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Muscle: myopathy – atypical
Synonym(s): Seasonal pasture myopathy, SPM, Hypoglycin-associated myopathy, Atypical myopathy, Rhabdomyolysis, Sycamore poisoning
Introduction
- Seasonal pasture myopathy/atypical myopathy is an acute highly fatal, toxic, non-exertional rhabdomyolysis that causes multiple acyl-CoA dehydrogenase deficiency (MADD). The postural, respiratory, and cardiac muscles are mainly affected.
- Cause: ingestion of hypoglycin A.
- Signs: lethargy, weakness, recumbency, depression, muscle fasciculations, choke, pigmenturia, dyspnea, respiratory failure, sweating.
- Diagnosis: clinical signs, blood biochemistry, identification of hypoglycin and acylcarnitine profiles in blood, histopathology of Type 1 muscle.
- Treatment: supportive.
- Prognosis: poor.
Presenting signs
- One or multiple horses grazing on pasture can be affected.
- Initially sudden onset of lethargy, stiffness and reluctance to move or exercise, and muscular weakness.
- Muscles are not excessively firm or sore on palpation but there may be fine muscle tremors.
- Inability/unwillingness to stand for more than a few minutes.
- Lowered head carriage may result in pharyngeal and generalized head edema, partial respiratory obstruction and exacerbated respiratory distress.
- Recumbency.
- Increased vocalization and head tossing.
- Choke Esophagus: obstruction.
- Pigmenturia (dark brown).
- Later on cases may show:
- Dyspnea and respiratory failure.
- Affected animals are painful with sweating and depression.
- Reduced appetite or may continue to eat.
- Colic.
- Congested mucous membranes and cardiac arrhythmias Poor performance: cardiac causes and treatment.
- Distended bladder on rectal examination Urogenital: rectal palpation.
Disease progression
- Variable progression, but deterioration may be rapid to lateral recumbency and death within 24-72 h.
- May be found dead.
- Mild signs may intensify and develop over 3-5 days.
- Variable survival rates between reports and outbreaks.
- 25% survival in European outbreaks 2006-2009.
- Reporting bias is likely to occur, milder cases are less likely to be hospitalized and reported.
Secondary complications
- Head edema.
- Pressure sores.
- Buccal ulceration/necrosis.
- Gastric ulceration Stomach: gastric ulceration.
- Esophageal obstruction (choke) Esophagus: obstruction.
- Intestinal impaction Colon: impaction.
- Diarrhea Diarrhea: idiopathic.
- Renal dysfunction.
- Priapism Penis: paralysis / priapism.
- Corneal ulcers Keratitis: traumatic - ulcerative.
Geographic incidence
- SPM occurs commonly in the upper Midwest of the USA but does occur across North America, including eastern Canada, and where box elder trees are located.
- In Europe all cases have been associated with the common sycamore Sycamore maple (Acer pseudoplatanus); box elder trees are present, but in ornamental gardens where horses are unlikely to come into contact with them.
- Horses are likely to be at risk wherever common sycamores or box elder trees are present.
- The Norway maple (Acer plantanoides) and field maple (Acer campestre) do not present a risk as they do not produce hypoglycin.
Age predisposition
- Younger horses are at higher risk.
Breed/Species predisposition
- No breed predisposition has been identified.
Public health considerations
- It is not known for how long hypoglycin A's toxin metabolite remains in muscle tissues; affected animals should not be used for human or other animal consumption.
Cost considerations
- Care for atypical myopathy can be intensive and expensive.
- Loss of animal.
Pathogenesis
Etiology
- Ingestion of hypoglycin A contained in samaras (fruit), seeds and/or seedlings from the common (European) sycamore maple tree (Acer pseudoplatanus) Sycamore maple (Acer pseudoplatanus) and box elder (Acer negundo) which results in a lipid storage myopathy. Year old sycamore saplings have also been found to still test positive for hypoglycin A.
- Rainwater that has come in contact with sycamore seedlings may also contain hypoglycin A.
- The toxic dose appears to vary markedly between horses and the concentration of toxin is highly variable between seeds. Estimates of the number of seeds that need to be ingested to cause disease varies from dozens to thousands.
- One study found that during some periods <20 g of samaras (approximately 50 seedlings) are enough to reach toxic levels. It also suggested that this dose may also be reached by ingesting 150 g of inflorescencs or 2 l of in-contact rainwater.
- Outbreaks are common and occurrence is seasonal.
Predisposing factors
General
Environmental
- Presence of seed-bearing trees: factors which determine individual seed toxicity are unknown at this time but may be related to climate.
- >90% of cases are recorded commonly in fall/autumn months, although occasional cases occur after first frosts/snow.
- A smaller rise in cases occurs in the spring in association with the emergence of seedlings.
- Inclement weather: heavy wind and rain often occur in the week preceding clinical cases; such weather likely increases seed dispersion.
- Sparse pasture and absence of supplemental forage; presumably because horses are more likely to ingest seeds. Pasture with many trees and dead wood on ground.
- Introduction of new horses to a pasture containing these trees, especially during high risk periods: horses that have recently moved to a new farm or pasture may be at increased risk for SPM/AM; may be higher risk in younger animals.
Horse
- Young horses are more likely to be affected; the disease has not been reported in foals.
- Pasture turnout >6 h/day.
- Horses that are not in work are at greater risk, probably because they are more likely to have extended access to pasture.
- Antioxidant deficiency such as seen with low selenium Selenium or vitamin E Vitamin E levels has been suggested as a possible contributing factor.
- Suckling foals can also consume the hypoglycin and associated metabolites via the mare’s milk.
Pathophysiology
- Upon ingestion, hypoglycin A is metabolized to methylenecyclopropylacetic acid (MCPA) which is then converted to MCPA-CoA.
- Short, medium and long-chain acyl-CoA dehydrogenases serve to convert their respective length fatty acyl-CoAs into acetyl-CoA for the citric acid cycle, releasing NADH and FADH2 for the electron transport chain in the process.
- MCPA-CoA serves as a substrate for and irreversibly inhibits short and medium chain acyl-CoA dehydrogenases essential for ß-oxidation of fatty acids.
- In addition, through sequestration of CpA and carnitine, MCPA also inhibits the carnitine-acyl-CoA transferase system required for transportation of long chain fatty acids into the mitochondria, impairing mitochondrial ß-oxidation of long chain fatty acids.
- Amino acid metabolism (isovaleryl-, glutaryl-CoA dehydrogenases) is disrupted by MCPA through modification of the flavin adenine dinucleotide cofactor.
- In sum, this results in an accumulation of acyl-CoAs that cannot be used for the citric acid cycle. These acyl-CoAs are transported into the blood stream as acylcarnitines, undergo alternate É oxidation and subsequently pass into the urine for elimination as acylglycines and other urine organic acids.
- The inability of the body to utilize its acyl-CoAs from lipids results in a negative energy balance and lipid storage myopathy that precludes normal myocyte functions, resulting in cell death.
- This category of metabolic derangements is known as Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), which is also known in humans as glutaric acidemia type II.
Timecourse
- A latent period of up to 4 days has been reported.
- Some affected horses appear to become quiet and lethargic for a few days prior to the onset of more severe clinical signs.
- Clinical signs tend to progress over a few days.
- Horses that survive 3-5 days are more likely to recover.
- Recovery from acute disease is reported to take 10.6 +/- 5.6 days, but in some cases may take considerably longer.
- Horses that recover make a complete recovery and will return to their previous athletic potential.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed papers
- Recent references from PubMed and VetMedResource.
- Sander J, Terhardt M & Janzen N (2021) Detection of maple toxins in mare's milk. J Vet Intern Med 35 (1), 606-609 PubMed.
- González-Medina S et al (2021) Detection of hypoglycin A and MCPA-carnitine in equine serum and muscle tissue: optimisation and validation of a LC-MS-based method without derivatisation. Equine Vet J 53 (3), 558-568 PubMed.
- Votion D M et al (2019) Potential new sources of hypoglycin A poisoning for equids kept at pasture in spring: a field pilot study. Vet Rec 184 (24), 740 PubMed.
- González-Medina S et al (2019) Atypical myopathy-associated hypoglycin A toxin remains in sycamore seedlings despite mowing, herbicidal spraying or storage in hay and silage. Equine Vet J 51 (5), 701-704 PubMed.
- Krägeloh T et al (2018) Identification of hypoglycin A binding adsorbents as potential preventive measures in co-grazers of atypical myopathy affected horses. Equine Vet J 50 (2), 220-227 PubMed.
- Boemer F et al (2017) Acylcarnitines profile best predicts survival in horses with atypical myopathy. PLoS One 12 (8), e0182761 PubMed.
- Żuraw A, Dietert K, Kühnel S et al (2016) Equine atypical myopathy caused by hypoglycin A intoxication associated with ingestion of sycamore maple tree seeds. Equine Vet J 48 (4), 418-421 PubMed.
- Baise E et al (2015) Samaras and seedlings of Acer pseudoplatanus are potential sources of hypoglycin A intoxication in atypical myopathy without necessarily inducing clinical signs. Equine Vet J 48 (4), 414-417 PubMed.
- Bochnia M et al (2015) Hypoglycin a content in blood and urine discriminates horses with atypical myopathy from clinically normal horses grazing on the same pasture. PLoS ONE 10 (9), e0136785 PubMed.
- Gröndahl G, Berglund A, Skidell J et al (2015) Clinical research abstracts of the British equine veterinary association congress 2015. Equine Vet J 48, 22 PubMed.
- Naylor R (2014) Managing muscle disease is horses. In Pract 36 (8), 418-423 BMJ.
- Unger L et al (2014) Hypoglycin A concentrations in seeds of Acer pseudoplatanus trees growing on atypical myopathy-affected and control pastures. J Vet Intern Med 28 (4), 1289–1293 PubMed.
- Valberg S J (2013) Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree. Equine Vet J 45 (4), 419-426 PubMed.
- VanGalenG & Votion D M (2013) Management of cases suffering from atypical myopathy: Interpretations of descriptive, epidemiological and pathophysiological findings. Part 2: Muscular, urinary, respiratory and hepatic care, and inflammatory/infectious status. Equine Vet Educ 25 (6), 308-314 VetMedResource.
- Votion D M et al (2014) Identification of methylenecyclopropyl acetic acid in serum of European horses with atypical myopathy. Equine Vet J 46 (2), 146-149 PubMed.
- Sponseller B T et al (2012) Equine multiple Acyl-CoA dehydrogenase deficiency (MADD) associated with seasonal pasture myopathy in the Midwestern United States. J Vet Intern Med 26 (4), 1012-1018