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Basics ⬇

Outline

BASICS

Overview!!navigator!!

  • Caused by hypoglycin A, a toxic amino acid found in seeds of the maple species Acer negundo (box elder) and Acer pseudoplatanus (sycamore maple)
  • A highly fatal nonexertional rhabdomyolysis of horses at pasture termed SPM (North America) or AM (Europe)
  • Methylenecyclopropylacetic acid, the toxic metabolite of hypoglycin A, inhibits various mitochondrial dehydrogenases, resulting in acquired MADD
  • MADD causes disruption of fatty acid beta-oxidation and subsequent lipid accumulation and degeneration in muscle with high oxidative capacity, such as postural, respiratory, and cardiac muscles
  • Large outbreaks in Europe. In North America only few horses on a given pasture are affected

Signalment!!navigator!!

No breed, sex, or gender predilection.

Signs!!navigator!!

  • Lethargy, acute muscular weakness, muscle fasciculations, stiffness, reluctance to move, recumbency
  • Congested mucous membranes, tachycardia, tachypnea, dyspnea
  • Myoglobinuria, dysuria, distended bladder
  • Sweating, colic signs
  • Esophageal obstruction, dysphagia

Causes and Risk Factors!!navigator!!

  • Typically occurs in the fall when seeds are abundant and pasture grass is sparse. Cases in the subsequent spring are common and may be caused by ingestion of seedlings
  • Young horses and naive horses recently introduced to the pasture are at increased risk
  • Lack of supplemental feed (hay, grain) encourages browsing and consumption of maple seeds
  • Inclement weather (cold temperatures, strong wind) may lead to a negative energy balance and dispersal of the seeds
  • Stress (exercise, transport, cold weather) may trigger clinical signs in subclinical cases

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Eupatorium rugosum (white snake root) toxicity caused by tremetone
  • Other causes of rhabdomyolysis
  • Ionophore toxicity
  • Laminitis
  • Other causes of colic

CBC/Biochemistry/Urinalysis!!navigator!!

  • Leukocytosis/neutrophilia
  • Marked increase in CK and aspartate aminotransferase activities
  • Hyperglycemia
  • Hypocalcemia
  • Lactic acidemia
  • Increased liver enzymes
  • Hyperlipemia
  • Myoglobinuria

Other Laboratory Tests!!navigator!!

  • Metabolic defect of MADD—elevated short, medium, and less frequently long chain acylcarnitines in serum and urine. Increased urinary excretion of ethylmalonic acid, methylsuccinic acid, butyryl-, isovaleryl-, and hexanoylglycine. Testing may be available through human metabolic institutes
  • Elevated cardiac troponin I possible
  • Elevated Hypoglycin A and MCPA carnitine in serum

Diagnostic Procedures!!navigator!!

Muscle biopsy of postural or intercostal muscle shows Zenker's necrosis and neutral lipid accumulation (Oil red O or Sudan III stain) in type 1 muscle fibers.

Pathologic Findings!!navigator!!

  • Multifocal areas of pallor or hemorrhage in postural and respiratory muscles and less frequently in myocardium
  • Histopathology—severe acute myonecrosis and lipid storage myopathy

Treatment ⬆ ⬇

TREATMENT

  • Require intensive care in a veterinary hospital
  • IV fluid therapy for diuresis to prevent pigment nephropathy
  • Frequent carbohydrate-rich meals or IV glucose to supply muscle energy from carbohydrate metabolism

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • No antidote is available
  • Insulin to combat hyperglycemia and stimulate insulin-mediated lipogenesis
  • Riboflavin (vitamin B2) is a precursor of flavin adenine dinucleotide, a cofactor of all acyl-CoA dehydrogenases affected in MADD, and supplementation may enhance residual enzyme activity
  • Antioxidants (vitamin C, vitamin E, selenium)
  • NSAIDs or other analgesics

Contraindications/Possible Interactions!!navigator!!

Oral carnitine—lack of evidence of beneficial effects and possibly arrhythmogenic side effects in human MADD patients.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

Monitor electrolyte derangements, renal, respiratory, and cardiac function.

Prevention/Avoidance!!navigator!!

  • Avoid exposure to box elder or sycamore maple seeds in fall and spring. If not possible, limit (<12 h/day) turnout on pasture and provide supplemental feeding
  • Co-grazers of SPM/AM-affected horses should be removed from the pasture. Monitor serum CK activity and avoid stress

Expected Course and Prognosis!!navigator!!

  • Case fatality rate is high (>70%)
  • Rapid progression with death or euthanasia within 72 h

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Abbreviations!!navigator!!

  • AM = atypical myopathy
  • CK = creatine kinase
  • CoA = coenzyme A
  • MADD = multiple acyl-CoA dehydrogenase deficiency
  • NSAID = nonsteroidal anti-inflammatory drug
  • MCPA = methylene cyclopropyl acetic acid
  • SPM = seasonal pasture myopathy

Internet Resources!!navigator!!

Michigan State University, Seasonal pasture myopathy. https://cvm.msu.edu/research/faculty-research/comparative-medical-genetics/valberg-laboratory/seasonal-pasture-myopathy

Suggested Reading ⬆ ⬇

Bochnia M, Scheidemann W, Ziegler J, et al. Predictive value of hypoglycin A and methylencyclopropylacetic acid conjugates in a horse with atypical myopathy in comparison to its cograzing partners. Equine Vet Educ 2016;30:24–28.

Sander J, Cavalleri JMV, Terhardt M, et al. Rapid diagnosis of hypoglycin A intoxication in atypical myopathy of horses. J Vet Diagn Invest 2016;28:98–104.

Votion DM. The story of equine atypical myopathy: a review from the beginning to a possible end. ISRN Vet Sci 2012;2012:281018.

Author(s) ⬆ ⬇

Author: Beatrice T. Sponseller

Consulting Editors: Wilson K. Rumbeiha and Steve Ensley

Additional Further Reading ⬆

Click here for Additional Further Reading