Degenerative Myelopathy and Excitotoxins
Shawn Messonnier, DVM

author, The Natural Health Bible for Dogs & Cats and 8 Weeks to a Healthy
Dog. Check out Dr. Shawn's Holistic Pet column each week in your local
newspaper, distributed by Knight Ridder News Service.

Degenerative myelopathy(DM) is a common yet misdiagnosed and
underdiagnosed condition in dogs. According to Dr. Roger Clemmons, the
leading expert on this condition, the age at onset is 5 to 14 years of
age.1 The disease can occur in any large breed dog, but appears most
frequently in the German Shepherd Dog (GSD,) suggesting the possibility
of a genetic predisposition. Many dogs may experience a degenerative
spinal cord disease; unless their disorders are caused by the same
immune-related mechanisms which characterize DM of GSD, the integrative
treatment protocol developed by Dr. Clemmons (and discussed fully on his
informative website, www.neuro.vetmed.ufl.edu/neuro/DM_Web/DMofGS.htm)
may not be effective. The breeds for which there is data to suggest that
they also suffer from DM of GSD are the Belgium Shepherd, Old English
Sheep Dog, Rhodesian Ridgeback, Weimeraner and, probably, Great Pyrenees.
According to Dr. Clemmon’s research, the microscopic neural tissue
lesions consist of widespread demyelination of the spinal cord, with the
greatest concentration of lesions in the thoracolumbar spinal cord
region. In severely involved areas, there is also a reduced number of
axons, an increased number of astroglial cells and an increased density
of small vascular elements. In the thoracic spinal cord, nearly all
funiculi are vacuolated. Similar lesions are occasionally seen scattered
throughout the white matter of the brains from some dogs, as well. Many
patients have evidence of plasma cell infiltrates in the kidneys on
throughout the gastrointestinal tract, providing a hint to the underlying
immune disorder causing DM. 1
The current proposed etiology of DM centers on abnormalities of the
immune system. Electrophoresis of immune-complexes that form during the
disease demonstrates that the proteins present are in fact inflammatory
proteins.1 These proteins increase in various disorders in which there is
inflammation in the nervous system.
While the exact cause of DM is unknown, there is overwhelming evidence
that DM is an autoimmune disease attacking the nervous system, and
leading to progressive damage of the involved nervous system tissue. In
many respects, the pathogenesis of DM is similar to the pathogenesis of
multiple sclerosis and it is likely that degenerative myelopathy is the
equivalent of multiple sclerosis in affected dogs.1
Initially, due to some unidentified trigger, immune-complexes are formed
and then circulate, leading to endothelial cell damage in the vessels of
the CNS with subsequent deposition of fibrin in the perivascular spaces.
When the fibrin degrades, inflammatory cells migrate into the lesions,
releasing prostaglandins and cytokines. The prostaglandins and cytokines
activate various tissue enzymes and form of oxygen free-radicals; the
enzymes and radicals cause tissue damage.1 The currently proposed
treatment is directed at these various pathologic processes.
I have an interesting yet probably controversial hypothesis on what
possibly could cause this. Excitotoxicity may be part of the explanation.
Excitotoxicity is defined as a “phenomenon characterized by the
triggering of neuronal excitation through over-stimulation of susceptible
neurons by the excitatory amino acids, primarily glutamate and
aspartate”.2 These toxins increase for a variety of reasons, including
exposure of the patient to mercury and in the presence of viruses.3,4

While controversial, there are some that believe that the increased
incidence of autism is related to mercury in vaccines and the number of
vaccines administered to young children with immature, developing nervous
systems.5 Mercury inhibits the glutamate transport protein GLT-1, which
allows glutamate to accumulate in the nervous system.3 Of particular
interest is the measles virus, which is closely related to the dog
distemper virus. When multiple vaccines are given together, especially
when these vaccines are composed of modified live viruses, the stress on
the immune system is increased.6 This leads to immune-directed damage to
the nervous system. Measles virus, and likely distemper virus, can induce
autoimmune reactions to myelin basic protein.6 In fact, 84% of autistic
children have antibodies against myelin basic protein, suggesting an
autoimmunity to the nervous system.7 Damaged myelin is the lesion
seen in people with MS, dogs with degenerative myelopathy, and in other
disorders as well. Is it possible that by administering multiple modified
live vaccines to puppies with immature immune systems, we are
predisposing some patients to degenerative myelopathy? Viruses produce a
lot of damage to the nervous system by stimulating the release of
glutamate and other excitotoxins.4,8 Antioxidant deficiencies may allow
viruses in vaccines (stealth viruses or modified live viruses) to mutate
from a non-violent form to a highly virulent form.9

While some will find this article controversial, especially since I have
extrapolated a lot of information from the human literature, I believe
the idea of excitotoxicity is certainly plausible, and may be the most
plausible inciting factor as a possible etiology for degenerative
myelopathy to date. The pathophysiology of DM, plus the integrative
treatment approach developed by Dr. Roger Clemmons and others, lend
credibility to the possibility of autoimmunity with subsequent oxidative
damage to the nervous tissue as outlined in this article. Of course not
all kids or pets that are immunized will develop these disorders; my
guess is that there is some genetic predisposition or other damage to the
immune system that may allow one or more vaccine components to act as the
trigger to incite the chain of events which allows damage to occur to the
nervous system. Still, if we can minimize the amount of vaccines given
to our patients, especially the younger ones, this will have a more
positive effect on the overall health of the patient and reduce damage to
the immune and nervous systems.

References:
1. Clemmons R. www.neuro.vetmed.ufl.edu/neuro/DM_Web/DMofGS.htm

That URL does not work. The correct URL is:

http://neuro.vetmed.ufl.edu/neuro/DM_Web/DMofGS.htm

2. Olney JW. Brain lesions, obesity, and other disturbances in mice
treated with monosodium glutamate, Sci 1969, 165:719-721.
3. Aschner M, Ganon M, Kimelberg HK. Methylmercury-induced
alterations in excitatory amino acid transport in rat primary astrocyte
cultures, Brain Research, 1993, 602:181-186.
4. Dories R. The role of T-cell-mediated mechanisms in virus
infections of the nervous system, Curr Top Microbiol Immunol, 2001,
253:219-245.
5. Blaylock R. The Central Role of Excitotoxicity in Autism Spectrum
Disorders, JANA, Vol 6, No 1, 2001:10-22.
6. Liebert UG, Hashin GA, ter Meulen V. Characterization of measles
virus-induced cellular autoimmune reactions against myelin basic protein
in Lewis rats, J Neuroimmunol, 1990, 29:139-147.
7. Singh VK, Warren RP, Odell JD, et al. Antibodies to myelin basic
protein in children with autistic behavior, Brain Behavior Immunity,
1993, 7:97-103.
8. Espey MG, Kustova Y, Sie Y, Basile AS. Extracellular glutamate
levels are chronically elevated in the brains of LP-BM5-infected mics: a
mechanism of retrovirus-induced encephalopathy, J Neurochem, 1998,
71:2079-2087.
9. Beck MA, Levander OA. Dietary oxidative stress and the
potentiation of viral infection, Ammu Rev Nutr, 1998, 18:93-116.