Healthy Pet Network

Portions of this article appeared in a two-part series in GREAT SCOTS MAGAZINE, Aug. - Sept., Vol. 13, No. 4 , and in Oct.-Sept. Vol 3., No. 5: "A Stone's Throw: Ripples Across Time with Scottish Terriers."

Bonnie Sue: One Scottish Terrier's Experience with Adrenal Exhaustion and SARDS

By Russie McDement-Fogarty

Page 6

Stress and Disease Development

Dr. Plechner has indicated that diet can be a stressful factor leading to adrenal exhaustion, and I went over again and again Bonnie's history in that light since the time we'd owned her. Although we had home-cooked for Bonnie at the beginning of her life with us, during the time I was ill, we had to abandon our regular home-cooking routine in favor of organic commercial dog foods. We are now back to cooking for our dogs and it is surprisingly cheaper, and no doubt, healthier. We haven't vaccinated our dogs in years and use organic products in our home and garden, so we've made every effort to minimize environmental stress as best we can.

We and also made the decision to be more cautious when adding new pets to our household. After watching the effects that new ones have had on all my old charges, I believe that this could be also be a huge stressor for some pets. The theory that young dogs bring new life back to old dogs may not be entirely correct in every case. For some pets (young or old), poised on the brink of illness, needing only some stressor to "pull the trigger," a more dominant pet, competing for affection, prized possessions, as well as prime sleeping spots, causing aggravation through typical playful or aggressive behaviors, may take years off the life of the submissive pet.

Consider the view of stress in submissive animals that has been studied by Dr. Carol A. Shively, Professor of Pathology and Psychology, Wake Forest University, and Assistant Director of the Wake Forest University Primate Center. Her work focuses on nonhuman primate response to social stress. She is evaluating the overall health effects of social stress on macaque monkeys, including atherosclerosis, coronary vasomotor reactivity, bone density and biochemistry, breast cancer risk, depression, lipid and carbohydrate metabolism, regional fat distribution and the metabolic syndrome and immune system function.

In 2005, Dr. Shively co-authored research that presented the first animal model of social stress-related depression and the first primate model of adult depression. She describes a behavior pattern in adult female cynomolgus monkeys that have several behavioral and physiological characteristics in common with human depression, including reduced body fat, low levels of activity, high heart rate, hypothalamic pituitary adrenal (HPA) axis disturbances, and increased mortality.

Shively CA, Register TC, Friedman DP, Morgan TM, Thompson J, Lanier T. Social stress-associated depression in adult female cynomolgus monkeys (Macaca fascicularis). Biol Psychol. 2005 Apr;69(1); 67-84.

Shively was recently featured in a PBS documentary called "Unnatural Causes . . . is Inequality Making Us Sick?" Part I explores the effect social stress has on human bodies using the model of stress adaptation. Shively explains what she has observed in her research:

"A dominant animal has complete control over his life. He can go wherever he wants in the pen to do whatever he wants. That animal has all the control that it needs to create an optimal environment for himself. In contrast, subordinate animals have almost no control over what happens to them. They have to be watching all the time. With that high-level vigilance comes increases in heart rate. They have higher levels of cortisol circulating in their blood. It's the same chemical that is released in human beings in response to stress. And when it is sustained at high levels it starts having negative effects on cellular function and tissues."

Shively compares the arteries of dominant and submissive monkeys:

"This is a cross-section of the artery of a dominant monkey. The hole in the center is large and that means that there's lots of room for blood to flow through. This is the artery of a subordinate animal. So what's happened here is that a subordinate monkey has developed a much larger atherosclerotic plaque than a dominant animal, who lived for the same amount of time, ate the same amount of diet and so on and so forth. And that is simply due to the stress of social subordination. Now, if this monkey keeps developing atherosclerosis at this increased rate relative to this monkey, this one is going to end up with an artery that is completely compromised and have a myocardial infarction."

Unnatural Causes: Is Inequality Making Us Sick? In Sickness and In Wealth - Episode 1. DVD. (2008; California Newsreel with Vital Pictures, Inc.)

"All animals that experience stressful events have physiologic responses that in the short term allow them to mobilize energy and resources to deal with the stress. But if the stress becomes chronic, and the physiologic responses to the stress continue unabated, health may be deleteriously affected. This is as true for Scotties as it is for people. Dogs, of course, are set up to find certain experiences more stressful then others. Since they are pack animals, being left alone may be quite stressful. Since they organize themselves along hierarchical lines, upheaval in their social hierarchy by the introduction of a new member, human (e.g., the new baby) or nonhuman (the new pet), may also be quite stressful. For most animals that live in a social status hierarchy, being the most subordinate is tolerable, but not optimal. Those low in the hierarchy, irrespective of species, are more likely to be less healthy."

Carol A. Shively, Ph.D., personal e-mail to the author, April 7, 2008

Researching the Causes of SARDS

When I read of Dr. Grozdanic's work and then later when I was actually in Iowa, his advice was something akin to a miracle. He offers valuable service to the public by giving the hope of continued sight to pets and offering his protocol to others. I also appreciate the fact that he is working diligently on the SARDS problem and spreading the word that if treated promptly, some sight can be restored. There is so little hope offered for blind dogs. I appreciate every resource and expert. I believe his interest to be completely sincere and he has been nothing but gracious and responsive in his assistance to Bonnie.

Once back at home studying all the information I could locate on adrenal exhaustion, I began to think that the way that Dr. Grozdanic had helped Bonnie was through the simple advice to administer steroid therapy, not through the promise of IVIg therapy.

Clarification may be hard to come by-at least for now. It seems that even within the veterinary community, differing ideas are offered about why and how SARDS may begin and whether autoimmune disease has a role. These different ideas can dictate whether steroid therapy is used.

Dr. Grozdanic has recently published his findings about a new eye disease he has discovered, Immune-Mediated Retinopathy ("IMR"), which can cause blindness in dogs. I found out much later that he suspected Bonnie to be suffering from IMR as opposed to SARDS.

IMR is similar to SARDS, one of the differences being that patients who have IMR always have detectable ERG amplitudes, whether they are "normal, supernormal or decreased." SARDS patients typically have flatline ERG. Dogs suffering from IMR always have a tiny pupil response to red light, but SARDS dogs do not. Both dogs respond to blue light of narrow wave length and high light intensity. SARDS dogs display no menace response, but do have phototopic blink or dazzle response (an involuntary blinking reaction to the sudden onset of bright light). Dr. Grozdanic connects both SARDS and IMR to an auto-immune process:

"Both diseases occur when the dog produces auto antibodies that attack the retinal cells. The antibodies mistake retinal cells for cancerous tumors or tissues that need to be destroyed. In the process of attacking the retinal cells, the auto antibodies cause the retinal cells to lose function and the dog to lose some or all of its vision. The difference between IMR and SARDS that Grozdanic identified is that the auto antibodies that attack the retinal cells in SARDS patients are produced in the eye. In the newly identified IMR, Grozdanic found that these auto antibodies are produced elsewhere in the dog and travel to the eyes in the blood."

* * *

"Tests show SARDS-affected eyes have almost no electrical activity. IMR-affected eyes have some electrical activity, and the retinal cells are not destroyed but have only lost function. These are the retinal cells that Grozdanic thinks can function again now that the origin of the problem is known."

"Iowa State University researcher identifies eye disease in canines"

What Dr. Grozdanic had to say about IMR and SARDS caused me to wonder whether autoimmune disease truly played a part or did the autoimmune disease process occur because an endocrine disorder affecting immunogloublins came first? Experts seem to have varying opinions about the timeline of this illness.

Bonnie's discharge papers from ISU contained the following notes, which I found somewhat puzzling:

"After contacting ISU-Ophthalmology service and careful review of clinical data, it was decided to initiate [a] course of therapy with systemic steroids and doxycycline. Owner reported improvement of behavior with this therapy (which is highly unusual, since SARDS is a disease which does not respond to immunosuppressive treatment.)"

I wondered if it is so highly unusual to see a response, why were steroids prescribed for Bonnie?

I wrote to Dr. Grozdanic to try and determine the reason steroids were given to Bonnie and his reply indicates a completely different reason for using prednisone (and doxycycline) therapy than Plechner might advocate. While I was not aware at the time, Dr. G originally felt that Bonnie might have IMR (an ocular disease differing from SARDS in only minor ways, as set forth above), in which case he felt steroids and doxycycline would have been useful. But he disputes that hormonal disease can play a role in SARDS or IMR. He believes that both begin with an autoimmune process, so it follows that prednisone was used because of suspicion of auto-antibody induced damage to Bonnie's retinal neurons and "other neuronal populations," i.e., sense of hearing and smell. Doxycycline is used because of its immunomodulatory properties.

Since Dr. Grozdanic believes there is no evidence that SARDS dogs have decreased levels of cortisol, his approach to therapy with steroids (prednisone) is strictly for its more commonly understood immunosuppressiive purposes--using drugs which can alter the immune response by suppression.

He kindly provided me with research he co-authored regarding SARDS and IMR, published just this year. From a personal standpoint, I found it interesting reading, but also somewhat contradictory. Yes, I admit it: like many Scottie owners, I find it sometimes necessary to play "armchair veterinarian."

I provide the following only to give readers a sense of the conflicting information they will find if they seek answers about the pathogenesis of SARDS or IMR. This from Grozdanic's recently published work:

"Although different hypotheses have been established as a possible explanation for SARDS etitology (exposure of photoreceptors to unidentified toxins, photoreceptor degeneration attributable to hormonal or metabolic abnormalities, and glutamate toxicity, the clinical appearance of sudden and painless onset of blindness is most similar to antibody-mediated retinopathies . . . in human beings. Early work . . . showed the possible presence of retinal autoantibodies in the serum of patients that had SARDS; however, these results have been disputed by recent studies demonstrating that patients that have SARDS do not have the detectable presence of retinal autoantibodies in serum or the presence of systemic neoplasia. Furthermore, Miller and colleagues demonstrated that retinas of dogs that have SARDS have extensive numbers of photoreceptors undergoing apoptosis, which is most likely responsible for the development of blindness. Because of the presence of metabolic and hormonal abnormalities in dogs that have SARDS, the most plausible hypothesis for photoreceptor damage in dogs that have SARDS was the presence of abnormal levels of hormones, which can have a toxic effect on photoreceptors. This hypothesis is not considered likely, however, because there is no published evidence demonstrating that hormonal abnormalities can have such a dramatic effect on retinal function." [Emphasis added]

Grozdanic SD, Harper MM, Kecova H Antibody-mediated retinopathies in canine patients: mechanism, diagnosis, and treatment modalities. Vet Clin North Am Small Anim Pract 2008 Mar; 38(2):361-87; pp.367.

When reading this information, I noticed what I felt were inconsistencies. Again, I'm no veterinarian, but I feel like I've learned quite a bit while researching and seeking treatment for Bonnie. In one sentence this paper states that abnormal levels of hormones can have a toxic effect on photoreceptors, but in the next goes on to say that there is no published evidence demonstrating the same.

I also didn't understand how one could say that metabolic and hormonal abnormalities were the most plausible hypothesis for the mechanism of SARDS, but that it is not considered likely.

I am not sure what veterinarians or professors would consider published evidence, but Levin's case studies (presented before the American College of Veterinary Ophthalmologists) clearly reflect that metabolic and hormonal changes go hand-in-hand with SARDS development. Dr. Grozdanic compares the autoimmune process in human retinopathy to be similar to canine SARDS and IMR.

A cursory surf of the net will show many studies linking human retinopathy to both depressed and elevated cortisol levels. Diabetes, the illness my Scottie friends mentioned as a possible cause for Bonnie's blindness, is a classic case of estrogens and protestogens affecting carbohydrate metabolism. Both dogs and humans develop diabetic retinopathy.

Guarneri P, et al. Neurosteroids in the Retina. Annals of the New York Academy of Science 2003; 1007: 117-128.

C. Cascio, et al. Pregnenolone Sulfate, a Naturally Occurring Excitotoxin Involved in Delayed Retinal Cell Death. Journal of Neurochemistry 2000; 74: 2380-2391.

                                                       
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