Myopathies

Question 1

What is equine rhabdomyolysis ?

Answer 1

Muscle cramping or pain that occours usually during or following excercise

Question 2

What are the 2 forms of equine rhabdomyolysis?

Answer 2

Acute (may require emergency Tx)

Between episodes in a horse with recurrent episodic attacks. Requires investigation of the cause

Question 3

Clinical signs of exertional rhabdomyolysis

Answer 3

Stuff movements, pain, sweating, tachycardia, myoglobinuria

• plasma CK and AST
• r/o other dz

Question 4

What does CK Stand for?

Answer 4

Creatine kinase (NOT creatinine)

Question 5

How long after an acute exertional rhabdomyolysis episode do plasma levels of indicative hormones rise?

Answer 5

CK peaks at 6hrs, halved by 24hrs
AST peaks at 24hrs, takes longer to decrease
- if seeing a horse after the acute attack, have to r/o liver disease as AST will be the only thing raised

Question 6

Tx acute rhabdomyolysis

Answer 6

• Analgesics (opioids, probably avoid NSAIDs d/t risk of renal failure with myoglobinuria and NSAIDs combo
• IV and oral fluids
• diuretics (prevent or minimise nephrotoxic effects of myoglobin)

Question 7

How can horses be investigated in between episodes?

Answer 7

Excercise test - 20 mins lunge excercise trot and canter

• pre and 6 hour post excercise CK measurements
• 100% rise regarded as significant but nothing magic about this number!

Question 8

Acquired aetiology of exertional rhabdomyolysis

Answer 8

Over exertion
- eccentric contraction worse (downhill or jumping work)
- metabolic exhaustion
- oxidative injury
Eletrolyte imbalance
Hormone? Females affected worse than males
Infectious causes

Question 9

What is DOMS

Answer 9

Delayed onset muscle spasm?

Question 10

Inherited aetiology of exertional rhabdomyolysis

Answer 10

Recurrent exertional d/t defective calcium regulation

Polysaccharide storage myopathy

Question 11

Which causes are more likely?

Answer 11

R/o acquired, but inherited more likely

Question 12

what is RER ?

Answer 12

Recurrent exertional rhabdomyolysis

• defect in calcium regulation that has been studied in detail in small group of related TB
• other TBs affected the same defect?
• similar disorder in other breeds?

Question 13

Which horses is RER most common in?

Answer 13

Young nervous fillies

5% TBs affected!!

Question 14

How can RER be prevented?

Answer 14

Oral dantrolene - calcium channel release blocker
- for TBs with presumed calcium homeostasis problem
High fat low carb diet
- rice bran, vegetable oil, commercial
Regular excercise and turnout

Question 15

What is PSSM1?

Answer 15

Polysaccharide storage myopathy

• 1 = the form with genetic mutation of glycogen synthase in skeletal muscle
• affects QH, warmbloods and draft horses, cobs and many others
• heritable autosomal dominant
• causes exertional rhabdomyolysis
• occasional muscle atrophy/weakness in draft breeds
• abnormal glucose metabolism

Question 16

Which breed is most commonly affected by PSSM1?

Answer 16

Belgian draft horses >50% carry dominant gene

- not necessarily clinically affected but would be microscopically affected

Question 17

Alternative names for equine rhabdomyolysis syndrome?

Answer 17

Monday morning disease, set fast, azoturia, myoglobinuria, tying up

Question 18

What is the action of glycogen synthase?

Answer 18

forms 1-4 links between glucose monomores -> glycogen

Question 19

How can PSSM be detected? Is it always detectable?

Answer 19

> diagnosis by muscle biopsy
- internalised nuclei = non-specific sign of muscle damage
- polysacharide inclusions diagnositic
DNA test also available
- submit blood (EDTA) or hair pluck
- if no mutation detected but clinical sings present = PSSM 2

Question 20

What are polysaccharide inclusions and how are they detected?

Answer 20

• muscle biopsy
• amylase added to break down polysaccharide
• should get rid of all pink staining material with PAS
• in PSSM some pink amylase resistance polysaccharide remains in the muscle cells

Question 21

Tx and management of PSSM1?@

Answer 21

= RER

• ^ fat, v carbohydrate diet
• advise regular daily exercise
• if necessary start with hand walking then increase gradually

Question 22

What is exhausted horse syndrome?

Answer 22

• long rides, hot humid conditions, esp in unfit animals
• endurance riding
• 3d event
• cross country/hunting
  > glycogen depletion from muscles
  > electrolyte loss from sweat
  > hypovolaemia

Question 23

Clinical signs of exhausted horse syndrome?

Answer 23

• depression
• dehrydration, anorexia, v thrirst
• ^ RR ^ HR
• pyrexia
• poor sweating
• poor jugular distencsion, ^ CRT, v pulse pressure
• v gut sounds
• lamnititis
• muscle pain and stiffness
• synchronous diaphragmatic flutter (esp. with hypocalcaemia)

Question 24

WHat is synchronous diaphragmatic flutter?

Answer 24

= Thumps

• electrolyte imbalance esp. hypocalcaemia
• phrenic nerve picks up depolarisation of the heart
• rhythmical contraction in time with the heart

Question 25

Is rhabdomyolysis seen in dogs?

Answer 25

Yes, esp sled dogs and greyhounds (probably different aetiology between the two)

Question 26

What signs are seen in dogs with rhabdomyolysis

Answer 26

- myoglobinuria - elevated CK - hyperthermia - renal failure

Question 27

Tx. exhausted horse syndrome?

Answer 27

- IV/oral fluids + electrolytes - rapid cooling - NSAIDs - check for evidence rhabdomyolysis (CK and AST)

Question 28

Prevention exhausted horse syndrome?

Answer 28

- trainaing, heat acclimitisation - free access to water - administer eletrolytes during the ride - frequent vet checks

Question 29

What is swimmer/limber/cold/rudder tail?

Answer 29

- coccygeal muscle injury - working breeds labs pointers etc. - esp if swim a lot - recovery over several days - cold, exercise, swimming and prolonged cage transport predispose

Question 30

Tx rudder tail

Answer 30

rest, NSAIDs

Question 31

Look at physiology of muscle contraction

Answer 31

- LMN - NMJ - T tubules - Na channels - Sarcoplasmic reticulum - Ryanodine - Reuptake of Calcium

Question 32

Give 3 examples of channelopathies

Answer 32

1. Sarcolemmal sodium pump - Hyperkalaemic periodic paralysis in Quarter HOrses (HYPP) - autosomal dominant - all descending from "Impressive" QH sire, very impressive muscling, but had mutation in gene -> leaky Na influx and constant K+ outflow to compensate - hyperkamaeia -> cardiac arrhythmias 2. Ryanodine Receptor (RYR1) - malignant hyperthermia in mixed breed dogs, Landrace pigs [PSE meat], QH 3. Calcium ATPase [returns Ca to SR] - dysfunction -> permenant contraction - Brodie's disease in humans

Question 33

Give an eg. of a cell signalling defect

Answer 33

> myostatin > TGFb protein , paracrine hormone that limits muscle growth - mutations in Belgian Blue and Piedmontese cattle -Bully whippets (heterozygotes run faster) - Baby superman - racehorses (depending on gene variation makes them better sprinters or endurance horses)

Question 34

What is muscle strain? How can muscle strain injuries progress to more severe disease?

Answer 34

> muscle strain: overstretching of muscle -> disruption of fibres - inflammation, healing with fibrosis - milkd - severe (complete rupture) - recovery rapid with low grade injuries - fibrous tissue may predispose to re-injury or contracture - palpation oand ultrasound to diagnose > fibrotic myopathy in horses - esp QH - usually semitendinosius, sometimes semimembranosus or gracilis - causes: Muscle tear, IM injection, neuropathy - characteristic gait (slapping, short stride of affected limb) - do not confuse with Stringhalt

Question 35

Tx fibrotic neuropathy?

Answer 35

- rest - NSAIDs - surgical resection fibrous tissue or tenotomy

Question 36

What is atypical myopathy?

Answer 36

Acute onset, severe myopathy in horses at pasture - - CK and AST massively increased - muscle biopsy pre/post mortem (triceps/intercostals/diaphargam) - accumulation of lipid in cardiac/skeletal muscle - NOT exccercise induced

Question 37

Clinical signs of atypical myopathy?

Answer 37

- myoglobinuria - cardiac arrhythmia - diaphragmatic failure - death

Question 38

Aetiology of atypical myopathy?

Answer 38

> Hypoglycin A - sycamore tree - unripe Ackee fruit (Jamaican national fruit) - Box elder in US - Acer species > Acyl co-a dehydrogenases inhibited by 'MCPA' metabolite - important for breakdown of fat and uptake into the mitochondria

Question 39

Speciulative tx of atypical myopathy

Answer 39

- riboflavin (Vit B2 supplement) - carnitine supplementation - support carbohydrate metabolism (?insulin/glucose CRI)

Question 40

Diagnosis of atypical myopathy?

Answer 40

- muscle biopsy or urine/plasma acyl carnitine, organic acids, hypoglycin measurement - commercial test likely to become available

Question 41

Muscular dystrophies

Answer 41

Not gone into yet.. .