Researchers are redefining how we categorize the age-old muscular disease called tying-up
A working draft horse was fine on Saturday, given a day off on Sunday, and come Monday is resistant to move forward, sweaty, and seemingly painful all over. A fit Thoroughbred racehorse walking off the training track is suddenly unable to walk and is sweating, painful, and colicky. And an athletic Warmblood is neither moving quite like she should nor performing at her typical level, though she doesn’t seem painful.
There was a time you might have lumped all three horses into the same category, deducing that they were “tying-up.” But while each of these horses has a muscular disorder that negatively affects their performance, they do not have the same myopathy (muscle tissue disease) and not all three are tying up.
“Many times, the expression ‘tying-up’ is used to cover all sorts of muscle disorders,” says Stephanie Valberg, DVM, PhD, Dipl. ACVIM, ACVSMR, of Michigan State University’s (MSU) McPhail Equine Performance Center, in East Lansing. “To be used correctly, owners should only use the term ‘tying-up’ for horses with a specific subset of muscle disorders. Only horses with sufficient muscle tissue damage resulting in the muscle cell contents leaking into the bloodstream should be referred to as tying-up.”
Veterinarians can distinguish horses with muscle damage that are tying up from horses with other types of myopathies based on a blood test. Horses with increased levels of the muscle enzymes creatine kinase (CK) and aspartate aminotransferase (AST) are the only ones truly tying up.
Given the confusion between horses with a “myopathy” versus “tying-up,” Valberg admits she is trying to move away from the term tying-up altogether.
“The phrase was popularized back in the 1970s and ’80s when we believed there was only one cause for tying-up and, therefore, only one muscle disease in horses called tying-up,” Valberg says. “This effort to shoehorn every muscle disease really held research back. Once we recognized there was more than one cause for muscle disease in horses—some exercise-associated and others non-exercised-associated, some that cause muscle damage and some that only cause poor performance without muscle damage—our ability to help these horses advanced.”
Extensive research in this field by Valberg, who is the Mary Anne McPhail Dressage Chair in Equine Sports Medicine and professor of Large Animal Clinical Sciences at MSU, and colleague Joe Pagan, PhD, of Kentucky Equine Research (KER), helped create diets designed to limit tying-up episodes and poor performance.
“Exercise and dietary management is so successful that about 75% of Quarter Horses with type 1 polysaccharide storage myopathy reportedly never tie up again, and 80% of Warmbloods with type 2 polysaccharide storage myopathy show some level of improvement,” says Pagan, owner of KER, an international equine nutrition, research, and consultation company with its home base in Versailles, Kentucky.
In this article we’ll describe a handful of the more commonly encountered exercise-related (exertional) myopathies in horses and present research-driven dietary recommendations.
Frequently Found Myopathies: RER and PSSM
Recurrent exertional rhabdomyolysis (RER) in fit Thoroughbred racehorses and polysaccharide storage myopathy (PSSM) in Quarter Horses are two of the most widely recognized myopathies in horses. Both of these fit the definition of tying-up and present similarly:
- Muscle stiffness;
- Shortened hind-limb stride;
- Reluctance to move;
- Firm, painful hindquarter muscles (loins, croup); and
- Anxiety, pain, sweating, and increased respiratory rates.
Recurrent exertional rhabdomyolysis (RER)
Fit horses in high-stress competition environments, like the racehorse in the introduction, most commonly suffer from RER. This form of tying-up can be seen in any type of racehorse, including Thoroughbreds, Standardbreds, Quarter Horses, and Arabians. Some show horses, like Warmbloods, might also be affected. The classic case is the stressed young Thoroughbred fed a high-grain diet (> 2.5 kilograms, or > 5.5 pounds, per day) that does not get exercised for a day or two.
“A diagnosis of RER can be made based on breed, use of the horse, triggers for episodes, clinical signs, and elevated CK and AST levels,” says Valberg. “Taking a muscle biopsy doesn’t usually facilitate a diagnosis.”
Horses with RER should generally consume diets that are not excessively high in nonstructural carbohydrates (NSC).
“This means limiting grains/concentrates, sweet feeds, etc. with high sugar contents if the horse is receiving more than 5 pounds of concentrates like sweet feed a day,” says Pagan. “Thoroughbreds that cannot meet their energy (caloric) demands with these low-NSC diets can add fat, up to 10-12% of the diet. Because racehorses in full training can be finicky eaters, it is important to transition the horses onto these high-fat, low-NSC feeds slowly.”
Polysaccharide storage myopathy (PSSM)
Researchers originally discovered tying-up caused by PSSM by examining muscle biopsies under a microscope. They were consistently able to see abnormal-looking polysaccharides (i.e., glycogen, or sugar stored inside muscle cells for energy, that formed clumps) in muscle tissue samples obtained from affected horses. In further research they identified two forms of PSSM distinguishable via genetic testing.
“Horses affected by type 1 PSSM have a genetic mutation in the glycogen synthase-1 gene (GYS1),” Valberg explains. “Horses lacking the GYS1 mutation which still have microscopically abnormal sugar in their muscle cells are classified as type 2 PSSM.”
PSSM1 occurs relatively commonly and can be found in at least 20 breeds in the United States, including Quarter Horses, Paints, Appaloosas, and continental European draft breeds.
“Bouts of tying-up usually occur in unfit horses near the onset of exercise or immediately afterward, particularly if a horse has taken a few days off from work,” she says.
PSSM1 is also likely the cause of the classic “Monday morning disease,” recognized for the past 200 years in draft horses like the one in the introduction. An estimated 30-60% of Belgians and Percherons have the GYS1 mutation.
“In draft breeds the mutation can be silent, and they may not show as consistent signs of tying-up as we see in Quarter Horses,” says Valberg.
PSSM in Quarter Horses
As many as 7-10% of all Quarter Horses have PSSM1, with the highest incidence in halter types. PSSM2 occurs far less commonly.
Quarter Horses with either form of PSSM can appear and perform similarly. Specifically, affected horses exhibit anything from repeated episodes of tying-up to profound exercise intolerance. Veterinarians can use elevated CK and AST levels to confirm tying-up and genetic testing to differentiate between PSSM1 and 2. Therefore, if a Quarter Horse’s genetic test is negative for the GYS1 mutation, then a diet and exercise trial or muscle biopsy should be the next steps.
“Increased staining for glycogen and the presence of abnormal polysaccharide in muscle cells are the defining features of a muscle biopsy diagnosis of PSSM2 in Quarter Horses,” says Valberg.
Feeding Quarter Horses to limit bouts of tying-up secondary to either PSSM1 or PSSM2 involves limiting grains/concentrates and sweet feeds with high sugar contents to a greater extent than is recommended for horses with RER.
“Diets high in NSC increase the risk of muscle pain and stiffness,” says Pagan. “We should therefore lower the NSC to about 12-15% of the diet for Quarter Horses and related breeds with PSSM1. If these horses are overweight, then NSC can be lowered even further, to less than 12%.”
Owners can add fat to fit Quarter Horse diets only if needed to maintain condition—no more than about 1 cup per day.
“Overall, the goal to feeding Quarter Horses with either form of PSSM is to lower blood glucose and insulin levels (to stop glycogen deposition in muscle cells) and provide fat as a source of energy for muscle cells instead of sugar,” explains Pagan.
PSSM in Warmbloods
PSSM1 occurs in only a small percentage of Warmbloods and not nearly as frequently as in Quarter Horses. Affected Warmbloods show classic signs of tying-up as well as elevated serum CK and AST levels. The GYS1 genetic test confirms the diagnosis.
More often, however, Warmbloods are diagnosed with PSSM2, and these horses have a “unique set of symptoms,” says Valberg.
Affected breeds include Trakehners, Dutch Warmbloods, Canadian Warmbloods, Selle Français, Oldenburgs, Irish Sport Horses, and Warmbloods bred for dressage and jumping but not Icelandic horses or Haflingers.
Warmblood country is where we might start getting confused. While PSSM1 causes tying-up in Warmbloods, PSSM2 does not.
“Remember that the term PSSM2 is a description of the appearance of muscle glycogen under the microscope,” says Valberg. “At this point, a specific cause of PSSM2 is not known. There very well could be different causes for PSSM2 in different breeds of Warmbloods with the same microscopic appearance of glycogen.
“Warmbloods with PSSM2 do not commonly have classic tying-up signs, such as sweating, stiffness, an inability to move, and high serum CK and AST levels,” Valberg says. “Rather, Warmbloods with PSSM2—like example No. 3 in the intro—develop exercise intolerance with a reluctance to go forward and engage their hindquarters once they begin a level of training where impulsion is required. The cause for PSSM2 in Warmbloods is likely different from that in Quarter Horses.”
Because of these vague signs of PSSM2 in Warmbloods, Valberg cautions us when dealing with Warmbloods with exercise intolerance. PSSM2 can look like other conditions contributing to exercise intolerance—gastric ulcers, lameness, poor saddle fit, and training fatigue. In fact, these other conditions are probably more common than PSSM2.
“It is very important to rule out these problems before considering a diagnosis of PSSM2,” she says.
If a Warmblood’s GYS1 test comes back negative, owners have two options: They can try feeding a diet designed for PSSM first to see if the exercise intolerance resolves, or they can have their veterinarian perform a muscle biopsy.
With biopsy, practitioners can confirm PSSM2 based on abnormal-looking small granules of glycogen in the muscle tissues.
“When we measure the actual amount of glycogen in a biopsy sample using biochemical analysis, Warmbloods with PSSM2 do not have an increase in the total amount of glycogen in their muscle like Quarter Horses do,” Valberg says. “Instead, the glycogen simply has an unusual appearance under the microscope.”
This finding provides more evidence that PSSM2 in Warmbloods is not a distinct glycogen storage disease like PSSM1 or PSSM2 in Quarter Horses.
And unlike racehorses and Quarter Horses, Warmbloods might not always benefit from a low-NSC and high-fat diet.
“If horses with signs of PSSM2 don’t improve on this type of diet, then owners may instead try increasing the level of NSC and decreasing the amount of fat in the ration,” says Pagan.
In other words, change to a moderate-NSC and lower-fat diet.
“Horses need NSC to provide energy,” Pagan explains. “Equine diets in North America have shifted toward decreasing the amount of NSC and increasing the amount of fat over the years. If Warmbloods lack energy under saddle, they could benefit from more NSC. Burning fat can be pro-oxidant (causing damage by creating oxygen free radicals), and that may not be of benefit to horses with PSSM2.”
Myopathies By Breed
Here is a summary of the diagnostic process of classifying the type of exertional forms of muscle disease. Note the importance of considering breed when navigating this process.
|BREED||MOST COMMON FORM OF EXERTIONAL MYOPATHY||OTHER FORMS OF EXERTIONAL MYOPATHY||RECOMMENDED DIAGNOSTICS|
|Thoroughbreds||RER||PSSM2 (very rare)
PSSM1 does not occur!
|CK, AST (elevated)|
|Standardbreds||RER||PSSM1 does not occur!||CK, AST (elevated)|
|Quarter Horses racehorses||RER||PSSM2,
PSSM 1 only rarely
|CK, AST (elevated)|
|Quarter Horses (halter, reining, cutting, working cow, pleasure)
(and malignant hyperthermia not addressed in this article)
|CK, AST (elevated)
GYS1 testing first, then response to diet/training
modifications and/or muscle biopsy if negative
|Arabian racehorses||RER||PSSM1 does not occur!||CK, AST (elevated)|
|Arabians and Arab crosses in endurance||RER, PSSM2, MFM||PSSM1 does not occur!||CK, AST (elevated)
Response to diet/training modifications then muscle
biopsy if no improvement
|Draft horses (e.g. Belgians, Percherons)||PSSM1
“Monday morning disease”
|CK, AST (elevated)
GYS1 testing first, then muscle biopsy if negative
|Warmbloods||PSSM2||RER, MFM, PSSM1||CK, AST (usually normal). If elevated then perform GYS1 testing. Response to diet/training modifications then muscle biopsy if no improvement|
A Modern Myopathy: Myofibrillar Myopathy (MFM) in Warmbloods
Examining muscle biopsies from Warmbloods showing clinical signs consistent with PSSM2 led researchers to discover that some horses have evidence of a myofibrillar myopathy (MFM) instead. Specifically, they saw disrupted contractile proteins (myofibrils) and clumps of a protein called desmin in areas of muscle.
“Horses with MFM show an insidious onset of exercise intolerance that begins around six to eight years of age, and they usually stagnate in their training,” Valberg says.
Serum CK and AST are usually normal (except for the rare, acute bout of tying-up), and signs suggestive of MFM include:
- A lack of stamina;
- An unwillingness to go forward;
- An inability to collect; and
- Abnormal canter transitions and an inability to sustain a normal canter.
Like PSSM2, the diagnostic test of choice for MFM is a muscle biopsy. Owners might prefer changing diet and exercise first, but Valberg advises only doing this after your veterinarian has completed a thorough examination for other more common causes of exercise intolerance. Again, similar to PSSM2, MFM must be diagnosed under a microscopic (histologically) and its underlying cause is unknown.
Feeding Warmbloods affected by MFM is similar to feeding those with PSSM2. Specifically:
- Go easy on the fat, limiting it to only about 4-6% of the concentrate.
- NSC levels can be as high as 20-30% of the diet.
- You can offer higher protein levels, but pay particular attention to specific amino acids, which are the building blocks of proteins—offer a high-quality amino acid supplement with branched-chain amino acids and cysteine.
“In addition, because oxidative stress is believed to contribute to muscle damage in MFM, I recommend supplying supplemental sources of antioxidants such as vitamin E and coenzyme Q10,” Pagan says.
The Tied-Up Arabian
When we throw Arabians into the mix, there really are no rules. While PSSM1 does not occur in this breed, Arabians and crosses can suffer from RER like Thoroughbreds do. Affected animals usually are fit, excited horses that tie up at the beginning of a ride. Veterinarians have also diagnosed PSSM2 and MFM in these horses. Arabians with MFM often show signs of mild tying-up at the end of an endurance ride, such as an odd lameness, stiffness, and dark urine due to the presence of myoglobin—a muscle breakdown product.
“Arabs and their crosses with MFM may seem far less painful than with other forms of tying-up, but they will still have elevated CK levels when symptomatic,” says Valberg.
Instead of jumping straight to a muscle biopsy, owners can first try changing the horse’s diet and gauging the response. In cases that do not improve, veterinarians perform a muscle biopsy, which will distinguish between RER (mostly normal biopsy), PSSM2 (abnormal type and amount of glycogen/polysaccharide), and MFM (disrupted myofibrils and desmin depots).
As in Warmbloods with MFM, the underlying cause for the desmin aggregates in affected Arabians’ muscle cells remains unclear. Researchers have shown that MFM could be related to oxidative stress and an imbalance in the type of antioxidants that rely on the amino acid cysteine.
“Horses should be able to make cysteine from another amino acid called methionine, but there may be problems with this process in endurance horses at the end of long rides,” says Pagan. “Endurance Arabians with MFM can be fed in a similar fashion to Warmbloods with PSSM2/MFM except that their concentrates can be higher in fat, about 6-8% of the diet.”
Pagan’s research also supports feeding Arabians with MFM higher protein levels (12-14% crude protein). He says a high-quality amino acid source is particularly important to ensure these horses receive sufficient levels of the branched-chain amino acids lysine, threonine, and methionine.
“Branched-chain amino acids can help stimulate protein synthesis to help replace muscle,” Pagan says.
In addition, he recommends supplementing diets with whey-based proteins rich in cysteine.
“Cysteine is a precursor to glutathione and peroxiredoxin, key antioxidants found in muscle tissues,” he explains. “Research in MFM shows a decrease in cysteine-based antioxidants like peroxiredoxin in MFM Arabians.”
Consider these main take-homes from this article:
- The myopathies discussed are breed-specific.
- Only some myopathies fall into the traditional category of tying-up based on the presence of increased CK and AST levels.
- With the exception of PSSM1 and malignant hyperthermia, the underlying causes of other forms of tying-up remain unknown. (Malignant hyperthermia is a skeletal muscle abnormality seen in Quarter Horses caused by a specific mutation of chromosome 10. Inhalant anesthesia can trigger episodes characterized by severely increased body temperature, a decrease in body pH, and sometimes death.)
- No single cure or therapy can help all horses with one of these myopathies.
Myopathies don’t fit into the original mold created for horses that tied up. Researchers will almost certainly continue to identify more specific causes of exertional myopathies, and dietary recommendations will likely also evolve to help manage affected horses.
Because you can’t easily distinguish certain myopathies from causes of poor performance unrelated to muscle cell function, Valberg urges owners to work with a veterinarian when facing poor performance issues.