Diagnosis

Establishing a diagnosis of atypical myopathy based solely on clinical signs is no straightforward task. Indeed, some horses afflicted with atypical myopathy may manifest clinical symptoms remarkably similar to those seen in horses with colic. However, confirmation of the diagnosis is paramount to protect potential field companions through the implementation of recommended preventative measures. Furthermore, confusion with other diseases can result in an inappropriate approach to the affected animal. For instance, walking is frequently recommended in cases of abdominal colic, whereas any exertion is strictly contraindicated for horses with atypical myopathy (1).

Prior to the discovery of the cause of atypical myopathy, a decision-making algorithm was employed to categorize reported cases within disease surveillance networks "with a high likelihood," "with a low likelihood," "doubtful," and "instances that do not qualify as cases." (2). Since the identification of the cause (3), new diagnostic tests have become available.

The diagnosis of atypical myopathy hinges on the four key steps of any diagnostic procedure:

1. Gathering Anamnesis

Access to pasture is a prerequisite for considering atypical myopathy in the diagnosis. Intoxication is closely linked to grazing, with 99.8% of horses being at pasture when clinical signs of intoxication appeared (i.e., more than 6 hours per day in the pasture (4))(5). The remaining 0.2% were stabled for less than a week, implying that they had the opportunity to come into contact with the toxin. To date, no cases in our database have been confirmed by blood testing of HGA and/or MCPA-carnitine in horses that did not have access to pasture and/or a paddock (unpublished data)(5). Moreover, the presence of several risk factors can increase the suspicion of atypical myopathy, such as the presence of trees (especially sycamore maples), deadwood, or dead leaves (non-exhaustive list).

2. Clinical Examination

Pigmenturia is one of the most specific signs of atypical myopathy without being pathognomonic: when present, the presumption of atypical myopathy is greatly increased. Its absence, however, does not exclude atypical myopathy, as darkening of the urine requires some time. Other clinical signs serve to bolster the diagnostic suspicion.

3. Laboratory Analyses

Serum creatine kinase (CK) activity (an enzyme present in muscles) is typically elevated, sometimes to the extent of hundreds of thousands or even millions (6, 7), and an increase equal to or greater than 10,000 IU/L is considered significant for muscle breakdown (myolysis) (8). However, when measuring CK activity early, it may appear within normal ranges. A delay is required between myolysis and the onset of elevated CK activity in the blood; a second blood sample taken a few hours later reveals a severe increase in CK activity.

4. Specialized Examinations

Blood tests for hypoglycin A and its toxic metabolite, methylcyclopropylacetic acid (MCPA), found in the form of MCPA-carnitine, are available in some laboratories. However, field companions without clinical signs can also have these compounds in their blood. As of now, there is no correlation between HGA or MCPA levels and the onset of clinical signs (9,10).

MCPA interferes with the β-oxidation of fatty acids [9], leading to an accumulation of acyl-coenzymes A (CoAs) that conjugate with carnitine into acylcarnitines. These acylcarnitines enter the peripheral circulation, resulting in a characteristic blood profile that confirms the diagnosis of atypical myopathy [11, 12, 13].

Therefore, to date, the specific serum profile of acylcarnitines in horses with atypical myopathy is the only reliable means of diagnosing the condition. Recently, a study highlighted that isovalerylcarnitine (C5 carnitine) is the most discriminating parameter for confirming a diagnosis of atypical myopathy and establishing a survival prognosis [13].