Myopathies Flashcards
Energy sources for contraction
Phosphocreatinine (quickly exhausted)
Carbohydrate - glycolysis and glycogenolysis (efficient source if aerobic, inefficient if anaerobic)
Fatty acid oxidation (preferred source for sustained exercise)
Myokinase reaction (only used when all other stores depleted)
Subdivitions of myopathies
Acute muscle injuries
Exertional rhabdomyolysis
Other myopathies
Most common nutritional myopathies
Selenium/Vit E deficiency (white muscle disease)
Clinical signs associated with muscle disease
Pain, heat, and/or swelling on palpation of muscle
Muscular cramping
Abnormal limb position e.g. muscle tears
Gait abnormalities
Weakness
Fatigue/poor performance
Muscle fasciculation
Muscle atrophy
Sweating
Myoglobinuria
Diagnosis of muscle disease
Serum muscle enzyme activity
- creatinine kinase (CK)
- Aspartate transferase (AST)
Urinalysis
- myoglobinuria
Specific blood tests
Muscle biopsies
U/S
Nuclear scintigraphy
Electromyography
Serum muscle enzyme activity (in muscle disease)
Increased because of defect in integrity of myofibre membrane and sarcolemma
Creatine kinase (CK)
○ Found in muscle and brain
○ Serum levels are muscle specific
Aspartate transferase (AST)
○ Amino acid metabolism enzyme
○ Not muscle specific
○ Also found in hepatocytes
Post-exercise muscle enzyme activity
Some physiological increase in CK and AST will occur after exercise, especially strenuous exercise.
Test looks to detect exaggerated responses to non-strenuous exercise
§ Sub-maximal test
Measure CK and AST before and 4 hours after 15-20 minutes of sub-optimal exercise
§ No more than 200-300% increase in CK
□ Subclinical exertional myopathy
§ No more than 50% increase in AST
Myoglobinuria
Myoglobin released into serum from damaged muscle cells
Filtered by kidney -> Presence of myoglobin pigment in urine
Pigment is nephrotoxic
Vitamin E/ Selenium assays for myopathy
Keep samples for Vit E analysis in the dark, and on ice
Selenium = component of GSH-Px which can also be measured
GSH-Px destroys hydrogen peroxide/lipoperoxides that are generated by muscle
ELectrolyte tests in myopathies
Hypochloraemic metabolic alkalosis
Serum electrolytes and fractional excretion of urinary electrolytes
Muscle biopsies
Commonly performed
Consider which diseases you’re aiming to rule in/out in order to sample relevant muscle
- Postural vs locomotor
Postural muscles
Mainly type I fibres
DDx: EMND, nutritional myodegeneration
Location: sacrodorsalis medialis
Locomotor muscle
Mainly type IIa/IIx fibres
DDx: RER, PSSM
Location: semimembranosus
Exertional myopathies
Sporadic exertional myopathy
Recurrent exertional rhabdomyolysis (RER)
Polysaccharide storage myopathy (PSSM)
Equine myofibrillar myopathy (MFM)
Non-exertional myopathies
Atypical myopathy
Hyperkalaemic periodic paralysis (HYPP)
Post-anaesthetic myopathy
Malignant hyperthermia
Nutritional myodegeneration (White Muscle Disease)
Vitamin E-deficient myopathy (adults)
Sporadic exertional myopathy - causes
‘Tying up’
Increase in work intensity without appropriate training
Exhaustion and overexertion
○ Pyrexic?
○ Electrolytes?
Racehorses/endurance horses
○ Hot and humid climate
Sporadic exertional myopathy- clinical signs
Weakness, ataxia, tachypnoea, sweating… (collapse)
Sporadic exertional myopathy- diagnosis
Myoglobinuria and increased CK, but muscles may palpate normal
Sporadic exertional myopathy- overexertion
Increase in work intensity without foundation of training
Can affect any horse
Common in polo ponies early in the season
Sporadic exertional myopathy- exhaustion
Racehorses/endurance horses, hot and humid climate
Weakness, ataxia, tachypnea, sweating… (collapse)
May be pyrexic
Myoglobinuria and elevated CK, but muscles may palpate normal.
Recurrent exertional rhabdomyolysis (RER) - Incidence
‘Tying up’, ‘Monday morning disease’, ‘Azoturia’
Common (4.9-6.7% Thoroughbreds)
Recurrent exertional rhabdomyolysis (RER) - signalment
Excitable/nervous horses
Female > Male
Historically draught animals fed high grain diets
Recurrent exertional rhabdomyolysis (RER) - clinical signs
Stiff, firm, painful muscles
§ Large muscle groups (gluteals, triceps)
Myoglobinuria (absence does not rule out RER)
Stiff gait, reluctance to move
Recurrent exertional rhabdomyolysis (RER) - cause
Likely to be autosomal dominant inherited trait
○ Yet to be fully elucidated…
○ We’ve probably selected for it alongside other desired characteristics,
Standardbreds with RER run faster than those without RER for example
Often the day following a rest day
Recurrent exertional rhabdomyolysis (RER) -diagnosis
History and signalment
○ Soon after onset of exercise, or shortly after cessation of exercise
Marked CK and AST elevation
Muscle biopsy
○ Often performed to rule out other myopathies
○ Chronic, non-specific changes
In vitro contracture studies
○ Gold standard, use intercostal muscle
○ Not performed in clinical practice really
Recurrent exertional rhabdomyolysis (RER) - diet
Low starch
Use fat for extra calories diet
○ E.g. RE-LEVE by Saracen
○ Competition animals: meet high calorie requirement
Access to a salt block
Vitamin E +/- selenium
Recurrent exertional rhabdomyolysis (RER) - exercise
Don’t exercise beyond scope of training
Avoid rest days
Minimise stress
Appropriate training
When in recovery period from myopathy, put in small pen so can walk around more than in a stable - loosening of stiffness and improvements to circulation. Rather than box rest.
Recurrent exertional rhabdomyolysis (RER) - treatment
Diet and exercise important
Dantrolene
* RYR1 antagonist -> inhibits calcium release from sarcoplasmic reticulum
* Detection time 48hrs (BHA) - not helpful from a competing point of view
Polysaccharide storage myopathy (PSSM) -signalment
Heritable: Quarter horses, Connemara, Warmbloods…
Polysaccharide storage myopathy (PSSM) - cause
Commonly triggered by exercise (can be less than 20min)
Polysaccharide storage myopathy (PSSM) - what is it?
Accumulate polysaccharide (abnormal glycogen) in the myofibre
Energy source is locked away in muscle cells
Polysaccharide storage myopathy (PSSM) - clinical signs
Recurrent episodes
may be mild (stretching out, ‘lazy’, may look like shifting lameness)
to severe (sweating, reluctance to move, recumbency)
Polysaccharide storage myopathy (PSSM) - PSSM 1
GYS1 gene mutation (autosomal dominant)
Increases glycogen synthase activity
Glycogenolysis doesn’t work as well -> less glucose -> less energy
Can see abnormal granules sitting in the cell
Myokinase reaction used for energy - inefficient
Polysaccharide storage myopathy (PSSM) - PSSM 2
a disease of abnormal polysaccharide storage
-But we don’t know why/mechanism…
Likely to be a group of conditions
Altered staining on a biopsy for glycogen, but absence of GYS1 mutation
Polysaccharide storage myopathy (PSSM) - diagnosis
May have persistently elevated muscle enzymes
○ Exercise test to challenge if muscle enzymes not elevated
○ Threefold increase in CK 4hrs after exercise
Biopsy semimembranosus muscle
○ Increased skeletal muscle glycogen
Gold standard – test for GYS1 mutation on hair roots/blood
Polysaccharide storage myopathy (PSSM) - Management (diet)
Limit glycogen synthesis (reduce insulin activity)
Promote breakdown of glycogen
Low starch, high fat
Provide 1.5-2% BWT as roughage
< 10% Digestible energy as non structural carbohydrates
> 13 % fat
Vegetable oil up to 1ml/kg/day
Supplemental Vitamin E +/- selenium
Commercial diets
Lose weight if overweight
Polysaccharide storage myopathy (PSSM) - management (exercise)
Maintain regular work/turn out routine
Avoid days off
Minimise stress
Minimise changes in management
Don’t exercise beyond scope of training
Prognosis fair if managed correctly
Equine myofibrillar myopathy (MFM) - signalment
disease in Arabians and warmblood horses
Equine myofibrillar myopathy (MFM) - histology
there is a disruption of the orderly alignment of myofibrils and aggregates of desmin (cytoskeletal protein) are identified using special stains
Equine myofibrillar myopathy (MFM) - clinical signs
Clinical signs are predominantly those consistent with an exertional rhabdomyolysis in Arabians and non-specific poor performance in warmblood horses
May not have increased CK/AST
Equine myofibrillar myopathy (MFM) - management
Recent advice is that horses seem to do best if ridden work is kept to 30-45min, and a long/low lunging warm up for 10-15min is incorporated prior to ridden exercise
Atypical myopathy - cause
Acute, severe rhabdomyolysis, affects horses at pasture caused by hypoglycin A toxicity
Seeds and seedlings of some Acer trees
UK: Sycamore (Acer pseudoplatanas)
Atypical myopathy - mechanism
Hypoglycin A forms toxic metabolite (MCPA), which binds to FAD.
MCPA deficiency, because they can’t use FAD as a cofactor.
This means that mitochondrial aerobic metabolism is impaired.
This deprives muscle of an energy source.
Type 1 muscle fibres are worst affected, so clinical signs are consistent with postural muscle disease.
Atypical myopathy - risk factors
Autumn and spring
Wet and windy weather
Presence of Sycamore trees (UK)
Access to pasture
Often poor body condition, young, or not being fed supplementary feed when on pasture
May be mistaken for cases of colic, severe laminitis, botulism
(neurological exam normal in AM)
Intrinsic horse factors?
Variable concentrations in different parts of the plant (even if from the same tree)?
Likely multiple factors
Atypical myopathy - clinical signs
Weakness, reluctance to move, may be found recumbent
Painful, firm muscles may be appreciated on palpation
Myoglobinuria
Tachycardia, tachypnoea, congested mucous membranes
Distended bladder on rectal palpation
Atypical myopathy - diagnosis
High muscle enzymes on serology
Myoglobinuria
Submit plasma for acylcarnitine/serum for hypoglycin A and conjugated MCPA
Confirmation takes 48-72h via RVC Neuromuscular Lab
You cannot wait this long before implementing treatment
Postmortem: samples of masseter/intercostal muscle
Atypical myopathy - treatment
Start treatment before definitive diagnosis if suspected
Require intensive supportive care and nursing
Fluid therapy (monitor renal function)
Add glucose (5% glucose to provide alternative energy source)
Analgesia
Vitamin E and selenium, riboflavin, oral carnitine
Atypical myopathy - prognosis
Very hard to predict – survival rates are improving
↓ prognosis: hypoxia, dyspnoea, tachypnoea, hypothermia, bladder distension, absence of intestinal sounds, remaining recumbent
↑ vitamin and anti-oxidant administration (advised for all cases, including subclinical
ones that are diagnosed alongside index clinical case)
Hyperkalaemic periodic paralysis (HYPP) - signalment
QH, Paint, Appaloosa
Hyperkalaemic periodic paralysis (HYPP) - cause
Gene mutation alters voltage-dependent skeletal muscle sodium channel = persistent depolarisation of muscle cells
Hyperkalaemic periodic paralysis (HYPP) - clinical signs
variable (muscle spasms and trembling)
Hyperkalaemic periodic paralysis (HYPP) - diagosis
Genetic testing (commercially available)
Hyperkalaemia and suggestive clinical signs, no/little change in CK
Post-anaesthetic myopathy
Localised rather than generalised myopathy
Hard, hot, swollen muscles
○ Gluteals, epaxial muscles, triceps
Onset may be delayed
Compartment syndrome
○ ↑ pressure within muscle -> ischaemia -> muscle swelling ->↑ pressure
Careful consideration RE positioning on table
○ Dorsal recumbency: symmetrical
○ Lateral recumbency: extend lower forelimb forwards/hindlimb back
Monitor and maintain blood pressure under anaesthesia
Symptomatic and supportive treatment
Malignant hyperthermia
QH/paints (and pigs!)
RYR1 (ryanodine receptor) gene mutation
○ Dramatic increase in intracellular calcium -> contraction -> muscle heat and necrosis
Exercise or anaesthesia induced
○ Worth screening before anaesthetising these breeds?
○ Pre-treat with dantrolene
○ Marked hyperthermia and acidosis
Nutritional myodegeneration (White Muscle Disease) - pathophysiology
Effects of a deficiency in Vitamin E and Selenium result in the destruction of cell membranes and proteins leading to a loss of cellular integrity.
The precise interrelationships among selenium/Vit E, other metabolic factors and triggering mechanisms in NMD are not fully understood because some deficient animals do NOT have disease.
Selenium appears to be the most important in foals however, and deficiencies in this nutrient are more likely to lead to NMD than vitamin E.
Nutritional myodegeneration (White Muscle Disease) - Clinical signs
Cardiac form and skeletal form
Dyspnoea, weakness, stiffness, trembling, recumbency, sudden death, irregular tachydysrhythmia
Aspiration pneumonia common secondary to tongue necrosis
Tongue, gastrocnemius, semimembranosus/tendinosus, biceps femoris, lumbar, gluteals, neck affected
Nutritional myodegeneration (White Muscle Disease) - diagnosis
Clinicopathologic abnormalities
○ CK/AST elevation
○ Myoglobinuria
○ Electrolyte derangements
Low selenium (whole blood), GSH-Px, α-tocopherol (vit E) (plasma)
Gross pathology
○ Pale, oedematous muscle, calcification
○ Hypercontracted muscle fibres
Nutritional myodegeneration (White Muscle Disease) - treatment
Cardiorespiratory disease -> poor prognosis
Skeletal muscle disease -> better prognosis
○ usually see improvement quickly
Selenium injections IM
○ irritant, can dilute before injection
Oral α-tocopherol supplementation
Supportive nursing
Vitamin E-deficient myopathy (adults)
Disease in its own right? Precursor to EMND?
Presence of myopathic not neuropathic change in SCDM biopsy
Vitamin E-deficient myopathy (adults) - clinical signs
Weakness, narrow-base stance
Animals with disease of postural muscles often look better when you
get them walking. May look worse when asked to stand still, weight
shift and look uncomfortable.
Muscle atrophy
Trembling and muscle fasciculations
Weight shifting
Vitamin E-deficient myopathy (adults) - diagnosis
SCDM biopsy
May have normal serum α-tocopherol
Vitamin E-deficient myopathy (adults) - treatment
Oral α-tocopherol supplementation
Not powders, needs to be v bioavailable
Is diet deficient, or can horse not absorb it? Re-test.
As with EMND could be because diet is deficient, often stabled animals.
Might consider glucose absorption test if suspect primary
absorption issue.
General principles of treatment for myopathy
Minimise continued muscle damage
- rest
- NSAIDs
- ACP
- Antioxidants
Analgesia
Correct fluid deficit/diurese
Analgesia for myopathy
NSAIDs
Opioids
○ Buprenorphine/butorphanol licensed for horses
○ Methadone more potent but use on cascade
○ Morphine commonly used, not licensed in any veterinary spp.
Paracetamol
○ Use as an adjunct, not sole analgesic
Lidocaine infusion
○ Logistics require hospitalisation
Ketamine infusion
○ Requires hospitalisation (scheduled drug and logistics require hospitalisation)
