1 Muscle Cases

• Synonymous terms for Rhabdomyolysis include tying-up, Monday-morning disease, and azoturia (antiquated).

Polysaccharide Storage Myopathy (PSSM)

• Accumulation of a non-bioavailable polysaccharide in type-2 (fast twitch) glycolytic muscle fibers
• Clinical signs range from muscle atrophy to exertional rhabdomyolysis
• Muscle biopsy histopathology reveals subsarcolemmal vacuoles, glycogen storage, and amylase-resistant inclusions in fast-twitch fibers, with muscle glycogen concentrations 1.5 times normal
• Horses with PSSM have low maximal achievable exercise speed.
• PSSM horses use more glycogen but have similar blood lactate with higher muscle lactate concentrations
• Glycogenolysis and glycolysis are functional
• Abnormal or excessive glycogen synthesis and increased insulin sensitivity is the origin of glycogen accumulation and polysaccharide abnormality
• Breeds affected include Quarter Horses, Paint horses and Warmbloods
• Autosomal dominant disorder
• Glycogen synthase mutation (GYS1) causes Type 1 PSSM resulting in a gain of function for glycogen synthase activity that results in a glycogenosis
• The mutation is an arginine to histidine at codon 309
• Some Quarter Horses have a gene mutation in their ryanodine receptors (RyR1) which results in malignant hyperthermia (MH)
• Individuals that co-express GYS1 and RYR1 gene mutations may suffer from fatal complications as a result of a very severe form of exertional rhabdomyolysis
• Abnormal accumulation of polysaccharide is common in Draft Breed horses and is also termed Polysaccharide Storage Myopathy (PSSM)
• Muscle biopsy is the most reliable way to diagnose PSSM in adult draft horses
• Reveals subsarcolemmal vacuoles, glycogen storage, and amylase-resistant inclusions in fast-twitch fibers
• History includes numerous “tying up” episodes, mildly affected horses have 1-2 episodes per year
• Clinical signs include mild stiffness to severe pain.
• Mild forms develop a tucked up abdomen, fasciculations in the flank region, and a camped-out stance
• Other signs include painful epaxial muscles, resistance to being tacked up, and alteration of stride
• Exercise intolerance is the most common complaint
• A severe tying-up episode in a Quarter-type horse is presumptive evidence with muscle biopsy providing definitive evidence
• Clinical signs of tying-up begin when the creatine kinase activity is elevated, typically > 20,000-40,000 U/L, with some cases > 100,000 U/L
• Aspartate transaminase (AST) will rise more slowly and will have a prolonged return to baseline.
• Myoglobinuria (dark brown, coffee-colored urine) is present in many cases during a clinical episode
• Screening exercise test (15-minute trotting on a lunge line) identifies approximately 80% of affected horses with an increase in CK to > 1000 U/L observed 4 to 6 hours after exercise
• DNA testing can determine Type I PSSM using a hair sample
• Diagnostic samples are submitted to the University of Minnesota
• Some horses without the GYSI mutation have PSSM (Type 2 PSSM), muscle biopsy is indicated
• Muscle biopsy involves the semimembranosis/semitendinosis
• Dietary management focuses on increasing oxidative capacity of skeletal muscle
• A high-fat diet (0.5 to 3.0 kg/day) accounting for 20-25% of daily calories
• Rice bran, corn oil, or spray dried fat supplements can be used
• Corn oil (1-2 cups/day) is mixed with soaked alfalfa cubes
• Feed high-quality grass hay
• Reduce nonfiber, nonstructural carbohydrates (sugars and starches) to ≤ 15% of total daily calories
• Corn should be avoided
• Sweet feeds contain 47% nonstructural carbohydrate, whereas commercial high fat diets contain 28-39% and alfalfa pellets contain 2%
• A high-protein diet (12 to 17%) is recommended for muscle support
• Vitamin E (1000 IU/day) and selenium (1 to 2 mg/day) supplementation is recommended
• High-fat diets prevent post-exercise elevation in creatine kinase and aspartate transaminase reducing clinical episodes after 3-6 months
• Box stall rest for more than 12 hours per day increases rhabdomyolysis incidence
• A 15-minute exercise test is used to determine the amount of exercise necessary in the initial training stages

Recurrent Exertional Rhabdomyolysis (RER)

• Thoroughbreds (Arabian, Standardbreds) are predisposed with young, nervous fillies overrepresented
• RER may have a familial basis, genetic transmission not as clear as PSSM
• Occurs with stress and stall rest
• RER occurs during aerobic exercise, muscle lactate is low, and is associated with metabolic alkalosis
• Abnormality in excitation-contraction coupling, abnormal intracellular calcium regulation
• Clinical signs include muscle fasciculations, stiff-stilted gait, myoglobinuria, firm painful muscles (particularly the epaxial and gluteal mm)
• Muscle biopsy reveals muscle necrosis and regeneration with centrally located myonuclei
• Biochemical testing identifies sensitivity to halothane and caffeine
• Prevention includes minimizing stress, standardized daily routine, vitamin-mineral supplement and quality feed
• Acepromazine prior to exercise
• Small paddock turn-out for exercise
• Dantrolene (2-4 mg/kg PO) 1 hr prior to exercise, inhibits release of calcium
• Phenytoin (1.4 to 2.7 mg/kg, po, BID) serum levels must be monitored

Acute Rhabdomyolysis Treatment

• Fluid therapy: Administer 40-60 L of isotonic fluids intravenously , monitor creatinine values and determine renal damage
• Analgesic medication: NSAIDs, Flunixin meglumine (Banamine®) 1.1 mg/kg IV, Butorphanol 10 mg IM
• Relieve anxiety: Xylazine (0.3-0.8 mg/kg IV), Detomidine (0.005-0.02 mg/kg IV), Acepromazine (0.02-0.06 mg/kg)
• Provide muscular relaxation: Diazepam 15 mg IV and Dantrolene 2-10 mg/kg PO

Additional Muscle Diseases

• Immune-Mediated (Strep. equi) Myopathy: Severe rhabdomyolysis days to weeks after natural exposure to strangles or vaccination against Streptococcus equi
• All syndromes are only described in Quarter Horses or Quarter-type breeds
• Myosin Heavy Chain Myopathy (MYHM) is a heritable disease of quarter horses and related breeds with a codominant mode of inheritance.
• Genetic testing should be performed on QH and related breeds
• M protein in streptococcal cell wall has amino acid sequences similar to myosin with lymphocytic myositis, massive muscle atrophy, and elevation in muscle enzymes
• Vascular thrombosis may be observed on mucosal surfaces, within lung, and intestinal organs
• Aggressive corticosteroid therapy should be administered
• Penicillin is administered to treat an apparent or occult Strep equi infection

Clostridial Myositis

• (Malignant Edema, Clostridial Myonecrosis)
• Clostridia are Gram+, spore-forming anaerobic bacteria that are ubiquitous
• Intramuscular colonization results in production of highly pathogenic extracellular exotoxins and enzymes
• Most cases result from a deep penetrating wound or an injection site
• C. perfringens is most common
• Other bacterial strains include C. septicum, novyi, sordelli, chauvoei
• α toxin – hydrolysis phosphatidylcholine and sphingomyelin (cell membranes)
• ϑ toxin (perfringolysin O) – pore-forming cytolysin
• κ toxin – collagenase
• Exotoxins cause tissue destruction and necrosis
• Intramuscular injection sites are a common inciting factor (82%)
• Lesions involve irritating, non-antibiotic meds (ivermectin, flunixin meglumine, PHF vaccine, antihistamines, vitamin B, etc)
• Lesions occur primarily from cervical injections, castration sites, deep puncture wounds, parturient injuries
• Site preparation and aseptic injection technique do not appear to have a significant effect
• Clinical signs include painful swelling +/- crepitation, 48-72 hours after IM injection, overlying skin that is warm then cold, fever, depression, and toxemia
• Rapid deterioration in clinical signs is common
• Inflammatory leukogram, hyperfibrinogenemia, elevated muscle enzymes, dehydration
• Diagnostic indications include history of recent IM injection with an irritating compound and rapid progression of clinical signs
• Diagnostic tests include impression smears of needle aspirate and ultrasound
• Treatment includes antimicrobial therapy (high-dose, frequent administration), Penicillin, metronidazole, oxytetracycline, chloramphenicol, NSAIDs for analgesia, antipyretic and antiinflammatory action, fresh plasma and supportive care
• Surgical fenestration involves opening discrete abscesses or multiple incisions through a diffusely affected area

Hyperkalemic Periodic Paralysis

• (HYPP) is a heritable defect of voltage-gated sodium ion channels
• Disrupts normal ion channel function, resulting in uncontrolled sodium influx
• Autosomal co-dominant genetic mutation that all are affected with homozygote > heterozygote
• Mutation of the voltage-gated sodium channel
• Single amino acid substitution where DNA reads TTG instead of TTC
• The resting membrane potential closer to threshold (hyperexcitable) with suboptimal function of Na/K pump
• Clinical signs includes intermittent episodes of muscular weakness and fasciculations, prolapse of nictitating membrane, sweating, anxiety, and tachypnea
• Episodes cannot be predicted and most episodes last 15 minutes to 2 hours
• High serum K+ concentrations may be observed
• Impressive was a top-winning stallion whose massive muscle is closely linked to the defective gene, and consequently, heterozygotes accumulate more AQHA points
• A DNA probe will show a single base substitution within the sequence of the sodium channel
• Electromyography can provide immediate supportive evidence of HYPP
• Homozygotes are more severely affected with upper airway dysfunction and possible need for tracheotomy
• Emergency treatment consists of intravenous calcium gluconate diluted in saline or 5% dextrose and alkalosis
• Intramuscular epinephrine increases uptake of K+ by muscle cells
• Prevention includes acetazolamide, diet containing less than 1.0% [K+], avoiding molasses, routine exercise, and pasture turn-out