Some Very Sad News for GSDS...DR Clemmons - Page 3

SORRY i HAVENT BEEN BACK SINCE MY ORIGIAL POST.  I have not been getting any better- if anything, just worse. I am on morpheine now, and it just dulls the pain, somewhat. Sleep is next to impossible. I fell asleep in the bathtub the other night.....LOL! My husband found me there in the middle of the night :( I lost 10 pounds, so far, as I cant keep anything down.  Aside from the burning, I feel like i am being stabbed, repeatedly.

My orginal post was my words,  although the diagnostic test results bears out what I have said. Dr C became fully boarded in Nuerology but he was at a standstill at the U of Fla. Giving up on DM research was the last thing he wanted to do. However, as stated, peer reviews on any  articles he might publish are subject to the review of all the AKCCHF good ole boys club, and the deck is stacked in such a way that he could never win. It was agonizing for him to have to turn in his resignation for he is as committed as I am to finding the truth about DM. However, courtesy of the AKCCHF and the ODA, he was placed in a box with the lid taped sht. The losers are the dogs. I know this is what set off my case of shingles, because it was traumatic for me too see the end of meaningful DM research.

I personally do not feel there is a juvenile form of DM, nor does DR C, although Missie T's case was dx at 4 1/2 yrs of age. Spinal Muscle Atrophy in Brittany Spaniels occurs in young dogs with progressive EMG changes leading to death. That might be more consistent with the “early onset DM reported in the GSD which is not the same disease as GSDM on histopathology.  DM is usually dx after 5 yrs of age, but, perhaps if one is very diligent and totally neurotic, as I was, already having had one dog with DM, I was able to hone in on it, in realtion to Missie T, earlier than other people would have realized what was going on. DM used to be an older GSD disease, but IMHO, because a small gene pool is being divided even further ( showlines to showlines, am bred to am bred, german bred to german bred, working lines to working lines, etc). DM has really been becoming more concentrated and as a result, it is no longer an older dog disease. When Jack Flash was first dx with DM, 10 yrs of age at dx was probably more the norm. However, through the years, I have continually watched as the ages of the dogs being dx dropped steadily. I do not think itis uncommon now, for dogs to be dx with DM and 6 and 7 yrs of age now :( Again, this is JUST MY OPINION.

I think the most upsetting thing to me, in relation to the OFA DM DNA TEST is the criteria used to take dogs into that research, and the decision to keep on pushing it, throwing good money after bad, when they were notified of clears and carriers developing DM right from the getgo.  If the criteria for taking the dogs into the research is flawed, than how could the result be anything BUT flawed? if the ctiteria is wrong, data can be easily manipulated. I guess its easier than eating crow... :( Personally, if I make a mistake I would rather say Hey, I F*cked up, and I was wrong, rather than keep throwing money into something that is so obviously incorrect.

 Here again, though, is the difference in the diagnostic test results between DM of the GSD and other breeds...

DR Coates has worked under the theory that DM is ALS. Amyotrophic Lateral Sclerosis and related diseases are motor unit diseases where the nerve cells in the body responsible for controlling movement die off leaving the patient weak and with varying degrees of Lower Motor Neuron dysfunction (loss of reflexes and flaccidity) or Upper Motor Neuron dysfunction (hyperactive reflexes and spasticity). Those causing LMN disease affect the EMG early in the course of the disease. Those causing UMN disease result is selective shrinkage of the motor cortex visible on MRI. Neither of these conditions exist in GSDM. 

Immune diseases like MS attack varying parts of the nervous system and one of them, Primary Progressive MS, specifically targets the myelin and axons of the spinal cord leading to UMN signs but without affecting the cell bodies of the neurons (which is what is seen in GSDM on histopathology). The CSF protein is usually normal in ALS, but abnormal in MS. Oligoclonal bands of IgG are common in MS and uncommon in ALS. The recessive forms of ALS are extremely slow in development and do not result in shortened life-span. Even the one motor unit disease known in dogs, Spinal Muscle Atrophy in Brittany Spaniels occurs in young dogs with progressive EMG changes leading to death. That might be more consistent with the “early onset DM reported in the GSD which is not the same disease as GSDM on histopathology. 

ALS diseases cause motor problems but not sensory ones. That is they do not cause CP deficits or hypermetria (ataxia in which movements overreach the intended goal.). People do not knuckle and scrap their toes when they walk, they only show weakness. Most of them are painful because of muscle spasms. (Does that sound like GSDM?....NO!) 

So, even if there is a genetic change in SOD1, Dr Clemmons believes that a change must also be explainable based upon the clinical signs. If not, it may just be a casual relationship not a causal one. GSDM as a pure motor unit disease just does not fit all of the available data. (Not just DR Clemmons…everyone's!) 

Incontinence is not, and has never been, associated with ALS! That is very disturbing to me, as ALL DM DOGS BECOME INCONTINENT!

To simplify- lay person's explanation:

DM Corgis, Boxers, : motor unit disease

DM GSD: Auto-immune disease

DM Corgis, Boxers : Protein is normal in the AO CSF

DM GSD: Protein is normal in the AO CSF but Protein is elevated in the Lumbar CSF

DM Corgis, Boxers: Oligoclonal bands of IgG are uncommon

DM GSDS: Oligoclonal bands of IgG are common in MS

DM Corgis, Boxers: affects cell bodies of neurons

DM GSDS: Does not affect cell bodies of neurons

DM Corgis. Boxers: muscle spams

DM GSDS: no muscle spasms

DM Corgis, Boxers:EMG is affected early in the disease

DM GSDS: EMG is normal

Where I once used to feel this test may have had credibility with other breeds, I am not leaning that way, anymore. I believe this test has very little, if any credibility, with ANY breed, as the results are showing this to be becoming more and more evident. The answer is not for the OFA and U Of M to sweep this under the rug, which is what is appearing to be done, rathr than using the data to seek the truth. I put the OFA DM DNA test questionnaire on the GSDBBR , http://www.gsdbbr.org, as well as on my facebook page  The OFA DM DNA TEST: Fact or Fiction? https://www.facebook.com/OFADMDNATESTGSD and even added a questionnaire, there,  for other breeds. I was wondering why I  never got any feedback there, and realized only yesterday, that I never publishedd the page! Duuuuuuuuuuuuh! I just kept getting PM's on facebook. Maybe now I will get some feedback...

Hope I have made some sense, here. If not, I will have a good laugh once my head  clears up from the meds I am on... LOL!

and excuse my typos- on a good day, they are horrid ;)

Dr. Coates has stated that since the gene involved in their work is the SOD1 gene, that DM is a motor unit disease and an animal model of ALS. In that, I still believe she is wrong. We have never been able to demonstrate selective motor unit involvement even in late cases. ALS does not have sensory abnormalities which would include proprioceptive deficits which are a predominate feature in DM. We do not think you can build a puzzle by starting with the last piece; the puzzle is built from all the pieces. Only when all the pieces fit together, can the whole picture be seen. Too much data says that GSDM is an immune mediate chronic neurodegenerative disease associated with demyelination and axonal loss. This is most similar to PPMS rather than ALS. 

Dr. Coates has made a few mistakes in her work on GSDM which is a bit surprising, but they are real. One study was nullified since the case selection led to only 3 dogs in the study of 12 that actually had GSDM. On the other hand, this confirmed our work and that clinically only 25% of the patients who present with signs of posterior paresis actually have DM. She suggested that all dogs have oligoclonal bands and, therefore, they were not important in DM. This is not true and we found that 60% of GSDM patients do have more than one unique clonal band in lumbar CSF which is the definition of oligoclonal band positivity. Finally, she keeps looking for CSF changes in DM in the AO CSF which we have repeatedly shown to be normal. CSF changes in DM occur in the lumbar CSF and if there are changes in the AO sample, there is something other than DM. 

Sadly, they have probably effectively dried up our sources of funding which may make it very difficult to continue our program to help GSDM. I still think that gene imprinting at puberty is what establishes the true risk of developing GSDM. 

Marjorie, please take good care of yourself! You are the strong one, enduring that is much worse than what I went through! 

We need you, GSDs need you---please take care!

jackie harris

I agree you need to take care of yourself, Marjorie! I'll be praying that you will get better very soon.

Marjorie, first off, my friend, you really, really have to refocus on your own health and put it ahead of your passion right now--there is nothing to be gained by anyone if you end up completely bedridden for the remainder of your life; it will only rob you, your husband and Casey James of any shared joy in your lives. I am worried on your behalf, and hope you allow your doctors to do whatever is necessary in order rebuild your constitution...

When I mention that I believe there are two forms of GSD DM, I refer only to the age of onset of clinicial signs; I do not think they are two different disorders, but I do think that there is some genetic modifier that can delay the demyelinization of the nerves until the dog is well into their senior years, as it is not uncommon to see dogs that show absolutely no evidence of the condition prior to their reaching 10+ years of age, yet we also see dogs that display the signalment at half that age, and the latter group go on to develop the full progression of the condition which includes the demyelinization impacting not just the dog's mobility and continence, but their breathing and digestion as well.  The dogs which become clinically affected at 10 yrs of age or older more typically don't decline to that degree, usually being lost to some other concurrent ailment--usually some form of cancer.  On necropsy, however, you'll see the same pattern or demyelinization in either age grouping--and it will be textbook of GSD DM.

I don't think there is much support among the GSD people for the 'animal model of ALS' theory, for the very reasons you describe--and most are inclined to view MS as more closely resembling GSD DM.  While I understand that the AKCCHF is a major player in the world of research monies, they are not the ONLY source of financial support, and when Dr C can convince the pharmaceutical manufacturers that there is a link between MS and DM, and provides them with data that supports his contention along with a proposal to either identify the genes responsible for the condition OR a method that could be successfully used in both dogs and humans to prevent the onset of the disorder, or delay or completely stop the progression, the AKCCHF will have no power to derail that.

I still have all faith in Dr C, and think he will land in a place and situation that is a much better fit for him than UFL could ever be--and it will be a spot that WILL nurture his reasearch, and allow him to apply it to both canines and humans equally.

But you, lady, YOU have got to put all of the passion you've heaped into DM research into allowing your mind and your body to heal themselves. In addition to the physical medical care, I dearly do hope you're also availing yourself of medical care for your mental state--you've had grief incident after grief incident served to you in rapid-fire succession, and you've never allowed yourself the time to do the work that's necessary to allow your psyche to heal. It's come time to devote yourself to that now, before all of the stress and physical damage has wreaked on your body and mind ultimately kills you...because it sure sounds like that's where you're heading, as quickly as if you were on the downhill track of the world's fastest roller coaster.

PLEASE take care of yourself, and it that means refraining from becoming involved with any of the dog-related email lists, message boards and social media, then that is what you need to do. Your heart is huge, but not huge enough to withstand everything it's been subjected to over the years.  I'd really like you to stick around, so you can see the win for the breed when the DM puzzle is fully solved and we're able to either select against it through breeding, keep it from being triggered, or manage it in such a way that an affected dog is still able to live a long, full, comfortable and happy life that doesn't call for the dog's owners to cause themselves irreversible injury.

I think the best thing we can do to help with the correct diagnosis and to prove or disprove the DNA test is to have all GSD's suspected  of DM DNA tested and then autopsied; those reports submitted to all interested researchers. We also need to make sure that all labs that are offering the DNA test are using the same protocol and it would certainly behoove the entire breed if every lab would offer a searchable database as does OFA. Owners should also include the registered name, sire and dam of the tested dog instead of just using a call name and no additional information. It does not benefit the breed to know that Rin Tin Tin XXX  with no listed sire or dam tested as risk.

Please take care of ourself Marj our breed needs you soooooooo much...  Better days ahead  Nan

 but IMHO, because a small gene pool is being divided even further ( showlines to showlines, am bred to am bred, german bred to german bred, working lines to working lines, etc). DM has really been becoming more concentrated and as a result, it is no longer an older dog disease. When Jack Flash was first dx with DM, 10 yrs of age at dx was probably more the norm. However, through the years, I have continually watched as the ages of the dogs being dx dropped steadily. I do not think itis uncommon now, for dogs to be dx with DM and 6 and 7 yrs of age now :( Again, this is JUST MY OPINION.

Marjorie, I believe you are SPOT ON!!   Anyone who TRULY understands how genetics works will agree with you, too!

Longevity is decreasing in the breed, too. I've heard of numerous well-known showlines dying suddenly at 8 and 9 years of age. The same thing started happening to the ASLs when everyone began linebreeding indiscriminately on Lance and his sons. I was stunned when someone on this board said they considered any years after 10 to be 'a gift'. When I first got into the breed in the '80, 12 or 13 years seemed to be about the average lifespan.

 I recently read scientists have not been able to discover any good reason why the giant breeds such as Great Danes and Irish wolfhounds have such short lifespans. Any good reason, that is, OTHER than inbreeding!  Longevity is a characteristic that's know to be highly heritable. Human doctors and scientist agree that if you want to get an idea of how long you will live, just look at your parents, grandparents and their siblings!

SS, the comment about considering "any years after 10 to be a 'gift" was mine.  That's not to say that I believe that's how it SHOULD be, but rather reflected what I've observed in the GSD--and am observing still.

When I got my 1st GSD in 1981 [American lines, sired by , it was already typical for each new issue of the GSDCA Review to contain several memorial ads for dogs that were lost at 7 years of age or younger; it was far less common to see the American lines reaching 10 years of age. As I started working as a vet tech around 1985, I began to see an even larger segment of the GSD population in the form of the practice's clients--virtually all of these were American lines in those days, from both well-established breeders as well as from the pet owners who wanted Heidi to have just one litter of pups before she was spayed. If the dogs weren't being lost to bloat and torsion [or to the expense involved in resolving the episode, so euthanasia was chosen instead of treatment], we saw them being lost to crippling hip dysplasia, the overwhelming effects of a host of allergies and a lifetime of prednisone to try and keep the allergic response manageable, DM, IMHA, hemagiosarcoma and other cancers...and far too many of these dogs weren't able to make it past 10 years of age. It was this that led me to my POV that 'every year after 10 is a gift'.  And though I've been fortunate to have been able to keep my dogs with me for 14 to 15 years, I still see far too many of them leaving their owners at the age of 10 or less.  

In truth, I think that reaching 10 years of age for ANY breed of dog is an accomplishment, what with all of the carcinogens in the world now--hell, where I live, there are far, far too many people under the age of 50 who are being lost to cancers affecting the brain, and an inordinate number of pre-pubescent children who die each year of bizarre cancers as well. It's blinders-based thinking that those illnesses have nothing to do with the environment we live in, and that of the places where the local families work [employment options are very limited here, with only a few industries to enter: cement manufacturing, decorative wood and composite material panel manufacturing, working on natural gas wells, farming, and the regional hospital are the major employers in the area],

The lifespan of IW's is generally short because they are extremely susceptible to osteosarcoma, which always ends up metastasizing to the lungs, even if the initially affected limb is removed; with Danes, it's typically bloat, lymphoma, or osteosarcoma that takes them out. It's been my observation that fewer members of these breeds are dying as young as used to be the case, however: faster diagnosis of the conditions that usually affect them, coupled with aggressive treatment protocols, have been successfully prolonging the lives of these dogs, though it is still uncommon to find 10 year old Danes & IWs.

I do agree with Marjorie and you WRT the over-concentration of the genes as a result of the popularity of tighter and tighter linebreeding; OTOH, that's case with virtually every recognized breed of dog, and all the more so in breeds with a very small population to begin with, such as New Guinea Singing Dogs, yet many of those breeds still have a limited number of health risks associated with them. It's been my observation that the breeds which have the fewest health issues are also the ones that have the least restrictive breed standards, with no issues regarding coat, eye, and/or nose/nails/pawpads/eyelid/lip coloration, and which don't include specified body ratios, exaggerated gait patterns, or extremes of angulation.