Atypical Myopathy

 

Anouk Frieling, MSc Equine Sciences, BSc (Hons)

Atypical myopathy (AM) is a seasonal, non-exercise related, disease causing acute rhabdomyolysis (rapid breakdown of damaged muscle tissue) which affects the muscles of the horse (Votion & Serteyn, 2008). Atypical means that it is an unusual disease which occurs sporadically and therefore does not fit into a diagnostic category. Through recent years research has been dedicated to finding possible causes that trigger the sudden onset of AM to be able to prevent AM or recognise the early signs of this highly fatal disease (Votion et al., 2007). The disease is most commonly seen in grazing horses during autumn but occasionally also occurs during other seasons (González-Medina et al., 2017). This article will review current information about the cause of this disease, the clinical signs, treatment and prevention.

Atypical Myopathy Causes and Pathophysiology

Equine atypical myopathy mainly affects the respiratory muscles and muscles that support the skeleton and maintain balance (Żuraw et al., 2016). Possible causes of AM in horses that have been identified so far are virus infections, bacterial or fungal toxins, plant toxins and nutritional deficiencies (Harris & Whitwell, 1990; Brandt et al., 1997). One of the most common causes of the sudden onset of clinical signs of AM are related to the ingestion of sycamore seeds, leaves or sprouts which contain the toxin hypoglycin A (HGA) (Fabius & Westermann, 2018). Westermann et al. (2016) suggested that the ingestion of a kilogram of sprouts of the sycamore tree is more dangerous in comparison to a kilogram of sycamore seeds. Interestingly, during spring there are more sprouts available and during autumn more seeds are available (Westermann et al., 2016). The number of affected horses differs per year, but as mentioned, most horses are affected by the disease during autumn when the sycamore seeds are present on pasture (Unger et al., 2014; Żuraw et al., 2016). This could imply that horses prefer the seeds over sprouts or that due to the better quality of spring grass horses do not feel the need to search for other feedstuff when out on pasture (Westermann et al., 2016). Currently, it is unknown why the number of affected horses differs annually, but it is suggested that it is influenced by factors that have an effect on the number of sycamore seeds on pasture such as a change in climate or tree maturity (Herrera et al., 1998; González-Medina et al., 2017).

Figure 1: During autumn the seeds from the sycamore tree fall on the pasture on which horses graze. These seeds can be toxic and horses ingesting these seeds can develop atypical myopathy.

 

After ingestion, HGA interferes with metabolic processes (Karlíková et al., 2016), and causes multiple acyl-CoA dehydrogenase deficiency (MADD) which is a form of rhabdomyolysis in horses (González-Medina et al., 2021). To date, the complete pathophysiology of AM is unknown but research in AM affected horses, and other animal and human studies with similar diseases, have given some insight into the pathophysiology of this disease (Karlíková et al., 2016). Studies analysing the muscles of affected horses have found that the degenerative process of AM mainly affects type I muscle fibres and has a lesser effect on type II muscle fibres (Cassart et al., 2007; Palencia & Rivero, 2007). In the affected type I muscle fibres an increased lipid storage has been registered which might imply that metabolism is compromised due to AM (Brandt et al., 1997; Votion, 2012). Type I muscle fibres are slow contracting muscle fibres depending on aerobic respiration (require oxygen), whilst type 2 are quick contracting fibres which are dependent on anaerobic respiration (without oxygen). A commonly accepted theory about AM is that after HGA intoxication the Coenzyme A of methylenecyclopropyl acetic acid, a metabolite of HGA, inhibits flavin adenine dinucleotide (FAD), a coenzyme associated with various proteins, and acyl-CoA dehydrogenases in the body (Karlíková et al., 2016). Type I muscle fibres derive energy from fatty acid metabolism in muscle cells, but the inhibition of mitochondrial enzymes influences this metabolism resulting in lipid accumulation, meaning there is no energy available for Type I muscle fibres (Westermann et al., 2008; Lemieux et al., 2016). This possibly explains the sudden muscular weakness and degeneration (Gonzalez-Medina, 2015). Due to this disturbance type I muscle fibres will rely on anaerobic respiration which results in lactic acidosis (accumulation of lactic acid) (Gonzalez-Medina, 2015).

 

Clinical signs and Diagnosis

Clinical signs often start with the sudden onset of muscle weakness and stiffness (Bochnia et al., 2015). It is possible that before clinical signs appear other signs such as depression, oesophageal obstruction, colic and anorexia appear, but this is rare (Votion & Serteyn, 2008). The disease progresses rapidly and only a few hours after development of clinical signs horses will be found lying down as they are unable to stand due to the muscles being affected by the disease (Brandt et al., 1997). There are a few horses that are able to stand, or stand up after lying down, but these horses often stand for only a few minutes before lying down again (Votion & Serteyn, 2008). Affected horses can become hypothermic (low body temperature) but once they are stabled this is usually resolved (Votion & Serteyn, 2008). Studies also suggest that AM is related to abnormal cardiac changes in horses (Verheyen et al., 2012). Other possible clinical signs are dark coloured urine, sweating, muscle tremors, a lowered head which can result in oedema due to the lowered position, increased breathing, appetite loss or in some cases increased appetite (Votion & Serteyn, 2008). Measurable signs in horses affected by AM are elevated lactate dehydrogenase (LDH) and creatine kinase (CK) which indicates tissue damage (Bochnia et al., 2015). The toxin HGA from the ingested sycamore seeds can be measured using blood and urine samples. Horses affected by AM can also experience electrolyte imbalances (Votion, 2012).

Figure 2: Atypical Myopathy affects the muscles of the horse. Horses that lie down and do not stand up is one of the clinical signs of AM.

 

Diagnosing AM based on the clinical signs is difficult and can often lead to a wrong diagnosis as the clinical signs are very similar to those of other equine diseases (Votion, 2012). To make sure the horse is correctly diagnosed, the environment of the horse should be checked for possible toxic feedstuff that the horse could have ingested which could lead to AM. The history of the horse and laboratory findings should also be taken into account alongside the clinical signs (Votion, 2012). A veterinarian will be able to measure the CK levels in urine and elevated CK levels will indicate muscle damage which can be related to AM (Karlíková et al., 2018).

Treatment

As mentioned, currently there is no specific treatment for AM affected horses (Votion, 2012). Current available treatment is mainly supportive and symptomatic to increase survival rates (Fabius & Westermann, 2018). Treatment options are resolving dehydration and electrolyte imbalances, provide enough energy for affected muscles, eliminate toxins in the body, provide pain relief, support the mitochondrial function within the muscle cells, and prevent further or continued intoxication and injury (Fabius & Westermann, 2018).

One of the symptoms of AM is secreting dark urine which is a signs of dehydration. Therefore, providing fluids is essential for rehydration, and will enhance renal clearance of excess metabolites and correction of blood parameters (Fabius & Westermann, 2018). A veterinarian is able to provide fluid intravenously (i.v.) until the urine colour is yellow again (Fabius & Westermann, 2018). A study involving people diagnosed with rhabdomyolysis has suggested to provide people approximately 6 to 12 litres in the first 24 hours after diagnosis (Zimmerman & Shen, 2013). This translates to approximately 0.1 and 0.2 L/kg body weight of fluids (Fabius & Westermann, 2018).

As previously discussed, due to AM the fatty acid metabolism in muscle tissue is disturbed and will shift from aerobic to anaerobic (Fabius & Westermann, 2018). Anaerobic fatty acid metabolism in muscle tissue creates metabolites which can disrupt homeostasis in the body (Mizock & Falk, 1992). Providing enough glucose for metabolism in the body can prevent this shift from aerobic to anaerobic metabolism (Fabius & Westermann, 2018). Therefore, administering glucose will increase the chances of survival, with a suggested glucose administration of up to 20 litres per day for a 500kg horse affected by AM  (Wüger et al., 2006; Fabius & Westermann, 2018). 

Studies suggest that the supplementation of vitamin E, selenium, carnitine and riboflavin can support AM affected horses and can increase chances of survival (Fabius & Westermann, 2018). Vitamin E is commonly supplemented to provide general muscle support due to its antioxidant properties (Fagan et al., 2017). Because of the supportive function of vitamin E, it is believed that it is able to provide muscle support to horses diagnosed with AM (Finno et al., 2006). Carnitine can increase leptin levels which stimulates glucose uptake from the bloodstream and glucose metabolism (Kranenburg et al., 2014). Riboflavin, also known as vitamin B2, is one of the components of FAD involved in MADD (Fabius & Westermann, 2018). Although, the role of riboflavin in AM is unknown, providing riboflavin to horses with AM has shown to be beneficial (van Galen et al., 2012).

Prevention

Preventing AM is important as currently there is no specific treatment. Firstly, to prevent AM in grazing horses, ingestion of toxic sycamore seeds or spouts should be prevented by checking the environment of the horse. If found, seeds and sprouts should be removed from the horse’s environment (Votion et al., 2020). Providing easy accessible feed, such as hay, in pastures with decreased grass availability, or lower quality grass, can also lower the risk as horses will not look for other feedstuff in the pasture (Votion et al., 2009; González-Medina et al., 2017). Grazing on fields surrounded by sycamore trees should also be avoided during autumn and spring to decrease the risk of AM (Votion et al., 2020). Good pasture management is essential for fields close to sycamore trees.

Conclusion

Atypical myopathy is an acute seasonal disease in grazing horses, affecting the muscles of the horse. The onset of the disease is caused due to ingestion of sycamore seeds, sprouts or leaves which contain the toxic compound HGA. After intoxication the disease progresses rapidly and is therefore highly fatal. Clinical signs include muscle weakness and stiffness but the signs of the disease are very similar to other muscle diseases in horses, making it difficult to correctly diagnose a horse with AM. Currently, there is no specific treatment for the disease as the full pathophysiology is still unknown. Available treatment is mainly supportive to be able to increase the chances of survival for affected horses. Because there is no treatment available, it is important to implement good pasture management and prevent horses from ingesting toxic composites.

 

References

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