Challenges in Diagnosing Atypical Myopathy

Amongst the acquired myopathies that afflict horses, atypical myopathy (AM) (multiple acyl-coA dehydrogenase deficiency (MADD)), is common. Evidence suggests that the prevalence has increased in recent years. The cause (in Europe) is ingestion of hypoglycin A toxin from sycamore (Acer pseudoplatinus) seeds and seedlings in the autumn, spring and winter, in horses at pasture. Mortality is high – approximately 60–70%. In horses with high toxic loads, rapid diagnosis, with subsequent removal from the contaminated land and administration of B vitamins, are likely key in helping these horses survive. Consequently, recognition is key.

Horses with severe AM often present with profound paresis, manifest as lethargy, head and neck drooping, unusual stance or gait and with muscle fasciculations. Their intense efforts to remain standing often makes them sweat, and, with enforced or voluntary recumbency, they can easily be confused with horses with colic. In the worst cases, muscle damage becomes so profound that that there is severe muscle trauma and with it, often profound myoglobinuria. Usually there is prominent tachycardia or arrythmias. Respiratory effort can be laboured or indeed, respiratory rate can be unusually low in an animal with otherwise severe metabolic compromise. In these severe cases, diagnosis can readily be made on the basis of clinical suspicion, although carefully ruling out other causes of pigmenturia and colic is essential, especially when there is no opportunity for clinical pathology testing or when the results of the latter are, by necessity, going to be delayed.

Horses with severe AM have (sometimes massive) elevations in plasma creatine kinase (CK) activity. This alone, in association with the signs described above, particularly in a pastured, otherwise unexercised horse, makes the clinical suspicion of AM very likely, especially when sycamore material is confirmed in the pasture. Other evidence of metabolic compromise is revealed by acid–base defects amongst other abnormalities. Confirmation of the presence of hypoglycin A toxin (and its metabolites, such as MCPA-carnitine, or MCPA-glycine) in serum or plasma confirms the diagnosis in such cases. In horses found dead, or that are euthanased, concentrations of toxin can be measured in muscle or other tissues, feasibly then aiding with insurance claims or when attempting to rule out other possible causes of unexpected (sudden) death. Results can be obtained within 24–48 hours. Other clinicopathological assessments (for example acyl carnitine profiling, or organic acid testing) can help confirm the diagnosis and offers prognostic value, though testing is likely to take longer. Muscle biopsy/post-mortem diagnosis can also be achieved, on the basis of profound rhabdomyolysis/necrosis, usually combined with sarcoplasmic lipid accumulation in oxidative muscle fibre types, detected with specific histological stains.

Data from my laboratory reveal that AM varies in clinical severity. While some horses present in the manner described above, there is a sizeable population of horses that have mild or moderate signs; some animals (for example field companions) might only have subclinical disease, and others present with poor performance or mild fatigue. Sometimes, hypoglycin A is found in horses with otherwise unexplained mild elevations in plasma CK activity. Identifying these animals and distinguishing them from the myriad of other causes of poor performance (and hyperCKaemia), is challenging and will be discussed. Serum toxin testing can prove beneficial but might lead to false positive diagnoses – given the high prevalence of sycamore trees in European pastures, it is entirely possible that horses could have detectable hypoglycin A toxin in their serum, but another (or additional) disease.

It is also becoming evident that occasional horses can present with classic features of AM, with severe nonexertional rhabdomyolysis, and yet hypoglycin A toxin or its metabolites is undetectable – in these cases, the suggestion is that another toxin is the cause. Alternatively, especially in neonates, a genetic form of MADD should be considered. Confirmation that the same underlying pathophysiology is involved (by measuring acyl carnitines and organic acids) is likely key in helping identify these cases.

In summary, this presentation will cover the diagnosis of AM, clinically and with the aid of clinicopathological testing. I will discuss the pros and cons of various approaches under the scenarios outlined above.

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