Sorting out muscle disorders
Researchers have made great strides in understanding the various forms of tying up and how best to help susceptible horses.
Researchers have made great strides in understanding the various forms of tying up and how best to help susceptible horses.
Aclassic case of tying up is pretty dramatic. The affected horse will hardly move as the large muscles of his hindquarters cramp into a solid, rock-hard mass. He is in obvious pain, shaking and sweating profusely. You’ll know something is wrong right away and have clear indications that the problem involves his muscles.
More often, however, equine muscle disorders produce vague
and shifting signs that are easy to overlook or misinterpret. A horse may simply seem slightly stiff after a day off, for example, or unaccountably lose suppleness. Or he may suddenly be resistant to work. As a result, many horses with chronic muscle disease go through life without accurate diagnosis or treatment.
One person hoping to change that is Stephanie Valberg, DVM, PhD. Director of the Equine Neuromuscular Diagnostic Laboratory at Michigan State University, Valberg has spent her career identifying the various muscle disorders that affect horses and helping owners and veterinarians recognize and manage them.
That’s no small task. Even equine muscle problems that arise from different causes often look similar and can be difficult to categorize.
“‘Tying up’ is an umbrella term now, just like the word ‘colic’ is a generalized description of a variety of conditions,” explains Valberg. “Tying up can be a one-off event caused by a
confluence of factors plus bad luck. When a horse repeatedly shows signs of tying up, however, that is classified as chronic exertional rhabdomyolysis (ER) and it’s much more likely there’s an ongoing physiological, and even genetic, cause.”
Working with a team of talented scientists, Valberg has developed better and more precise methods of diagnosis for equine myopathies. Her work has also led to the development of management protocols that can keep affected horses healthy and active, even at the highest levels of competition.
THE BREAKTHROUGH: PSSM TYPE 1
One of Valberg’s first milestones came in 1992 when she identified polysaccharide storage myopathy (PSSM), a condition characterized by an inability of a horse’s body to properly store and utilize glycogen for energy during periods of exercise. Her initial work focused on abnormal findings in muscle biopsies taken from a subset of horses prone to chronic ER.
Originally, PSSM was diagnosed only through muscle biopsy. Pathologists would stain the samples to identify the type and levels of accumulated glycogen. “In normal horses, sugar is stored in skeletal muscle in the form of a highly branched polymer called glycogen, which is sensitive to digestion by the salivary and pancreatic enzyme amylase,” says Valberg. Normal horses can readily break down glycogen to fuel muscles as it is needed, but Valberg recognized that horses with PSSM store sugar as an abnormal amylaseresistant polysaccharide that cannot be easily utilized. By 2008, Valberg and her team discovered there was a genetic mutation in a gene known as GYS1 in horses with amylase-resistant
polysaccharide. Now a genetic test can identify a horse with this form of PSSM before he shows clinical signs. Valberg called this form PSSM type 1 (PSSM1).
While the exact physiological mechanism at work in PSSM1 is complex, the upshot is that the accumulation of excess and/or abnormal glycogen disturbs the normal patterns of energy metabolism during exercise, leaving the horse with an energy deficit in the muscle cells that leads to mild to moderate cramping, resistance to work and sometimes full-blown tying up. These signs are most often seen in horses when they return to work after a lay-up period, about 10 to 20 minutes into a ride.
“This genetic defect with PSSM1 originated thousands
A genetic test can identify a horse with PSSM type 1 before he shows clinical signs.
of years ago and was incorporated into light horse breeds at the time,” says Valberg. “Our best theory is that when some heavier European draft horses, particularly Belgian drafts, were crossed with lighter breeds to create a horse that could carry men in armor breeders unknowingly included horses with PSSM1. At that time, before the era of improved pastures and concentrates, the ability to store an extra amount of energy in your muscles was a good thing. These horses were working eight-hour days, every day, and would utilize much of that glycogen.” In the modern horse, though, that mutation becomes problematic.
“In the modern breeds, you see PSSM1 in the Quarter Horses, Paints, Appaloosas and, to a lesser extent, the Morgan, Tennessee Walking Horse and Rocky Mountain Spotted Saddle horses,” says Valberg. “You’ll also see it in some horses with draft blood, like the Belgian, Percheron and Haflingers. We see it in warmbloods at a lower frequency and don’t see it at all in Thoroughbreds, Arabians or Standardbreds.”
The effects of PSSM1 vary by breed. “In Quarter Horses, the primary complaint is tying up,” says Valberg.
The combination of a low-starch diet and consistent exercise works well in Quarter Horses with PSSM types 1 and 2 with up to 90 percent having no more episodes of tying up.
“That’s the dramatic, very apparent cramping of the large muscle groups and muscle cell damage. In some draft horses, PSSM1 can be asymptomatic.”
SAME EFFECT, DIFFERENT CAUSES: PSSM TYPE 2 AND MFM
While working to develop the genetic test for PSSM, Valberg made a surprising discovery. “We had literally hundreds of biopsy samples from horses with clinical signs of PSSM and abnormal glycogen accumulations in their muscle cells,” she says. “Once we were able to test for the mutation, we went back and tested all those samples. Only 72 percent of Quarter Horses diagnosed with PSSM by muscle biopsy had the genetic mutation. And in warmbloods, we found the mutation in only 8 percent of horses diagnosed with PSSM by muscle biopsy. That told us that all cases of PSSM didn’t have the same underlying cause and it might not even be the same disease process.” Valberg began classifying these horses ---whose biopsies showed abnormal glycogen accumulations but who did not carry the genetic defect---as having PSSM type 2 (PSSM2).
“The primary difference, from a practical standpoint, between PSSM type 1 and type 2 is that one can be tested for genetically and the other cannot,” she says. “You might be able to find genetic variants between the horses, but there isn’t a scientifically verified test for a mutation that is clearly linked to the classic muscle biopsy findings associated with PSSM type 2 horses.”
Valberg estimates that approximately 20 percent of Quarter Horses and 80 percent of warmbloods with PSSM have type 2. That is not to say that 20 percent of all Quarter Horses have type 2 PSSM, she says, rather it means that 20 percent of those horses with muscle biopsies showing abnormal glycogen staining have PSSM2. Unlike type 1, type 2 has been found in other light breeds, such as Arabians, Standardbreds and Thoroughbreds.
PSSM type 2 isn’t fully understood, but a key difference from PSSM type 1 might be the amount of glycogen stored in cells. Horses with type 1 have higher levels of glycogen (stored glucose) in their muscle cells, in addition to abnormal amylase-resistant clumping. There appear to be breed differences with PSSM2: Recent findings show that Quarter Horses with PSSM2 have high muscle glycogen, but warmbloods and
From a practical standpoint, the primary difference between the two types of PSSM is that you can do a genetic test for type 1 but not for type 2.
Arabians with type 2 do not appear to store excessive amounts of glucose.
“This is where our research is currently focused. The glycogen looks abnormal under the microscope in both types of PSSM, but our breed-specific findings suggest that this means there are different causes in different breeds. We are measuring the amount of glycogen biochemically, and that information may eventually lead us to a better understanding of the difference between forms of PSSM.”
To further explore these differences Valberg developed new stains to evaluate muscle with PSSM2. She found that Arabians and warmbloods previously diagnosed with PSSM2 actually have clumping of glycogen that forms in breaks in the muscle’s contractile proteins. “We have found a protein that is abnormal called desmin. Desmin’s job is to create an orderly alignment of the contractile proteins in the muscle cells,” says Valberg. “With a new stain for desmin, muscle biopsies could be responsible for the clinical signs of muscle pain and reluctance to want to go forward or collect that we see in certain PSSM2 horses.”
Termed myofibrillar myopathy (MFM), this condition is defined by clumping of desmin in specific areas of the muscle cells. (Valberg notes that this condition is different than MFM in people, and relying on human literature for information is unwise.) Evaluating a biopsy to detect MFM can be tricky because the horse’s age and the handling of the sample can produce false positive or negative results. Valberg suspects there is a genetic component to MFM, but no scientifically validated genetic test for the condition is available yet. “We find genetic variants exist between MFM and healthy horses, but there has not been one specific variant that is present in all MFM horses and absent in controls in our research,” Valberg says.
CHALLENGES OF DIAGNOSIS
Valberg stresses that not every sore, resistant horse has a muscle disorder or myopathy. In fact, most don’t. “There are a million things that can make a horse muscle sore,” she says. “It’s not always, or even usually, muscle disease.”
The diagnostic process begins with an investigation of the more common causes of soreness and reluctance to exercise, Valberg explains. “You have to look at saddle fit, possible training issues, whether or not it’s a mechanical lameness or sacroiliac disease. These are all diagnostics that your veterinarian can do. The problem is this can be expensive, so many people are reluctant to go through that whole process. But it’s the only way to find those much more common causes.”
Your veterinarian will start by taking a blood sample to measure muscle enzymes. “If those are elevated,
The accumulation of excess glycogen in muscles disturbs energy metabolism during exercise, which can lead to cramping, resistance to work and full-blown tying up.
no point in going that route because they just don’t have it. If you have a warmblood, the likelihood of PSSM type 1 is small, but it’s a place to start and if the genetic test comes back positive, you’ve found your problem without having to take a biopsy.” In Quarter Horses there is another form of exertional rhabdomyolysis, called malignant hyperthermia, that can be diagnosed by a genetic test. Horses with this form of tying up often have an increased body temperature when they have muscle cramping and they can develop severe muscle damage.
If the genetic test comes back negative, Valberg then considers the horse’s clinical signs, breed and even temperament to determine what is the most likely cause of the ongoing problem. “One disorder, that we call recurrent rhabdomyolysis (RER) is found mainly in Thoroughbreds and Standardbreds who are very successful when they aren’t tying up, but also tend to be very reactive and with a nervous temperament. It occurs when they are being held back at a gallop or jigging. If the horse is tying up after a situation like that, he likely has RER.”
For a horse who frequently ties up but doesn’t fit the profile for RER and tests negative for PSSM1, the next step is a muscle biopsy. “When we look at a tissue sample under the microscope, we are looking at the size and shape of the cells, evidence of degeneration and regeneration, the amount of glycogen stored in them as well as clumping of glycogen and desmin,” says Valberg. “From all of that, we will diagnose a subset of these horses with PSSM type 2 or myofibrillar myopathy.”
Valberg stresses that, absent a genetic test, diagnosing PSSM2 remains a bit subjective: “You can’t base the diagnosis on the muscle biopsy alone. The biopsy is not specific
Not every sore, resistant horse has a muscle disorder or myopathy. In fact, most don’t.
enough to use as a tool for prepurchase exams or making breeding decisions. Muscle biopsy is most accurate when it is used in horses that have a high suspicion of disease based on their clinical signs.”
As tricky as myopathy diagnostics can be, the treatments are remarkably straightforward. In fact, for PSSM1 and PSSM2 in Quarter Horses where the problem is too much glycogen, the management recommendations are identical.
The first step is a change in diet. Feedstuffs that are high in sugar and starch, such as corn, wheat, oats, barley and molasses, appear to exacerbate PSSM1 and PSSM2 in Quarter Horses. “Getting these horses onto a low-sugar/ low-starch diet is key,” says Valberg. “That might mean restricting grazing if the pastures are high in sugar. We replace the energy of starch and sugar with fat in the diet and this improves the horses’ exercise tolerance.”
The second management step is faithful daily exercise, which enhances glucose utilization and improves energy metabolism in skeletal muscles. The horse doesn’t need to work hard, Valberg stresses, but he does need some organized exercise every single day. “Turnout in a pasture isn’t enough because some horses just stand around,” she says. “You need to get on these horses and ride them or handwalk them or longe them. Even if it’s only a bit of trotting for a few minutes. That can make all the difference.”
The combination of diet and exercise works well in Quarter Horses---up to 90 percent have no more episodes of tying up---but Valberg says warmbloods may not respond to the same degree: “The fact that [treatments] don’t work as well in some breeds as others speaks to the different underlying factors that we don’t fully understand. But those recommendations were the best we had at that point for all horses, and if you’ve ruled out everything else, it’s worth trying.”
Dietary changes of low starch and sugar don’t seem to be as crucial in horses with MFM, but Valberg still recommends a diet that is moderate in sugars and starches: “Many feed companies have now developed supplements of high-quality amino
acids and we now recommend these supplements for warmbloods and Arabian horses with PSSM2 or MFM.”
Valberg hopes, through research, to determine if this type of diet optimizes turnover of structural proteins in the muscle and builds muscle strength. “We are also working on supplements to enhance energy generation and antioxidant function,” she says.
Meanwhile, exercise recommendations for horses with MFM are a bit more specific than for those with either type of PSSM. Valberg has found that MFM horses seem to respond best to work that initially encourages them to stretch their topline, in a “long and low” frame for about five to 15 minutes each day before being asked to do more collected work. And bringing an MFM horse back from a lay off needs to be done gradually, with a least two weeks of walking, followed by at least two weeks of trotting before the horse canters. Intervals of walk and trot are recommended.
Research into myopathies continues. “With each new thing we learn, we realize how much we still don’t know,” Valberg says, “but we’ve come such a long way already.” Even though there are much more common causes of mild to moderate muscle soreness in horses, being able to accurately identify and successfully manage the relative few who have these conditions can mean the world of difference to those horses and their owners.
Disclosure statement: Stephanie Valberg, DVM, PhD, and her colleagues license the PSSM1 test and receive royalties. This conflict is managed by Michigan State University, East Lansing, Michigan.
A cross section of muscle fibers from a biopsy of a horse with PSSM type 2 shows abnormal aggregations of muscle glycogen.
Normal horses can readily break down glycogen to fuel muscles as it is needed. In contrast, horses with PSSM store sugar as an abnormal polysaccharide that cannot be easily utilized.