Lecture 14: exertional myopathies or rhabdomyolysis (muscle 3)

- sporadic rhabdomyolysis = no previous history + intermittent increased CK

- chronic rhabdomyolysis = repeated history + repeated increased CK

How do sporadic rhabdomyolysis and chronic rhabdomyolysis differ based on clinical presentation and CK?

1. RER: recurrent exertional rhabdomyolysis

2. MH: malignant hyperthermia

3. PSSM 1: polysaccharide storage myopathy

4. PSSM 2: polysaccharide storage myopathy - ER

5. MFM: Myofibrillar Myopathy - ER

What are the 5 examples of chronic exertional rhabdomyolysis?

MFM = WB = myofibrillar myopathy

What is an example of chronic exertional myopathy?

Mismatch between overexertion and dietary imbalance in all breeds

- can be confused with colic based on clinical signs

What is sporadic exertional rhabdomyolysis (SER)? What can it be confused wtih?

- Muscle PAIN: unwilling to move, stiffness (recumbency), postures to urinate, painful muscle palpation

- HIGH TPR

- pigmenturia = bronwish (due to myoglobin)

What are the clinical signs seen with sporadic exertional rhabdomyolysis (SER)?

HUGE increase in CK then AST

• CK rises fastest (10K - 100K)

- hyperkalemia

- will become dehydrated and acidosis overtime

- urine: pigmented and casts (myoglobin in urine over time)

What can be seen on lab work for sporadic exertional rhabdomyolysis (SER)?

1. Minimize movement (do not move or transport)

2. Calm horse with sedation (alpha 2-a)

3. Treat dehydration and elecrolyte abnormalitis

4. Relieve pain (NSAIDS) after you hydrate animals

5. Stimulate diuresis (furosemide or dopamine)

6. Limit muscular lesions

7. Rest horse and monitor clinical signs and CK

8. Progressive return to work (prevention/testing)

How do you treat sporadic exertional rhabdomyolysis (SER)? 8 steps

- caused by abnormal intracellular Ca metabolism

Recurrent exertional rhabdomyolysis (RER) is commonly seen in thoroughbreds. What is it caused by?

Young, fit, nervous, easily triggered, (females) Thoroughbreds, standardbreds, arabians

- horses often have a history of episodes

- muscle cramps = stiffness, pain, migrating lameness

- pain = sweating, tachypnea, reluctant to move

How does recurrent exertional rhabdomyolysis (RER) often present?

4-6 hours (when CK peaks)

In a non-symptomatic horse, how many hours after exercise would you draw blood to measure CK (to compare to baseline values)?

- CK and AST will be 3-4x base value 4-6 hours post exercise (can fluctuate in 2 year olds)

- muscle bx for hard cases

- fractional excretion

- exercise testing

Recurrent exertional rhabdomyolysis (RER) is often diagnosed based on history and clinical signs. What diagnostics can be used?

NOOO none available

Can you use genetic testing to diagnose RER since there in an unknown genetic component?

1. Treat rhabdomyolysis

2. Decrease triggers (meds or management)

3. Mange diet = a HIGH FAT LOW STARCH commercial diet or quality grass AND manage exercise

How do you treat recurrent exertional rhabdomyolysis (RER) in horses?

Defect: Calcium regulation issue

NSC: LOW

Fat: HIGH

What is the primary defect and NSC/Fat requirement for RER?

- PSSM1 = autosomal dominant trait impacting glycogen synthesis from a GYS1 mutation

- PSSM2 = no mutation --> NO GENETIC TESTING

How are polysaccharide storage myopathy (PSSM) 1 and polysaccharide storage myopathy (PSSM) 2 different?

- AQH and related breeds

- European derived draft breeds

What are the common breeds that get polysaccharide storage myopathy 1 (PSSM 1)?

Autosomal dominant mutation in glycogen synthase (GYS1)

- triggered by rest before exercise

What is the etiology and trigger of polysaccharide storage myopathy 1 (PSSM 1)?

- breed

- diet

- exercise

- other environmental factors

- influence from other genes

Not all horses are equally effected by polysaccharide storage myopathy 1 (PSSM 1). Why?

- episodes of rhabdo at a young age with little exercise

- tucked in abdomen and camped out stance

- lazy and shifting lameness

- muscle fasciculations/tremors and sweating (HYPP differential)

- gait asymmetry and hindlimb stiffness

- reluctant to move and signs of colic

What are the clinical signs for polysaccharide storage myopathy 1?

Genetic testing

How do you diagnose PSSM-1?

1. PSSM2 - ER: AQH

2. MFM- ER: Arabians (endurance horses)

3. MFM- WB: WB horses

What are the categories of PSSM2? What breed is correlated?

1. PSSM2 - ER: increased CK

   1. True glycogen storage disease

2. MFM- ER: increased CK

   1. Desmin aggregates in endurance horses

3. MFM- WB: NORMAL CK

   1. Desmin aggregates with exercise intolerance

What is the etiology for the 3 PSSM 2 categories and what does their CK look like?

Higher muscle glycogen with abnormal polysaccharide & glycogen storage

• less than in PSSM1

• NO genetic mutation identified

What is the etiology of polysaccharide storage myopathy 2- ER?

- Pain, sweating, firm hard muscles,

- Stiffness, and reluctance to move after light exercise

- Less frequent:

• Rhabdomyolysis on pasture.

• Low grade, lameness, stiffness, and muscle fasciculations

What are the clinical signs for AQHs with polysaccharide storage myopathy 2- ER?

Clinical signs with increase muscle enzymes after exercise

NO VALIDATED GENETIC TEST

Muscle biopsy

How do you diagnose PSSM2 - ER?

Defect: Excessive sugar storage (abnormal glycogen)

NSC: strictly LOW

Fat: HIGH (need alternative source)

What is the primary defect and NSC/Fat requirement for PSSM?

- 70% improvement with management!!!!

- avoid rest!! = allow turn out and limit confinement

- manage exercise with reg incremental programs

- manage nutrition: low NSC, high fat

How do you treat/prevent polysaccharide storage myopathy 1 or 2, even know the horse will always be susceptible?

1. MFM-ER (Arabians)

2. MFM- WB (Warmbloods)

What are the 2 distinct presentations of Myofibrillar Myopathy?

Active horse: older Arabian endurance horses

• intermittent episodes of ER

• occur at the end of prolonged endurance rides

2 weeks off work:

• 5 miles into a ride after this rest period

◦ Muscle stiffness and pain

What is the clinical presentation of MFM-ER in Arabians? Active vs Off work

Clinical signs and elevated CK

How do you diagnose MFM-ER in Arabians?

Promising as a young horse BUT at 6-8years sudden onset of issues:

• Lack of stamina

• Unwillingness to go forward

• Persistent exercise intolerance after very little exercise

What is the clinical presentation of MFM-WB?

Rule out others & muscle biopsy > 8 years old

How do you diagnose MFM-WB?

Defect: Structural breakdown of muscle

NSC: Moderate

Fat: low/moderate

Protein: VERY HIGH

What is the primary defect and NSC/Fat/Protein requirement for MFM?

Autosomal dominant mutation in the ryanodine receptor gene

- dysfunction in Ca release channel

What is the etiology for malignant hyperthermia seen commonly in AQHs?

- stress

- anesthesia (halothane) = less common now

What are the triggers for malignant hyperthermia?

- tachycardia, hyperthermia, muscle rigidity

- severe lactic acidosis, increased CK, electrolyte derangement

What are the clinical signs and lab work seen with malignant hyperthermia from anesthesia?

- Excessive sweating, tachycardia, tachypnea, hyperthermia, muscle rigidity

- Sudden death

What are the clinical signs and lab work seen with malignant hyperthermia from exertional rhabdo?

PSSM 1

What can MH occur with?