LA Muscle Disease Flashcards
Disease causing muscle pain/cramping?
Diseases causes muscle pain / cramping –
- Equine Rhabdomyolysis Syndrome
- Sporadic exertional rhabdomyolysis(including the exhausted horse)
- Chronic ER –
- Recurrent Equine Rhabdomyolysis(RER) –
- Polysaccharide Storage Myopathy (PSSM) –
- Canine Exertional Rhadomyolysis
- Atypical myoglobinuria
- Malignant Hyperthermia
Disease causing muscle weakness?
Diseases causing weakness –
- Atrophy (disuse, neurogenic, cachexia)
- Equine Motor Neurone Disease
Disease causing collapse?
Diseases causing collapse
- Myotonia
- Hyperkaleamic Periodic Paralysis
Other disease need to consider?
- Fibrotic myopathy
- Muscle rupture
- peroneus tertius, gastrocnemius
- Aorto-iliac thrombosis
- Spastic paralysis
- Stringhalt
- PPID
Clinical signs of muscle disease in LA?
- Muscle atrophy
- Muscle stiffness and pain - Focal or generalised
- Myoglobinuria
- Recumbency/ collapse
- Hyperthermia
- Exercise intolerance
- Abnormal contraction
What is the diagnostic approach to muscle disease?
History
- Temperament, diet
- Occurrence (acute crisis/recurrent)
- Other diseases
Physical examination
- Muscle pain
- Stiffness / weakness
- Other MSK abnormalities
Discuss biochem associated with muscle disease?
Creatine Kinase (CK)
- Skeletal and cardiac muscle
- Short half life (2hrs)
- Peak activity –4-12 hours
- Indicative of ongoing pathology
Aspartate aminotransferase (AST)
Skeletal muscle, Bone, Liver
- Long half life (7-8 days)
- Peak activity at 24 hours post injury
What do CK and AST correlate to in terms of mild, moderate to severe muscle disease? With renal involvement?
Creatinine and urea may be elevated if renal involvement
Discuss Myoglobinuria?
What is it suggestive of? What is it toxic to?
- Suggestive of significant disease (exceeds renal threshold)
- Toxic to renal tubules
- NB pre-renal azotemacan occur after exercise
What does the exercise test determine?
Determination of chronic recurrent pathology
Normal if:
- CK < 200% increase between 2 and 6 hours
- AST <50% increase at 24 hours
- Use a STANDARDISED TEST –15 minutes of mild exercise
Name other biochem markers for detecting muscle pathology?
Lactate Dehydrogenase (LDH)
- 5 isoenzymes
- Need to measure specific isoenzyme
- LDH 1 –cardiac
- LDH 5 –skeletal muscle
- Half-life 24 hours
Serum Myoglobin
- Concentration
- Under development as a potential marker of the severity of disease
What can be assessed in urine?
Myoglobinuria
- Positive on urine dip-stick
- Differentiate from
- BLOOD
- HAEMAGLOBIN
Fractional excretion of electrolytes
- More indicative of intracellular ions than serum measurement
- The kidney preserves K+ and Ca if deficient
What can muscle biopsy tell us?
- Biochemistry will tell us there is a problem in the muscle and the biopsy will tell us what is wrong
- Confirmation of disease: degeneration, necrosis and regeneration versus lysis or oedema
- Identify underlying mechanisms
- Estimate % fibres affected
What are these muscle commonly effected by:
- Semitendinosus
- Sacrodorsalis caudalis medialis
- Gluteal
- Semitendinosus: RER/PSSM
- Sacrodorsalis caudalis medialis EMND
- Gluteal RER
Key:
Recurrent Equine Rhabdomyolysis(RER)
Polysaccharide Storage Myopathy (PSSM)
Equine Motor Neurone Disease (EMND)
Look at some images of muscle biopsy?
What is being done here?
MUSCLE BIOPSY Gluteal –very sore as the muscle moves more (but the horse will be on box rest anyway)
How should muscle biopsies be handled for the lab?
- Contact lab beforehand as they may want also some fresh unfixed tissue sample (e.g. avoid to biopsy on a Thursday/Friday)
- Samples (also those fixed in formalin) should be pinned on a tongue depressor to avoid contracture which makes histopathology interpretation more difficult MUSCLE BIOPSY
Discuss Equine Rhabdomyolysis Syndrome
What is it? How can it be split up?
Complex syndrome of conditions, with different risk factors and trigger factors
Usually precipitated by exercise
SPORADIC ER – Exertional rhabdomyolysis
- Monday morning disease, Azoturia, Set fast
- Exhausted horse syndrome
- Note Canine exertionalrhabdomyolysis
CHRONIC ER
- Recurrent equine rhabdomyolysis
- Polysaccharide storage myopathy
What is equine Rhabdomyolysis Syndrome AKA?
“ tying up”
Clinical signs of equine rhabdomyolysis syndrome range from?
- Exercise intolerance (sub clinical)
- Stiff gait
- Reluctance to move
- Recumbency
- Muscle pain, hard muscles,
- Myoglobinuria
- Pain -Sweating, tachycardia, tachypnoea, may present as colic
- Hyperthermia
When may clinical signs or equine rhabdomyolysis syndrome occur?
- May occur before, during or after exercise
- After prolonged exertion can lead to particularly severe syndrome –e.g. endurance ride or excessive training
- Recurrent or chronic types are frequently before exercise or during or after only light exercise
What are the potential consequences of myoglobinuria?
Potential consequences
Pre-renal azotaemia
- Animals are often hypovolaemic
Renal azotaemia
- Pigmenturia (myoglobin)
Describe this equine rhabdomyolysis syndrome pathology
Rhabdomyolysis
- lysis of muscle fibres, especially Type II fibres
- Look smaller –lost shape
Describe sporadic exertional rhabdomyolysis
When and why may it occur?
- Like us running a marathon with no training apparently
- No underlying muscle defect
- Any age, breed, sex
- May recur but usually completely recover
- Overexertion
- Heat exhaustion
- Dietary imbalance
- Electrolyte imbalance
- Viral, immune mediated
NOTE THIS ALSO INCLUDES DOGS (Greyhounds, sled dogs)
What are the trigger factors for sporadic ER?
Overexertion
- Exercise beyond level of training
- Muscle stiffness, mild increases in CK
- Mild pathological change on light microscopy
Heat exhaustion
- The exhausted horse
Dietary imbalance
- High non-structural carbohydrate feeding
- Often associated with day of rest (Monday morning disease) –Vitamin E / Selenium deficiencies = severe muscle problems
- Electrolyte imbalance
What problems occur with the exhausted horse? How does this affect thhe muscles?
- Hypovolemia –less oxygen to the muscle= lactic acid = damage
- Hyperthermia
- Low muscle pH (high-speed exercise)
- Depleted glycogen (long slow exercise). Glycogen is the main muscle energy store. Once it runs out –> horse stops or the muscle hasn’t got enough energy and muscle will die
- Impair membrane pump function –Electrolyte imbalances –Deficiency in ATP –Na + /K + , Ca 2+ /Mg 2+ , Ca 2+ /ATPase
- Increased sarcoplasmic Ca 2+ –disruption of cell
- Ileus, cardiac dysrhythmias
- Synchronous Diaphragmatic Flutter (Thumps)
Exhausted horse syndrome:
treatment and prevention?
Treatment :
- rapid cooling
- rehydration
- NSAIDs (ensuring dehydration is corrected or being corrected first in case of renal damage)
- correction of electrolyte imbalances
Prevention :
- training, heat acclimation
- free access to water and food
- high roughage diet
- veterinary checks throughout ride
Discuss which breeds are prone to chronic equine rhabdomyolysis?
Underlying muscle defect
- Recurrent exertional rhabdomyolysis
- Thoroughbred
- Autosomal dominant
- Thoroughbred
- Polysaccharide storage myopathy
- Quarter horse, draft horse
What causes recurrent exertional rhabdomyolysis(RER)?
Abnormal intracellular calcium regulation
- Thoroughbred, standardbred, ?Arabs
- Prevalence of 5-9% in racing TBs
Prevalence affected by level of exercise
- More frequent when fit
- When training rather than racing
What are the risk factors for recurrent equine rhabdomyolysis?
Risk factors
- Mares (unrelated to stage of oestrus cycle)
- Temperament (nervous)
- Diet (high grain diet)
- Other MSK disorders (lameness)
What is the pathogenesis of Recurrent ER?
- Inherited autosomal dominant trait
- Abnormal regulation of muscle contraction
- May be similar to MH
Clinical signs of Recurrent ER?
Clinical signs and diagnosis
Can present as a subclinical disease
- Exercise test can be useful for diagnosis
History of repeated episodes of ER with raised CK, AST
Biopsy
- Increase in mature muscle fibres with centrally displaced nuclei
- No amylase resistant polysaccharide
What are type 1 and type 2 polysaccharide storage myopathy (PSSM) disorders?
Which horses are affected for each and which is more common in the UK?
Type 1: Quarter Horses –Confirmed GYS1 mutation –Won’t see this very much in this country
Type 2: ~Warmbloods, Drafts –Histopath evidence of disease without GYS1 mutation –Have to muscle biopsy
Glycogen storage disorder –Amylase resistant inclusion. Hows would this look on histology?
What is the pathogeneis of type 1 and 2 PSSM?
Which mutation is present in which one?
TYPE 1 : confirmed mutation of GYS1 gene which causes :
- Abnormal glycogen branching in muscle cell with increase glycogen storage (1.8-fold) via enhanced sensitivity to insulin
- Reduced ability to utilise such glycogen
- Being glycogen main muscle source of energy result is exercise intolerance, muscle atrophy/weakness
- Muscle necrosis due to abnormal energy metabolism
- Exact mechanism unclear AND different between QH and other breeds
TYPE2 :
- unknown mutation but same histopathologic features
What are the clinical signs of PSSM?
Onset of clinical signs
- 5 years
- Onset 20 mins after onset of exercise
- Worse after period of rest
What is the diagnosis of PSSM?
Persistently INCREASED activities of CK
- Three fold increase in CK after exercise test
Muscle Biopsy –Semimembranosus
- Amylase resistant inclusion
Blood test
- Genetic test for GYS-1 mutation
- Excellent sensitivity for QH
- Poor sensitivity in WB, Draft which may have a different mutation
What are the treatments for all forms of ER?
REST
- Depends on disease, but essential in early stages
Analgesia
- NSAIDS –Flunixin, carprofen, meloxicam
- Opioids –Pethidine(morphine –NO VPL)
- Other –Lidocaineinfusion (No VPL)
- Detomidine, ACP -anxiolytic and may improve perfusion
Other
- Dimethylsulphoxide–DMSO –cell membrane stabilising, free radical scavenging
- Vitamin E (effective anti-oxidant)
- Corticosteroids –VERY CONTROVERSIAL AND NOT PERSONALLY RECOMMENDED –
Discuss fluid therapy and ER?
Why do we give fluid therapy? How can we give fluid to a mildly affected horse and a severely affected horse?
Fluid therapy is essential in cases of ER
Myoglobin is reno-toxic
- Exertion may have led to fluid deficits
Mildly affected horses
- Fluid and electrolytes by nasogastric tube
- 22.5g NaCl, 22.5g LoSalt (NaCl and KCl) per 6l
Severely affected (and exhausted horse)
- Intravenous fluid therapy
- Fluid type is not important although specific abnormalities may require management
How should an acute case of sporadic ER be treated?
Box rest and then pasture turn out
CK and AST should be within normal range
- CK should be <200% normal
- Reassess 3 days after recommencement of exercise
PREMATURE EXERCISE WILL RESULT IN FURTHER MUSCLE DAMAGE
How should exercise be approached with chronic cases of ER?
Limited stall confinement
- PSSM –pasture rest as soon as possible
- No more than 48 hours stabled
- Very gradual return to exercise
- Steady/Regular low level of exercise
- Once in full exercise NO days off
RER
- Limited time off
- Once in full exercise no days off (increases CK)
What is the management of chronic ER?
Environment
- Reduce stress, turnout with others
Exercise
- Avoid days off
- Prolonged warm up, rest periods during exercise (interval training)
Diet
Drugs
What should be considered in an ERS diet?
Carbohydrates
level of carbohydrate relative to exercise and weight <20% of diet should be non structural carbohydrate
Oil
10% as source of energy
Fibre
amount and type -1% BWT minimum(ideally 2%)
Protein
not excessive protein
Vitamins and minerals
Calcium, magnesium and phosphorus
Salts -Na, K, Cal
Vitamin E and selenium
- storage and handling may be important
What drugs should be considered when treating ERS?
Sedation prior to exercise (Acepromazine)
- temporary benefit
Dantrolene(Dantrium)
- inhibits Ca release from SR
- 800mg/day 1 hour pre exercise (NOT IN FOOD)
- On day of return to exercise
- Reduced affect of exercise on CK rises and ERS
- Prevents episodes
- Used mostly in the racing industry
Phenytoin
- affects ion channels and increases the threshold for Ca release from the SR
Discuss atypical myopathy seasonal pasture myopathy?
What do we see and when do we see it?
Sudden onset myoglobinuria
- Horses at pasture (poor quality)
- Sudden onset exertion
Stiffness, myoglobinuria
- Spring or autumn
What causes atypical myopathy seasonal pasture myopathy?
Recently shown to be plant toxin
HyperglycinA
- Box Elder Tree (USA)
- Sycamore Tree (UK/EU)
What is the management for seasonal pasture myopathy?
Supportive therapy
- IVFT
- Glucose, insulin
- Carnitine and Vitamin C may be of benefit
- No matter what you do the horse will probably die
- such a massive breakdown the kidneys are full of myoglobin
How can you prevent seasonal pasture myopathy?
- Hoovering-up/picking up sycamore seeds
- Fencing off areas where sycamore seeds have fallen from trees
- Supplying extra forage (hay or haylage) especially where pasture is poor
- Reducing stocking density so there is plenty of palatable grazing for every horse
- Turning out horses for only short periods rather than extended periods of the day (ideally <6 hrs)
Discuss malignant hyperthermia?
Which animals is it seen it, what is the treatment?
- Disease of Pigs (and horses)
- Autosomal dominant mutation of Ryanodine Receptor (RYR)
- Results in increases [Ca 2+] within cell
- Heat from Ca 2+ /ATP ase
- Depletion of ATP
Treatment
- Ryanodine receptor antagonist
- Dantrolene
What is post anaesthetic myopathy?
- Prolonged recumbency following anaesthesia
- Low BP, excessive pressure, poor positioning
- Dd neuropathy and myelopathy
- High CK/pain
- Tries to get up and just struggles
Discuss equine motor neuron disease?
What kind of disease is it and what pathology is seen?
Sporadic disease
- Related to restricted pasture access
- Poor quality hay
Type 1 fibre pathology
- so they will look very weak when they stand!
- Pull the tail and they fall
- When they walk and move they are fine.
- Muscles of posture
- Oxidative damage
- Muscle fasciculation, weight loss
- Weak on standing, tremors but then trot them up and they are fine
Discuss bacterial muscle disease?
Whihc bacterial agent causes it commonly?
Clinical signs?
Clostridial myonecrosis
- Affects all large animals affecting different muscle groups with different organisms
- Black leg, malignant oedema, gangrene
- Rapidy progressive with high mortality
- Pyrexia, depression PAIN, lameness DEATH
How does clostridial myonecrosis occur?
Clostridial myonecrosis
Bacteria are ubiquitous in soil
- Spores maintain survival
Locate within muscle activated by trauma
- Anaerobic environment
- Necrotisingmyositis
- Horse –injection site/ puncture wound –espirritant drugs
- Cattle–blunt trauma –High stocking densities in high plane of nutrition
- Sheep –Shearing / dipping
What is the treatment for Clostridial myonecrosis?
Treatment
- Debridement and fasciotomy
- Antibiotics –High dose penicillin q2h
- Metronidazole in horses NO IN FOOD ANIMALS
- Avoid IM injections
- General supportive management
How can clostridial myonecrosis be prevented?
Prevention
- Vaccination –From 3-4 months q 6m
- Removal of all dead bodies
What is the pathology of clostridial myonecrosis?
Swelling and autolysis
- Rancid odour
Blood stained fluid at orifices
- Mouth, eye, vulva etc.
Swell and crepitus -gassy
Haemorrhagic dark muscles when you cut them
- Cl. perfringens –horse
- Cl. sordelli –cattle
Name other infectious agents causing that can cause muscle damage?
S equi var equi (“ strangles ”)
- Rare complication
- Immune mediated myositis 4 weeks post inf
- Tx corticosteroids
Parasites
- Sarcocyctosis
- No clinically significant but important VPH implications –see VPH for more details of parasitic muscle diseases
Discuss nutritional muscle disease?
Which muscles can be affected, what age?
DDx?
Peracute to subacute myo degeneration
Cardiac and skeletal muscle
- Selenium and or vitamin E
- Young rapidly growing LA (<1yr)
- Often Se deficient dams
- In utero form
Dx: Low Selenium and GSHPx Histopathology: inflammatory myositis
What can be seen here?
Nutritional Muscle Disease
Discuss the two forms of myodegeneration?
Cardiac form
- Sudden onset
- Death
- Depression, respiratory distress
- Rhythm disturbances
- Remaining cardiac damage
Skeletal form
- Slower onset
- Weakness and stiffness
- Recumbency
- Muscle pain
- Can affect respiratory muscles
What is this indicative of?
EMND
- Narrow-Base stance –stands like an elephant on a ball
- Disease from VitE deficiency and subsequent oxidative muscle damage
What are the lab findings for equine EMND?
Laboratory findings
CK and AST
- Occasional changes
CSF
- Inflammatory changes
Pigment Retinopathy
Vitamin E
- <1ug/ml very low (so we supplement)
OGAT
- (decrease glucose absorption)
Muscle biopsy
- Sacrocaudalisdorsalis medialis
How can EMND be treated?
- Vitamin E supplementation
- Hydro soluble forms of VitE (e.g. Nano-E) better absorbed
- Supplement selenium too but DO NOT EXCEED 3mg/kg Selenium
- Selenium toxicosis
- Prognosis POOR
What other things can cause muscle myopathy?
Viral, toxic?
Viral myopathy
- Equine influenza
- Foot and mouth disease, MCF, BVD, Bluetongue
- Skeletal or cardiac
Toxic myopathy
- Gossypol (cotton seed) in pigs
- Ionophores
- Abxin poultry so may eat these if they get into the bar. Cardiotoxictoo = death
- Organophosphate
- Trematone containing plants
- Cassia spp and white snake root –V rare
Discuss myotonia?
What is it? What do you see with it in horses and goats?
Diagnosis and treatment?
Delayed relaxation of skeletal muscle
- In goats
- Chloride channel
- In horses
- not chloride related
- Stiff gait
- Atrophy weakness
- Horses –Quarter horses (proximal limbs)
- Goats –Fainting goat
- Diagnosis –EMG
- Treatment –drugs used in humans (phenytoin)
Discuss Hyperkaleamic Periodic Paralysis (HYPP)?
What causes the disease? What sign do you see with it?
- Genetic disease
- Point mutation
- Normal between episodes
- Sodium channels
- Voltage gated
- Remain open when triggered
- Do not inactivate
- Sodium channels
- Precipitated by increased serum [Potassium]
- Hyper excitable then unexcitable
Draw a schematic of HYPP pathophysiology?
What are the triggering factors for HYPP?
Trigger factors
High K + intake
- Alfalfa, molasses etc
Increased mobilisation
- Fasting
- Stress
- Anaesthesia
- Vigorous exercise
What are the clinical signs of HYPP?
Mild and severe cases
Mild:
- Pronounced muscle development (thus selected for breeding)
- Prolapse of third eyelid
- Muscle fasciculations and weakness
- Onset 2-3 years
Severe
- Muscle weakness,
- Recumbency, dog sitting
- Dysphagia, Pharyngeal collapse, Laryngeal Paralysis Can be fatal
Normal after episode
What is the diagnosis of HYPP?
Serum biochemistry
- Normal CK activities
- Increased K + during episodes
EMG (between episodes)
- Abnormal fibrillation potentials
- Complex repetitive discharges
- Myotonic potentials
DNA testing
How can you treat HYPP?
Acute
- Calcium borogluconate (IV)
- (0.2-0.4ml/kg of 20% solution in 1 litre saline)
- Raises membrane threshold potential
- (0.2-0.4ml/kg of 20% solution in 1 litre saline)
- Glucose (IV)
- 6ml/kg as a 5% solution
- Stimulates insulin secretion
- 6ml/kg as a 5% solution
- Tracheostomy
Chronic
- Acetazolamide (3mg/kg BED PO)
- Carbonic anhydrase inhibitor
- Renal loss of potassium
- Diet
Summarise muscle diseases?
- Muscle disease is important for production and performance
- Important clinical conditions
- SIMILAR diagnostic and therapeutic option
- Definitive diagnosis often based on histopathological appearance
- Although often a clinical diagnosis based on serum biochemistry
What is fibrotic myopathy?
Fibrotic myopathy is the classic “mechanical lameness” of the hind limb. The gait change is caused by a mechanical limitation on movement of the hind limb and is not necessarily caused by pain.
Injury and scarring of the hamstring muscles in the upper hindquarter of the horse causes a classic change in gait with shortening of the front phase of the stride, loss of the stretchability of the normal muscle, and slapping of the foot to the ground. The injury can result from a single traumatic injury to these muscles (hyperextension injury) but can also can result from repetitive strain, seen most commonly in Western performance horses, especially reiners, cutters and rope horses. In some cases, scarring can occur from repeated IM injections into the hamstring muscles.
“Goose-stepping” is the name given to horses that move their hind limb in this characteristic way – the hoof is raised, then brought rearward and slapped to the ground. Fibrotic myopathy is very different from “stringhalt” as are the causes. Importantly, other lameness conditions can cause similar but rarely this classic gait.
What is Aorto-iliac thrombosis?
- Vascular obstruction of the hindlimbs
- Progressive exercise intolerance and hind-leg lameness
What is stringhalt?
Stringhalt is a gait abnormality characterized by exaggerated upward flexion of the hindlimb that occurs at every stride at walk. The gait abnormality usually lessens at trot and is not evident at canter. It may occur unilaterally or bilaterally. All degrees of hyperflexion are seen, from mild, spasmodic lifting and grounding of the foot, to extreme cases in which the foot is drawn sharply up until it touches the belly and is then struck violently on the ground. In severe cases, there is atrophy of the lateral thigh muscles. In Australian stringhalt and lathyrism, the condition may be progressive and the gait abnormality may become so severe that euthanasia is warranted. Mild stringhalt may be intermittent. The signs are most obvious when the horse is sharply turned or backed. In some cases, the condition is seen only on the first few steps after moving the horse. The signs are often less intense or even absent during warmer weather. Although it is regarded as unsoundness, stringhalt may not materially hinder the horse’s ability to work, except in severe cases when the constant concussion gives rise to secondary complications. However, the condition may make the horse unsuitable for some equestrian disciplines (eg, dressage).
The etiology is unknown, but lesions of a peripheral neuropathy have been identified in the sciatic, peroneal, and tibial nerves. Severe forms of the condition have been attributed to lathyrism (sweet pea poisoning) in the USA and possibly to flat weed intoxication in Australia.
Diagnosis is based on clinical signs but can be confirmed by electromyography.
