Degenerative Myelopathy: My unpopular view

I’ve been accused of being unfeeling or some such great evil because I pointed out that degenerative myelopathy is an old-age disease that is painless. And I agree, I AM unfeeling, when it comes to this kind of thing. Not because I don’t adore dogs, but because I don’t think you can answer scientific questions by making yourself cry. So even though I am so incapacitated when one of my dogs dies that I die myself inside, when it comes to asking whether we should stop breeding dogs I try to not change anything until I am not just emotionally but rationally convinced.

The argument is that it’s painful to the owner, and all involved, and we’ve GOT to get rid of it.

Here’s the thing.

Every dog is going to die. And every time a dog dies, it is intensely emotionally painful. Whether the dog is young, old, or in between, it rips your heart out.

And yet, every dog dies. If any form of death is a failure on our part as owners or breeders, then we are ALL failures and we are ALL failing EVERY time.

So the question is not whether we can keep dogs from dying. The question is whether we can give dogs as long and happy and functional and pain-free a life as they can possibly have.

There are a few ground rules we have to follow, HAVE TO, when we talk about degenerative myelopathy.

1) There is no such thing as a DM diagnosis without an autopsy. DM is a disease that looks like other diseases and many other diseases can look like DM. DM is a VERY SPECIFIC disorder that is the result of an autoimmune response. It is NOT “back problems” or “going down in the back” or limping or progressive paralysis. It is not the only nerve disorder and it is not the only thing that makes dogs lose rear function. Dogs can “go down” because of disc disease, a whole bunch of muscle diseases, other nervous disorders, vestibular issues, a huge range of injuries, and even the simple muscle atrophy of old age. Any one of these can mimic DM. So no matter how much it “looks like” or “acts like” DM, until the nerves are examined under a microscope there’s no true diagnosis. Dogs with DM can have normal myelograms, normal bloodwork, and very subtle symptoms. And, conversely, dogs WITHOUT DM can have abnormal myelograms, abnormal movement, very dramatic symptoms. And (KEY): All these other things can happen to a dog with a positive DM gene result. Even if a dog has a gene-positive result, it cannot be diagnosed without an autopsy.

2) THERE IS NO SUCH THING AS A DM DIAGNOSIS WITHOUT AN AUTOPSY. So you can’t say “We now know that dogs we thought died of injuries had DM” or “We believe there’s a much higher incidence than we had thought” or anything of the kind. If the dog did not have an autopsy, it cannot go in the disease statistics.  Oh, and did I mention that

3) THERE IS NO SUCH THING AS A DM DIAGNOSIS WITHOUT AN AUTOPSY.

Let’s look at numbers. Most of our good numbers for degenerative myelopathy in corgis are in Pems, because they are much more numerous as a breed and are more frequently affected by the disease. In other words, they have a much bigger problem with DM than Cardis do. Chessies are also very helpful.

* Pembrokes have a 60% gene-positive rate for DM.

* Pembrokes, when euthanized for DM, die at an average of 13 years.

* PWCCA reports an average estimated Pem lifespan of 13 years. This would seem to correspond well with what we see in Cardigans, where 13-14 is our normal end of life for a healthy dog.

* Pembrokes do not get clinical DM at a rate that even approaches their gene-positive rate. There are very few good incidence studies out there (one of the big problems in analyzing this disease) but the highest rate of DM Berghaus found was 2%, in GSDs.

* Like it or not, the statement “The disease is painless” really is true. If a dog has to die of something at age 13, this is not the worst one.

We honestly know ALMOST NOTHING about the conection between this gene and this disease. But we are immediately ready, because we hate the idea of dogs dying, to RADICALLY change the entire genetic makeup of multiple breeds in order to eliminate the gene. When we know JACK ALL about the gene. So yes, I strongly object to the idea of making breeding decisions yet. Because I am pretty dang sure that if we screw around with our existing gene pool this much, cut out this many dogs, we’ll discover that dying at 13 was not so bad after all. We’ll uncover something, or many somethings, that kill them far earlier and far more painfully.

These are several posts I put on ShowCardi-L last year. I’ll come back and editorialize later tonight.

We ALL KNOW how this works. Everybody promises that we’ll still use
carriers, but it becomes “Oh, he’s a great dog, fabulous
temperament…but you know he’s a DM carrier, right?” Or “I’d love to
use XX dog, but… he’s a DM carrier.” Or, even more deadly to the
breed, “I know he’s not perfect, but he doesn’t carry DM.”

I just attended an absolutely wonderful lecture by Francis Collins, head
of the Human Genome Project. He’s arguably the world’s top expert on
genetic issues. He said point-blank that relying on genes to determine
the course of a life is bankrupt and insane. If there’s one thing we
have learned, it’s that environment is everything.

It seems to me that the only proper response both to DM and to IVDD, and
realistically to any brand-new genetic test, is to test like crazy (and
I do intend to test my girls) and then do absolutely nothing for 15
years. We need to see if the generations being tested actually end up
dying from the disease, and in what proportion, whether diet affects it,
whether vaccination affects it (if vaccination can strongly influence
autoimmune hypothyroiditis, no reason it can’t cause this autoimmune
disease too), whether family X gets it when the dogs are 14 but family Y
gets it when the dogs are 5, and so on. The Pem studies show that median
age of euthanization for DM in that breed is 13 years. And as much as I
hate the idea of any genetic disease, good grief, they’ve gotta die from
something! If I had to choose between a disorder that kills at 13 and a
host of other issues, I’m going for the old-age disease every time.

We need to take a lesson from the Basenji breeders, and we need to look
at it very hard. They created the Fanconi epidemic by breeding rigidly
away from another disorder. The difference is that they can go (and are
going) back to Africa to get new foundation stock and hopefully solve
the problem. We don’t have a pocket of fresh Cardigan genetics somewhere
in Wales. We’re stuck with what we’ve got. So deliberately narrowing the
gene pool should be done only with GREAT fear and trembling.

Knowing this is an unpopular opinion, I just wanted to mention the
statistical data for a minute.

We are IN NO WAY ready to make any statements about DM in the breed
based on the OFA results for Cardigans thus far. With so few turned in,
we’re in a margin of error that is probably 20% or higher–in other
words, the number at risk could actually be as low as approaching 0% or
as high as 30% or more.

OFA-type results already break one of the major rules of statistical
surveys–that you don’t wait for the results to come to you; you go get
them. Volunteered information and responsive surveys (where it’s the
people involved that send you the information, rather than you using a
random number generator and polling a truly random segment of the
population) are always skewed because the people who care enough to send
back a survey or click on your link or send in a blood test are rarely
totally uninvolved. They all have an axe to grind, whether positive or
negative, so their input is far less than optimal when it comes to
saying something trustworthy about statistics.

Even if we ignore that, if we look at the numbers as though they’re a
genuine sample, we have an incredibly tiny number of submissions right now.

It’s like spooning up alphabet soup–if you have a bowl that holds 8 oz
and a big soup spoon, each spoonful will look like the soup as a whole.
But if you have a bowl the size of a coffee table and a teaspoon, some
of the spoonfuls will be all broth, some all letters, some broth and
celery, etc. You have to take many, many more spoonfuls before you know
what the soup really looks like.

If we assume a population of 10,000 Cardigans in the US (of all ages,
registered or not, etc.) we won’t be looking at an even close to
accurate survey (plus or minus about 4 percent) until we’re up to
several hundred, probably over 500, submissions.

To give you the sources of the statistics I know:

The under 2% affected is Roy Berghaus’s study of dogs coming into vet
universities. Two percent incidence in GSDs, 1.51 in Cardis, .83 in
Chessies, etc. He analyzed records of a total of 432,467 dogs; 664
Cardis, 19,000 GSDs, 1500 Chessies, and the list goes on. I think you
could argue that those numbers are actually high, because dogs with DM
are more likely to end up at vet universities than at local vet offices.
If better incidence statistics exist (and by better I mean newer,
involving a larger group of dogs, and more controlled), I would love to
be corrected.

The median euthanasia age in Pems was from Coates, March, Oglesbee,
Ruaux, et al., in J Vet Intern Med in late 2007. Again, if better
studies exist, tell me so I won’t go spreading misinformation.

OK, personal opinion (though hopefully not one without thought) on:

The Chessies are beating us all hollow in terms of submitting dogs.
They’re up to 131 dogs [edited 2009: 421 dogs] tested. And of that number, 60% are either
carriers or at risk. For a breed with, according to Berghaus, a LESS
THAN ONE PERCENT clinical rate. Twelve percent [edited 2009: 14%] are genetically at risk.
They need to get up to several hundred submissions before making a
statistical statement would be wise, but–just building air castles
right now, so don’t take this with too much weight, but it’s VERY
interesting–IF this proportion holds true and IF Berghaus’s
retrospective was correct, 93% of at-risk dogs will not die from DM. [Edited 2009: This rate seems to be holding true]

Ninety-three percent.

Or let’s look at Pems, with a 60% at-risk rate. This is a VERY OLD
disease, so if 60% are testing at-risk now, it’s likely been close to
that for decades. Are even close to that number dying of DM? Are even 6%
dying of DM? If the rate is closer to 3%, which seems more reasonable,
then ninety-five percent of at-risk Pems will never get this disease.

Oh, and a super key statement from one of the UK Chessie breeders–a
very influential dog in the UK was imported because he was PRA-negative.
Turns out he has DM. This is why you don’t freak out and dump gene
pools–or start entirely new ones–when you have a disease discovered.

DM and IVDD are the disaster of the month, and humans have very short
memories. THERE WILL BE A NEXT MONTH. There will be a next year, and a
next decade, and (should the Lord tarry) 50 years from now when we’re
all gone, purebred dogs will have a vial taken at eight weeks old and
there will be a printout of seventy or eighty acronyms, most of which we
haven’t even conceived of yet. Right now, it seems like the worst thing
in the world is this set of diseases. I strongly suspect that we aren’t
even at the tip of the iceberg. Radically changing our breeding habits
to accommodate this disease, which we have almost no accurate hold on
yet, will open us up to concentrating many more diseases that have the
potential to be far more damaging. Please note that I don’t mean we
never change our breeding habits, just that we don’t change them YET. We
just simply don’t know how to do it right.

I’m also seeing a boatload of bad science, not from the researchers but
from the statements about the disease incidence for DM. Everybody’s
saying “The breed incidence has always been very low, but we assume
that’s because people weren’t necropsying,” or “We’ve always thought
that very few of breed X had DM, but now we assume that many of the
deaths we have seen are the result of undiagnosed DM.” Assume
schmassume, people. It’s bad science. It’s because the incidence of
at-risk dogs is so shockingly high that everybody is now scrambling to
attribute deaths to DM. Statistics do NOT work that way. You never take
a result and apply it to the population; you take the population and
develop a result. What we KNOW is a picture of an extremely low
proportion of clinical DM compared to the at-risk (“positive”) dogs. If,
over the next two decades, good controlled studies show that proportion
to be higher, we can say something. We should not be assuming or
conjecturing now.

And, holy hannah, we should not be removing dogs from the gene pool yet.

I sometimes feel like, in contrast to the bad breeders and puppy mills
who will look for any opportunity to breed, we make the opposite
mistake. We’ll jump all over the slightest excuse to NOT breed an
individual dog. And then, in an example of massive irony, we end up
reducing the gene pool so much that we are stuck with a set of genetic
diseases that exactly fulfills the “Don’t buy a purebred; they’re all
riddled with health problems” propaganda. We MUST reduce disease, or at
least maintain the healthy breed we have. But we MUST do it cautiously
and with ALL the information we need to make a good, wise, considered
decision.

Rant off.

Adding today: Nancy Willoughby brings up a very important point, that a
gene like this could be one that influences a broad range of autoimmune
disorders. Which begs the question “What is an autoimmune disease?”
These are not simple equations. Autoimmune diseases, whether this one
(DM) or looking at the entire spectrum, are extremely complex and we
really don’t know how much genetics influences them–or, I should say,
we know it does but we have no idea to what extent. I am most familiar
with autoimmune hypothyroidism, which (at least in the Dane study) was
heavily influenced by vaccination because (it was conjectured) the dogs
were becoming sensitized to the adjuvant of the vaccines in a way that
encouraged them to attack their own thyroids. So do you then say “Well,
it was a genetic weakness, dogs shouldn’t do that,” or do you say “The
dog was fine until it was vaccinated; it’s the vaccine’s fault.” (I’m
not anti-vaccine, by the way.)

Even if it DOES turn out to be a generalized measure of a certain
predilection toward autoimmune disorders, we still would be looking at
environment, injury, and assaults on the immune system as heavy, even
primary, causes.

If I can distill my soapbox, which I know is not popular, into one
paragraph, it would be this.

Please do not EVER think that I am not in favor of testing, or in favor
of shaping a population to lessen the incidence of a disease.
Maintaining, if not bettering, a breed is our sacred duty; nothing can
be more important. I just think that with DM we are nowhere near that
point yet. This is NOT like PRA, this is not like thyroid, this is not
like heart, this is not even like hip dysplasia. We need a lot of years
of testing and observation to confirm that this gene is the correct one
and that we have a handle on its action before we take the extremely
risky step of narrowing our gene pool.

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10 thoughts on “Degenerative Myelopathy: My unpopular view

  1. Can you give me the title of the Berghaus study with the breed incident rates? I searched PubMed and found 19 papers published by Berghaus but couldn’t find this specific one. If it’s not published in a journal, can you direct me to a website or other location? I am really into gathering as much info. about DM as I can right now. Thanks.

  2. I still can’t find an actual published paper with these stats, but I did find a brief article where the date is referenced:

    http://www.americanboxerclub.org/purina1.html

    In the article, Berghaus is quoted as saying:

    “One thing to keep in mind is that dogs presenting to veterinary teaching hospitals are not necessarily representative of the general population of dogs, and the prevalence of DM in the general population is probably different.”

    Different–he doesn’t say higher or lower. Just different.

    While you argue that the rates he quotes are probably high because dogs with DM are MORE likely to end up at vet universities, I would actually argue the opposite.

    There are 28 veterinary teaching universities in the United States that are members of the AAVMC:

    http://www.aavmc.org/students_admissions/vet_schools.htm

    If a dog owner doesn’t live in a state with a veterinary teaching university or if they live more than a few hours away from such an institution, how likely are they to take their dog to such a location as opposed to driving 5 or 10 miles to their local veterinarian? DM is not such a unusual or uncommon problem that a local vet can’t provide some preliminary diagnostic tools and ideas for treatment.

    Doesn’t it also seem odd that Cardigan Corgis were included in the data set and Pembrokes apparently weren’t?

  3. Unfortunately, you’re now deep into the supposition of rates land. Remember the cardinal rule: It’s not DM until the dog has been necropsied. So unless you have an incredibly savvy local vet who happens to know an extraordinary amount about neurological issues on necropsy, what your vet is giving you is a best guess and not a diagnosis.

    Berghaus comes the closest to an actual study, and I tend to think is more reliable because teaching hospitals are, as a rule, employers of more highly trained/specialized vets and more rigorous in terms of testing and diagnosis.

    One of the reasons more data about incidence is so DESPERATELY needed is that we really don’t know much about the actual penetration or incidence of DM. We have a lot of dogs that we think may have DM or we’re assuming have DM or we’re assuming DON’T have DM. But the insisting on necropsy results is for a very good reason–DM is a very specific disease that shares symptoms with a whole bunch of other things, both diseases and injuries.

    It’s possible that part of our behavior change when it comes to thinking about DM is that we’ll begin to ask that all dogs with a suspected DM diagnosis be escalated to a teaching hospital or all dogs with a suspected diagnosis be necropsied.

  4. THANK you for this article – I love your thoughtful pieces on genetics and population issues, because they always make me think.

    One TINY thing I think I would mention though is that PRA in Cardis is not the only type of PRA. In some breeds (Springers and Eskies), they’re having an issue with the DNA test for the specific type of PRA they have not being 100%, and in those cases it’s an old age thing. If the dog dies with early stages of PRA at 15 (especially in springers!) and no other health problems, that’s still a darn good set of genetics for a breed that is losing ground on the age-of-death statistics.

  5. Well see–we are finally beginning to agree about some things: like the idea that there may not be any ACTUAL studies out there about DM rates (things that ‘come close to actual studies’ are just so darn hard to get published in those pesky peer-reviewed scientific journals).

  6. The lack of real data is EXACTLY why I think it is a really, really bad idea to start changing our gene pool because of this. I don’t understand why we have a situation where the scientific community says:

    So we have this gene that appears in DM dogs. It also appears in lots and lots and lots of normal dogs. We have no idea how much it decreases life span, though we think it’s very little, and we have no idea what triggers the dog to actually develop DM or even what role this gene has in the development of DM.

    And breeders go:

    AAAAAAAAAAAAAAAAAAAAAAAAHHHHHHHHHHHHHHHH! OMG! OH NOES! Must stop breeding dogs with the gene! Must stop!

    It makes no sense to me. We are so far from knowing how to wisely address this situation that it’s not an exaggeration to say several decades will go by before we really know the implications of this gene discovery. We are in no place to screw with our gene pool.

  7. I absolutely agree there is a lack of real (scientifically published in a peer-reviewed journal) data in regards to rates of DM in various breeds of dogs.

    We do have real data showing that a very specific mutation in the SOD1 gene consistantly shows up in dogs that have been strictly diganosed with DM. And, if you look at the Awano et al. paper (figure 5) you will see that approximately 35% of the ‘normal’ dogs (those not showing symptoms of DM) who test positive for the DM SOD1 mutation are ages 6 and under–thus we wouldn’t necessarily expect them to show signs of the disease yet.

    And yes, there are several A/A dogs older than 6 (up to age 15) in the study that weren’t yet exhibiting signs (hence the idea of other genetic or environmental factor playing a role in disease development).

    Are there still more questions to be answered about DM? Sure. But the authors of the Awano et al. paper did a good enough job presenting their collective evidence that a group of their peers–researchers who work in the same fields as they do–felt the information they were presenting was not only valid but also compelling enough to publish in a journal (PNAS) considered to be among the most prestigious around (see PNAS.org for more information about the journal and it’s editorial board).

  8. The Awano paper was accepted because it did what it said it was going to do–it suggested that canine degenerative myelopathy is a valid model for human ALS because it shares a genetic region and has some similarities in physical expression.

    That paper was not about the implications for dog breeding and offered no normative recommendations for dog breeding. The only remark about breeding is that it’s going to take a long time to eradicate in dogs, and can’t be done without affecting a huge proportion of the breeds involved, so there are a lot of years left to use DM dogs as ALS models.

    It said a very narrow thing (as all good studies do): The gene is strongly conserved in dogs with DM (true) and DM is similar to ALS and therefore dogs with DM are theoretically better experimental models and subjects for ALS than rodents with the rodent version of ALS (true). I have no problem with the conclusions of the study, but I have no illusions that the study meant to say anything about how dog breeders should deal with the DM gene.

  9. Also, in terms of the ages of the normal dogs, there’s no reason we should conclude anything from the fact that 35% of them were under the age of six. Average dog lifespan is about twelve or thirteen, so if there was anywhere close to a normal spread of dog ages in the study, around half would be under six.

    It’s a little like the Pit Bull dog bite statistics–the proportion of serious dog bites attributed to Pits is disproportionate only if you think that every breed in the US has the same number of individual dogs. When you realize that Pit-type dogs are by far the most numerous breeds in the country, representing about a quarter or a third of the entire purebred dog population (they are far more common than Labs, far more common than coonhounds, which would be the #2 and #3 if you look at AKC/UKC statistics), then the fact that a third of all bites are attributed to Pit-type dogs makes sense.

    The study was NOT about age of onset of DM. It never even pretended to say anything about that, and we should not ask it to. It was NOT about how many gene-positive dogs eventually develop DM. It was ONLY about whether that particular gene is conserved in clinically ill dogs, and whether therefore DM dogs represent a valid model for human ALS research.

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