Five years before multiple sclerosis onset: Phenotyping the prodrome (2018) Wijnands et al

[Webdog]

Study:
Five years before multiple sclerosis onset: Phenotyping the prodrome
http://journals.sagepub.com/doi/full/10.1177/1352458518783662

Press Release:
A constellation of symptoms presages first definitive signs of multiple sclerosis
http://www.med.ubc.ca/a-constellati...first-definitive-signs-of-multiple-sclerosis/

During the five years before people develop the first clinically recognized signs of multiple sclerosis (MS), they are up to four times more likely to be treated for nervous system disorders such as pain or sleep problems, and are 50 per cent more likely to visit a psychiatrist, according to new research from the University of British Columbia.

The study, the largest-ever effort to document symptoms of people before they know they have MS, could enable physicians to diagnose the disease – and thus start treating it – earlier

Dr. Tremlett and former postdoctoral fellow José Wijnands found that fibromyalgia, a condition involving widespread musculoskeletal pain, was more than three times as common in people who were later diagnosed with MS, and irritable bowel syndrome was almost twice as common.

Two other conditions with markedly higher rates among people to be diagnosed with MS: migraine headaches and any mood or anxiety disorder, which includes depression, anxiety and bipolar disorder.

The higher rates of those illnesses also corresponds with higher use of medications for musculoskeletal disorders, nervous system disorders, and disorders of the genito-urinary tract, along with antidepressants and antibiotics.

The study, published in Multiple Sclerosis Journal, provides definitive evidence that MS can be preceded by early symptoms – known as a prodrome – that aren’t considered “classic” manifestations of the disease, like blurred vision or numbness or weakness in the limbs. As recently as 2000, medical textbooks asserted that MS did not have a prodrome.

“The existence of such ‘warning signs’ are well-accepted for Alzheimer’s disease and Parkinson’s disease, but there has been little investigation into a similar pattern for MS,”

Does ME/CFS have a prodrome and will it ever be studied? Dr. David S. Bell writes that facial flushing can precede ME/CFS onset in adolescents. In the same article, Bell also writes about children having some symptoms, such as sleeping more and repeated viral infections, prior to developing the whole symptom pattern of ME/CFS.

 

[ScottTriGuy]

So we have the MUS brigade making inroads toward denying patients with physical symptoms appropriate medical testing, while at the same time researchers essentially finding that some 'medically unexplained symptoms' are really 'multiple sclerosis symptoms'.

How much do you want to bet the vast majority of 'medically unexplained symptoms' will eventually be found to be 'new disease symptoms'?

How many people will suffer, how many will die, due to the long arm of MUS?

 

[Forbin]

As far as prodrome goes, probably the weirdest thing I had in the months before onset was an odd intolerance to cold. On several occasions, I would climb into a cold car around 10 PM to drive home and I would just be swept by waves of a kind of shivering that I had never experienced before. It passed in a couple of minutes and I felt fine, but I'd never had that reaction to being cold before - and it wasn't super cold. The shivering was was more similar to something you might get with an infection, but it clearly was brought on by the temperature.

Whether it was connected to ME, I don't know.

I never mentioned it to anyone because I knew their reaction would be, "It was cold and you were shivering. So what?"

 

[JaimeS]

An interesting post to show up today.

I just looked at all my 2011 bloodwork again for RBC- and blood volume-related stuff. At the time, I half-accepted my doctor's reassurances that the bloodwork wasn't much of anything to worry about. But I think if any other doctor had looked at that bloodwork they would've sent me off for IV antibiotics. It looks like active infection pattern (high monocytes) but there are also some signs of compromised immune function (low IgA and low numbers of some WBC types). Other unusual bloodwork included platelet and RBC irregularities (my RBCs were too small), and both iron and B12 were very low. (Yes, I ate meat.)

If I saw this today -- presuming I could somehow have all the knowledge I have about other diseases without any knowledge of ME at all -- I'd wonder if I were looking at someone with malaria, maybe.

Results of this are that I took Floridex (liquid B12 and iron supplement). That was the prescription I got: take iron pills.

No one wondering how I got anemic all of a sudden, both pernicious and iron-based. No one even mentioned the IgA until years later, even though it was clinically low. Taking all that into account, I'd consider generalized gut barrier dysfunction to be something to check, esp with the sub-normal B12 on a normal diet. But no one said that either.

All of this was about 3 years before my "point of no return" event.

This is all my personal story, but I'm far from the only person here or on PR who's mentioned that iron, Vitamin D, and B12 all were low at the start of their illness. It would be super-useful to get data on this so we could have more than apocrypha.

 

[FreeSarah]

Damn, that feels like important research. I'm not competent to assess its quality, though. Is it well conducted?

 

[Amw66]

Damn, that feels like important research. I'm not competent to assess its quality, though. Is it well conducted?

My thoughts exactly. At least 3 coffees required

 

[Forbin]

This is all my personal story, but I'm far from the only person here or on PR who's mentioned that iron, Vitamin D, and B12 all were low at the start of their illness. It would be super-useful to get data on this so we could have more than apocrypha.

Following onset, I developed mild anemia with low RBC's, high MCH and normal hemoglobin. I think this is called "macrocytic anemia," but I could be wrong. The physician attributed it to loss of appetite, but I never told him I had lost my appetite... because, at that point, I hadn't. Actually, at the point where I had lost my appetite, the blood tests no longer showed anemia.

 

[Mithriel]

"Dr. Tremlett and former postdoctoral fellow José Wijnands found that fibromyalgia, a condition involving widespread musculoskeletal pain, was more than three times as common in people who were later diagnosed with MS, and irritable bowel syndrome was almost twice as common.

Two other conditions with markedly higher rates among people to be diagnosed with MS: migraine headaches and any mood or anxiety disorder, which includes depression, anxiety and bipolar disorder.

The higher rates of those illnesses also corresponds with higher use of medications for musculoskeletal disorders, nervous system disorders, and disorders of the genito-urinary tract, along with antidepressants and antibiotics."

OK, I may be too picky but I know a lot of people with MS some of them from before they were diagnosed. When they went with their first symptoms, they were fobbed off by being told they had anxiety, maybe put on antidepressants. Their MS symptoms - suddenly dropping things, feeling unsteady were ignored. Starting to feel ill with no idea why will make people anxious and no answer that fits will make them depressed. One friend was fired for taking too many days off work. If she had been diagnosed she would have been treated differently.

Inability to empty the bladder properly leads to UTIs, MS symptoms but fobbed of as "women get that". Pain and fatigue, oh that must be fibromyalgia. Does MS cure fibro? I don't know anyone with MS who says they have fibro as well.

I think what they are detecting in this paper is misdiagnoses. Rather than prodrome it is early symptoms of MS that are presenting but doctors are not asking the right questions. I suspect that the autoimmune process has started but the effects are not major enough to be detected easily, rather than different diseases being present. Unless that is what they mean by prodrome.

 

[JaimeS]

I think this is called "macrocytic anemia,"

yep, and mine was 'microcytic', which can happen if your iron drops very low. Not saying that was why I had microcytic anemia, only that this COULD have been why I had microcytic anemia.

 

[JaimeS]

OK, I may be too picky but I know a lot of people with MS some of them from before they were diagnosed. When they went with their first symptoms, they were fobbed off by being told they had anxiety, maybe put on antidepressants.

No, you're not being "too picky". I thought the exact same thing: of course they were dxed with some kind of mood disorder, first; that's doctor for "I don't know".

 

[Sasha]

OK, I may be too picky but I know a lot of people with MS some of them from before they were diagnosed. When they went with their first symptoms, they were fobbed off by being told they had anxiety, maybe put on antidepressants. Their MS symptoms - suddenly dropping things, feeling unsteady were ignored. Starting to feel ill with no idea why will make people anxious and no answer that fits will make them depressed. One friend was fired for taking too many days off work. If she had been diagnosed she would have been treated differently.

Inability to empty the bladder properly leads to UTIs, MS symptoms but fobbed of as "women get that". Pain and fatigue, oh that must be fibromyalgia. Does MS cure fibro? I don't know anyone with MS who says they have fibro as well.

I think what they are detecting in this paper is misdiagnoses. Rather than prodrome it is early symptoms of MS that are presenting but doctors are not asking the right questions. I suspect that the autoimmune process has started but the effects are not major enough to be detected easily, rather than different diseases being present. Unless that is what they mean by prodrome.

Seriously, I think it's worth writing into the journal to say that.

 

[Forbin]

I suspect that the autoimmune process has started but the effects are not major enough to be detected easily, rather than different diseases being present. Unless that is what they mean by prodrome.

I think you're right, and that "prodrome" does not mean that the disease process hasn't started, just that it doesn't meet the official diagnosis yet. If that's right, then, by most current definitions, the "prodrome" of ME/CFS technically lasts at least six months - since that's how long you have to be "fatigued" before being diagnosed.

 

[duncan]

I suspect that the autoimmune process has started but the effects are not major enough to be detected easily, rather than different diseases being present

I believe there is an MS school of thought that holds infectious diseases may be at play - and in fact that school is growing - but perhaps not.

 

[duncan]

Following onset, I developed mild anemia with low RBC's, high MCH and normal hemoglobin. I think this is called "macrocytic anemia," but I could be wrong.

Hmmm, me, too. Macrocytic anemia. Low platelets as well. Interesting that you also had vestibular issues.

 

[rvallee]

So we have the MUS brigade making inroads toward denying patients with physical symptoms appropriate medical testing, while at the same time researchers essentially finding that some 'medically unexplained symptoms' are really 'multiple sclerosis symptoms'.

How much do you want to bet the vast majority of 'medically unexplained symptoms' will eventually be found to be 'new disease symptoms'?

How many people will suffer, how many will die, due to the long arm of MUS?

I have seen a few articles lately about replicated findings of high levels of prior anxiety diagnoses in many autoimmune diseases. It's looking more and more like a high proportion of anxiety diagnosis may simply be early symptoms before the disease can be detected.

Occam's razor suggests the same as well. It seems likely that medicine will take a detour in looking at whether anxiety may cause autoimmune disease for a while then finally look at it from the right angle that it's the other way around, that early symptoms of disease are misdiagnosed are anxiety.

It will likely cause a lot of conflicts with the current nonsense about MUS and trying to psychologize every disease. Hopefully this could lead to the fall of this nonsense faster than if it were just us fighting it.

 

[Amw66]

An interesting post to show up today.

I just looked at all my 2011 bloodwork again for RBC- and blood volume-related stuff. At the time, I half-accepted my doctor's reassurances that the bloodwork wasn't much of anything to worry about. But I think if any other doctor had looked at that bloodwork they would've sent me off for IV antibiotics. It looks like active infection pattern (high monocytes) but there are also some signs of compromised immune function (low IgA and low numbers of some WBC types). Other unusual bloodwork included platelet and RBC irregularities (my RBCs were too small), and both iron and B12 were very low. (Yes, I ate meat.)

If I saw this today -- presuming I could somehow have all the knowledge I have about other diseases without any knowledge of ME at all -- I'd wonder if I were looking at someone with malaria, maybe.

Results of this are that I took Floridex (liquid B12 and iron supplement). That was the prescription I got: take iron pills.

No one wondering how I got anemic all of a sudden, both pernicious and iron-based. No one even mentioned the IgA until years later, even though it was clinically low. Taking all that into account, I'd consider generalized gut barrier dysfunction to be something to check, esp with the sub-normal B12 on a normal diet. But no one said that either.

All of this was about 3 years before my "point of no return" event.

This is all my personal story, but I'm far from the only person here or on PR who's mentioned that iron, Vitamin D, and B12 all were low at the start of their illness. It would be super-useful to get data on this so we could have more than apocrypha.

We don' t do the same bloodwork, but i managed to persuade GP to test Vit D, which was very low. Iron borderline too.I will have to check files for other values. We don' t test B12, and were supplementing by the time the suggestion had been accepted

Are there any studies re vit D and epigenetics - if gene expression is a factor, ( as suggested by some studies) then low vit D may have a role to play? ( or have i got this wrong?)

 

[JaimeS]

Are there any studies re vit D and epigenetics - if gene expression is a factor, ( as suggested by some studies) then low vit D may have a role to play? ( or have i got this wrong?)

You're not wrong: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010791/

[Edit: Vitamin D has some immune effects, so it may also drop in acute infection? So maybe the 'prodrome' I'm looking at is a kind of immune depletion picture.]