An Introduction To Exertional And Non-Exertional Rhabdomyolysis (“Tying Up”)
Exertional Rhabdomyolysis (ER) is a potentially life-threatening disease that primarily affects horses used in sports or for labor. Affected horses experience cramping and pain in their muscles associated with exercise and muscle damage. A sanctuary should not place residents in such potentially harmful situations. It could even occur if a resident is being chased by other residents. A resident who was previously used in such situations and has a chronic or non-exertional form of the disease will be more prone to repeat occurrences, hence the name “chronic exertional rhabdomyolysis”. Non-exertional Rhabdomyolysis (NER) presents similarly and is caused by sources other than exertion, including genetics and can be triggered by stress, reactions to certain vaccines and infections (particularly streptococcus), and a poor diet.
Signs of ER and NER include muscle stiffness, unwillingness to move their body due to muscle pain and cramping, as well as excessive sweating. In some cases, urine may be brown and they may have increased heart and respiratory rates. Episodes can range from mild, treated with careful management, to severe during which muscles may begin to necrotize and the kidneys may fail. ER is divided into sporadic exertional rhabdomyolysis and chronic exertional rhabdomyolysis. Sporadic ER is caused solely on environmental factors, namely overexertion, and is not caused by any defects or disease processes.
In a sanctuary environment, a resident should not be placed in situations where they may develop ER. Many cases of ER are caused by training or using horses for sport, riding, or work. When made to perform in particularly hot or humid environments, they are more likely to develop an episode. It often happens when horses are pushed in an exercise program that is too challenging for their bodies and they have likely not had a gradual increase in the frequency and duration of exercise regimes. At a sanctuary, resident welfare should always come first. Any exercise programs should be put in place solely for the benefit of the individual and not for human gain. This generally means that any exercise programs residents participate in should not reach the levels of difficulty other horses are made to participate in. This will hopefully limit the number of residents experiencing episodes of ER, but it can still happen. Non-Exertional ER can certainly affect residents as well.
Chronic ER is caused by underlying physical conditions which are triggered by exertion and is further broken down into two main different disease processes:
Recurrent exertional rhabdomyolysis (RER) and Polysaccharide storage myopathy (PSSM). Each has a different cause and results in different symptoms, though many symptoms may be shared. While there are still some uncertainties about the causes of these disease processes, there has been research that points to certain possibilities. Some research points to abnormal regulation of calcium within the cells of muscles as being the cause of RER. It is believed that horses suffering from PSSM are unable to appropriately use the sugar within those muscle cells, which cause the muscles to “starve”, causing serious damage when they exert a lot of energy.
To add another layer of complexity, there are actually two types of PSSM: PSSM I is associated with genetics, while the cause of PSSM II is unknown. Which brings us to myofibrillar myopathy. Myofibrillar Myopathy (MFM) is another type of exertional rhabdomyolysis that presents with similar clinical symptoms but has a different underlying cause that is being studied. There is some question as to whether MFM and PSSM II are the same disease. However, there have been no conclusive findings.
Are you confused yet? Don’t worry, here is a summary followed by details of each condition.
Bullet Point Breakdown:
- There are 2 types of Rhabdomyolysis: Exertional and Non-Exertional Rhabdomyolysis
- There are 2 types of Exertional Rhabdomyolysis:
- Sporadic and Chronic
- Sporadic ER does not involve underlying disease processes and is caused solely by environmental factors, namely overexertion.
- Chronic ER is caused by underlying disease processes usually triggered by exertion.
- Chronic ER is further broken down into 2 different disease processes, each with a different cause that can result in additional symptoms:
- Recurrent Exertional Rhabdomyolysis (RER) and Polysaccharide Storage Myopathy (PSSM)
- RER is believed to be caused by abnormal regulation of calcium in muscle cells though this is still uncertain.
- PSSM is caused by the inability of muscle cells to use sugar appropriately.
- There are 2 types of PSSM, Type I and Type II.
- PSSM I has a genetic cause.
- The cause of PSSM II remains unknown.
- Myofibrillar Myopathy (MFM) is another type of exertional rhabdomyolysis that may or may not be the same disease as PSSM II.
- Non-exertional Rhabdomyolysis (NER) is caused by sources other than exertion, including genetics and is triggered by stress, reactions to certain vaccines and infections, particularly streptococcus.
- All forms of ER and NER involve similar symptoms in common though certain disease processes may have additional symptoms that vary from the rest.
- Muscle stiffness
- Muscle pain and cramping
- Muscle tremors
- Reluctance to move their body
- Excessive sweating is sometimes seen
- Brown urine may be present
- Increased heart rate
- Increased respiratory rate
It is probably clear by now that ER (and NER) are a complicated set of diseases. To give you a better understanding of each, we will break them down individually.
Sporadic Exertional Rhabdomyolysis (SER)
As mentioned above, SER isn’t caused by an underlying disease or genetic defect. It is caused when a healthy horse is overexerted to the extent that muscle cells are damaged. In a sanctuary setting where horses are not used for sport or work, this might look like a resident participating in an exercise program that is too strenuous, too fast or is exercising in temperatures that are too hot or humid. It might also look like a horse resident that is being relentlessly chased by other residents. Metabolic imbalances that can occur during these hot, humid conditions can lead to issues with the muscle. These imbalances may look like excessive sweating causing a loss of electrolytes and fluid, dehydration, and high body temperature. There seems to be some correlation between a horse who has recently recovered or is still recovering from respiratory conditions and exercise, potentially making a horse more prone to ER.
A horse suffering from a milder case of SER will need to rest for up to a couple days in a small living space, like an appropriately-sized stall. A veterinarian should always be consulted and examine the resident. When they show signs of being able to move without signs of intense stiffness, the vet may recommend they can progress into a slightly bigger space, like a paddock. At this time, the horse should not be participating in any exercise. Even walking them slowly for any extended amount of time could trigger another episode. After a week or two of this gentle care, a veterinarian should re-examine the resident and clear them for easing back into their normal routine, particularly if they participate in any positively reinforced exercise program or run with other horses in their outdoor living space. If the individual is being chased, you should consider how to create a separate herd that can better meet the needs of all residents.
Residents with SER should be given a well-balanced diet (as should every resident). Ensuring they receive the proper amount of vitamins, minerals, and other nutrients, will help prevent future episodes. Most notable of the vitamins and minerals are Vitamin E and selenium. While a lack of these isn’t likely to cause an episode, they can help keep muscles healthy and help with the recovery process. Of course, you must still be careful not to over-supplement their diet with selenium, especially if they are being fed a commercial food made especially for horses with ER, as it will already contain selenium.
You should speak with your veterinarian about offering salt and electrolytes in the right amounts, which will depend on the temperature and activity level of the individual resident. There has been some research that has found imbalances of potassium, calcium, and sodium in horses with ER, so ensuring they receive the correct amount of each can have an important impact on recovery.
If a resident participates in any exercise activities, they should begin again gradually to prevent any future episodes of ER.
Chronic Exertional Rhabdomyolysis
As we touched on above, chronic ER is a bit more complex as there are multiple underlying causes to address. To review, recurrent exertional rhabdomyolysis (RER) and Polysaccharide storage myopathy (PSSM) are the two main disease processes making up chronic ER. Each has a different cause and results in different symptoms, though many symptoms may be shared. While there are still some uncertainties about the causes of these disease processes, there has been research that points to certain possibilities. Some research points to abnormal regulation of calcium within the cells of muscles as being the cause of RER. We will learn more about PSSM after this, but for now, let’s focus on RER.
As the name suggests, horses with RER experience intermittent episodes of ER, thought to be caused by some abnormality in the calcium regulation process on a cellular basis. Generally speaking, the horses that are most affected are thoroughbred and standardbred horses that are put through rigorous training for racing. That shouldn’t be an issue at a sanctuary, but it is still possible for a sanctuary resident to develop RER. A diagnosis of RER is not as simple as a single diagnostic test, unfortunately. A veterinarian will make a diagnosis based on the history of episodes to date and identify if the individual is fed a balanced diet and is exerting what would be considered a reasonably safe amount of energy. They may also perform an exercise test and check for any elevations of serum CK activity that result from the exercise or AST activities. Muscle biopsies are used to diagnose certain types of ER and can be useful, at times, in diagnosing difficult cases by finding evidence of certain characteristics in the muscle, using certain stains. However, a muscle biopsy in a horse with RER will not necessarily show any evidence of abnormalities within the muscle or other evidence of the disease.
Polysaccharide Storage Myopathy (PSSM)
PSSM refers to an inability to properly store and make use of sugar within the skeletal muscles. Originally this was identified as a genetic problem due to a gene mutation. This is still true, however, researchers have discovered there are two types of PSSM and only one is caused by genetics, PSSM 1.
As mentioned above, PSSM 1 is caused by a genetic mutation that affects the ability of muscle cells to properly store and use sugar. More specifically, glycogen accumulates in the muscle, as does another form of sugar, in higher amounts than normal.
Because of this abnormal storage of sugar in the muscle tissues, high sugar and high starch diets are likely to make PSSM 1 worse and should be avoided. Examples of foods high in starch include wheat, oats, molasses, barley, and corn. Instead of feeding a high starch diet, horses with PSSM 1 should derive the needed calories from fat such as from corn or soybean oil which is rich in omega-3 fatty acids. There are now also commercial foods developed especially for horses that must avoid high sugar/starch diets.
For forage, hay or pasture should be provided. However, residents with PSSM 1 should not have access to lush pasture grasses. Ideally hay and pasture grass should be analyzed for the nonstructural carbohydrate levels, which should be less than 12%. In addition to dietary changes, it is important for horses to get exercise in a way that takes into account their health condition. Exercise programs should be gradual and gentle to prevent an episode of ER. Having access to pasture is helpful as it can increase their activity. However, care must be taken that they are not consuming lush grass. A grazing muzzle may be beneficial in these cases as it allows the individual to eat throughout the day without running out of forage early on and can allow them access to pasture with their companions while still protecting their health. Clicker (positive reinforcement) activities can encourage residents to participate in exercise in a way that can also provide mental stimulation and develop a trusting relationship with care staff. These diet and exercise changes can greatly reduce the occurrence of an episode of ER.
PSSM 1 can be identified through genetic testing. A muscle biopsy can also point to whether an individual has PSSM 1, but a genetic test is most accurate for a definitive diagnosis.
While inappropriate levels of exercise can bring on an episode of ER, horses with PSSM 1 can experience an episode that is not exercise related. Signs of ER match other causes: Stiffness, reluctance to move, sweating and in more severe cases, recumbency, inability to rise, and dark brown urine. If a resident presents with any of these signs, call your veterinarian immediately. Depending on the individual’s history and symptoms, they may want to do some tests or recommend a treatment plan.
If a resident presents with these symptoms, do not force them to walk. If they are still moving on their own and their indoor living space is close, guide them slowly into a quiet indoor living space. Remove any grain they may have in their living space. A veterinarian may recommend providing small sips of water with or without electrolytes if they are dehydrated. Your veterinarian will manage their pain and anxiety with medication. Keeping them calm is important.
Quarter horses and paint horses may also inherit a genetic condition called malignant hyperthermia (MH). Similar to PSS in pigs, this condition can be triggered by stress, excitement, or by being exposed to certain anesthetics or succinylcholine (a muscle relaxant). Horses that are affected by genetic malignant hypothermia may have more severe cases of ER if they also have the PSSM Type I gene mutation. Prognosis is poor for those who experience an episode while under anesthesia. If your resident is a Quarter horse or related breed, a veterinarian may recommend DNA testing before any procedure using general anesthesia.
As mentioned earlier, the cause of PSSM II is unknown, but is representative of at least one, often more, other muscle diseases that can be identified through the abnormal staining of a small piece of muscle obtained from a biopsy and examined on a microscopic level.
There is no cure for PSSM, but it can often be managed successfully. Approximately 50% of affected horses with PSSM 1 show improvement under dietary management alone. Of those that adhere to dietary and exercise management, 90% have few to no episodes of tying-up. However, clinical signs will likely resume if there are disruptions to the management program.
Horses that test positive for 1 or 2 copies of the GYS1 mutation should be carefully managed through diet and exercise to help prevent the onset of the disease. For many horses affected by PSSM 1, strict control of diet and exercise can reduce, or even prevent the onset of symptoms related to PSSM 1. Eliminating many high sugary foods in their diet and consistent exercise are two simple ways to help prevent the disease from developing. Although taking these simple steps may not be effective in every situation, research has shown that often they will provide positive results.
Myofibrillar Myopathy (MFM)
Myofibrillar Myopathy (MFM) is another type of exertional rhabdomyolysis that presents with similar clinical symptoms but has a different underlying cause that is being studied. It has been theorized that Myofibrillar Myopathy may even be the same disease as PSSM II. Because the causes are unknown, there is no firm answer to this question. As with PSSM II, a diagnosis can be made through microscopic examination of a staining of muscle biopsy. However, if the horse has quickly regenerating muscle cells, it can lead to a false positive. Additionally, a false negative may happen if the muscle biopsy is too small or if shipping takes too long to reach the laboratory, or even if the horse is particularly young.
Getting a Diagnosis
In order to determine what is causing the ER, a veterinarian will want to evaluate the individual and may order a number of tests to learn more about what is happening in muscle. It is common for a diagnostic plan to include some or all of the following:
- Exercise Test: A veterinarian may want to do an exercise test if the horse is suspected to have some form of ER but isn’t showing any signs of muscle stiffness. During this test, the horse is encouraged using positive reinforcement to exercise for around 15 minutes. If signs of muscle pain and stiffness occur, exercising must stop immediately as this is not the goal of the test. Rather, the usefulness of this test is determined by a blood test hours following the exercise in order to identify any signs of slight muscle damage.
- Blood Test: The blood test is ordered so the veterinarian can look at levels of two proteins in the blood (creatine kinase or CK and aspartate transaminase or AST), which can determine the level of muscle damage.
- Genetic Testing: Depending on a number of factors, such as breed, age, clinical signs, and recurrence of ER, the veterinarian may recommend genetic testing as this can help get a definitive diagnosis for MYHM, PSSM I, and Malignant Hypothermia, in addition to other muscle diseases that can help identify the source of ER.
- Muscle Biopsy: Muscle biopsies can be useful in identifying what is causing muscle atrophy or ER in a horse. Different myopathies will show different patterns of damage, leading to a diagnosis.
Once there is a diagnosis, the veterinarian can implement an appropriate treatment plan. In cases of ER, it is recommended that they be rested in a stall for the rest of the day or up to 2 days, depending on the case. Then they can be given access to a small paddock. The vet may or may not recommend short bouts of encouraged walking and then want to assess the individual after a couple of weeks. At this time they can make recommendations regarding the level of exercise they can gradually return to.
Other aspects of a treatment plan may include pain relievers for muscle pain, oral or intravenous fluids if they are dehydrated, and in more severe cases, a flush of myoglobin from the kidneys.
Longer term, horses with PSSM I can often be managed quite well with appropriate diet and exercise plans. Though there is less research on managing PSSM II, they are often treated the same.
Non-exertional rhabdomyolysis (NER) has clinically similar symptoms that are brought on by causes other than exertion. Horses that develop NER have a genetic component that may predispose them to developing this disease when triggered by certain environmental stimuli.
NER can be caused by a mutated gene called Myosin Heavy Chain Myopathy (MYH1). Mutations to the MYH1 gene can cause horses to present with NER or Immune Mediated Myositis. We cover Immune Mediated Myositis in more detail below. The main difference between the two is IMM is an autoimmune disease characterized by muscle atrophy (wastage) and NER is characterized by muscle damage without atrophy. Horses with NER will present with muscle damage that is not connected to exercise, and a veterinarian can confirm the diagnosis by checking the levels of serum creatinine kinase levels, which will be high. Even with these levels, the afflicted horses may not present with muscle atrophy. NER occurs more commonly in younger horses. Many horses develop this disease when it is triggered by bodily stress from infections or vaccinations for equine influenza, streptococcus, or equine herpesvirus 4.
Afflicted horses can fully recover from NER, a large percentage (40-50%) are likely to have recurrent episodes of the usual symptoms. Horses heterozygous for the MYH1 mutation often recover with no long term consequences, while horses homozygous for the MYH1 mutation are more likely to experience more recurrent and severe episodes. In either case, it is imperative that horses receive treatment as soon as possible as this can seriously affect their prognosis. Horses who receive timely treatment should begin to get their appetite back within a couple of days and muscle recovery within the following weeks and months. However, depending on the severity of muscle damage, there may be a permanent indent of lost muscle in some horses. For those with severe recurrent episodes, there may be muscle atrophy so severe that their quality of life is significantly diminished. In these cases a veterinarian may recommend euthanasia.
A diet consisting of a good balance of vitamins, minerals, and high-quality protein (such as soybean meal) is generally recommended during recovery.
Vitamin E can be added to their diet for added benefit to their muscle health, specifically the strength of their muscle membrane and preventing the leaking of enzymes from the muscle. Talk to your veterinarian about the appropriate dosage and types of Vitamin E to supplement, as synthetic and natural sources have different levels of absorption. Vitamin E can be provided with nice green grass or quality hay, as well as through the supplementation of rice bran.
Selenium is also an important nutrient for maintaining muscle health, and care should be taken that their diet is not deficient in either of these areas. Many pastures produce grass with low selenium levels. The selenium levels in the soil can be tested to give you a better idea of how much selenium may need to be supplemented. There are some commercial diets available for horses with ER. The easiest way to determine whether a resident’s Vitamin E and selenium levels are adequate is through blood/serum testing.
Getting A Diagnosis
In cases of Non-Exertional Rhabdomyolysis, an exercise test doesn’t provide the information needed to determine the cause of NER and therefore wouldn’t be part of a diagnostic plan. Due to the potential triggers or NER, like infection, the following covers possible diagnostic avenues a veterinarian will take:
- Blood Test: A complete blood count (CBC) is ordered to identify any signs of existing infection. Another blood test will look at levels of muscle proteins in the blood, much like in cases of ER. In cases of MYHM, creatine kinase levels can help get a diagnosis. A polymerase chain reaction assay (PCR) test may be ordered as well in order to identify and diagnose Streptococcus equi., the most common trigger on NER. This can also be diagnosed through a culture.
- Genetic Testing: Depending on a number of factors, such as breed (Quarter horse and related breeds can be tested), age, and clinical signs, the veterinarian may recommend genetic testing as this can help get a diagnosis for IMM (discussed in the next section) or Non-Exertional Rhabdomyolysis. Horses with one copy of IMM mutation are likely to have autoimmune episodes, if triggered. Horses with two copies of the IMM mutation are susceptible like the other, but have the additional susceptibility to recurrent autoimmune episodes.
- Muscle Biopsy: Muscle biopsies can be useful in identifying what is causing muscle atrophy or NER in a horse. However, this is usually only used if the genetic testing results are negative for the MHY1 myopathy and the cause is still unknown. Examining muscle biopsies can reveal characteristics of rhabdomyolysis.
Once the diagnosis has been confirmed, a treatment plan can be developed and implemented by the veterinarian. In cases of an autoimmune episode, a veterinarian may prescribe corticosteroids, which can start to help around 3 days time. In cases of an infection-triggered episode, antibiotics and guttural flush may be recommended. If it is determined the episode was caused by a vaccination, the veterinarian may suggest a new vaccination plan for the individual that may include longer breaks between vaccinations. A medication may also be prescribed to lower CK levels in their blood.
Immune-Mediated Myositis (IMM)
Immune-Mediated Myositis is an autoimmune disease that generally affects horses under 8 or over 17. Quarter horses and related breeds are much more likely to suffer from this disease than other breeds.The immune system attacks certain fibers in skeletal muscle cells, most notably in their hindquarters and topline (back). While there is a genetic component, stress to the body, particularly through infection, is often the trigger for the development of IMM. A streptococcus infection is the most likely trigger for the development of IMM. However, signs of IMM have also been reported after a horse has received flu or strangles vaccinations or immune stimulants. It is characterized by sudden muscle wasting; up to 40% of muscle can atrophy within just 48 hours.This is seen along a horse’s topline and hindquarters. Other possible symptoms include fever, depression, stiffness, difficulty standing, and loss of appetite. A veterinarian may recommend steroids and antibiotics to stop the atrophy of the muscles. It is important that horses afflicted with IMM are fed a high quality concentrate with protein and a good balance of vitamins and minerals. Alfalfa and amino acids supplements can provide additional support while muscles are built back up.
As with NER, afflicted horses can fully recover from IMM, a large percentage (40-50%) are likely to have recurrent episodes of the usual symptoms. Horses heterozygous for the MYH1 mutation often recover with no long term consequences, while horses homozygous for the MYH1 mutation are more likely to experience more recurrent and severe episodes. In either case, it is imperative that horses receive treatment as soon as possible as this can seriously affect their prognosis. Horses who receive timely treatment should begin to get their appetite back within a couple of days and muscle recovery within the following weeks and months. However, depending on the severity of muscle damage, there may be a permanent indent of lost muscle in some horses. For those with severe recurrent episodes, there may be muscle atrophy so severe that their quality of life is significantly diminished. In these cases a veterinarian may recommend euthanasia.
Although we have mentioned nutritional management in some of the sections, here’s nice overview with all nutritional information in one place:
In terms of appropriate nutrition for horses with exertional (and non-extertional) rhabdomyolysis, a diet that is lower in starches and sugars is ideal (while still providing a well balanced diet). A diet consisting of a good balance of vitamins, minerals, and high-quality protein (such as soybean meal) is generally recommended during recovery. It can help prevent issues with vitamin deficiencies or electrolyte imbalances. For horses with ER, steps should be taken to prevent undue exertion in residents with this condition. If they are active, particularly if their activity causes them to sweat, then ensuring they have balanced electrolytes (sodium, calcium, and potassium) is crucial.
Vitamin E can be added to their diet for added benefit to muscle health, specifically the strength of their muscle membrane and preventing the leaking of enzymes from the muscle. Talk to your veterinarian about the appropriate dosage and types of Vitamin E to supplement, as synthetic and natural sources have different levels of absorption. Vitamin E can be provided with nice green grass or quality hay, as well as through supplementation of rice bran.
Selenium is also an important nutrient for maintaining muscle health, and care should be taken that their diet is not deficient in either of these areas. Many pastures produce grass with low selenium levels. The selenium levels in the soil can be tested to give you a better idea of how much selenium may need to be supplemented. There are some commercial diets available for horses with ER. The easiest way to determine whether a resident’s vitamin E and selenium levels are adequate is through blood/serum testing.
Horses with PSSM store more glucose in their muscles and are more sensitive to insulin, so limiting the amount of starch and sugar in their diet to 10-15% is an important aspect of dietary management of this disease. Horses with RER can generally have a little more, up to 20% in their diet. With lower percentages of sugars and starches being provided, you’ll want to be sure they still have the right amount of energy provided in their diet. Supplementing easily digestible fibers, such as low-carbohydrate soy hulls or beet pulp, can increase the density of the diet, as can supplementing with oil or rice bran for added fats. There is research that suggests that providing horses prone to exertional rhabdomyolysis a low carb/higher fat diet can reduce the number of recurrences. It is possible that, because there are easily accessible amounts of fat that can be used for energy, this reduces the body’s heightened response to insulin. This translates as less glycogen storage in muscle cells, which is particularly helpful for horses with PSSM. Diets for MH generally follow PSSM guidelines.
A horse with IMM requires a high quality protein diet. Amino acids supplements can be offered to promote health muscle development. As with all diets, it should be properly balanced with minerals and vitamins.
While this is a complex set of diseases, we hope this gives you a basic understanding of the causes, processes, and management of exertional and non-exertional rhabdomyolysis. We hope you never need this information, but if you do, this resource can help you better understand the issues, making it easier to discuss the condition with an experienced veterinarian.
Exertional Rhabdomyolysis (ER) | MSU College Of Veterinary Medicine | (Non-Compassionate Source)
Tying-Up In Horses | Rutgers Cooperative Extension (Non-Compassionate Source)
Myofibrillar Myopathy (MFM) | Equiseq (Non-Compassionate Source)
IMM – Immune Mediated Myositis And MYH1 Myopathy | Animal Genetics (Non-Compassionate Source)
Myosin Heavy Chain Myopathy (MYHM) | MSU College Of Veterinary Medicine (Non-Compassionate Source)
Recommended Diagnostic Work-Up For Myopathies | MSU College Of Veterinary Medicine (Non-Compassionate Source)