Review of Muscle Diseases in Sport Horses Stephanie J.
Valberg, DVM, PhD, DACVIM Authors address: Department of Veterinary Population Medicine, College of Veterinary Medicine, 1365 Gortner Avenue, University of Minnesota, St Paul, MN 55108; e-mail: email@example.com. Take Home Message There are numerous causes for muscle disorders in sport horses including 4 potentially inherited myopathies.
Optimal management of exertional myopathies requires an accurate diagnosis, appropriate period of rest, targeted medications and dietary therapy, as well as rehabilitation therapy with a gradual reintroduction of exercise up to the intended level of performance.
Introduction Sport horses require optimal function of skeletal muscle to be successful athletes.
Even minor derangements in muscle function will impact power output, coordination, stamina and desire to work during exercise.
While many muscle disorders are readily apparent in acute stages, low grade muscle strains, weakness and chronic myopathies may not be readily diagnosed.
The classic clinical signs of exertional myopathies include muscle stiffness, sweating, firm painful hindquarter muscles, and reluctance to move.
However, more subtle signs of exertional myopathies include pain on palpation, firm areas within muscle, muscle atrophy, shifting lameness not attributed to a skeletal lesion, poor impulsion, and exercise intolerance.
The challenges of identifying the contribution of muscle pain to poor performance in sport horses include the following: 1) differentiating between true pain or exercise intolerance and an uncooperative attitude 2) locating and assigning significance to focal muscle pain 3) determining the degree to which orthopedic pain contributes to muscle pain 4) determining the degree to which myopathies contribute to orthopedic disorders The purpose of this paper is to review a diagnostic approach to exertional myopathies, potential differential diagnoses and strategies for managing exertional myopathies in sport horses.
Diagnostic Approach Exertional myopathies can be due to a primary muscle disorder or can be secondary to compensatory changes in gait that arise from orthopedic pain involving one or more limbs.
Distinguishing primary and secondary causes of muscle pain requires a thorough history, physical and lameness examinations as well as selected ancillary diagnostic tests. 107 History: It is important to fully document the amount and type of feeds comprising the horse’s diet, supplements provided, medications, amount of turn out, performance level expected and achieved, fitness level, exercise schedule, as well as the exercise intensity, duration and other factors that initiate clinical signs, the severity and frequency of clinical signs and any previous lameness.
Physical Exam: A detailed physical evaluation of the muscular system includes careful inspection of the horse standing perfectly square for symmetry of muscle mass and evidence of fasciculations.
The entire muscle mass should be palpated for heat, pain, swelling or atrophy by comparing with contralateral muscle groups.
Running a blunt instrument over the lumbar and gluteal muscles should illicit extension (swayback) followed by flexion (hogback) in healthy animals.
Guarding against movement may reflect abnormalities in the pelvic or thoracolumbar muscles, or pain associated with the thoracolumbar spine or sacroiliac joints.
The horse should then be observed at a walk and trot for any neurologic or gait abnormalities, followed by flexion tests for lameness.
Blood samples should be drawn before any exercise for a CBC and serum biochemistry profile.
Exercise Challenge: An exercise challenge can be helpful in detecting subclinical exertional rhabdomyolysis and in observing the progression of a gait abnormality with exercise.
Blood samples to evaluate peak changes in CK activity should be taken before exercise and about 4-6 hrs after, but NOT immediately after exercise.
The exercise test in unfit horses may involve 2 minute intervals of walk and trot repeated for up to 15 min.
Clinical judgment should be used and horses should not be pushed if they seem reluctant to continue to exercise after a brief rest.
For fit horses, 4 min of walk and 11 min of continuous trot can be used.
During the test, horses should be observed carefully for exacerbation of lameness, changes in impulsion, stiffness, shortened stride and development of a sour attitude.
In addition to quantifying the extent of rhabdomyolysis during mild exercise, the test is helpful in deciding how rapidly to put a horse back into training.
Marked elevations of serum CK 4 hrs following light exercise further underscores the need to gradually reintroduce exercise once the cause of the myopathy has been established.
Ancillary Diagnostic Tests: Depending on the breed of horse and clinical signs, tests such as DNA testing for hyperkalemic periodic paralysis (HYPP), malignant hyperthermia and type 1 polysaccharide storage myopathy (PSSM1), serum vitamin E concentration (particularly if there is reduced muscle mass or weakness), whole blood selenium concentration (if horses are not receiving supplementation and are in a deficient area) and muscle biopsy may be indicated.
For horses with atrophy, biopsies of the atrophied muscle +/- sacrocaudalis dorsalis muscle should be considered.
For horses with exercise intolerance or exertional rhabdomyolysis, gluteal or semimembranosus biopsies are preferable in order to look for generalized myopathies.
Fresh muscle that is shipped cooled on ice packs and then frozen using advanced techniques in specialized laboratories, rather than formalin-fixed muscle, is preferred because muscle fiber type composition (% of type 1, 2A and 2B fibers), fiber oxidative capacity (degree of 108 oxidative staining), lipid storage, and many more metabolic parameters can only be assessed in frozen sections.
In complex cases, repeated evaluations may be required, including examination of the horse under saddle, use of scintigraphy to localize inflammation, nerve blocks to confirm the source of pain and radiography and ultrasound examination to characterize lesions.
In addition, if horses have exercise intolerance, a standardized incremental exercise test that incorporates monitoring heart rate, blood lactate may be of value to assess horses for metabolic derangements.
Differential Diagnosis of Muscle Disorders in Sport Horses Following a complete evaluation, the origin of muscle dysfunction often falls into one or more of the following categories: 1) Pain Muscle contusions or tearing Primary muscle strain either focal or generalized from overuse Muscle strain secondary to skeletal pain and altered gait Neuritis 2) Weakness Myogenic atrophy Disuse Deficiency of Vitamin E Immune mediated myopathy Malnutrition/malabsorption Cushing’s disease Neurogenic Atrophy Lower Motor Neuron lesions o trauma, chronic Vitamin E deficiency, EPM, polyneuropathy 3) Inadequate oxidative metabolism Insufficient training of those myofibers that contribute to the expected performance leading to fatigue Skeletal muscle oxidative enzyme defects1 4) Disruption of glycogen/glucose metabolism and energy regulation PSSM type 1 due to GYS1 mutation2 PSSM type 23,4 5) Inadequate fat metabolism Lipid storage disorders5,6 6) Disruption of excitation contraction coupling Malignant hyperthermia (MH)7,8 Recurrent exertional rhabdomyolysis (RER)9,10 Classification of Exertional Myopathies Horses with exertional myopathies often fall into one of two main categories; 1) horses in which an intrinsic muscle defect does not appear to be present, but a temporary 109 imbalance within the muscle cells causes a sporadic exertional myopathy and; 2) horses in which the primary underlying susceptibility appears to be the result of an intrinsic defect in the muscle resulting in a chronic exertional myopathy.
Sporadic Exertional Myopathies Sporadic exertional myopathies are usually characterized by a history of adequate performance before onset of episodes and a successful return to performance following a reasonable period of rest, provision of a balanced diet, and a gradual training program.
Horses with these sporadic occurrences may be of any age, breed, or sex, and involved in a wide variety of athletic disciplines.
Episodes of muscle pain may recur over a short period of time before resolving the external perturbations which affect muscle function.
In many cases, horses are initially presumed to have sporadic exertional myopathy; however, if over time episodes of muscle pain recur despite the best management, further investigation may lead to a diagnosis of a form of chronic exertional myopathy.
Over-Exertion: A history of an increase in work intensity without a foundation of consistent training for this level of intensity is usually the basis for suspecting a training imbalance as a cause of ER.11 Signs of muscle stiffness and gait changes may be mild and are accompanied by modest elevations of serum creatine kinase (CK) activity.
Heat Exhaustion: Heat exhaustion (temp 105 – 108 F; 40 – 42.2 C) occurs most commonly in horses exercising in hot, humid weather.
Signs of heat exhaustion include weakness, ataxia, rapid breathing, muscle fasciculations, sweating, and collapse.
Muscles are frequently not firm on palpation, serum CK activity can be markedly elevated and myoglobinuria may be noted.11 Dietary Imbalances: Episodes of exertional muscle pain may be triggered by diets with a high nonstructural carbohydrate (NSC) content, inadequate selenium and vitamin E, or electrolyte imbalances.
Horses with sporadic exertional myopathies are infrequently deficient in selenium;12 however, anecdotal reports suggest that in some cases supplementation may prevent further episodes of muscle pain.
Vitamin E deficiency may produce muscle damage and increased CK activity.13 Electrolyte Imbalances: Electrolyte balance within the body is difficult to determine accurately.
Measurement of urinary electrolyte excretion as an indicator of electrolyte balance is complicated because marked variation can occur from diet, exercise, and sampling technique between individuals as well as within individuals from day to day.14 Furthermore, the high calcium crystal concentration of alkaline equine urine requires acidification to accurately assess calcium and magnesium content.
Chronic Exertional Myopathies (EM) Known causes of chronic EM include recurrent exertional rhabdomyolysis, type 1 and type 1 PSSM and malignant hyperthermia.
There may well be yet other unrecognized causes. 110 Recurrent Exertional Rhabdomyolysis (RER) RER refers to a subset of chronic exertional myopathies that is believed to be due to an abnormality in intracellular calcium regulation that is intermittently manifested during exercise.
Intact intercostal muscle fibers obtained from Thoroughbreds with RER have a lower threshold for force generation in response to halothane and caffeine compared to normal horses.9 In addition, calcium imaging modalities reveal enhanced calcium release in response to caffeine in myotubes derived from RER horses.15 Although, several characteristics of RER muscle are very similar to those of humans and swine with malignant hyperthermia (MH), a defect in the ryanodine receptor associated with MH has not been identified in RER horses.
At present the exact defect in intracellular calcium regulation with RER is not known.
The prevalence of RER in Thoroughbred racehorses is approximately 5% in the US16 and Australia,17 and 7% in the UK.18 Episodes are observed more frequently once horses achieve a level of fitness and occur most often when horses are restrained to a slower pace during exercise and occur infrequently after racing.16 Thoroughbred horses often show evidence of rhabdomyolysis after a steeplechase event or at the beginning of the cross-country phase of a three-day event.
Chronic exertional myopathies in Standardbred, Arabian and Warmblood horses may also be due to RER.11 Although mares show signs of RER more frequently than males, no general correlation has been observed between episodes of rhabdomyolysis and stages of the estrus cycle.17,19,20 The proportion of affected females to males is much higher in young horses compared with older age groups.16,19 Nervous horses (usually young fillies) have a higher incidence of rhabdomyolysis than calm horses.16 Horses on a high grain diet are more likely to show signs of RER, and one study found a higher prevalence of rhabdomyolysis among horses with lameness.16 Genetics: A genetic susceptibility to RER appears to exist in Thoroughbred horses where RER-afflicted horses may pass the trait along to 50% or more of their offspring21,22 Studies of Standardbred horses with RER suggest that there is potentially a heritable basis for this condition in this breed as well.23 There are anecdotal reports of higher prevalence of RER in certain Arabian horse families.
Diagnosis: A number of factors may affect muscle enzyme elevations in serum, and reliability can be improved if blood samples are obtained at a standardized time, preferably four to six hour after exercise (when CK peaks), and consistently with regard to exercise on the preceding day, since serum CK activity is higher on exercise days that are preceded by a day or more of rest.
Two-year-old fillies generally appear to show greater fluctuations in serum CK activity during race training than three-year-old fillies or geldings.19 A presumptive diagnosis of RER is based on clinical signs of muscle pain and the presence of risk factors commonly associated with RER.
Skeletal muscle biopsies from Thoroughbred and Standardbred horses with active signs of RER often show an increased 111 number of mature muscle fibers with centrally displaced nuclei, increased subsarcolemmal staining for glycogen, and a variable amount of muscle necrosis and regeneration.10 There is a notable absence of abnormal amylase-resistant polysaccharide in muscle biopsies from RER horses.
Research is currently underway to identify a genetic marker that would help identify horses susceptible to this genetic disease.
Polysaccharide Storage Myopathy (PSSM) PSSM represents a category of myopathies in horses that are characterized by accumulation of glycogen and abnormal polysaccharide in skeletal muscle.24 Several other acronyms have been used for this condition including EPSM and EPSSM.25 The variety of acronyms used are in part related to preferences of different laboratories, as well as to differences in the criteria used to diagnose polysaccharide storage myopathy.
Recently, an autosomal dominant mutation in the glycogen synthase 1 gene (GYS1) has been identified in horses diagnosed with PSSM by muscle biopsy.2 However, a subset of horses diagnosed with PSSM by muscle biopsy do not have this genetic mutation.3,4 Thus, there appear to be at least two forms of PSSM: the form caused by a GYS1 mutation which is now termed type 1 PSSM and the form with accumulation of polysaccharide in skeletal muscle whose origin is yet unknown now termed type 2 PSSM.
Type 1 PSSM: The GYS1 mutation appears to have been present in horses for over a 1000 years, and likely represents the same disorder described as “Monday Morning Disease or Azoturia” in draft horses in the early 20th century.2 The GYS1 mutation is found in high prevalence in North American Belgian and Percheron breeds and several Continental European Draft horse breeds.
Quarter Horses and Paint horses, Appaloosa horses, some Warmblood breeds, Haflinger, Morgan, Mustang, Rocky Mountain Horse, Tennessee Walking Horses, as well as mixed breed horses are also affected by type 1 PSSM.4 Quarter Horses: The most common signs of both forms of PSSM in Quarter Horses are firm painful muscles, stiffness, fasciculations, sweating, weakness and reluctance to move.24,26 The hindquarters are frequently most affected, but back muscles, abdomen, and forelimb muscles may also be involved.
During exercise, horses may stop and posture as if to urinate perhaps as a means to alleviate muscle cramping.
Signs of pain can last for more than 2 hours and about 10% of cases becoming recumbent.27 There is no significant temperament, body type, or gender predilection for PSSM.
Muscle pain often occurs with less than 20 minutes of exercise at a walk and trot, particularly if the horse has been rested for several days before exercise on a high grain diet.
The average age of onset of clinical signs is approximately 6 years and ranges from 1 to 14 years of age.
Serum CK and possibly AST activity are often persistently elevated in Quarter Horses with PSSM.26 The median CK and AST activity for all PSSM Quarter Horses with muscle biopsies submitted to the University of Minnesota was 2,809 and 1,792 U/L, respectively.
Draft Horse and Draft Crosses: North American Belgian and Percheron breeds and Continental European Draft breeds appear to have a high prevalence of type 1 PSSM and 112 the prevalence is low in Shire and Clydesdale horses.
Many draft horses with PSSM are asymptomatic.28 Signs of severe rhabdomyolysis and myoglobinuria may occur in horses fed high grain diets, exercised irregularly with little turn out or horses that undergo general anesthesia.
Other signs include progressive weakness and muscle loss resulting in difficulty rising in horses with normal serum CK activity.
Gait abnormalities, such as excessive limb flexion, fasciculations, and trembling are also reported in draft horses.
Although the condition Shivers was previously attributed to PSSM,29 a recent study found no causal association between these two conditions.28 The average age of draft horses diagnosed with PSSM is about eight years of age.
No particular gender predilection has been identified.
The median serum CK and AST activity in draft horses from which biopsies were sent to the University of Minnesota was 459 and 537 U/L.
Diagnosis: Genetic testing of hair roots or whole blood for type 1 PSSM is now available at the University of Minnesota Veterinary Diagnostic Laboratory (http://www.vdl.umn.edu/vdl/ ourservices/neuromuscular.html.
A diagnosis can also be made by identifying amylase-resistant abnormal polysaccharide in muscle biopsies.
Type 2 PSSM: Although clinical signs can be similar between type 1 and type 2 PSSM, it is more common for horses with type 2 PSSM to present with an undiagnosed gait abnormality.3,4 Quarter Horses with type 2 PSSM may present at less than one year of age with an inability to rise or a stiff hind limb gait and elevated serum CK activity.3 Research suggests that type 2 PSSM is less common than type 1 PSSM in Quarter Horses based on muscle biopsy characteristics and GYS1 genotypes.4 In contrast, type 2 PSSM is the most common form of PSSM in Warmblood breeds based on the same diagnostic criteria.
Dutch Warmbloods, Hanoverians, Friesians, Selle Francais, Westfalian, Canadian Warmblood, Irish Sport Horse, Gerdlander, Hussien, Icelandic horses, Quarter Horses, Morgans, Arabians and Thoroughbreds have been diagnosed with type 2 PSSM.
The most common clinical signs reported in Warmbloods with PSSM are painful firm back and hindquarter muscles, reluctance to collect and engage the hindquarters, poor rounding over fences, gait abnormalities, and atrophy.30 The mean age of onset of clinical signs in Warmbloods is between 8 and 11 years of age with the median CK and AST activity being 323 and 331U/L, respectively.
Diagnosis: Type 2 PSSM must be diagnosed by muscle biopsy where increased or abnormal PAS positive material that is usually amylase-sensitive is apparent particularly in sub-sarcolemmal locations.3 Determination of what constitutes an abnormal amount of amylase-sensitive glycogen can be subjective.
Some laboratories grade polysaccharide accumulation as mild, moderate, and severe where mild accumulation represents a category which has a higher chance of being a false positive diagnosis.
Mild PSSM cases in particular should receive a full physical examination to ensure that there are not other underlying causes for performance problems.
A muscle biopsy of any locomotor muscle that provides a 2 cm by 1 cm block of tissue for evaluation is often sufficient for diagnosis of PSSM.
The site most easily sampled in the field using an open surgical approach is the semimembranosus or semitendinosus muscle.
Clinics that can rapidly process muscle for frozen sections often use a modified Bergstrom biopsy instrument 113 inserted into the gluteal muscle through a 1 cm incision.
A diagnosis can be made irrespective of diet and proximity of sampling to recent episodes of rhabdomyolysis.
Malignant Hyperthermia (MH) MH is due to an autosomal dominant mutation in the skeletal muscle ryanodine receptor and is present in 1% or less of American Quarter Horses and Paints.7,8,31 Affected horses may intermittently show signs of tying up and high body temperatures.
Some MH affected horses have died suddenly after an episode of tying up.
The MH defect can coexist with the GYS1 mutation for type 1 PSSM.32 The combination of these two mutations makes signs of tying-up more severe, increases recurrence of high serum CK and makes horses more resistant to improvement with changes in diet and exercise.32 In addition, horses with MH may develop classic signs under general anesthesia of excessive body temperature, rigor, metabolic acidosis, and death.31 Genetic testing is recommended in Quarter Horse and Paint horses with difficult to manage forms of PSSM or a family history of post-anesthetic complications.
Testing is available through the Veterinary Diagnostic Laboratory at the University of Minnesota http:// www.vdl.
Umn.edu/vdl/ourservices/neuromuscular.html and University of California, Davis www.vgl.ucdavis.edu.
Management of Exertional Myopathies Sporadic Exertional Myopathies For sporadic cases of tying-up, a few weeks of rest in a small paddock after the initial episode and nonsteroidal anti-inflammatory medication form the basis for initial treatment.
Once muscle enzymes in the bloodstream return to normal, a horse can gradually resume exercise.
Sore muscles in many horses may be secondary to changes in gait or overt lameness arising from hoof balance, ligament, tendon, bone, or joint pain.
In such cases, changes in diet and exercise regimes will be unsuccessful until a long term holistic approach is taken which combines treatment of orthopedic disorders and rehabilitation therapy in addition to a balanced moderately low nonstructural carbohydrate diet and a gradually increasing exercise regime.
In addition, the degree to which the muscles necessary for a given type of performance are recruited during a fitness program should be evaluated to ensure these muscle groups are adequately trained during conditioning.
A program designed to provide gradually increasing intervals of recruitment of these muscle groups may be necessary.
For example, horses competing over cross country courses should be exposed to intervals of speeds that replicate speeds attained during competition.
Horses competing in dressage need to gradually develop the strength and coordination necessary to perform specific movements and sustained collection.
Chronic Exertional Myopathies Rest and turn out: For chronic cases, prolonged rest after an episode appears to be counterproductive and predisposes RER and PSSM horses to further episodes of muscle 114
Read more about Hypp : Ancillary Diagnostic Tests Depending on the breed of horse and….: