Moch final

Large Animal Medicine

Ruthie Reinken, Jessica Reese, Maritza Rodriguez

9 year old Warmbloodgelding

Junior Equitation horse

With current owners since February

4-5 month progressive onset: Poor performance

Ataxia

Personality change

Two weeks prior to presentation, almost fell while handwalking

Previously treated with doxycycline and ponazuril with no improvement.

PE WNL

Neuro exam: Grade 1 ataxia in all 4 limbs

Weakness post-exercise

Quickly fatigued

Lameness exam: Grade 2/5 lame LF

Grade 2/5 lame RH

Weakness/ataxia

History stumbling, bucking

Lameness

Neuropathy Cervical spinal cord compression

EPM

Neuroborreliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness/orthopedic

Diagnostic analgesia Bilateral abaxial

Nuclear scintigraphy

Neuropathy Cervical spinal cord compression

EPM

Neuroborreliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness

Neuropathy Cervical spinal cord compression

EPM

Neuroborreliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness

Neuropathy Cervical spinal cord compression

EPM

Neuroborelliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness

Neuropathy Cervical spinal cord compression

EPM

Neuroborelliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness

Neuropathy Cervical spinal cord compression

EPM

Neuroborelliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness

Neuropathy Cervical spinal cord compression

EPM

Neuroborelliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness

Muscle disorder in horses characterized by abnormal polysaccharide accumulation in skeletal muscle & clinical signs of rhabdomyolysis

1st recognized as a specific myopathy in 1992

Since then, the disease has been diagnosed in at least 35 different breeds in the USA and UK

Considered a common cause of neuromuscular disease in Quarter horse and Draft breeds

Affected horses were reported to have a 2-fold higher muscle glycogen concentration compared to normal horses Increase synthesis of glycogen, NOT an inability to

metabolize glycogen

2 linked biochemical abnormalities associated 1. Enhanced sensitivity to insulin in Quarter horses

2. Abnormal regulation of glycogen synthase

2 types of PSSM recognized

Mutation in glycogen synthase 1 gene (GYS1) resulting in excessive accumulation of

glycogen

Inherited in an autosomal dominant manner

The increased activity has an association with regulation of energy generation in muscle fibers during exercise under certain dietary conditions

Muscle samples from PSSM1 horses showed less than normal branched polysaccharide in the muscle fibers

Related to chronic enhanced activity of GYS1 gene Leads to less highly branched polysaccharide

Becomes resistant to amylase digestion when stained

Important for differentiation between PSSM type 1 and 2 via muscle biopsy

1st study differentiating Type 1 from Type 2 in 2009 (McCue et al)

Current knowledge based on retrospective studies of cases of diagnosed PSSM No genetic mutation associated

Origin is yet unknown

Valberg SJ. Muscling in on the Cause of Tying-Up. AAEP Proceedings/Vol.58/2012; 106-113

PAS stain Amylase-PAS stain

Type 1

Type 2

Highest prevalence appears to occur in draft horses derived from Continental European breeds

Valberg SJ. Muscling in on the Cause of Tying-Up. AAEP Proceedings/Vol.58/2012; 106-113

Highest prevalence appears to occur in draft horses derived from Continental European breeds

Valberg SJ. Muscling in on the Cause of Tying-Up. AAEP Proceedings/Vol.58/2012; 106-113

Estimates of PSSM1 in Quarter Horses range from 6-10% of the breed

Valberg SJ. Muscling in on the Cause of Tying-Up. AAEP Proceedings/Vol.58/2012; 106-113

Prevalence is low to nonexistent in light horse breeds Thoroughbreds, Standardbreds, Arabians

Valberg SJ. Muscling in on the Cause of Tying-Up. AAEP Proceedings/Vol.58/2012; 106-113

Warmbloods: about 80% of cases of PSSM diagnosed by muscle biopsy (Valberg 2012)

Quarter Horses: approximately 28% of cases of PSSM diagnosed by muscle biopsy (Valberg 2012)

Range significantly from one individual to another Pain Weakness recumbency Muscle atrophy Muscle spasms/fasciculations/contractions Gait abnormalities Poor performance Exercise intolerance Exertional rhabdomyolysis Other problems reported by owner – back soreness, difficulty trimming/shoeing rear

hooves, behavior problems under saddle or in harness, episodic spasmodic colic

Acute episode signs can last >2 hrs 10% become recumbent

Most affected muscles Gluteal, semimembranosus, semitendinosus, longissimus

Range significantly from one individual to another Pain Weakness recumbency Muscle atrophy Muscle spasms/fasciculations/contractions Gait abnormalities Poor performance Exercise intolerance Exertional rhabdomyolysis Other problems reported by owner – back soreness, difficulty trimming/shoeing rear

hooves, behavior problems under saddle or in harness, episodic spasmodic colic

Acute episode signs can last >2 hrs 10% become recumbent

Most affected muscles Gluteal, semimembranosus, semitendinosus, longissimus

Evidence of muscle-fiber necrosis: Elevated CK (>350 u/L) and AST (>420 u/L) 4-6 hours

after exercise

Other possible laboratory changes: Low blood selenium levels

Low vitamin E levels

Type I: Gold standard – genetic testing for GYS1 mutation Histopathology of muscle biopsy – PAS-positive amylase-

resistant inclusions in fast-twitch myofibers Risk of sampling error and false negatives

Type II: Histopathology of muscle biopsy – subsarcolemmal

aggregates of PAS-positive, amylase-sensitive (usually) glycogen Risk of false positives

Histopathologic findings don’t always correlate with severity of clinical signs or with increase in CK or AST post-exercise

Long-term therapy:

Diet change Very high in fat, high in fiber, low in starch and

sugar Goals: Decrease glucose load, increase availability of

NEFA for muscle metabolism, lower serum insulin levels

How is this achieved? At least 20% of total calories should be from fat

additive

Feeds should contain less than 33% starch/sugar

Hay with 12% or less non-structural carbohydrate to prevent insulin concentration increases

Regular daily exercise/turnout

Response to treatment takes up to 4 months for full fat adaptation

Good chance for return to acceptable performance-Variability in prognosis is based on severity of individual’s

clinical signs

PSSM horses will always have an increased tendency to have muscle soreness

CK

Pre exercise: 125 U/L

Post exercise: 134 U/L

Muscle biopsy

Results pending

Neuropathy

Cervical spinal cord compression EPM

Neuroborelliosis

Myopathy Polysaccharide Storage Myopathy (PSSM)

Nutritional (Vit E/Selenium deficiency)

Lameness

Thank you Dr. Sweeney

Dr. Tomlinson

Dr. Moore

Dr. Johnson

Dr. Davidson

Our rotation mates, Sam, Annie, and Alex

McCue ME, Armien AG, Lucio M, et al. Comparative skel-etal muscle histopathologic and ultrastructural features in two forms of polysaccharide storage myopathy in horses. Vet Pathol 2009;46:1281–1291.

McCue ME, Valberg SJ. Estimated prevalence of polysac-charide storage myopathy among overtly healthy Quarter Horses in the United States. Am J Vet Res2007;231:746–750.

McCue ME, Anderson SM, Valberg SJ, et al. Estimated prevalence of the type 1 polysaccharide storage myopathy mutation in selected North American and European breeds. Anim Genet 2010;41 (Suppl2):145–149.

McCue ME, Ribeiro WP, Valberg SJ. Prevalence of poly-saccharide storage myopathy in horses with neuromuscular disorders. Equine Vet J Suppl2006;36:340 –344.

Valberg SJ. Muscle disorders: Polysaccharide storage myopathy, in Proceedings. Am Assoc Equine Pract 2006;52:373-380.

Valberg SJ. Muscling in on the Cause of Tying-Up. AAEP Proceedings/Vol.58/2012; 106-113

Valentine BA. Equine polysaccharide storage myopathy: tutorial article. Equine vet Educ. 2003; 15 (5): 254-262.

Valentine BA, Van Saun RJ, and Thompson KN. Role of dietary carbohydrate and fat in horses with equine polysaccharide storage myopathy. JAVMA 2001; 219(11): 1537-1544.