EQUINE SHIVERS


EQUINE SHIVERS



INFORMATION ON EQUINE SHIVERS
FOR HORSE OWNERS AND VETERINARIANS



Brenda Bishop, VMD



1976 Graduate of the University of Pennsylvania School of Veterinary Medicine.

Brenda Bishop has spent many years researching equine immune mediated diseases.

She has included in this website a practical guide for horse owners as well as a guide for veterinarians interested in a new thought process for dealing with
Equine Shivers.

She answers questions that have gone un-answered for too long.



Podcast



THE LEPTOSPIROSIS HORSE



Copyright 2012 by Brenda Bishop, VMD. No portion of this publication may be without prior written permission of the author. Portions of this work have previously appeared in Natural Horse magazine: volume 12 issue 2 (2010) “Demystifying Equine Shivers” by Brenda Bishop, VMD and volume 5 issue 3 (2003) “Deciphering Equine Fibromyalgia Syndrome (EFMS)” by Brenda Bishop, VMD.


The most common zoonotic bacterial infection in the world is Leptospirosis. Due to its number one status, much is known about its appearance in humans, dogs, cats, cattle, sheep, pigs and goats. Comparatively little is known about its existence in horses. Of the many different serovars (there are over two hundred known to date) the serovar L. pomona is associated with two clinical entities in horses: equine recurrent uveitis (ERU) and spontaneous abortion in mares. ERU is considered to be an autoimmune problem by many scientists leptopirosis is suspected in mares that abort for no apparent reason. Both ERU and abortion represent consequences of previous (usually unrecognized) exposure to one or more Leptospira serovars. Whether the affected horse had a healthy immune system or a compromised one at the time of exposure, these horses have won the initial skirmish (acute infection) but lost the war, eventually suffering loss of one or both eyes or a fetus.


Bacteria that have a spiral shape, such as Leptospira and the Lyme disease spirochete Borrelia, have a predictable course of action once established in their respective hosts. They characteristically elicit a biphasic response the initial acute infection, which may or may not provoke a fever and general malaise, lasts a short time (days) the second phase takes weeks or months to manifest. The symptoms of this second phase are a reflection of an immune system struggling for control. When immune system imbalance goes on long enough, a certain threshold is reached wherein autoimmune conditions (such as Shivers) can result. Researchers have found that spirochete infections produce the same clinical pictures in various animal species and humans, some of whom develop ‘Persistent Human Leptospirosis’ (PHL). Horses are thought to be a reservoir in nature for certain Leptospira serovars it is known that wild animals shed Leptospira in their urine which can easily be ingested by grazing livestock. If in fact some horses embody a carrier state for the bacteria, these should not be confused with those individuals whose immune systems are engaged in an ongoing active battle with chronic infection.


The easiest way to envision this second phase is in terms of a prolonged allergic reaction. Unlike the initial acute phase which can be life threatening (due to lung, kidney and/or liver damage), this phase amounts to a progressive complex cascade of events which leave the affected host with a wide array of complaints. To further oversimplify the picture of how specific problems are created, it is helpful to consider the role of mast cells in the host horse’s body. An important but poorly understood part of the immune system, mast cells live abundantly in connective tissues (such as skin and ocular conjunctiva) and mucosal linings (respiratory, reproductive and gastrointestinal tracts). They cluster around nerve endings, the smallest of blood vessels and lymphatics. Another crucial part of the immune system, plasma cells, circulate freely and produce antibodies (immunoglobulins) such as IgG, IgM and IgE. Mast cells have an affinity for IgE which attaches to their surface. When leptospiral antigens make contact with this IgE, the mast cell becomes activated and explodes like a bomb. Among the many substances released into the surrounding tissues are histamine, prostaglandins, cytokines and leukotrienes. These in turn produce constriction of the airways, gastric acid secretion, spasms of the gastrointestinal tract, itching, irritated nerve endings, swollen blood vessels and lymphatics, and needless to say inflammatory pain.


Horses in the early stages of persistent leptospiral infections demonstrate chronic fatigue, occasional toe dragging, itching body parts (mainly the head), depression and poor appetite. As time goes on, they might exhibit some of the following: urogenital discomfort, biting at themselves, transient peripheral lymphadenopathy, cording of the lymphatics, vasculitis in the hind legs, a mucoid nasal discharge, hyperventilation at rest, asthma, insulin resistance, difficulty standing up, hind leg gait deficits, anxiety and/or hallucinogenic behavior. Both allergic and autoimmune states reflect alterations of the immune system. If an allergic response lasts over a long period of time (weeks), IgE remains abundant and other immunoglobulins eventually enter the fray. Both Myasthenia Gravis and Lambert Eaton Myasthenic Syndrome involve antibodies of the IgG class, acetylcholine receptor antibodies and calcium channel antibodies respectively. (This is why a percentage of babies born to mothers with MG or LEMS have ‘neonatal MG’ or ‘neonatal LEMS’ until the antibodies from the mother’s blood disappear within the first week or two of life.) Both pre-synaptic (LEMS) Shivers horses and post-synaptic (MG) Shivers horses already have plenty of IgE MG is characterized by high levels of mast cell density in certain tissues and LEMS has been linked to mastocytosis (an excessive number of mast cells) in humans. Regardless of which came first, i.e., Leptospirosis or Shivers, for a Shivers horse dealing with a leptospiral infection, the stage is set for all the results of mast cell stimulation to escalate in intensity. Small animal veterinarians have observed that Leptospirosis vaccination appears to trigger mast cell tumors in some dogs there is no approved vaccine for horses.


Even though testing for up to seven serovars of Leptospirosis is available for horses, results are subject to personal interpretation. Another diagnostic challenge hinges on spirochete biology, namely an adaptive ability to morph into ‘round bodies’ (a different shape) when the local environment changes. Clarification of spirochete round body relationships with their vertebrate hosts will be lacking until sorely needed research regardless of species is accomplished. As with Fibromyalgia and systemic fungal infections, not all Leptospirosis horses develop Shivers nor do all Shivers horses have active Leptospirosis. If a horse displays signs of massive mast cell stimulation, with or without the presence of Shivers, Leptospirosis should be high on the list of possible scenarios. In the case of a horse with Shivers and a head that simply loves to be rubbed with a soft towel after exercise, Leptospirosis should be considered. Oral Doxycycline is one of the antibiotics of choice for spirochete infections. It has the added benefit of having an anti-inflammatory effect on immune mediated neuritis. (Immune mediated neuritis can manifest as mild itching, stringhalt, Shivers, head shaking, hypersensitivity to hot and/or cold weather or any number of other syndromes such as EFMS and/or any combination thereof.) For a horse with Leptospirosis the dose should be 5 milligrams per pound twice daily for up to sixty days. Ideally a blood sample is tested at the start and again after antibiotic therapy. Short term benefits can be obtained with antihistamines, aspirin and/or ibuprofen, however use of these drugs is like closing the barn door after the horse is out they have a place but are not practical for long term use.


With the exception of autoimmune hemolytic anemia, one drug that IS useful for maintenance of horses with a wide range of immune mediated problems such as Leptospirosis is Pentosan. Pentosan polysulfate sodium is gaining popularity in the treatment of several human diseases, among them Crohn’s disease (an autoimmune gastrointestinal disorder). It stabilizes mast cells by inhibiting allergic mast cell stimulation. This powerful effect results in reduced histamine release, an effect more potent than that of hydroxyzine, a drug that merely competes for histamine receptor sites on target cells and is often prescribed for horses with Cushing’s syndrome. An example of symptom overlap that can be addressed with Pentosan is the skin hypersensitivity common in Fibromyalgia horses. People with Fibromyalgia have up to four times the usual number of mast cells just below their skin surface. Imagine how much discomfort (itching and burning) such a horse would have upon being groomed with stiff brushes and/or heavy hands. Additionally Pentosan lowers intracellular calcium. An essential signaling molecule, calcium levels must be maintained in a precise balance, in a ratio of about twenty thousand times more outside than inside individual cells. When intracellular calcium rises, cells die and different neurodegenerative diseases result. One of the key regulators of intracellular calcium is the voltage gated calcium channel, which is dysfunctional in LEMS. Pentosan’s effects are dose dependent, appear quickly (24 hours) and last long after it has washed out of the body (weeks).


The little known herb Butterbur is a perfect therapeutic partner for Pentosan, useful because it is complementary at worst and synergistic at best. It is a natural beta blocker, i.e., it reduces spasms of capillary muscles and lowers blood pressure. Improved arterial blood flow results and is probably amplified in the presence of Pentosan which is heparin like. (It has been shown that Pentosan improves blood supply to subchondral bone in horses’ joints.) Butterbur gives dramatic relief to most sufferers of migraine headaches, one of many human diseases now viewed as ‘calcium channelopathies’. That a simple herb could give relief to throbbing blood vessels within the central nervous system suggests an exciting possibility for controlling spasms in the peripheral nervous system, an overlapping symptom of Leptospirosis, MG, LEMS and FMS. While Pentosan stabilizes mast cells, Butterbur lowers the effects of leukotrienes and prostaglandins which leak into tissues when mast cells do explode. Pain relief is the end result. For a thousand pound horse a dose of 300 milligrams Butterbur root extract added twice daily to the feed can be used until results are seen. Herbs can take weeks to garner improvement but provide a horse friendly alternative to aspirin or ibuprofen and like Pentosan can be pulse dosed over the long term. Horses allergic to daisies, chrysanthemums or marigolds should not be fed Butterbur, which belongs to the daisy family. Both Pentosan and Butterbur, used alone or together, appear to yield impressive clinical improvement by working at both the central (CNS) and peripheral (PNS) nervous system levels, a fact which lends excitement to this rapidly expanding field of twenty-first century research known as ‘autoimmune channelopathies’.



"A new scientific truth does not triumph by convincing its opponents and
making them see the light. but rather because its opponents eventually die,
and a new generation grows up that is familiar with it".





Casey Johnson





MULTIDIMENSIONAL MEDICINE



Copyright March 1, 2020 by Brenda Bishop, VMD All rights reserved.

No portion of this publication may be used without prior written permission of the author.

The author asserts her moral right to be identified with this work.




“When we know better we do better.”

-Maya Angelou-




Shining the light of our awareness into historically dark corners is a metaphor for the shifting paradigms we as horse owners face in this new year of 2020. Traditional linear thinking has served us up to a point and now it is time to take an accounting and ponder the gaps in our knowledge regarding horse health care. Prevailing mindsets have become comfortable with using drugs for anything and everything that amounts to a problem. This approach chooses “better living through modern chemistry” over broader mindfulness of deeper implications and fails to serve the whole horse. All the humans in horses' lives have become drug buyers and/or drug sellers. Equine supplements alone have become a multimillion dollar industry in a relatively short time. A small minority of horse people outside this grid fall into the network called healers. “Healers don't heal anyone. They re-balance.” (Abraham Hicks) Re-balancing centers around three principles: the principle of contraction, the principle of expansion and the principle of plurality.


Horses are by nature peaceful grazing prey animals. They are born equipped to run away from predators. When this ability is hampered by unsoundness of limb or limbs they become fearful and naturally prone to panic. Shortened forward phase of stride, delayed forward extension, flexors restricted by inflammatory agents, delayed over-extension (for example clicking heels), hypermetric gaits with spasms in abductor muscles (for example stringhalt, shivers), postural tremors, contracted heels, etc. are examples of contraction leading to tendon sheath rupture, suspensory strain and untold anxiety. The mental stress alone contributes to multisystem dysfunction such as gastrointestional ulcers, adrenal exhaustion syndrome, and increased permeability of the blood brain barrier. The principle of contraction is (from the horse's point of view) characterized by fear and potentially self destructive behavior. In order to re-balance it is necessary to get the horse's body and mind back to a natural neutral state of well-being.


The principle of expansion is essentially a one way street. “The mind, once stretched by a new idea, never returns to its original dimensions.” (Ralph Waldo Emerson) Healing takes place from the inside out when any and all impediments, restrictions, obstacles are removed. If the horse's garbage cans (lymphatics, liver, kidneys) are brimming with toxic debris, infection, parasites, etc. a cleansing is required to open (expand) the channels. If the lungs are not able to expand after contraction with each breath, the stress level is exponential. The interconnectedness of all things dictates that multiple systems will come into play on the path to well-being. The brain and central nervous system can compensate for small neuronal deficits but eventually imbalance will create downstream issues. Questionable integrity of the blood brain barrier is something healers tend to think about and factor into their protocols because it is so fundamental and necessary for promoting good health going forward.


The principle of plurality incorporates aspects of expansion and contraction from a higher perspective. Linear thinking is useful but it falls short when the rubber meets the road on the path to lasting balance an expanded paradigm is required. Standing at the bottom of a mountain we can only see a short distance up standing at the top allows us to see everything below. This higher view organizes horse keeping into more obvious groups of choices. If we simply focus on three areas of healthcare (nutrition, chronic infection status and parasite status) the convoluted puzzle pieces will fall into place. When the inside of the horse is right the outside takes care of itself. Horse nutrition has been very well researched and can be learned by anyone taking the online course given by Eleanor Kellon, VMD, a pioneer in this field. Chronic stealth infections such as Borrelia (Lyme) and Bartonella operate in relative darkness due to lack of funding for needed research. (See Frequently Asked Questions on the Bartonella page of this website.)


Plurality is analogous to a modern Physics term for explaining the inter-relatedness of the distant parts of a phenomenon, 'entanglement'. Linear thinking cannot get there from here. Entanglement deals with answers which generate whole new lines of questions. We know that chronic bacterial stealth infections are synonymous with multiple system overlap. But we frequently fail to realize that chronic zoonotic parasitic infections are usually part of the total picture we label immune system compromise. Layers of infection are inevitable the longer a body is out of balance. Healers like to think of their work as 'peeling the onion'. One layer that grows more omnipresent over time is that of worms with a filarial stage in their life cycle. Examples are Onchocerca cervicalis, Oxyuris equi and Setaria equina. Because these worms live under the skin conventional “fecal exams are not worth the paper they are printed on” (Marvin Cain, DVM) when it comes to these parasites. Additional concerns arise by virtue of the fact that systemic filariasis is perpetuated courtesy of a symbiotic bacteria (Wolbachia) belonging to the same phylogenetic class as Bartonella spp., an avenue currently being explored by the World Health Organization.


New questions we should be asking ourselves go something like this: are frequent draining foot abscesses and/or subsolar abscesses bacterial, microfilarial or both? Are ill defined (dormant) cysts seen on diagnostic imaging of stifles, hocks, fetlocks, navicular areas microfilarial? Are horses diagnosed with COPD harboring millions of microfilaria in their lungs? Are seasonal skin pruritis problems linked to microfilarial populations positioning themselves to be siphoned off by blood sucking insects? Are club feet associated with small vessels clogged with microfilaria acquired through the placenta? Are microfilarial parasites inhabiting the pituitary in IR and/or Cushings horses? Are a horse's “Lyme/Bart” symptoms worse during a full moon because unrecognized microfilaria become active during certain lunar cycles? Are my horse's symptoms consistent with 'nocturnal periodicity' typical of microfilariasis? Is there a symbiotic relationship between this group of parasites and chronic stealth bacteria? What role do microfilaria play in acute onset co-infections such as tetanus, neurologic herpes and so-called protozoal myelitis? What are the inter-relationships between chronic Lyme disease, brain fog and filariasis? A review of the Symptom Check List under Bartonellosis will spark a plethora of additional questions for the reader.


Parasite resistance to chemical dewormers (drugs) is a well documented phenomenon in horses. Traditional deworming plans almost never take into account the possibility of worms with microfilarial stages. Fortunately there are a number of effective options that should be considered on a case by case basis. These include but are not limited to the following: resveratrol, arnica, Para-X (Omega Alpha), silicia, Silver Lining Maintenance, BVC (Advanced Biological Concepts), Source Micronutrients, dandelion root, white sage, prebiotics (garlic, bananas, custard apples, watermelon), and custom herbal Parasite Blends made specifically for addressing filariasis. Deworming strategies such as custom blends paired with nutritional balancers maximize blood brain barrier integrity by incorporating vitamins B6, B9, B12, resveratrol, curcumin, vitamin C, and anti-oxidants (green tea, raw barley, raw oats, Colloidal Silver, vitamin E). Stress reduction can be achieved with balanced targeted nutrition, chronic stealth infection and parasite elimination, and by limiting exposure to electromagnetic fields. Ideally we should remove anything electronic from our horses' immediate environment. This requires a return to natural environments far away from high voltage power lines and turning off the barn radio.


Additional Reading:


http:// www.copperfieldequinetherapy.com/ biodiversity-and-what-lies-beneath-the- connection-to-equine-diseases-2-2-2/


https://www.sciencedirect.com/topics/ agricultural-and-biological-sciences/ onchocercidae


Microbial population analysis of the midgut of Melophagus ovinus via high-throughput sequencing Parasites and Vectors 2017 PMID 28793927


https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC106837/ Zoonotic Filariasis


https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4893572 A Rare Case of Ovarian Filariasis



Filariasis Symptom Check List













​



Cell Danger Response in Horses
Part One “Switch Flipping”



Copyright June 22, 2024 by Brenda Bishop VMD
All rights reserved.
No portion of this publication may be used without prior written permission of the author.
The author asserts her moral right to be identified with this work.
“When you write things down, they sometimes take you places you hadn't planned.”- Melanie Benjamin



At this pivotal time in earth's history (2024 marks the closing window of the precession of the equinoxes), horse lovers across the planet can celebrate the impactful work of two brilliant minds, that of Steve Jobs and that of physician-scientist Dr. Robert Naviaux, both of whom still had more to give before passing prematurely. We all enjoy access to instant high speed communication from just about anywhere on the planet thanks to Apple technology and we now have a road map “Cell Danger Response” (CDR) for addressing and reversing chronic progressive immune mediated afflictions across species lines thanks to Dr. Naviaux. Examples in humans are Parkinson's and Alzheimer's diseases. Examples in horses border on too many to count in Part Two we will focus on Polysaccharide Storage Myopathy (PSSM2) which has already been studied extensively by many and up until now has remained challenging. The time has come for all of us to pick up the slack in the reins, take a deep seat and a long hold (as they say on the racetrack), kick ourselves forward, and focus on the bigger picture. Mountain moving is never ending hard work but it's easier in the presence of sincere gratitude for those who have gone before us gratitude opens the door wider. Here are some examples of traditional cowboy wisdom:
“The two best friends a horse ever had are Mother Nature and Father Time.”
“Horses have to go through 4 seasons (12 months) in one location before they acclimate.”
“Horses are born with a suicide switch it's our job to keep them from using it.”
“Your horse is your mirror.”
“Horses never lie.”
“Horses have to see the distant horizon in order to orient their perception.”
Since horses themselves are impeccable teachers, we will review the historical clues left to us by four thoroughbred race horses: Seabiscuit, Ruffian, Barbaro (all of whom died young) and Wise Dan of whom it was said, “The day Wise Dan found his OFF switch he became unbeatable.” These four Champions have contributed precious contextual clues (histories) that amount to teachings by way of illustration on the far reaching impact of Cell Danger Response in our horses.


Dr. Naviaux managed to identify specific patterns and common denominators involving a wide range of known biochemical feedback loops within the body that are modulated (switched ON) when danger is perceived at the cellular level. He then organized this data from a multidimensional perspective, making the astute observation that mitochondrial walls start to fall apart (disintegrate) when the ON switch stays on, i.e., gets stuck in the ON position. For horses, their first line of defense is flight, running away from danger. At the cellular level they switch into survival mode when threatened. The longer their cells prioritize survival mode, the harder it is for them to revert back to equanimity. In this event the affected horse cannot rebalance and becomes a danger to himself and all others around him. Opposites over-ride normal this can manifest as perception (my space/your space) issues, argumentative behavior, aggression, running backwards, absolute refusal to move forward, facial expressions that appear like 'the lights are on but nobody's home', attention deficit hyperactivity disorder (ADHD), high headed hollow backed posture (opposite of long and low), nervous habits such as teeth grinding, staying apart from the herd as opposed to within the herd, hypersensitivity to grooming, touch, bathing, rain, biting insects, needle sticks, chemical hypersensitivity to drugs (especially sedatives), allergies of every description, lower than normal panic thresholds, unexplained weight loss, abnormal sweating (insufficient or excessive), dull haircoat, chronic fatigue, chronic gastrointestinal dysbiosis, immune system compromise leading to evidence of multiple chronic stealth infections, and so on. Endorphin release which modulates inflammatory cytokines can provide temporary relief and tends to entrain habits that become increasingly irreversible. Examples are cribbing, refusal to being passed by another horse or a herd, 24/7 agitation, stall walking, weaving, intermittent head shaking and in some cases an allergic state, Mast Cell Activation Syndrome (MCAS).

Seabiscuit exemplified a horse who alternated between operating in the OFF position and racing in the ON position. He was fortunate to have an old school horseman for a trainer, who catered to his comfort level in every situation. Horses with CDR get extremely dizzy in a moving transport conveyance they will fall down even at low miles per hour. In Seabiscuit's day the only way to move from the east coast tracks to the west coast (Santa Anita in California) was by rail. His trainer arranged for one railroad car to be deeply bedded in clean straw his companion track pony was installed at one end before 'the biscuit' was walked aboard. Even before the train started moving he would promptly lie down in the deep bedding and never stand up again until the destination was reached. (A good example of “the horse will always tell you”.) Toward the end of his career he ruptured a suspensory ligament in the Santa Anita Handicap. Horses with chronic microfilarial infestations can blow out (“bow”) tendons just standing around repetitious pounding at top speed for any or all of the major tendons behind the canon bones is an accident looking for a place to happen. Laura Hillenbrand's epic biography of Seabiscuit contains no less than eighteen clues that characterize filariasis. (See the Filariasis Symptom Check List.) During his racing career, Seabiscuit would appear drowsy (sleepy) in the saddling enclosure and cantering out to the starting gate once the gate was sprung open however he flipped into warrior mode, aggressively running down and passing any horse in front of him. In retirement Seabiscuit was found dead at the age of fourteen from 'an apparent heart attack'. It would appear that repetitious switch flipping coupled with chronic imbalance(s) might lead to the point of no return.

Ruffian was described by many as a freak of nature. At barely twelve months old she weighed about nine hundred pounds and grew into a massive athlete. Excessive growth hormone (acromegaly) most commonly is caused by a non-cancerous tumor of the pituitary in humans when horses are born infected with filarial worms (via microfilaria through the mare's placenta), dormant abscesses of microfilaria will start populating low oxygen body parts. The central nervous system makes an ideal low oxygen hiding place the filly was doomed from the start. Making matters worse, filarial worms and their endosymbiotic Wolbachia bacteria are masters of stealth, living under the radar of human recognition. Wolbachia confers massive upregulation of fertility in female worms, thereby ramping up danger for their host, in this case a horse, relative to the body parts infected. In addition to growth hormone, ACTH (adrenocorticotropic hormone) is made in another region of the pituitary ACTH gets released into the bloodstream and finds its way to the adrenal glands next to the kidneys. The adrenals secrete a range of hormones including epinephron (adrenaline), norepinephron, and cortisol which get released in times of stress (the 'flight or fright' response) while synchronistically the body dials back non-essential cellular functions: textbook CDR. The meticulous research compiled by Jane Schwartz for her biography of Ruffian led her to use a prophetic subtitle “Burning From The Start”. Her descriptive writing captures the essence of her subject's life history. Even as a coming yearling the filly's unique demeanor was described by those around her as “calm but wired at the same time”. A horse's body wired from head to tail 24/7 in stress mode is a danger to themselves and anyone around them. Due to circumstances beyond anyone's recognition, Ruffian's internal demons had established themselves high up in her central nervous system, totally out of sight and working 24/7 to keep her firmly captured, i.e., stuck in CDR mode switched ON. Among her more dramatic anomalies were her lack of sweating that normally accompanies extreme muscular exertion (anhidrosis) which traces back to endocrine imbalance, and consistently violent reactions to two procedures every race horse is expected to handle: post exercise bathing with a wet soapy sponge high between the hind legs, and tightening the girth of a race saddle. It actually required two men to wash between her massive hind legs without getting kicked. Girth tightening was done as efficiently as possible to avoid anyone getting savagely bitten. Horses infected with filarial worms are particularly sensitive in both these areas major lymphatic channels lie along the girth channel area and also between the hind legs. Even the slightest pressure on these vessels creates excruciating pain. The lymphatics are the garbage can of the body (along with the spleen) and operate more and more slowly over the horse's lifetime clearing out accumulated toxins from normal exercise as well as dead parasite debris. Even the Triple Crown champion War Admiral suffered with painful lymphatics, which is why he became quite adept at walking on his hind legs once the saddle was tight his photographers learned early on to stay out of harm's way. He too was likely born infected.

Barbaro had much in common with Ruffian. While in Florida prepping for the Kentucky Derby he came back from a workout and was sweating profusely. His regular groom held his head while his trainer took over the bathing duties when it came time to slosh warm water between the colt's hind legs, Barbaro summarily kicked his trainer into the stall wall hard enough to fracture his arm. Horses avoid pain naturally but swollen lymphatic channels evoke another level of sensitivity. At Pimlico for the Preakness Stakes, Barbaro was erratic in the starting gate, broke out prematurely and had to be reloaded like Ruffian in her final race, he broke less than perfectly and didn't get far before breaking a hind leg. He received state of the art orthopedic surgery on his fractured hind leg and after many months was put to sleep due to sudden onset painful laminitis in a front foot. (Both acute and chronic laminitis can result from rupture of dormant filarial abscesses in the feet.) The last of Barbaro's full brothers, Pennmarydel, weighing in at 138 pounds at birth, had a successful racing career but retired with a history of EIPH (exercise induced pulmonary hemorrhage) refractory to the drug normally given to these cases. Acromegaly and EIPH have both been linked to filariasis. Thanks to the thorough history left to us by Barbaro, we can safely suspect he represented another case of CDR switched ON.

Wise Dan is a great example of CDR switched OFF. He had the good fortune to be trained by an old school horseman who had worked his way up the ladder under a number of professional thoroughbred race horse mentors. This trainer's over-riding approach was to provide a natural lifestyle that catered to a horse's mental as well as physical well being. For Wise Dan, home base (Keeneland race track in Kentucky) was a short distance from the trainer's expansive cattle farm. His trainer did not move the horses in training from track to track during the year, and they always had an extended break on the farm every winter. If Wise Dan had a race at Saratoga, he shipped in, collected the winner's paycheck and shipped back home to Kentucky. Every time he raced, his behavior in the saddling ring was opposite from that of the other runners. Young horses jumping around, nerves on edge, hollow backed and high headed contrasted sharply with Wise Dan who calmly stood still observing their behavior as if as to say “ What the heck are they doing?”. His neurotransmitters were balanced he was a model citizen even when others around him were 'nervous nellies'. He enjoyed surveying the grandstand while standing in the starting gate, which occasionally delayed his first stride out but he would calmly proceed to work his way to the head of the pack, almost as if he knew where the finish line was. Retired at age seven on his trainer's farm he holds multiple records at multiple venues and a long list of awards such as Horse of the Year (twice) in 2012 and 2013. His calm demeanor set him apart from the crowd and he now enjoys a huge pasture with his retired half brother and a few young cattle.

Another famous example of CDR switched OFF was the multiple stakes winning nearly black steeplechaser Happy Intellectual. “Happy” could win big races at topnotch tracks like Saratoga even with an amateur jockey. The joke on the backside was that his groom could walk him over to the saddling ring with the lead rope in the groom's hip pocket. Like Wise Dan, his posture was always long and low and interestingly both horses had appropriate names Wise Dan was very smart and Happy Intellectual was always happy. Both horses were accustomed to farm life and both earned multiple year end awards. Now in well-earned retirement, Wise Dan maintains an enormous fan base as does his humble trainer, now semi-retired. Yet another classic example of CDR switched firmly OFF was Stonewall Jackson's horse Little Sorrel. Well loved by many during and after the Civil War he was frequently referenced in historical accounts that described the little horse's quiet demeanor. His owner was an astute horseman who spotted Little Sorrel among a group of cavalry horses on a captured Union supply train at Harper's Ferry, West Virginia early in the war. Jackson had been looking for a quiet mount for his wife so they could ride out together during brief visits home. But as he correctly ascertained, the horse proved his worth in every skirmish, every major battle, and multiple dangerous combat settings. Jackson had a habit of riding on the front lines to encourage his men forward during important battles. Many first hand reports mention how in the heat of heavy fire, Little Sorrel calmly dozed while bullets flew in every direction over his head. The perfect partner for his rider, his other priceless quality was unflagging endurance on very long marches. A small red Morgan horse standing 15.3 hands, he was a model citizen in every regard. Late in the war General Jackson was hit by friendly fire while sitting on his horse and passed away the following day. After the war ended Little Sorrel was returned to his owner's widow (Anna Jackson) who was living in Lexington, Virginia. People in those days kept written records and we are fortunate to have Anna's reporting that supplies interesting facts about Little Sorrel. He was easy to care for, extremely smart and sometimes mischievous over time he learned how to let himself out of his stall. It wasn't long before he started turning himself loose first then he would proceed down the line of stalls working the latches loose setting every other horse in the enclosure free. The entire herd would wander around to their hearts' content until their jailbreak was discovered. It was as if he had a sense of humor. Little Sorrel enjoyed his retirement and finally died at the age of 36.

General Robert E. Lee maintained a number of horses during the Civil War. Traveler was a 16 hand gray American Saddlebred who was always moving, hence his name. The horse was high- spirited, impatient, hard to hold, and pulled the General down a steep bank breaking his hands. It was then that General Jeb Stuart (who could see Traveler wasn't a good horse in combat) found Lucy Long, bought her and gave her to him. She was a small, easy moving, quiet sorrel mare. When purchased by General Stuart she was said to be 5 years old by her thirty-fourth year she was thin in flesh, though her eyes had not lost their brightness and her health was remarkable. During the grazing season she gained weight on pasture. She was General Lee's primary mount during the war and she outlived all his other horses, dying in 1891 at age 34. Traveler and Lucy Long exemplify internal CDR switched ON versus internal CDR switched OFF within the same external context. Building on Dr. Naviaux's work we can modify diets and deworming plans that facilitate switching from ON to Off naturally the body will heal itself spontaneously if we optimize internal balance. Horses NEVER lie. Horses with CDR switched OFF tend to live longer happier lives, a reality that applies to their owners as well.



Cell Danger Response in Horses
Part Two “PSSM2”



Copyright June 22, 2024 by Brenda Bishop, VMD
All rights reserved.
No portion of this publication may be used without prior written permission of the author.
The author asserts her moral right to be identified with this work.
“Always work hard on something uncomfortably exciting.” -Larry Page



A sterling example of immune mediated dysfunction in horses is a group of novel myopathies that started appearing on equine veterinarians' radar in the 1990's. Among these the prevailing consensus is that polysaccharide storage myopathy1 (PSSM1) and genetic variants described as muscle integrity myopathies (MIM's) (P2, P3, P4, Px, P8, K1) are an area of research deserving of our collective consideration, i.e., a learning opportunity. For veterinarians these myopathies are a worthy opponent the devil is in the details and so is the truth. One has to ponder whether new age chemicals are involved and whether (for example) modern farming practices have somehow contributed to the surge in symptoms we are seeing. Today the only grain in horse feeds that has not been grown in the presence of glyphosate is oats. Historically oats were the main energy source fed to thoroughbreds (a hot blooded breed), only occasionally fed to warmbloods and practically never fed to cold blooded breeds such as draft horses. It's useful to factor in the differences in basal metabolic rates between these three groups. Race horses such as thoroughbreds and other breeds bred for speed (quarter horse race horses and paint race horses) have lightning fast neuromuscular junction times for example most quarter horse race horses are faster out of the starting gate than thoroughbreds. When in training, these athletes live in stalls with little to no turnout and eat two to three servings of grain a day with copious amounts of high protein hay. Warmbloods include eastern European breeds bred for dressage, eventing and combined driving events as well as athletic thoroughbred and/or quarter horse crosses. They can be hard keepers or fairly easy keepers depending on their individual genetic basal metabolic rate. The draft breeds are bred for long days in the furrows at nothing faster than a walk, the exception being commercial eight horse hitches that delight their admirers trotting around the show ring. Slower neuromuscular junction times align with lower basal metabolic rates in breeds that burn calories slowly and easily maintain their bodyweight (hence the term 'easy keepers'). Cold blooded breeds are commonly fed low octane forage with a mineral balancer and normally live outside in the vicinity of large swaths of croplands. Today's genetically modified crops (soybeans, corn, sugar beets) frequently contain residues of glyphosate. Why is this relevant? Glyphosate interferes with neurotransmission and is thought to contribute to mitochondrial dysfunction, oxidative stress and neuroinflammation, all of which are hallmarks of Cell Danger Response. Prolonged transmission at the neuromuscular junction in a horse with a moderate to low basal metabolic rate creates significantly delayed muscle contraction. Repetitive delays can only lead to severe painful cramping and the downstream tipping point: “tying up”, ruptured muscle tissue, electrolyte imbalance, blood in the urine, and/or paralysis. For a grazing animal whose only defense is running away from danger, one can only imagine how stressful this dilemma must be for any horse. Neurotoxins aside, we need to consider the likelihood that an external triggering factor is also in play, overlaid across genetic parameters. Traditionally, horses spend their early years (like all grazing wild animals) outside, exposed to Mother Nature. They experience wind, rain, hot days, cold days, and four seasons. Late spring, summer and early fall are typically seasons friendly to blood sucking biting insects. As humidity retreats and the first killing frosts approach, biting insects go into their seasonal feeding frenzy. With just one blood meal, a single mosquito or tick or horse fly can transmit half a dozen or more chronic stealth pathogens. Examples are Borrelia (Lyme disease), Bartonella (several species), Wolbachia endosymbionts, Babesia species, Corynebacterium pseudotuberculosis (Pigeon Fever), Leptospirosis (multiple serovars), Toxoplasmosis, Anaplasmosis, EIA (swamp fever) in addition to as many as 30,000 microfilaria per drop of blood. (See the Filariasis Symptom Check List.) IT IS EXTREMELY NAIVE TO ASSUME STEALTH PATHOGENS TRAVEL SOLO, without company. “Birds of a feather flock together” as do chronic stealth pathogens. These liaisons (an unholy alliance) are particularly problematic when symbiotic relationships develop over thousands of years completely in the dark, hidden away from the light of human awareness. Stealth pathogens tend to congregate and evolve in mutualistic self-serving ways that ensure their survival and promote their spread with absolute impunity. One biting insect's blood meal amounts to a reservoir of multiple stealth pathogens randomly transferable to a variety of hosts: humans, horses, wildlife etc. Biting insects are the taxi drivers their payload will get unloaded, become established and propagate faster in larger slower moving horses than in smaller highly sensitive lightning fast horses. The key to recognizing systemic immune system compromise lies where internal and external environments intersect. It pays to remember (1.) worms come to the surface when it rains, and (2.) filarial worms respond to the lunar cycle, i.e., full moon periods. What we call Equine Recurrent Uveitis the old horsemen called Moon Blindness and for good reason. ERU caught early enough will go into remission if filarial worms are addressed i.e., blindness is preventable.


Filarial worms have been on the planet for thousands of years. The dog and cat heartworm (Dirofilaria immitis) has been studied in much greater detail than the two filarial worm species found in horses: Onchocerca cervicalis and Oxyuris equi. Historically the discovery of ivermectin led to it's addition to veterinary and human pharmacies in the early 1980's. Not surprisingly the reduction in lymphatic filariasis in humans has been a major advance for thousands of people in endemic countries (mainly in Africa) over the last forty plus years. In African countries it's well known that filariasis can lead to “river blindness”. Ivermectin was formulated for oral use in horses in the mid 1980's interestingly the disorder named PSSM2 was first recognized about ten years later. Regardless of the exact time frame, one has to wonder about eventual drug resistance and the appearance of super worms. Ivermectin is a GABA agonist it prolongs the neuromuscular junction timing such that the interval between the nerve firing and the respective muscle contracting is lengthened. This mechanism of action effectively paralyzes tiny microfilaria at the micro level. Adult filarial worms can survive this assault but immature worms are vulnerable. The fly in the ointment so to speak is the fact that female adult filarial worms are extraordinarily fertile. A single adult can produce around 10,000 offspring every 24 hours. These tiny immature microfilaria are adept at crossing the blood/brain barrier and entering the central nervous system which is predominately white. They thrive in low oxygen environments and therefore seek poorly perfused (supplied with arterial blood) white connective tissues like bone marrow, tendons, ligaments, the ligamentum nuchae in the neck, and connective soft tissues which are primarily collagenous (white) tissue. Well oxygenated red tissues like skeletal muscle are not worm friendly. The reason adult female filarial worms are so fertile is their live-in (endosymbiont) room mates, Wolbachia species. Wolbachia is a stealth bacterial pathogen closely related to the genus Bartonella in the phylogenetic tree. It cannot be emphasized enough that multiple stealth pathogens travel together and are transmitted together. This creates a considerable amount of symptom overlap which is inevitable. It's not a question of if they are present it's a question of when their destructive footprints become apparent. The more time horses spend in natural environments the greater the risks of exposure and infection which accrue exponentially in a horse's lifetime.


The combination of glyphosate exposure (through the diet) and regular ivermectin treatment (dosed orally) can be expected to have an additive net effect (like tree limbs on a power line) on skeletal muscle, namely delayed neurotransmission. Superimposed on this scenario we must factor in exposure to blood sucking insects which contribute parasites (filarial worms) harboring among other bad actors Wolbachia bacteria. Why exactly does this matter? A little known fact about Wolbachia is that it modulates (up regulates) insulin signaling to their host worms' advantage and to the horses' disadvantage. Energy in the form of glycogen or polysaccharides gets shelved into storage, creating a deficit of cellular fuel in precisely the location where it's needed most for proper 'on demand' skeletal muscle contraction. Making matters worse for the horse, up regulated insulin enhances uptake of potassium into cells, lowering the serum presence of potassium. Low blood levels of potassium (hypokalemia) limit blood flow to skeletal muscles and are associated with rhabdomyolysis (destruction of skeletal muscle cells) aka “tying up”. PSSM2 horses typically have high serum potassium levels following skeletal muscle disintegration and leakage. Little Wolbachia bacteria don't just start a fire, they fan the flames, hanging around for years repeating their destructive activities again and again.


The good news is there is plenty of light at the end of this very dark tunnel. The horse's body will re-establish a healthy state of homeostasis once two criteria are met: A1 balanced nutrition and regular A1 holistic deworming that jump starts cleansing of the septic system of the body: the spleen and the lymphatic channels. Remission of PSSM2 can be achieved if a customized plan for each case is deployed. Parameters such as mitochondrial damage (a hallmark of prolonged Cell Danger Response), whether the affected horse was likely infected at birth through the dam's placenta or later, abnormal behavior patterns (example: cribbing), chemical deworming history, historical switch flipping episodes, soundness history and so on should be taken into consideration. Using a holistic TCM (plant based) deworming protocol and exactly zero pharmaceuticals we can kill Wolbachia, i.e., sterilize the female worms, kill microfilaria and foster good health with ongoing attention to good housekeeping. (Adult filarial worms will shrivel and die within about seven years.) Armed with even a rudimentary understanding of Cell Danger Response, a multitude of immune mediated dis-ease states can be successfully targeted. Arguably the most useful tool to have in our toolbox is a twelve month calendar that notates the lunar cycles and/or a Farmers' Almanac. Parasite resistance to chemical dewormers has ramped up exponentially over the last forty years. Synchronistically we are seeing earlier onset of career ending diagnoses as more and more horses are born infected with microfilaria acquired through the dam's placenta. Examples are RER (recurrent equine rhabdomyolysis), ERU (equine recurrent uveitis), EIPH (exercise induced pulmonary hemorrhage), COPD (chronic obstructive pulmonary disease), acute onset and chronic laminitis, and early onset Cushing's disease (pituitary dysfunction, insulin dysregulation etc.): reflections of textbook CDR. Add in drug resistance and possible neurotoxin exposure and career ending injuries are not a matter of if, they are a matter of when. Full moons trigger inmate release (lasting up to 72 hours or longer) when microfilaria wake up to cavort on their moonlit playground. Consider the fact that Ruffian suffered her life ending catastrophic injury within hours of a full moon the previous night. Descriptive labels that include the words 'recurrent', 'periodic', or 'intermittent' should make us pause, strive to collect a thorough history (including diet, deworming history, correlation of symptoms with lunar cycles, maternal health history, etc.), and review any and all available testing options for PSSM2.


“You cannot connect the dots looking forward you can only connect them looking backwards....................... and then you can move mountains.” - Steve Jobs



Systemic Lupus Erythematosus (SLE)
Symptom Check List



(updated 09/01/2021)

Copyright September 1, 2020 by Brenda Bishop, V.M.D. All rights reserved.

No portion of this publication may be used without prior written permission of the author.

The author asserts her moral right to be identified with this work.


​



Simultaneously as filarial parasites infiltrate horses' bodies via the circulation into every available nook and cranny within soft tissues (preferentially tissues built upon a collagen matrix), a certain percentage of horses escalate from chronic immune suppression to self destructive overdrive their immune systems start attacking themselves. Consequently autoimmune conditions tend to co-exist some examples are autoimmune hemolytic anemia, pemphigus, immune mediated keratitis, inflammatory bowel disease (IBD), cutaneous lupus and systemic lupus erythematosus (SLE). Unfortunately for affected horses, SLE is rarely recognized for two reasons every case is uniquely different symptom-wise (NO TWO CASES ARE ALIKE), and repeated exposure to specific high risk factors is commonplace. Many possible indicators of autoimmunity, convoluted in and of themselves, are challenging to appreciate due to layering of systemic stealth bacteria, filarial worm loads, mycoplasmas, biofilms, viruses, and so on. The following list of diagnostic criteria reflects a considerable amount of symptom overlap with Filariasis and Bartonellosis. Helping a compromised immune system is akin to closing the barn door after the horse is out. For veterinarians trained in developing a linear differential diagnosis list it doesn't help matters that autoimmune states tend to cluster, more or less superimposed upon each other reflecting multidimensional dysfunction.


Indices of Suspicion

__age of onset (early adulthood, 5 to 10 years)

__breed predilection (none however larger individuals are at higher risk)

__sex predilection (mares appear to be at higher risk due to presence of estrogen)

______(see Drug Induced Lupus below)

__history of malnutrition and/or repeated vaccinations early in life

__history of months or years living in tropical / subtropical climates

__history of stress followed by sudden hair loss (around eyes / total head / total body)

__history of repeated exposure to high risk factors

______feeds containing soy (soy is estrogenic and estrogen makes lupus worse)

______supplements containing garlic (many insect control products)

______alfalfa products (hays / cubes / pellets / sprouts / powder)

______sulfamethoxazole / trimethoprim (antibiotics)

__food allergies (allergy panel is exceedingly useful if in doubt)


Lupus Flares

__hypersensitivity to strong UV light (consider face masks in summer)

__livedo reticularis (plain zinc oxide paste is the ideal sunscreen for faces)

__rapid shallow breathing / fluttering nostrils at rest

__spontaneous periodic deep hyperventilation at rest (5 to 20 minute episodes)

__depression / eyes half closed / ocular pain

__hypersensitivity reactions to vaccines / drugs

__hypersensitivity reactions to alfalfa (organic and GMO)

__hypersensitivity reactions to garlic

__hypersensitivity to lectins (contained in grains such as corn, oats, barley)

__hypersensitivity to coconut oil

__deterioration on feeds containing soy

__lupus nephritis / frothy urine / blood in urine (hemoglobinuria)


Neuromuscular Predilections (that wax and wane randomly)

__non-specific muscle spasms tetanic in nature

__recurrent exertional rhabdomyolysis (RER) (commonly in young nervous mares)

__lower back / sacroiliac area chronic regional pain (CRPS) / transverse myelitis

__postural tremors (difficulty holding legs up against gravity )

__proximal suspensory desmitis (PSD) / suspensory strain

__cold hind legs / cold feet

__swollen joints (hocks, stifles)

__spasms of diaphragm (thumps aka hiccups)

__cardiac conduction disturbances (dropped beats / atrial fibrillation)

__pericarditis / transient ischemic attacks / sudden collapse / chest pain

__chronic fatigue (CFS) / fibromyalgia (EFMS) / poor exercise tolerance


Dysbiosis

__periodontitis

______mouthiness

______liver dysfunction / burping (not to be confused with thumps)

______endocrine imbalance

__ulcers (gastric, hind gut and frequently both)

__leaky gut syndrome (LGS) (manure can be normal, tight or loose) / IBS / IBD

______chronic protein deficiency

______loss of gut integrity / loss of glutamine (siphoned off by microfilaria)

__chronic oxidative stress / improvement on antioxidants

__biofilms / fungal overgrowth / Candida overgrowth

__'protein losing enteropathy' (poor haircoat, poor hoof quality)

__sensitivity to glyphosate contaminated feeds (soy / alfalfa / corn / beet pulp)

__multiple food allergies / improvement on elimination diets


Central Nervous System / Cranial Nerve anomalies

__'lupus psychosis' / immune mediated neuritis (multiple expressions)

__sporadic hallucinations

__brain fog that waxes and wanes

__optic neuropathy / uveitis (ERU) / keratitis (IMMK)

__hypersensitivity to sound

__dry mouth and/or dry eyes

__random seizures

__dizziness (during and after transport and/or repetitive forced exercise

__autoimmune transverse myelitis


Multiple Co-infections

__filarial parasites

______Onchocerca cervicalis (thread worms)

______Oxyuris equi (pin worms)

______Dirofilaria immitis

______Setaria spp.

__chronic stealth bacterial infections

______Wolbachia spp (see Filariasis Symptom Check List)

__________chronic cellular oxidative stress

__________unusual skin changes / chronic 'rain rot'

__________disseminated granulomatosis

__________semicircular white hair spots (shoulders / torso / thighs)

__________sweet itch (face, chest, ventral midline, neck, groin, tail head, lower legs

______Bartonella spp (see Bartonellosis Symptom Check List)

______Borreliosis (lyme disease)

______mycoplasmas (numerous)

______biofilms (respiratory and/or digestive and/or urinary tracks)

__Leptospirosis

__Toxoplasmosis

__Piroplasmosis (Babesia spp)

__Anaplasmosis (Ehrlichia equi)

__Potomac Horse Fever (Neorickettsiae risticii)

__Sarcocystis spp (Equine Protozoal Myelitis)

__Corynebacterium pseudotuberculosis (Pigeon Fever)


Neonatal Lupus (history of)

__neonatal myasthenia gravis (Shivers)

__failure to thrive (foals)

__orphan foals / foals weaned too early


Dermatologic Lupus

__disseminated granulomatosis

__alopecia areata (around eyes)

__sudden total hair loss on entire head and/or entire body


Drug Induced Lupus (history of)

__minocycline (antibiotic)

_sulfamethoxazole (antibiotic)

__butazolidin (non-steroidal anti-inflammatory)

__phenothiazines (tranquilizers)

______acepromazine

______fluphenazine (illegal antipsychotic)

______chlorpromazine (illegal antipsychotic)

__________tissue residues persist for long periods (years)

__________**males are more prone to chlorpromazine induced lupus than females

__________lingering hypotension, pseudoparkinsonism, spasms, restlessness

__omeprazole (proton pump inhibitor / ulcer preventative)

__synthetic progesterone (exogenous hormone withdrawal / endocrine imbalance) ​



***Contributions from around the planet courtesy of Catherine Cooper (www.copperfieldequinetherapy.com)***





A series of 6 videos



FOR MORE INFORMATION CONTACT:

Brenda Bishop,VMD


Phone number: 910-783-9740
Email:sporthorse@carolina.net

Carthage, North Carolina



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