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  Home > Neuromuscular Diagnostic Laboratory > Seasonal Pasture Myopathy > Information for Pathologists
 

Information for Pathologists

The research project
Although we have made great strides in the last year in determining the cause of SPM in North America as hypoglycin A found in the seeds of the box elder tree, there is still much to know about how to detect SPM early, identify subclinical cases, prevent cases where possible, and devise the best treatment. To help us, owners are completing an on-line risk assessment survey and veterinarians are asked to submit urine, serum and fresh muscle samples (one or all three if possible) to the University of Minnesota Neuromuscular Diagnostic Laboratory for screening for SPM and hypoglycin A ingestion. The only cost to owners will be shipping charges to get samples to the lab for analysis if the horse is strongly suspect for SPM. Post mortem assessment of tissues is very helpful in identifying SPM as the cause of disease, particularly as 75-90% of cases die despite therapy.

What is Seasonal Pasture myopathy (SPM)?

  • An acute, highly fatal form of severe rhabdomyolysis affecting postural, respiratory, and cardiac muscles
  • A lipid storage myopathy caused by multiple acyl-CoA dehydrogenase deficiency (MADD), the same pathophysiologic cause of Atypical Myopathy (AM) in Europe; this causes a disruption of mitochondrial enzymatic pathways and leads to an accumulation of specific organic acids and enzyme-specific substrates (acyl-CoAs) that are transported in the bloodstream as acylcarnitines and eliminated in the urine as acylglycines, creating specific patterns of elevated serum acylcarnitines and urine organic acids
  • Caused by ingestion of hypoglycin A in box elder tree seeds in North America; AM is potentially caused by this as well
  • Possible contributing factors include antioxidant deficiency such as low selenium or vitamin E
  • One or multiple horses grazing on pasture can be affected
  • Cases have been documented in Eastern Canada, the Midwest, Texas, and the Southern USA but have likely gone unrecognized in many other areas of North America

What are the clinical signs?

  • Key differentials include acute onset colic, laminitis, and other causes of rhabdomyolysis
  • Mortality rate is 75-90%, even with treatment; true morbidity is unknown at this time
  • Initially: reluctance to move, muscular weakness, stiffness, fine muscle tremors, choke, myoglobinuria
  • Later: Depression, sweating, congested mucous membranes, tachycardia, and tachypnea with expiratory dyspnea
  • Progresses rapidly to lateral recumbency and death within 24-72 hours


What are the gross post mortem findings?

From: Finno et al JAVMA, Vol 229, No. 7, October 1, 2006
We have performed post mortem examinations on 12 horses with SPM. Findings included:

  • Moderate to marked subcutaneous edema along the neck and sternum and between the hind limbs (8/12)
  • No grossly visible skeletal muscle lesions in 3 horses or cardiac lesions in 6 horses
  • Lesions in the myocardium of 6 horses including diffuse or multifocal pale areas with ecchymoses, full-thickness white streaks extending through the myocardium of the ventricles, and focal areas of hemorrhage
  • Pallor in skeletal muscles in 6 horses and skeletal muscle hemorrhage in 3 horses
    • The specific muscle groups affected included the caudal aspect of the neck and shoulder (trapezius, brachialis, rhomboideus, subscapularis, triceps, and pectoralis muscles), hindquarters (psoas major, gluteal, rectus femoris, gracilis, semimembranosus, and semitendinosus muscles), back (longissimus dorsi muscle), intercostal muscles, tongue, and diaphragm.
  • In 2 horses, the kidneys were soft, pale, and friable with an indistinct corticomedullary junction
  • In 5 horses, the urinary bladder contained dark-brown urine
  • A large amount of yellow to brown watery fluid was detected in the pericardium in 5 horses, in the thoracic cavity in 3 horses, and in the peritoneal cavity in 2 horses
  • Lungs were diffusely congested, wet, and heavy, and foam was reported in the trachea and bronchi of 3 horses
  • Four horses had linear gastric ulcerations or an edematous and thickened cecal wall mucosa (n = 1), esophageal impaction (1), or hemorrhage on the jejunal serosa (1) or on the serosa of the right dorsal colon (1)

What are the histopathologic lesions?

  • Skeletal muscle lesions include acute severe muscular degeneration and necrosis.
    • Zenker’s degeneration, characterized by loss of cross-striations, fiber swelling, hypereosinophilia of the sarcoplasm, hyaline fragmentation of the sarcoplasm of individual muscle fibers, and pyknotic nuclei were seen (Figure 1).
    • Macrophage infiltrates varied from minimal (n=6 horses) to extensive (n=2). Mild to moderate infiltration of neutrophils along the skeletal muscle fibers and mineralization of skeletal muscles were detected in 1 horse.
  • Frozen sections of diaphragm and deep postural muscles stained with oil red O show a characteristic marked accumulation of intramyofiber lipid (Figure 2).

Figure 1—Photomicrograph of a longitudinal section of skeletal muscle fixed in neutral-buffered 10% formalin obtained from a horse with seasonal pasture myopathy. Notice acute necrosis and hyaline degeneration (arrow) in multiple myofibers with fragmentation of the sarcoplasm. H&E stain; bar = 100 μm.

Figure 2—Photomicrographs of serial cross sections of the iliopsoas muscle near its insertion from a horse with seasonal pasture myopathy (PanelB) obtained within 2 hours of euthanasia. PanelB—Three fibers are undergoing acute myonecrosis

The intracellular lipid content of myofibers is markedly increased, compared with that in control tissue from a 2-year-oldhorse euthanized because of cervical vertebral malformation (Panel A). Sections are stained with H&E (A) and oil red O (B); bar = 50 μm.

  • Myocardium: moderate to severe myocardial degeneration and necrosis without inflammatory infiltrates (6/12)
  • Acute, focally extensive subendocardial hematomas without evidence of myocardial degeneration (3/12)
  • No notable abnormalities in cardiac tissue from 2 horses.
  • Kidneys: Mild to moderate acute tubular necrosis in most horses and granular casts

 

CVM SPM Finno figure one               CVM SPM Finno figure two

Figure 1                                                Figure 2

 

How is a definitive diagnosis established?

  1. Relevant history and clinical signs in horses on pasture combined with marked elevations of serum muscle enzymes CK and AST, myoglobinuria, and severe myonecrosis of postural and respiratory muscles provide a presumptive diagnosis
  2. A definitive diagnosis is provided by;
    1. Fresh muscle samples that show excessive lipid staining in the intercostals, diaphragm or postural muscles (Oil red O)
    2. Fresh muscle samples should be placed in a hard container, kept chilled, and submitted on icepacks to the University of Minnesota Neuromuscular Laboratory (click here for sample submission information). If samples are submitted as part of this research project, please notify us of the submission at nmdl@umn.edu to avoid charges.
    3. Assays of urine organic acids or serum acylcarnitines ) to confirm MADD can be submitted to the Baylor Metabolic Institute http://www.baylorhealth.edu/Research/InstitutesCenters/IMD/Pages/Tests%20and%20Forms%2005-11.pdf
  3. Results will be emailed to you within 7-10 days
     

 


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