Pathophysiology of Muscle Disorders in Horses

Exertional Myopathies

  • Sporadic Rhabdomyolysis (Tying-Up)

  • Most prevalent muscular disorder in horses, often occurring after periods of rest followed by intense exercise.

  • Alternative names: Monday-morning disease, azoturia.

  • Symptoms:

    • Stiff gait accompanied by difficulty in movement, excessive sweating, increased respiratory rate, firm and painful muscles, reluctance to move, and dark or brown urine indicative of myoglobinuria.

  • Causes:

    • Typically results from overexertion without proper musculoskeletal preparation, often exacerbated by dietary imbalances (especially low sodium (Na) and calcium (Ca) intake), and environmental factors like high temperatures and humidity leading to dehydration and exhaustion.

  • Recurrent Exertional Rhabdomyolysis (RER)

  • Characterized by intermittent episodes of rhabdomyolysis that often occur during or after exercise, linked to dysfunction in calcium regulation within myofibers.

  • Prevalence:

    • Affects approximately 5% of Thoroughbreds and 6.5% of Standardbreds, with a notably higher incidence in certain breeds.

  • Risk Factors:

    • Particularly affects fit horses with a nervous temperament, young mares, and those kept in confinement with little turnout or being over-restrained during exercise.

  • Mechanism:

    • Increased epinephrine as a result of stress or excitement leads to heightened activity of the SERCA receptor, which negatively impacts calcium handling during muscle contraction and relaxation, causing muscle stiffness and pain.

  • Polysaccharide Storage Myopathy (PSSM)

  • PSSM-1: Genetic mutation (GY1) affecting glycogen metabolism, primarily observed in draft breeds (e.g., Percherons, Belgians), leading to abnormal glycogen storage within muscle cells.

    • Symptoms:

    • Muscle stiffness and pain post-exercise, reluctance to move, mild myoglobinuria, with some horses exhibiting signs of exercise intolerance or impaired performance.

  • PSSM-2: A less understood variant with an unknown aetiology, characterized by milder clinical symptoms, poor performance, and less pronounced enzyme elevations compared to PSSM-1.

  • Hyperkalemic Periodic Paralysis (HYPP)

  • A genetic condition primarily affecting Quarter Horses due to mutations in sodium channels (leaky), causing aberrant ion flow and muscle excitability.

  • Symptoms:

    • Characterized by sporadic bouts of muscle stiffness, muscle tremors, weakness, potential for collapse, breathing difficulties, and laryngeal paralysis, especially following exercise or stress. Elevated potassium diets and related dietary factors can exacerbate these symptoms, prompting management strategies to mitigate risks.

Non-Exertional Myopathies

  • Atypical Myopathy

  • A rare but serious toxic condition linked to the ingestion of Hypoglycin A, primarily found in certain plants such as sycamore.

  • Symptoms:

    • Rapid onset of muscle weakness, severe stiffness, sweating, and myoglobinuria with a high mortality rate if untreated, requiring immediate veterinary intervention.

  • Immune-Mediated Myopathy

  • A condition often associated with preceding respiratory infections (e.g., Streptococcus), leading to an autoimmune reaction targeting muscle tissue.

  • Symptoms:

    • Results in muscle stiffness, rapid muscle atrophy, and inflammation, typically observed 7-10 days post-infection.

  • Myonecrosis

  • Typically caused by Clostridium spp. following intramuscular (IM) injections or traumatic injuries, leading to significant muscle tissue damage.

  • Symptoms:

    • Fever, profound pain in the affected muscle, stiffness, swelling, and potential for necrosis or gangrene, necessitating urgent surgical and medical management.

Pathophysiology Insights

  • Muscle Contraction Mechanism:

  • The regulation of muscle contraction involves calcium release through the ryanodine receptor (RYR-1) during stimulation, while the SERCA receptor plays a critical role in calcium re-uptake, enabling muscle relaxation.

  • Genetic Factors in Muscle Diseases:

  • Mutations in genes related to muscle function (e.g., GYS1 for PSSM-1, SCNA4 for HYPP) significantly contribute to the development and severity of various myopathies, highlighting the importance of genetic screening in affected breeds.

Key Diagnostic Indicators

  • Muscle Biopsy:

  • A crucial diagnostic tool used to confirm specific diagnoses like PSSM by assessing muscle fibers' glycogen metabolism efficiency and the presence of any pathological changes.

  • Blood Tests:

  • Essential for monitoring muscle enzyme levels (e.g., creatine kinase, AST) post-exercise, which can aid in distinguishing between different types of myopathy based on their enzymatic profiles and muscle damage levels.

Differential Diagnosis for Muscle Disorders

  1. Myofibrillar myopathy

  2. Sporadic rhabdomyolysis

  3. Atypical myopathy

  4. Immune-mediated myopathy

  5. Infectious myositis (e.g., due to clostridia)

References and Further Reading

  • Equine Sports Medicine and Surgery (2014) Chapters on muscle physiology, disorders, etc.

  • Durwark-Arkhus 2018. Immune-Mediated Muscle Diseases of the Horse, Veterinary Pathology.