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What
is degenerative myelopathy?
http://www.upei.ca/cidd
related terms: chronic degenerative
radiculomyelopathy, German shepherd dog myelopathy
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This disorder
affects dogs 5 years of age
or older. There is a slowly progressive
loss of coordination in the hind limbs, with increasing
weakness. This occurs because of deterioration of
structures in the spinal cord that are responsible
for conduction of nerve impulses (specifically the loss
of myelin and degeneration of axons in the white matter).
Although the changes may be found anywhere in the spinal
cord, they are most severe in the lower back (thoracolumbar)
region.
The cause of these changes is not known.
There is evidence that an inappropriate immune
response (to a neural antigen) may be involved.
How is degenerative myelopathy inherited?
The mode of inheritance is not known.
What breeds are affected by degenerative
myelopathy?
This condition is seen most often in the
German shepherd and German shepherd crosses.
Degenerative myelopathy has also been reported
in other large and medium breeds, including the Kerry
blue terrier, collie, Siberian husky, Belgian shepherd,
old English sheepdog, Labrador retriever and Chesapeake
Bay retriever.
For many breeds and many disorders, the
studies to determine the mode of inheritance or
the frequency in the breed have not been carried
out, or are inconclusive. We have listed breeds for
which there is a consensus among those investigating
in this field and among veterinary practitioners,
that the condition is significant in this breed.
What does degenerative myelopathy mean
to your dog & you?
The condition is seen in dogs 5 years of
age or older. The changes develop slowly and
may initially be blamed on hip dysplasia. The first
signs are weakness and lack of coordination in the hind
limbs, which are more apparent when the dog is
walking on a smooth surface. One side may be more severely
affected than the other. The condition does not appear
to be painful, and dogs retain the ability to control
urination and defecation, although as they become
progressively weaker they will be unable to move to an appropriate
spot or assume the necessary posture.
These signs gradually worsen until the
dog is unable to walk, usually several months
to a year after the neurologic problems are first
noticed.
How is degenerative myelopathy diagnosed?
There are several conditions that can
cause this kind of weakness in the hind end,
in middle-aged medium to large breed dogs. Your veterinarian
will do a thorough neurologic exam on your dog
and x-rays, to rule out other causes.
For the veterinarian: Rule-outs include
diskospondylitis, myelitis, intervertebral
disc protrusion, and spinal neoplasia. Abnormalities
on neurologic examination are consistent with an
upper motor neuron lesion in the T3-L3 region, and
include decreased proprioception and placing reactions
in the hind limbs, normal to exaggerated patellar and
hind limb withdrawal reflexes, normal anal sphincter tone,
and sometimes crossed extensor reflexes in the pelvic limbs.
Occasionally patellar reflexes are depressed or absent
in one or even both legs, but this is an afferent rather than an
LMN lesion.
How is degenerative myelopathy treated?
Although there is no specific treatment
for this condition, supportive care can generally
be provided for several months.Your veterinarian
will suggest ways to help you adjust to your dog's
gradually increasing limitations, and to recognize
the point at which euthanasia becomes the best option.
This is usually within a year of the initial diagnosis,
when your dog is no longer able to walk.
Some believe that treatment with a combination
of increased exercise, vitamin supplementation
and aminocaproic acid can slow the progression
of this disease (see Clemmons below), but controlled
studies have not been carried out that demonstrate
this.
Breeding advice
Because clinical signs don't develop until
well after sexual maturity, it is safest
to avoid breeding any dogs from families where degenerative
myelopathy has been diagnosed.
FOR MORE INFORMATION
ABOUT THIS DISORDER, PLEASE
SEE YOUR VETERINARIAN.
Resources
LeCouteur, R.A., Child, G. Diseases of
the Spinal Cord. In S.J. Ettinger and E.C.
Feldman (eds) Textbook of Veterinary Internal Medicine,
pp.650-652. W.B. Saunders Co., Toronto.
Clemmons, R.M. 1992 Degenerative myelopathy.
Vet Clin North Am 22(4):965-971
Copyright © 1998 Canine Inherited
Disorders Database. All rights reserved. Revised:
October 30, 2001.
This database is a joint initiative of
the Sir James Dunn Animal Welfare Centre at
the Atlantic Veterinary College, University of Prince
Edward Island, and the Canadian Veterinary Medical Association.
reprinted
with kind permission from:-
Alice
Crook, DVM,Coordinator, Sir James Dunn Animal Welfare
Centre, Atlantic Veterinary College,University
of Prince Edward Island, 550 University Ave.Charlottetown,
PEI C1A 4P3
http://www.upei.ca/cidd
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The New Knowledge of DM (“GSD Myelopathy”)
by Fred Lanting
Copyright April, 2004 - 2007
German Shepherd Dog
Myelopathy, also known as DM for Degenerative
(chronic and progressive) Myelopathy (spinal
cord disease), is the first disorder that comes to
mind when German Shepherd Dogs and spinal lesions are spoken
of together. Almost peculiar to Shepherds, the first
symptoms are usually seen at more than 5 years of age and typically
last 5 to 30 or so months, perhaps a bit longer if aggressive
measures are taken to forestall euthanasia. All accounts to
date concede that there is great variation in age of onset: the
youngest case reported to Glasgow researcher Pamela Johnston in
the course of her studies at the University of Glasgow, Scotland
was five years old, and the eldest 14 years while the majority were
about nine years old at first presentation. Most early signs are seen
at or shortly after about 6 years of age, if the observer is experienced
and keenly looking for it. In my experience, many cases drag on for
2 years, a few go three or more years, and several I have seen last
little over 6 months. Thanks to that excellent research recently done
by Johnston, we now have a better understanding of the disease, although
no more hope than before regarding its prognosis. I have taken the liberty
to edit her work, rephrasing where helpful to the organization of this
article and clarifying for the lay reader. Where I have repeated her
work verbatim or nearly so, I use a different inset-page width. Some
typically British spellings in Johnston’s dissertation have been retained.
You will also see, in place of “DM”, the frequent use of the abbreviation
CDRM, which stands for Chronic Degenerative Radiculomyelopathy. As
her study was “dedicated solely to the investigation of CDRM in GSDs”,
the most populous breed in the world, “it would provide the largest
database so far collected on this disorder.”
Chronic degenerative radiculomyelopathy (CDRM)
is a well-recognised neuro-degenerative disease
of unknown aetiology which affected large breed dogs,
primarily the German Shepherd Dog (GSD). There were other
progressive neurodegenerative conditions which
had been reported in a number of different dog breeds,
but these conditions were too dissimilar to CDRM to warrant
discussion in this thesis. CDRM affects selected areas of
the spinal cord and brain stem. The underlying aim of the Glasgow
study was to improve the clinical knowledge of CDRM by regularly
examining a large group of affected dogs. The most common presenting
sign(s), the age at onset, and whether there was any previously
unreported sex predisposition were of particular interest. Additional
aims were to tabulate rates of degeneration and note the most
commonly seen clinical “syndrome”. This project is the first to
study a large number of affected dogs repeatedly throughout
the course of disease. The previously reported clinical signs
have been confirmed and the relationship between age of onset and
rate of deterioration has been addressed for which no definite correlation
was found.
First described as a specific, separate disease
in 1973, it gets its common name from the fact that
German Shepherd Dogs are affected most often (studies
report a range from 56% to 82% in this breed) and relatively
often (one estimate is that 20% of the breed population
develop clinical signs of DM at some stage in their lives).
GSDs are not the only breed affected. It is much less common
in a few other large or medium-size breeds and large breed crosses
such as German Shepherd Dog, Irish Setter, Collie cross, Rough
Collie, Rhodesian Ridgeback, and Labrador cross.
Dr. R. M. Clemmons, neurology professor at University
of Florida’s veterinary school, feels that
the peculiar syndrome seen in our breed is also
seen only (and even then rarely) in the Belgian Shepherd and
the Old English Sheepdog, and he has believed that what
is seen in other breeds may well be a different disorder.
Those other degenerative myelopathies are probably not
caused by the same immune-system-related deficiency as
we have in the GSD, he thinks. The president of the Kerry
Blue Terrier Club reported DM in her breed, and there has been
another indication that Auburn University was about to publish
a study of a disorder that appears to be DM in Bernese Mountain
Dogs. It is important to remember, though, that while other
breeds apparently get some spinal myelopathies that are also
degenerative, the DM of the GSD, at least, is probably an autoimmune
disease. Dr. Dennis O’Brien from the University of Missouri has
been working with the PWCCA (Pembroke Welsh Corgi Club of America)
Genetics Committee, according to correspondence from Dr. Sylvia
Lueck of Lacey, WA. A $45,000 grant proposal was submitted to the
AKC Canine Health Foundation with support from the PWCCA to do a 2-year
study, with 9 investigators, on DM in Pembrokes. Researchers include
Dr. O’Brien and principal investigator Dr. Joan Coates of Texas
A & M who had been doing a DM project in German Shepherd Dogs.
The Corgi project was to be different, quite a bit more involved, Dr.
Lueck says. Three major projects (DNA fingerprinting, epidemiologic
data collection and a leflunomide trial) were proposed. At the time
I corresponded with Dr. Lueck, she was unable to get any response
regarding cooperation from the GSD Club of America.
CLINICAL SIGNS
“Diagnosis” (purposely put in quotation marks
here) is by process of elimination, since regular
neurological tests aren’t satisfactory, except perhaps
for the presence of a brain fluid protein in the lumbar
area of the cord. True diagnosis is only possible upon autopsy.
Your best bet for a clue while the dog is living would be to
consult an experienced breeder who’s been through it with
his own dog or dogs, read the literature (this is a good start),
and consult your vet for confirmation and medication. He will see
what you have seen, including some of the following.
Initially, the dog does not seem to realize what
position his rear legs are in; soon he will begin
to drag his toenails and the top part of his paws, and
may tremble as if palsied. The dog sooner or later begins
to atrophy in the haunches and croup. He may “dance” with the
rear limbs because he does not realize how high he is stepping.
Proprioception is the ability of the animal to recognize the
location of his limbs, and this is increasingly lost in the
afflicted dog. He will get his hocks “tangled up” (one hooked
behind the other) and trip over them or drag both. Later, he will
have more difficulty getting up and “steering” the rear quarters.
Eventually, he will be unable to get up on all four legs, and by
this time most owners will have decided upon euthanasia. There
were only two cases in the U.K. study, that were maintained for
two years after first signs of thoracic limb involvement, such as
stumbling in front; these had both been in a “K-9 Kart” for more
than 12 months, their back halves being supported by the wheeled
contraption. My own cut-off date for euthanasia is when a dog
can no longer get up and squat to defecate. Everyone has to decide
on his own deadline, but you must have a plan and stick to it, or
the event will be even harder on you.
It is not possible to diagnose CDRM definitively
in life. A presumptive diagnosis [best guess] could
be made, however, based on typical history and clinical
signs. Clinical signs of CDRM had been well documented. The
dogs showed a slowly progressive pelvic limb ataxia and
paresis with loss of proprioception. Initially they scuffed
the middle two toes of one or both hind feet. Subsequently
they developed problems with circling and with stairs,
especially going down; they often scuffed, misjudged distances
and showed hypermetria (ataxia in which intended movements
overreach the intended goal). The dogs were often affected
asymmetrically [more or earlier in one limb than the other] although
both pelvic limbs were usually involved. Disuse muscle
atrophy developed over the trunk and hindquarters several months
after disease onset. With time, prolonged scuffing resulted
in excoriation and ulceration of the feet. Eventually the
disease resulted in marked paraparesis; the dogs could not rise
without assistance and would pull themselves along with their
thoracic limbs. A degree of faecal and urinary incontinence would
often develop late in the disease. Dogs maintained beyond this
stage could show thoracic limb signs. It had been reported that
brain stem involvement eventually occurred (Clemmons, 1992)
which could result in a number of signs including asymmetrical
tetraparesis, cranial nerve abnormalities and altered mental
status. The clinical signs were inexorably progressive and whilst
they may have stabilised for short periods of time, improvement
did not occur. Typically, the signs, which developed as the disease
progressed, were as follows: wearing of the nails became increasingly
noticeable and more persistent; all dogs started to have problems
turning, developing a tendency for the hindquarters to fall to the
outside on a turn. These difficulties were more obvious on slippery
surfaces and on stairs. Most cases were still keen to exercise at this
stage. Crossing of the pelvic limbs then developed, where one leg
would get caught behind the other, which often resulted in the dog falling
over. Collapsing to one side when walking in a straight line followed.
Eventually, after a period of six to 18 months, the dogs were unable
to rise to a standing position, so pulled themselves along with their
thoracic limbs.
In the brain, the lateral vestibular nucleus (LVN)
is the one most commonly affected in CDRM. The axons
of all these cells pass to the spinal cord in the
vestibulospinal tract. Cerebello-vestibular fibres
from the cerebellar cortex provide a feedback mechanism
between the vestibular nuclei and the cerebellum.
Maintenance of equilibrium or orientation of the body in the
vestibular righting reflex is largely reflex activity governed
primarily by general proprioceptive impulses from muscles,
tendons and joints in the trunk and limbs, and special
proprioceptive nerve endings which initiate impulses conveyed
via the vestibular nerve to the vestibular nuclei. The LVN,
by way of that vestibulospinal tract, exerts a facilitatory
effect on spinal reflexes that control muscle tone, especially
to maintain appropriate posture or strength of supporting and
balancing movements. This is compromised in the case of DM, and
the dog is unable to sense that its rear feet are not in the right
place or doing the right thing, and likewise is unable to exercise
normal control over them. These tracts have an effect on the spinal
cord nuclei supplying the antigravity (i.e. the postural and extensor)
muscles. [Thus, the DM-affected dog will tend to gallop or bunny-hop
rather than trot or walk with as much extension of the hocks as
previously or normally.] A failure in the normal activity of the
vestibular system due to DM or other lesions may cause disequilibrium,
staggering, postural changes, falling or rolling to the same side,
and other reactions. [Most owners choose euthanasia long before
these symptoms appear.]
METHODS [From Johnston’s work]: A full case history
was obtained from the owner and referring veterinary
surgeon and the relevant details were recorded.
All cases underwent full systemic examination, full physical
assessment, and neurological examination and the following
functions were found to be the most useful in the
assessment of CDRM.
Gait was assessed initially for lameness, coordination
and weakness with the animal moving in a straight
line on a flat surface. This was observed from the
side, in front and behind the animal. This was followed
by assessment of gait during circling or when going up and
down stairs.
“The wheelbarrow” [in which the dog is picked
up at either end and made to walk on the other two
legs] and hopping tests were used primarily to
detect weakness of limbs and to highlight any asymmetry
between limbs.
Neurological tests used to evaluate the sensory
modality of proprioception also required adequate
motor function by the animal to perform properly. Conscious
proprioception and motor function were assessed by paw
position, reflex step, and hip sway tests. The hip sway
test was carried out by holding the dog either side of
the midline in the flank region and gently moving the dog over
to one side then the other. A dog with normal proprioception
will immediately move the relevant foot such that the
body is properly supported. Proprioception was severely
affected either unilaterally or bilaterally, depending
to some extent on the duration of disease.
Muscle tone was assessed by passive flexion and
extension of the limb; muscle bulk and symmetry
were assessed by palpation; and the local spinal
reflexes (patellar reflex and pedal reflex) were assessed
in the pelvic limbs with the dog in lateral recumbency.
The pedal reflex was tested to evaluate flexor muscle group
strength and to assess cutaneous sensory fields in the distal
limb. In the thoracic limbs a similar examination was made.
Joints were examined for the presence of musculoskeletal
disease.
Mentation [mental activity] and posture were
noted and the owners questioned about any change
in behaviour or attitude. The presence or absence
of conscious pain perception was noted. Additional signs
of importance were a lack of any spinal pain and no evidence
of faecal or urinary incontinence (except very late in
the course of the disease).
The clinical signs indicated both motor (paresis)
and sensory deficits (abnormal proprioception)
and suggested that the major abnormalities occurred within
the T3 to L3 region of the spinal cord. Based on these and
other findings, an attempt was made to localise the lesion to
this region.
ACTUAL DIAGNOSIS
Previous studies had identified the major
clinical signs of pelvic limb ataxia and weakness to
have resulted from degeneration of tracts in the white
matter portions of the spinal cord.
Autopsy will not help you or your dog, but would
find the obvious demyelination (loss of the insulating
sheath) of the spinal cord, destruction of some
large axons (nerve cells leading from the cord to smaller
branch nerves), and abnormal cells (or certain cells
in abnormal locations). Similar signs may be seen in the
brain’s white matter, and plasma cell infiltrates in the kidneys
and intestines give further evidence of the immune system
failure at the root of this disease.
PATHOLOGY
It had been reported that brain stem involvement
eventually occurred (Clemmons, 1992) which could
result in a number of signs including asymmetrical tetraparesis,
cranial nerve abnormalities, and altered mental status.
The pathology in the spinal cord had been described in
detail by a number of authors. Lesions were considered to be
typical of Wallerian-type degeneration and affected both the
axon and myelin sheath. Observed clinical asymmetry correlates
with pathological asymmetry. This loss of axons and myelin
sheaths is seen in many cervical and cranial thoracic segments,
but occasional axon and myelin sheath loss is also noted in the
lumbar and sacral cord segments. In an area of the cord known
as the lateral funiculus, the corticospinal tract is most severely
affected in the caudal thoracic segments. In the thoracic cord, Clemmons
saw vacuolation, swollen axons, and other things that represented
degenerate and regenerate axons. The present study [Johnston] also
identified significant brain pathology. The intermediate horn [column
of cells] is the region in the grey matter of the cord that is most
often affected in CDRM, but most agreed that the white matter areas
of the spinal cord were the most consistently affected, with degeneration
involving both axons and myelin, often with an associated gliosis.
The caudal thoracic segments were consistently the most severely
affected. Only one author suggested that there was evidence of
axonal regeneration in the spinal cord (Clemmons, 1989), the same author
mentioned the possibility of changes occurring in unspecified white
matter areas of the brain. Detailed examination of the brains of
affected dogs revealed novel (not seen in other disorders) pathological
changes in specific brain nuclei. Such changes included neurones
with eccentric nuclei, chromatolytic neurones and neuronal loss
often with an associated gliosis. These changes affected the
red nucleus, lateral vestibular nucleus and lateral (dentate)
nucleus to varying extents. Such changes were found consistently in CDRM
dogs but only rarely in dogs with focal spinal cord lesions. Furthermore,
gliosis in the red nucleus was found only in the dogs with CDRM.
Dogs with DM often develop lick granulomas, which
are ulcerations or (if you are lucky) callous-like
reactions of the skin to extremely frequent licking,
sometimes chewing, at the location of a supposed itch.
It is probably a case of the limb feeling as if it has “fallen
asleep”, to put it into terms familiar to human experience.
The tingling sensation caused by incomplete and erroneous
signals by the nerves serving that place is much like
the irritation caused by an ant bite, or hairs out of place,
or anything in between. In trying to lick it away, the dog actually
softens and wears away the hair and skin. The best I could do
for my dog was prick a vitamin E capsule, squeeze out a little for
topical application to the granuloma, pop the rest into his mouth,
and then give him some distraction such as go for a walk. These
ulcers on the feet or elsewhere don’t easily respond, but the battle
must be waged if the dog’s life and comfort are to be prolonged. If
vitamin E does help in immune system insufficiency, it may be temporary,
though it is more often just “managed” or covered up, or it
may be worth the effort. It may limit itself to just one or two
symptoms such as the biting/nibbling/licking.
Symptoms and histological changes of canine DM
are very similar to those in human multiple sclerosis
(MS) but most scientists do not admit to the probability
of a genetic relationship. Still, I cannot help but
suspect that most of these various canine immune-system
deficiencies might be related: DM, demodex sensitivity, hormone
and endocrine gland irregularities, corneal dystrophy,
cauda equina, some allergies, pannus, and other problems,
and perhaps even some human ailments. A big problem is that
so many gene-mediated disorders of these types also have a
large environmental component.
Since DM is so similar to multiple sclerosis, many
thought it worth trying the nutritional approaches
used by some who treat that human disorder. Wheat
germ oil contains octocosanol, a fatty or waxy high molecular-weight
alcohol also given to patients with encephalitis
and cerebral palsy, and also contains linoleic acid
(as do several vegetable oils). But one fatty acid, docosahexanoic
acid, is not at all abundant in normal diets, yet seems
to be the first one depleted from the nerves’ myelin sheaths
in such disorders as MS. In many diets for MS patients, foods
such as sardines and mackerel are emphasized, because they are
among the very few foods that can supply this compound. Of
course, vitamin B complex high in inositol, B6, B12, and choline
frequently is also highly recommended as an adjunct to vitamin
E for nerve-muscle disorders. Since only a percentage of patients
with MS or DM respond satisfactorily to a vitamin-only approach,
the concomitant use of drugs and exercise perhaps should
always be prescribed. As of this writing, there were three FDA-approved
drugs for MS that not only help manage symptoms but also appear
to “impact disease course” in relapsing MS, according to the
National Multiple Sclerosis Society. They are Copaxone (Teva
Marion), Avonex (Biogen), and Zanaflex (Athena Neurosciences).
Your vet would have to decide whether or not he wanted to “go off-label”,
since these have not (yet) been approved for dogs.
For several years, there was no generally accepted
treatment, but as breeders became aware of the benefits
of high vitamin E dosages in other immune-related
disorders, the veterinary profession began to look into
its efficacy and the relation to the immune system. When I
first encountered it, I imagined that I got an extra one
or two years useful life out of one of my dogs by giving him
800 units (IU) a day, plus vitamin C for its synergistic effect.
Years later Clemmons and others claimed that 2000 IU of vitamin
E daily, 500 mg of vitamin C twice a day, and a high-strength
vitamin B complex twice a day was the best dosage. Vitamin E
is an important nutrient with a number of physiologic and pharmacological
effects. As an antioxidant it helps reduce oxidation of
fats and increases the production of HDL cholesterol. At higher
doses it decreases production of prostaglandins and has anti-inflammatory
action. There are no known side-effects to vitamin E at levels
less than 4000-6000 IU per day (except in cats, where levels above
100 IU/day can create hepatolipidosis. In DM, low serum and tissue
concentrations of vitamin E have been observed, although recent
research by Johnston indicates this may be equivocal. I recommend
that vitamin E be given to older German Shepherd Dogs for a variety
of benefits. Dr. Clemmons recommends the vitamin E be dropped temporarily
to about 100 IU if the dog has to be given aspirin for any reason
during the treatment, and recommends that daily DEC (diethylcarbamazine)
replace the monthly heartworm medications ivermectin (Heartgard,
Heartgard Plus, Ivomec) and Interceptor because these increase
immune responsiveness; also use the DEC in place of styrid caracide
or Filaribits, he says. Personally, I would simply stop all use
of heartworm medication, because the dog with DM probably isn’t going
to last as long as it takes for a case of heartworm to become life
threatening, anyway. Flea control should possibly be limited to Precor™
for the house, and carbamates or pyrethrin/pyrethrum on the dog.
Chemical-pharmacological treatment has largely
been via the use of aminocaproic acid, something
my friend Wayne Riser (founder of OFA) told me about
many years ago — he recommended it for pain relief in hip
dysplasia patients. More recently, acetylcysteine three
times a day has found acceptance. According to Clemmons,
it now appears the best treatment is a combination of all
three approaches (these two and the vitamin therapy), along
with exercise. According to some, alternate-day dosage
with a steroid such as prednisone, plus acetylcysteine,
added to the aminocaproic acid and vitamin formula, is
enough to keep the dog owner very busy and tied to the home,
but it might offer a chance at reducing progression, thus
prolonging life considerably more than in the past. More recently,
Clemmons has been quoted as saying that steroids are no longer
recommended for DM dogs. He found that steroids lead to muscle
wasting. Therefore giving steroids to a dog with DM is like pouring
gasoline onto a fire. A dog with DM that is given steroids will lose
muscle mass much more rapidly than one that is not on steroids. Hydergine,
a prescription drug derived from ergot fungus, is being studied,
since it seems to promote nerve regeneration. For dogs with advanced
DM, Dr. Clemmons suggests trying 5 mg three times a day for at
least three months. There is still some disagreement among researchers
as to both the nature and the preferred treatment of DM, but the
work by Johnston is the most comprehensive and detailed, and she indicates
that these approaches are dubious in reputed value.
Unpublished reports from the U.K. indicate that
of the dogs diagnosed with DM, 88% of those still
walking at 12 months and 80% of those walking at 18
months after symptoms were recognized were being treated
with, at least, aminocaproic acid.
I mentioned exercise, and this is the third of
what might be considered a four-part fight against
the disease. Every other day, the dog perhaps should
be given at least 30 minutes of aerobic activity such
as vigorous walking or swimming; if you start late, build
up to the strenuous level gradually; if your dog can’t do the
most, do less, but make it regular and stretch the limits where
you can. The alternating days of relaxation are important for
repair and renewal. If the dog acts sore, give him the analgesic
prescribed by your vet (after he has “read up” on the interactions
of medications in regard to DM).
NUTRITION AND “ALTERNATIVE MEDICINE” CLAIMS
The fourth part is stress reduction. The vitamin
C, that anti-stress vitamin, is there for a good
reason, but take steps to avoid stressful situations,
including surgery; if the dog needs surgery, make sure
he gets the acetylcysteine as well.
The approach to treatment of DM that is proposed
by Dr. Clemmons is called “integrative treatment”.
It combines conventional pharmaceutical treatment
with “alternative medicine” or “supportive therapy”.
Paraphrasing some of his comments might be helpful here.
Conventional drug therapy (medicines) has been of little
lasting help to patients with DM. However, the combination
of exercise, vitamins, and certain drugs (he says) has
delayed the progression of DM in many dogs. Treatment has been
directed at suppression of symptoms, and since until recently
the actual cause or causes of this autoimmune disease were
not known, little had been done in the way of finding out how
to prevent it. We now know that the genetic component is the major
factor. Saying that Degenerative Myelopathy is an autoimmune disease
means that the animal’s immune system attacks its own cells; in
this case, the central nervous system. The myelin insulation sheath
around the nerves and axons (fibers) is gradually destroyed. It’s
worst in the thoraco-lumbar area of the spinal cord, but can also
affect the brain stem and other nerve tissue.
Integrative or supportive treatment of DM, as
promoted at the University of Florida vet school,
suggests the use of dietary alternatives and supplements
to combat the immune system, and is derived from an approach
to treating Multiple Sclerosis. You probably know at
least one person with MS, and can recognize the similarity
in symptoms. It has been postulated that besides the vitamins
E and C, the drugs, and the exercise mentioned above, avoidance
of toxins such as is found in pesticides and lawn chemicals,
and perhaps in some processed foods, is possibly helpful. Clemmons
recommends “stress formula” B-complex containing 100 mg of most
of the B vitamin components. Or use yeast as a good source of
these B-complex vitamins, trace minerals, and some protein. It
is relatively inexpensive; try half a tablespoon mixed in each meal.
If your dog gets flatulence from this, as most do, use a discount or
mail-order vitamin B complex pill instead.
Antioxidant vitamins E and C are synergistic;
i.e., they work together better than they do separately.
While dogs produce vitamin C, those with DM may need
more than they can manufacture. In excess, it also can cause
flatulence. Tolerance in the intestines may be for as
much as 3000 mg per day, but up to 1000 mg twice a day
should be enough unless it causes diarrhea. Selenium also
is synergistic, helping vitamin E to be more effective. It can
be toxic to medium-size dogs if given at more than 200 µg
(micrograms) of selenium per day. I take 200 µg
whenever I feel I’m not getting much western grain (good
source of selenium) in my daily diet (which is rarely, such
as when I’m out of the country for an extended time), and I
weigh twice as much as my largest German Shepherd Dog. I keep
it in the house to give it (100 micrograms daily) along with
vitamin E to my old stud dog in an attempt to control prostate
enlargement.
Clemmons says that “Omega-3 fatty acids such as
EPA (eicosapentanoic acid) and DHA (docosahexanoic
acid) are the constituents of fish oils that act
as anti-inflammatory agents and may be worth trying if
your dog has an autoimmune disorder or arthritis.” Fortunate
is the owner who can give an afflicted dog a couple of
cooked sardines or a small piece of salmon as a daily, natural
source of such fatty acids. A 1000-mg fish oil capsule,
tablespoon of ground flax seeds, or flaxseed or wheat germ oil
supplement can do about the same thing. If you are really
“into” the health-food store shopping, 500 mg twice a day
of GLA (gammalinolenic acid), a fatty acid found in evening
primrose and black currant oils, is an alternative anti-inflammatory
without the side effects of most anti-inflammatory drugs.
All of the above should be considered as optional adjuncts
to conventional treatment with the drugs, vitamins, and exercise,
not replacements for them. Johnston found none of these
therapies to be effective, however.
Clemmons (1992) suggested, among other ideas,
the presence of an 85kDa antigen in dogs with CDRM.
However, no other authors have mentioned such a
possibility. He has also made numerous other observations
and conclusions that have not been duplicated by other researchers,
so one must look with care at his “data” until verified
in the scientific community. His treatment regimen has also
been controversial, as the claims made therein have not
been substantiated elsewhere. High doses of vitamin E (2000
IU/day), high-potency B vitamin complex, and epsilon aminocaproic
acid (EACA) had all been used as treatments (Clemmons, 1989
& 1992) although their efficacy appeared questionable. Since
EACA has anti-protease activity, Clemmons considered that it
would therefore be helpful in CDRM, as it would presumably block
the final step in the inflammatory pathway, thus helping to prevent
tissue destruction. There was no further evidence suggesting that
any of the therapies suggested by Clemmons were beneficial in the
treatment of CDRM, which was still considered untreatable. All
authors agreed that maintenance of regular exercise and optimal
body weight seemed beneficial to affected dogs. Clemmons has
been the only author in the scientific literature who suggested
a treatment regime would be effective which included vitamin E, vitamin
B, and EACA; this was not confirmed by other workers in the field.
Clemmons in 1989 and 1992 suggested that a combination of vitamins,
evening primrose oil, and essential fatty acids might slow the
rate of neuro-degeneration in cases of CDRM. These claims remained
to be substantiated, although a number of owners have decided
to give their dogs these therapies. The rate of deterioration in
the studies reported by Johnston was not obviously altered in the
cases given the vitamins and evening primrose oil therapies.
Clinical and pathological similarities between
CDRM and neurodegenerative disorders due to vitamin
E deficiency in horses and humans had implicated
vitamin E as a potential factor in the aetiology of CDRM.
This stimulated a study of serum vitamin E concentrations.
Data presented in this thesis suggests that affected GSDs
do not have significantly lower serum vitamin E concentrations
than other breeds of dog. In contrast, GSDs with CDRM appear
to have elevated levels of serum vitamin E in comparison with
the general canine population. [That may be because owners
are supplementing.]
[Johnston found that]: The significance of the
possible involvement of vitamin B 12 must be questioned,
as the study this idea was based on did not include
a control population of unaffected dogs. CDRM may
occur due to the abnormal absorption of some other nutrient(s)
such as vitamin E, or the reported biochemical abnormalities
might be occurring secondary to (a result of) the neurologic
dysfunction. It has been postulated that since “ataxia
with vitamin E deficiency” (AVED) in man responds to the
administration of high doses of vitamin E, and that loss of
axons and myelin sheaths had been associated with chronic vitamin
E deficiency in rats and rhesus monkeys as well as humans,
the deficiency of this free radical scavenger that protects
neuronal cell membranes from peroxidation could lead to increased
membrane fragility and ultimately neuronal cell death. Barclay
and Haines (1994) suggested that an immune-mediated spinal
cord destruction might be occurring, because they found
immunohistochemical evidence in the spinal cords of affected
dogs which was not present in the normal dog. Further, the
pathogenesis for this or a similar condition in horses is not
understood.
As the owners in the U.K. study represented a
highly motivated population, the inevitable result
was that the vast majority of cases seen were on the
dietary supplements (26/34). A further problem with analysing
this information was the fact that dogs with CDRM do deteriorate
such that they have periods of deterioration interspersed
with periods of no apparent deterioration. Thus in the short
term, the supplements could have appeared to slow down the degeneration
depending on the precise timing of the initiation of therapy.
However, as the dogs were being objectively reassessed
at Glasgow on a regular basis throughout the clinical course
of disease, any such discrepancies should have been minimized.
Analysis of vitamin E concentrations for dogs
in the preliminary investigation using the two-sample
t-test, suggested that there was no significant
difference between vitamin E concentrations in GSDs with
CDRM and non-GSDs unaffected by CDRM. Williams et al
(1985) investigated a small number of GSDs with CDRM
(n=7) and found that they had a slightly lower serum vitamin
E concentration than control dogs. These latter authors
consider that the GSDs with CDRM also had an enteropathy which
could cause improper absorption of essential nutrients.
Williams (1984) investigated the possible involvement of vitamin
B 12 deficiency but ruled this out as a possible cause of CDRM.
Serum vitamin E concentrations, when measured, were lowered
in neurological disorders in other species which had been attributed
to vitamin E deficiency. Work done in other species had suggested
that serum vitamin E concentration was decreased quite considerably
before any associated disease occurred. The data presented
in this work, in the light of findings associated with vitamin
E deficiency and disease in the dog and other species, suggested
that deficiency of vitamin E is unlikely to be a primary
factor in the aetiology of CDRM.
DISORDERS WITH SIMILAR SYMPTOMS
Cauda equina syndrome, giant axonal neuropathy,
tumors, and other disorders may also mimic or
be mistaken for signs of DM. Many cases of spinal
and related nerve damage are due to sudden trauma, but
some can result from encroachment of bone or tumors into
the space occupied by the cord. Since nervous tissue
generally does not regenerate, such conditions result
in partial or complete paralysis. Symptoms similar to myelopathy
may be brought on by a nerve cell degeneration normally associated
with age. However, with the latter disorder, the rapidly progressive
nature of GSD myelopathy is not seen. Neoplasms also cause
the dog to display symptoms similar to those of GSD myelopathy.
These tumors on the spinal cord, neuroepitheliomas, have
a special predilection for German Shepherd Dogs from six months
to maturity at three years of age. There were other progressive
neurodegenerative conditions that had been reported in
a number of different dog breeds, but these conditions were
too dissimilar to DM to warrant discussion in Johnston’s thesis.
GENETIC EVIDENCE
The finding of CDRM in several littermate pairs,
combined with the acknowledged high incidence of
the disease in the German shepherd breed in general
suggested that a genetic factor may well be involved
in the aetiology of the disease, as previously suggested
(Clemmons, 1989). Due to this unusually high incidence
of CDRM in one breed of dog and the discovery of at least
two pairs of affected littermates, the investigation of a
possible genetic factor was indicated. Following a literature
search for diseases in other species with clinical and pathological
similarities to CDRM, a working hypothesis was established:
CDRM is caused by a CAG trinucleotide repeat expansion in an unknown
gene. A number of molecular biological techniques were employed
to test this theory, including the Repeat Expansion Detection
(RED) technique. This work is still in progress but there is
some evidence, still inconclusive, that CDRM may be the result
of a trinucleotide repeat expansion. Undoubtedly, CDRM has
a complex aetiology which probably involves several different
factors but most authors agree there is almost certainly a genetic
factor due to the very high incidence of the disease in one
breed. [The results from the Glasgow experiments provided some
evidence that CDRM is principally genetic, and specifically of
an “expansion” as noted, in the CAG nucleotide sequence on a
gene that yet has to be found or marked.]
CONCLUSIONS BY JOHNSTON
This project aimed to examine clinically and pathologically
a large number of GSDs affected by CDRM. Clinically,
we wished to confirm the previously reported clinical
signs, and look for any that may not have been reported.
We proposed to follow the dogs through the clinical
course of the disease, re-examining on a regular basis
to establish whether the rate of degeneration was constant
or variable. If variable, were there a number of recognisable
patterns, which might suggest we were dealing with a syndrome
rather than a single disease? In addition, we wished to confirm
whether or not GSDs with CDRM had lower serum vitamin E concentrations
than other dogs, since this vitamin had been associated with a
number of neurodegenerative diseases in other species. The initial
aim of the pathology investigation was to carefully examine the
spinal cord using immunocytochemistry and electron microscopy,
as well as classical techniques, to confirm the pathology previously
reported and to look for new clues to the pathogenesis and aetiology
using the more modern techniques. The next step was to carefully
search through the brain, in particular those structures which,
on the basis of the clinical signs, were most likely to be involved
in CDRM. This search resulted in the discovery that specific brain
nuclei and areas of white matter were altered in dogs with CDRM. These
findings suggested marked clinical and pathological similarities between
CDRM and a group of late-onset progressive human neurodegenerative
conditions which were the result of CAG trinucleotide expansions.
This led into an investigation of the hypothesis that “CDRM is the
result of a [genetic] CAG trinucleotide repeat expansion”. However,
further work would be required to definitively prove whether or not
this was the case.
If you have lost a dog to this neurological disorder,
I offer my condolences in the form of a poem:
Rondeau on the Death of a
Dog
They whimper
in their darkness and their pain,
But oh, so softly
that one has to strain
To hear. The life
that Folly whispered low
Would stay (and how
we wished that it were so!)
Ebbs out, although
we grasp for it in vain.
Steady the flow,
invisible the stain
Their life-blood
leaves on those who here remain.
Unwilling to desert
us as they go,
Fred Lanting, Canine Consulting.
Seminars: Canine HD & Other Orthopedic
Disorders; Gait & Structure 