MS is truly a benefit. It may not be a cure, but it works for me.

(now if I could only get rid of the spasticity and stiffness...That damage is IMO, directly related to NOT being able to have Tysabri when it was off the market, causing damage that has not repaired. I still have hope for that problem, when I look at the data on famipridine (4-AP))

The way I've read it explained before (but it was in reference to how they thought PML was occurring with the use of Tysabri) . . . Tysabri's mechanisms are based on the belief that Multiple Sclerosis is caused when T-cells (which are the soldiers in the immune system), "mistakenly attack the lining of nerves in the brain. Without this lining, cells stop functioning and die. Tysabri works by preventing the T-cells from entering the brain. (But those same T-cells normally keep the virus that causes PML in check. If that virus, which is dormant in most people, is allowed to run rampant, it damages or destroys the brain)."

So, I see where you are coming from with the explanation on Tysabri managing new lesions/inflammation, etc. and how it could be effective for that purpose.

The part I'm still confused about though is how an infusion would seem to be CAUSING a fever for Natalie. While I can see how Tysabri might be controlling the inflammation from causing more inflammatory lesions (which is perhaps why she had so many fevers before Tysabri, and isn't now), I still don't understand why is it that every time she has an infusion she seems to get a fever for a few days?

Cherie

Idunno... my brain isn't focusing.

Maybe a mild tooth infection? Maybe it's why they often prescribe tylenol along with benadryl before infusion? Maybe there's something else going on? Maybe it's all those WBCs signaling the body that fever is associated with immune response?

Maybe you can find the answer? I'm just too tired and I have to work a ten hour OT shift tonight. I'm going to bed...again

Yes, I see what you are saying about the use of Tylenol, perhaps because Tysabri would "appear" to cause fever for many people (not just Natalie).

If that's the case (it's "normal" to get a fever), I guess it doesn't really matter what the mechanism is that "causes" it. Everyone is still doing well . . . so it's all good.

Sleep tight.

Cherie

Hi Cherie,

I was having continual low grade fevers from the time I had mono until I was diagnosed with MS (about 1 year and 8 months). There was a break in between at one point. My theory is that the mono may have tripped the MS switch and then the lingering fevers became just a symptom of the MS. No one could figure out what they were coming from--my rheumatologist at the time of the MS diagnosis consulted with a well known MS specialist and he said he had seen some patients with low grade fever. Even so, I just assumed it wasn't from the MS but some sort of left over chronic fatigue syndrome or post-viral syndrome from the mono. But then I went on Tysabri and a few times I would get a fever for 2 days after the infusion but the general long term fevers (usually weeks at a time, and a little higher) completely went away. It was so strange. My temp went down to below normal -- 98-98.2. It was heaven because I felt a SO MUCH better. So the little and low 2 day fever after the Ty. infusion is very different than what I had before. I have no idea what it means but it doesn't phase me since most of the time I no longer have fevers which is a godsend! I will ask my neuro next month about why I get the little fever afterward. Maybe it because of a mild over suppression of the immune system the first couple of days (higher amount of Ty. in the blood)??? But that doesn't explain much. Although, I've only had 5 infusions and I've heard you don't reach steady state medication in the body until after 6 months.

Natalie