Follow-ups

Here is the latest on recent experiments I’ve tried:
 
 
At my next appointment, my doctor explained to me that dosage as high as was required for this protocol was not (yet?) available in this country, but taking fistfuls of the lower dose capsules as I was, was doing more harm than good.  With it, I was also ingesting more fillers and coatings daily than was safe.  
 
He said if I could find a compounding pharmacy I trusted (referring to a recent incident in SF that had exposed one being run solo by an older pharmacist who had made a life-threatening mix-up), he would certainly write a prescription for me to take there, but he also said that there was still no definitive proof that dosages that high made any difference in the disease.
 
I decided that improvements I thought ! had to my bladder could just as easily have been psychosomatic and in deference to my mobility, I decided to abandon this test for now.
 
 
I’m always hopeful about dietary changes, but I’m also easily discouraged when I can’t see immediate changes. When you think about that for a minute, you recognize how incongruous this is. This has proven to a silent, behind-the-scenes, slow-building disease (in my case, anyway); why should I expect dietary “tweaks” to make a quick, discernible difference?
 
On the one hand I say “No one cares about you as much as you do” suggesting that you can’t whole-heartedly trust medical advice, that you may be the exception to any rule, so if it doesn’t threaten your life, try whatever makes sense to you.
 
But on the other, whenever I’m giving up on diet, I go back to the standard belief that  “no specific diet has shown any long-term benefit.”
 
So ultimately, I rely on how it makes me feel.  In this case, the idea sounds good, but it has proven to be difficult to put into practice at this time. Making kale smoothies in my “mini-kitchen” is hard. I know I could set up a process to make it easier, but I guess part of me doesn’t feel it’d be possible to sustain.
 
 I decided to have a kale smoothie whenever I can, but not to go out of my way to insist on it daily for now.
 
 
This is still the situation for me.  That the jury is still out.
 
I read a disappointing article here. It reports that some researchers believe that “the drug is nothing more than an ‘expensive, overdosed version of Rituxan’…” That it was approved solely because the original was going off-patent, so the manufacturers raised the dosage level and ‘surprise!’: new test data.
 
I guess I don’t want to believe that is true, that it is a crass money grab at the expense of patients. But I also recognize that big pharma has every incentive to make money and little incentive to find a cause, much less a cure.
 
The silver lining that I stumbled across in reading this article is mention of the GRIT Freedom chair!  More to come on that!
 
Related stuff
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Recent MS studies

On SIRT1 and nanoparticles

Recently, some exciting M.S. research results were forwarded to me by friends.

In May 2013, results of an M.S. study was reported in Inside Stanford Medicine, a publication by the Stanford University School of Medicine. The study itself, entitled "Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain” was published in the journal Nature Cell Biology (Nat Cell Biol. 2013 Jun;15(6):614-24).

Usually, the protein SIRT1 is considered to be beneficial for health. However, in M.S. and other demyelinating diseases, inactivating it seems to show that it then stimulates the production of neural stem cells that make the myelin sheaths.

The work suggests that SIRT1 may normally limit the production of myelinating cells after childhood development and that it has to be inactivated to again allow the production of these cells.

These researchers think that eventually it may be possible to induce the brains of patients with M.S to heal themselves by blocking SIRT1. Of course, lots more research is needed. 

Another trial, "Antigen-specific tolerance by autologous myelin peptide–coupled cells: a phase 1 trial in multiple sclerosis" (Sci. Transl. Med. 5, 188ra75 (2013) suggests that reintroducing a patients' white blood cells back into the body, like a Trojan-horse, secretly carrying modified myelin antigens, results in the immune cells starting to recognize myelin as harmless. It only had nine participants, which is “too few to be called a study” according to our primary doctor, but it does suggest an exciting new line of research.

And nanoparticles, which are cheaper and more readily available than a patient’s white blood cells, are proving to be just as effective as delivery vehicles.

This is good news! I’m really interested in stem cell therapy, and this seems to me to be a way to get it without first entirely knocking out the existing immune system.

So go, go, go!

But researchers still don’t know what causes the disease.

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A tale of two (MS) pathologies

A friend recently forwarded me an article from the Inside Stanford Medicine newsletter. It seems that a small, recent study showed that there may be two different schemas for MS. 

So MSers’ responsiveness to the available therapies, and interferons in particular, might depend on which pattern of MS we have.

This totally fits with my experience: my disease has never seemed to be halted by the meds, or even overpowered temporarily by steroids.  Even chemotherapy didn’t seem to have any effect.

And when my neurologist told me that in his opinion I had transitioned to secondary-progressive, I thought “Well, duh?!  I’ve been thinking that for several years now!”

In fact, this study may be suggesting that I’ve been progressing since day one, that although my diagnosis was Relapsing-Remitting Multiple Sclerosis (RRMS), it may actually have been some progressive form all along.

In truth, once getting this diagnosis 20 years ago, I suspected that doctors often gave the diagnosis as RRMS then they could prescribe one of the first-line drugs for MS that are only approved for this type.

MS medication is so expensive and has required self-administered, regular shots, sometimes as often as every day.

This study seems to confirm for me that giving myself the regular, sometimes painful, shots did nothing to slow the progression of my disease.

And that’s the mystery for all of us: there is yet no way to measure the effects of any of our medicines.  I have no way to measure this, so I only have my gut feeling.

My doctor agreed that the latest medication I was administering faithfully had obviously not impeded my progression, so we agreed that I should stop.

The silver lining is “Yay, no more shots!” 

On the other hand, “Whoa, no more shots. Of any kind.”

He explained to me that prevailing theory at the moment is that MSers who transition from RR to SP eventually reach a plateau and that we can hope that I’ve already reached it.

He did arrange for me to try a new oral drug for MS, A——-, which helps some of the affected walk more confidently.  I’ve been taking it for two months now but have experienced no change.

If the results are replicated by other labs and larger studies, MSers may someday be able to take a blood test at diagnosis to see which type they have.

It’s another small piece of the puzzle.

Related links

Postscript

Readers are now asking good questions based on my last post.
 
Was the improvement of M.S. symptoms shown in all of the patients or only some? Did the panel say how long the improvements lasted? Were there any bad side effects to the angioplasty procedure? Can’t the patient just go ahead and have the procedure even if doctors aren’t sure why a positive change happens?
 
I’ll try to answer them here for all to see.
 
***WARNING: What follows should not be taken as medical advice. It must be considered my opinion. You should always defer to your doctor.***
 
At this point, any improvement in symptoms is all anecdotal. We can’t measure it. There is no way to prove it. So unfortunately we have to consider the placebo effect a possibility. Which is why more trials are needed: to rule this out.
 
If the blockage recurs, we can see that on an x-ray but we don’t yet know what this means. Does this also mean the symptoms come back? Also, there is no established time frame by which, if a recurrence is going to happen, it would have and if it hasn’t, a patient is in the clear.
 
At this point in history, the only tool we have to check in on the progress of M.S. is an MRI (magnetic resonance imaging) scan. But in M.S. this has been an imperfect tool: the scarring that happens on the brain and spinal cord, which we can see on an MRI scan, does not correspond in any way with a patient’s symptoms.
 
Multiple scars are enough to tentatively diagnose the disease, with both visible and self-reported progression over time. But it’s a mystery how the scarring we can see in a scan relates to damage that we can’t see happening deeper in the brain.
 
And just when you think that at least it’s something we can use to gauge disease activity, it disappears. Sometimes what shows up in one scan is no longer visible in the next. I know, weird.
 
Based on an MRI, there is no way yet to tell what is being affected: speech, cognition, mobility, vision, even swallowing. We can have any one of these or all of these, at different times, or at once, or even one incident and nothing more.
 
Can we figure out how to translate what we see on an MRI into discrete symptoms? Or maybe it could be an indicator of symptoms to come? But I digress: this is a separate line of study, maybe for another time.
 
Nevertheless, one of the first questions has to be whether improvement to CCSVI corresponds to the images on the MRI.
 
As far as bad side effects, Dr. Zamboni reports that the angioplasty procedure is safe and well-tolerated, with nothing riskier (yet?) than headache, nausea and possible recurrence. But further reading warns that vein rupture and stroke should also be considered risks. As is permanent nerve pain.
 
A doctor at Stanford was performing his version of this treatment, inserting stents, which have successfully been used to widen clogged arteries of the heart, into the jugular veins of M.S. patients. The problem that developed here becomes apparent when you consider the biology.
 
Arteries carry blood away from the heart and thus go from narrower to wider as they get further from the heart. A stent can break free and travel downstream without causing a life threatening complication.
 
But veins carry blood to the heart. Veins go from narrower to wider as they get closer to the heart. So a stent here can break free and end up in the heart. And it appears to have happened here.
 
This doctor treated about 35 patients, then the treatment option was discontinued because one of his patients died from a brain hemorrhage and another had to have emergency open heart surgery to remove a stent that had dislodged and traveled to his heart.
 
Now the family of the woman who died maintains that she did not die from the procedure but from an adverse reaction to the medications prescribed for aftercare. This may well be, but it highlights again that this is a brand new discovery and treatment. Maybe the aftercare could have been more closely monitored.
 
Ultimately, we expect doctors to both know and fully disclose the risks of a procedure. It is unclear how much warning of risks was given in this instance. It is also unclear to me if that could have even been predicted..
 
The moral I take away from this is that a doctor must balance patient safety with scientific discovery. I guess I have realized that I’d prefer that he or she err on the side of the patient. Then when confronted with all known facts, let the patient decide. Some patients are still willing to be the “first” and assume the unknown risks.
 
I’m not. As an active patient it’s my duty to be pushing for more aggressive treatments and discoveries, but I’m not willing to risk dying or even permanent nerve pain. At this point in my life, I have too much to lose.
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A new next-big-thing

I recently listened in on the live web forum on chronic cerebrospinal venous insufficiency, or CCSVI, hosted jointly by the American Academy of Neurology and the National Multiple Sclerosis Society at the AAN annual meeting.
 
CCSVI is a narrowing or even blockage of the jugular veins, causing faulty blood drainage from the brain that may contribute to nervous system damage in M.S. This hypothesis has been put forth by Dr. Paulo Zamboni from the University of Ferrara in Italy. [Spectacular name!!!]
 
Based on his report on approximately 65 M.S. patients, published in June 2009 (J Neurol Neurosurg Psychiatry 2009; 80:392-399), venous hypertension treated by the standard endovascular angioplasty, seems to immediately improve the M.S. symptoms of these patients.
 
Angioplasty is where a doctor threads a thin tube through a blood vessel in the arm or groin over to the involved site in the vein. Once the tube is in place, the doctor inflates the tiny balloon at the end of the tube to disturb the plaque build-up and encourage it to move outward against the walls of the vein. This widens it and restores blood flow; it is often even an outpatient procedure.
 
In the U.S., early findings of a high prevalence of venous hypertension in the M.S. population seem to suggest that there is an association, but larger clinical trials are needed to confirm that fact. And if CCSVI plays a role in M.S., it is not yet known whether the condition is a symptom or a trigger.
 
There are other questions as well.
 
For example, since CCSVI occurs in many people who don’t have M.S. as well, does this indicate that the condition is just a false clue, an interesting red herring? (For example, I once heard that M.S. and gout are mutually exclusive: it seems that you can only have one but not both. Interesting but not necessarily relevant.)
 
Also, according to one panelist, the venous system has many redundancies. So does this blockage even need to be corrected?
 
He also reports that the blockages in CCSVI are not plaque but fibrous lesions.
 
Also, some patients who have had the angioplasty procedure subsequently have had the venous obstruction recur. What causes this and are there things patients can do to reduce the incidence?
 
Bottom line: this is one of the next big discoveries in M.S. research and the community is anxious to have larger clinical trials.

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Advice to the newly reclassified


I personally think the only reason the doctors differentiate between
“types” of M.S. is to give the patient an idea of what is appropriate
to expect. But because of that, there are drugs that are only approved
for one “type” of M.S. so if a doctor wants you to try one you must
be classified as that type. And it really is such an individual, unique
disease: tell J. not to let the label dictate what she is or isn’t
experiencing.


This is a description from an MS Society booklet called “Managing
Progressive MS” that you can download for free at http://www.nationalmssociety.org/download.aspx?id=314


“Progressive MS manifests itself differently in everyone. Whether
your MS is “secondary-progressive” which followed a period of
“relapsing-remitting” MS or “primary-progressive” meaning it has been slowly
progressive from the beginning, it is important to realize that “progressive”
does not necessarily mean severe disability. But it does mean that there are
few or no relapses, and few or no recovery or remission periods when major
symptoms abate.”


Also see http://www.nationalmssociety.org/living-with-multiple-sclerosis/living-with-advanced-ms/index.aspx


With Tysabri (what you called “the chemo”), tell J. not to worry
about the “multifocal leukoencephalopathy” (PML) at this point.
It has been reported in only a few cases and always with people who were
currently taking other immunosuppressants as well. The National Library
of Medicine reports that “there is not enough information to tell whether
using it alone also increases this risk” and that is because it hasn’t
happened.

The Multiple Sclerosis Quarterly Review, published by the United
Spinal Association and the Consortium of Multiple Sclerosis Centers, reports
that there have recently been reports of liver dysfunction and two cases of
malignant melanoma associated with its use. But it also reminds us that although there continue
to be safety concerns, it is still “the most effective FDA-approved drug
for treating” M.S. Tell her to have
her liver enzymes checked with regular blood tests.


I got Tysabri once when it was first approved and was tired but fine (I always
think that except for this “pesky M.S.” our immune systems are
superstars). But the following Monday it had been pulled from the market
because of the initial PML discoveries. In the meantime I had an MRI and
there was little change so my doctor decided not to resume it for me when it
came back on the market. The bottom line is that there are both risks and
benefits to all drugs and also that chemotherapies tend to have less side
effects in recent times.It has really
helped some people.


Also, I can totally relate to being too proud to ask for help. When OH
was in the hospital and I was spiraling downhill, I was finally able to ask my
mom for help. She was so pleased to be able to do something,
so I think it might help J. to ask if she knows how helpless you feel and don’t
know unless she tells you what you can do that she would really
appreciate. My mom washed, folded and put away laundry, washed dishes,
scrubbed the shower and cooked meals for my freezer for months.


Learning to ask for help is one of the lessons this disease is trying to teach
me.

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