Exertional Myopathy

Muscle diseases have many causes, and because of overlapping clinical symptoms, classifying different forms can be difficult. One of the most common diagnoses is Exertional Myopathy (EM).

Exertional Myopathy is a symptom-based diagnosis; the name is a description of any muscle disorder that leads to an abnormal response when the muscles are subjected to normal or increased strain. It therefore can have many causes. These can include external factors involved in management (feeding, over-training, riding), factors that influence a horse’s metabolism (stress, age, etc.), or specific genetic predispositions.

Symptoms often include:

• Reluctance to move
• Muscle weakness
• Pain
• Rapid fatigue
• Muscle tension or cramping
• Difficulty in building muscle or rapid muscle loss

The occurrence, severity and extent of symptoms depend on a multitude of factors and their interactions. Of the hereditary factors involved, 9 can be examined by genetic testing.

A variety of environmental and genetic factors can lead to the symptoms of exertional myopathy. These include Problems with management (feeding/training/handling/riding), Metabolic issues (Stress/age/pregnancy/weather), and genetic predispositions. It is common for all of these factors to interact to bring about a clinical picture.

In humans, more than 300 genes have been identified as being involved in neuromuscular diseases. In horses with symptoms of exertional myopathy, mutations have been identified in 9 genes. These fall into several categories, including metabolic (malignant hyperthermia), immune-mediated (MYH-1 myopathy), polysaccharide storage (PSSM1), and muscle integrity myopathies (“P variants”). It is clear that many more genetic mutations involved in neuromuscular disease have not yet been identified in horses; researchers worldwide are studying this area of research.

Causes of Exertional Myopathy

Disruptions of muscle structure or function compromise muscle integrity, which can then lead to symptoms of exercise intolerance and exertional myopathy. Six genetic variants which disrupt muscle integrity have been identified thus far.

The previous use of the umbrella term of “PSSM2” for the disease complex caused by these genetic variants was based upon a description of symptoms (clinical and pathological) and is not appropriate for a “cause-based” naming system, where the focus is on the reason for the symptoms. We therefore will transition to using the more precise name of Muscle Integrity Myopathy (MIM) to address this subtype of Exertional Myopathy in the future.

The genetic variants known as P2 (MYOT gene), P3 (FLNC gene), P4 (MYOZ3 gene), Px (CACNA2D3 gene), P8 (PYROXD1 gene), and K1 (COL6A3 gene), are therefore properly positioned as hereditary predispositions in the area of muscle structure and function. The effects of the specific variants can be found here: 

Presence of these genetic variants puts an animal at high risk of developing symptoms of exertional myopathy, especially if faced with external stresses/triggers. They are tested in the MIM - 6 Variant test (“PSSM2”) panel.

Order MIM 6-Variant-Test now.

There are currently 3 more genes know in which mutations can cause symptoms of exertional myopathy:

• GYS1 - a mutation in this gene causes Polysaccharide Storage Myopathy type 1 (PSSM1) 
• MYH1- a mutation in this gene causes MYH1-Myopathy, previously called Immune-mediated Myopathy (IMM)
• RYR1: Maligne Hyperthermie (MH) 

These nine genetic mutations can be tested for over the Exertional Myopathy 9-gene panel test in our webshop

EM-9-gene panel Test order now.

Of the genetic causes of Exertional Myopathy, only malignant hyperthermia (MH; RYR1) is 100% penetrant, (all horses with this mutation will develop symptoms). However, the other mutations that cause symptoms of EM can be somewhat compensated for by genetic background (other genetic variants) and environmental factors (nutrition, handling, training), and the disease may remain subclinical for longer periods of time.

Initial symptoms of MIM (“PSSM2”) often appear after a trigger from a management or metabolic issue, and may appear as an acute symptomatic episode, or a series of recurrent episodes. Most of the hereditary diseases classified under the EM designation are progressive; furthermore, muscle damage from acute episodes can accumulate, further complicating the clinical picture. Fortunately, due to the strong influence of the environment on symptoms, it is often possible to partially mitigated symptoms by adjustments in feeding and training.

Management

Nutrition is extremely important for muscle health, and it is obvious that insufficient calories can lead to a horse that is weak and unwilling to move. Less obvious are more specific deficiencies:

Insufficient supplementation of essential amino acids - lysine, threonine, methionine. Horses cannot synthesize these animo acids, and if not provided with a complete protein source in the diet, these essential amino acids must be supplemented.

Trace Minerals deficiencies - while most horses are able to get sufficient levels of trace minerals in their hay, in regions where there are soil deficiencies it is necessary to supplement specific minerals. Selenium is particularly important, as are magnesium, manganese, copper, and zinc.

Overexertion - pushing an animal to levels of exercise for which they are not prepared, or concentrating daily on training specific movements can put muscles under high stress. Similarly, riders not well matched to their horse can also cause overexertion issues.

Metabolic

Age, weather, pregnancy, and other stresses (operation, infection, injury, vaccination) are all conditions that can lead to an increased protein requirement. If sufficient protein is not provided, this can disrupt the metabolism to such an extent that the body is no longer receives adequate levels of nutrition. The deficit (also referred to as a negative nitrogen balance) must be compensated for by breaking down the body's own protein mass, leading to muscular atrophy. In conjunction with other negative factors, including the genetic variants that predispose animals to exertional myopathy, the effect increases and leads to the symptoms of the disease.

In horses with genetic variants leading to Muscle Integrity Myopathy (MIM, “PSSM2”), the consequences of a negative nitrogen balance often appear earlier and more severely, since there is already an increased need to compensate for faulty muscle building blocks. (case examples)