Muscle / Sport Flashcards
What are the myopathies associated with Streptoccus equi equi infection ?
- Infarctive PH : serum CK activity is markedly elevated (>35,000 U/L) and horses are painful with firm swollen areas in pectoral, abdominal and crus muscles, muscles that are compressed when horses are lying down. Aggressive and prolonged corticosteroid treatment is essential in cases of infarctive PH to prevent fatal infarction of the gastrointestinal tract, lungs and other tissues.
-
Myosin Heavy Chain Myopathy (MYHM) : Quarter Horse-related breeds are particularly susceptible to compli-
cations from S. equi infection because of a genetic proclivity for myosin heavy chain myopathy (MYHM) caused by an E321G mutation in the myosin heavy chain 1 gene (MYH1) encoding type 2X myosin. In approximately 40% of cases of MYHM, a history of exposure to S. equi, other infectious diseases or vaccination with S. equi or influenza / rhinopneumonitis precedes clinical signs. Both horses heterozygous and homozygous for the MYH1 mutation develop MYHM with clinical signs being more severe and difficult to manage in homozygotes.
Horses with MYHM may present with : immune-mediated myositis (IMM), calciphylaxis, nonexertional rhabdomyolysis (nER). -
IMM : Immune-mediated myositis usually develops in horses < 8 years of age or >16 years of age and is characterised by rapid profound atrophy of gluteal and epaxial muscle initially concurrent with moderate serum CK and AST elevations (often < 20,000 U/L). The aetiology of IMM has been proposed to be a loss of self-tolerance to type 2X myosin. The amino acid sequence of SEM overlaps that of type 2X myosin creating the possibility that antigenic mimicry is an instigator of disease.
In the early phase of gluteal and epaxial muscle atrophy, lymphocytes infiltrate type 2X muscle fibres and cuff small blood vessels. -
Calciphylaxis : Systemic calcinosis or calciphylaxis is a rare sequelae to IMM in young (less than 9 years of age) horses with the MYH1 mutation. Severe atrophy is followed by diverse organ failure due to systemic dystrophic calcification.
A high product of serum calcium multiplied by serum phosphorus (>65 mg/dL) is common in calciphylaxis. -
Nonexertional rhabdomyolysis : 67% of nER cases in Quarter Horse-related breeds were associated with the MYH1 mutation of which 75% were homozygotes and 25% heterozygotes. Severe, generalised muscle degeneration occurs with serum CK and AST in the hundreds of thousands. Triggering factors include infection with S. equi, Anaplasma phagocytophilum, Corynebacterium pseudotuberculosis and other infectious agents but often the trigger is unknown.
Muscle biopsies of gluteal or epaxial muscles show acute muscle degeneration, glycogen depletion in large muscle fibres and, unlike IMM, < 18% of horses have lymphocytic infiltrates in muscle fibres. This suggests an alternate aetiology to immune-mediated muscle fibre destruction. The MYH1 mutation appears to enhance the calcium sensitivity of muscle fibres which could result in a hyper-contractile state where muscles are more likely to contract and fail to relax triggering myodegeneration.
Myopathies associated with Streptococcus equi equi infection
eve 2024
What factors predispose horses to RER ?
- Age effect : younger
- Gender effect : female
- Temperament effect : nervous
- Lameness effect
- Diet effect : more than 5 kg of grain/day
- Exercise intensity : most often with gallop training
- Other data : most common during 3-day-event
- Racehorses : TB, SB
What is the underlying defect in the muscle that causes RER in TB ?
Horses susceptible to RER have enhanced muscle cell storage of calcium in sarcoplasmic reticulum (SR). Under conditions of chronic high stress, excessive release of calcium occurs from the SR during exercise → persistent muscle contracture, interruption of energy metabolism, and loss of mitochondrial and myofiber integrity.
How do I manage a TB that is predisposed to RER ?
Management that avoids the stressful triggering factors :
- Quiet area of the barn
- Turn-out, avoid stall rest
- Avoid holding back at the gallop
- First in training
- Treatment of lameness
- Medication that affect intracellular calcium regulation → dantrolene
- Diet : Low NSC (<20% of daily DE), high-fat diets (20-25%) may decrease muscle damage by assuaging anxiety and excitability.
What are the histologic findings of horses with RER ?
The RER diagnosis is also supported by examination of a skeletal muscle biopsy, where histological features include an increased number of centrally located nuclei in mature muscle fibers and the absence of abnormal polysaccharide and excessive glycogen storage, which are characteristic of polysaccharide storage myopathy (PSSM).
What causes PSSM1 in horses ?
Polysaccharide storage myopathy (PSSM1) is characterized by the abnormal accumulation of amylase-sensitive glycogen and amylase-resistant polysaccharide in muscle tissue, synthetized by the mutated glycogen synthase enzyme (GYS1), stimulated by insulin.
PSSM1 is inherited as an autosomal dominant trait → homozygous P/P for the mutation are rare and often more severely affected and harder to manage.
What breeds are affected by PSSM1 ?
Over 20 different breeds : QH bloodlines (QH 6%, Paint 7%, Appaloosa 6%), Draft and WB (Percheron 62%, Belgian 39%, Comtois 80%).
How is diagnosis of PSSM1 established ?
Muscle biopsy : taken from the semimembranous muscle, evaluated with special periodic acid Schiff’s (PAS) stain to look at the amount of glycogen stored in the muscle. With PSSM1, the intensity of this stain is very dark indicating a large amount of glycogen.
A definitive diagnosis of the type 1 form of PSSM requires genetic testing (hair roots or whole blood).
A 8-year-old Quarter Horse gelding, Dakota, presents with increasing episodes of muscle stiffness, sweating, and reluctance to move after exercise. Diagnostic tests confirm a diagnosis of Polysaccharide Storage Myopathy Type 1 (PSSM1) and the presence of the Malignant Hyperthermia (MH) mutation. Given these findings, what is the most appropriate management strategy to minimize the risk of muscle damage and prevent a potential malignant hyperthermia crisis in this horse?
A. Increase exercise intensity to improve muscle conditioning and prevent stiffness
B. Implement a low-intensity exercise regimen, avoid stress, and provide a low-starch, high-fat diet
C. Sedate the horse using volatile anesthetics to control pain and stress during procedures
D. Administer corticosteroids to reduce inflammation and prevent muscle stiffness after exercise
Correct Answer:
B. Implement a low-intensity exercise regimen, avoid stress, and provide a low-starch, high-fat diet
Explanation:
For horses diagnosed with PSSM1, a low-intensity exercise program is crucial to reduce the risk of muscle damage and stiffness. A low-starch, high-fat diet helps manage glycogen accumulation in muscle fibers, which is key to controlling PSSM1 symptoms. Additionally, stress management is important, as stress can exacerbate both PSSM1 and the risk of a malignant hyperthermia crisis. Volatile anesthetics and high-stress situations should be avoided due to the MH mutation, which predisposes the horse to potentially fatal reactions to certain anesthetics and stressors. Corticosteroids (option D) are not typically used to manage PSSM1 or MH and may have side effects that worsen muscle function in these horses.
What second genetic mutation makes signs of PSSM1 more severe in QH and related breeds ?
Malignant hyperthermia (MH) is a rare inherited autosomal dominant disease, identified in Quarter Horses and American Paint Horses.
It causes a life-threatening condition in susceptible horses triggered by anesthesia drugs (such as halothane, isoflurane, and succinylcholine), and occasionally by stress or excitement.
A mutation in the ryanodine receptor 1 (RYR1) gene results in an excessive release of calcium inside skeletal muscle cells. The increase in muscle metabolism raises the body temperature and triggers a potentially fatal hyper-metabolic state.
Presence of the MH mutation can result in more severe clinical tying-up in horses that also have the PSSM1 mutation, with very recurrent or difficult to manage episodes of tying-up.
How do I prevent another episode of tying-up in my PSSM1 horse ?
- Dietary nonstructural carbohydrate (NSC) intake in affected horses should be limited to less than 12% of the diet to keep blood insulin levels low and reduce glycogen storage in muscle.
- Horses must exercise daily to maximize the muscles’ ability to burn glycogen.
- Affected horses are often easy keepers and management through a low-NSC grass hay and a good-quality ration balancer is usually sufficient.
- If additional calories are needed, a low-NSC and/or high fat feed source should be incorporated.
Since small management changes can have a big impact, fine-tuning the diet over time may be necessary. Ensuring an adequate source of quality protein in the diet appears to be important.
Reintroducing exercise : needs to be gradual after an acute episode of exertional rhabdomyolysis.
1. Providing adequate time for adaptation to a new diet before commencing exercise (2 weeks)
2. Recognizing that the duration of exercise is more important to restrict than the intensity (< 5 min walk/trot to start)
3. Ensuring that exercise is gradually introduced and consistently performed
4. Minimizing any days without some form of exercise
At least 3 weeks of walk and trot should precede work at a canter.
Can I manage only the diet of my PSSM1 horse ?
If only the diet is changed, ∼50% of horses improve.
If both diet and exercise are altered, then 90% of horses are improved.
A 7-year-old Quarter Horse gelding, Rusty, has been diagnosed with Polysaccharide Storage Myopathy Type 1 (PSSM1) after presenting with recurring episodes of muscle stiffness, sweating, and reluctance to move following exercise. Despite implementing a low-starch, high-fat diet and a carefully monitored, low-intensity exercise regimen, Rusty’s symptoms are not well-controlled. The owner reports that episodes of muscle stiffness are still frequent, and the gelding seems particularly affected by stress, even during routine handling. Given Rusty’s poor response to conventional management, what is the most likely additional genetic mutation that could be contributing to his symptoms?
A. MYHM mutation (Myosin Heavy Chain Myopathy)
B. HYPP mutation (Hyperkalemic Periodic Paralysis)
C. MHS mutation (Malignant Hyperthermia Syndrome)
D. RER (Recurrent Exertional Rhabdomyolysis)
Correct Answer:
B. HYPP mutation (Hyperkalemic Periodic Paralysis)
Explanation:
As discussed earlier, HYPP (Hyperkalemic Periodic Paralysis) is a genetic disorder that causes episodes of muscle stiffness, weakness, or paralysis, often triggered by exercise or stress. Given the chronic nature of Rusty’s symptoms despite management of PSSM1, the presence of the HYPP mutation could explain the additional signs of muscle stiffness under stress.
RER (Recurrent Exertional Rhabdomyolysis) is also a potential differential but is not a genetically defined disease with a single mutation like HYPP or PSSM1. It’s more of a condition triggered by various factors, including stress, exercise, and potential imbalances in calcium regulation in the muscle, and it’s less likely to be the primary cause in this scenario. Mostly affect Thouroughbred and Standardbred racehorses.
The MYHM mutation and MHS mutation (Malignant Hyperthermia Syndrome) are rare and less likely in this particular case, as they are not typically associated with chronic muscle stiffness in response to exercise in the same way that HYPP would be.
What genetic diseases are identified in QH ? Are they recessive or dominant ?
- Malignant hyperthermia (autosomal dominant)
- PSSM (autosomal dominant)
- GBED (autosomal recessive)
- MYH1 myopathy : Immune-mediated myositis and Non-exertional myositis (autosomal dominant)
- HYPP (autosomal dominant)
- HERDA (autosomal recessif)
What is myosin heavy chain myopathy ?
- Specific genetic mutation in the gene MYH1 in horses of QH-related breeds can develop myosin heavy chain myopathy (MYHM).
- MYH1 encodes a muscle specific protein called myosin heavy chain 1 that is found in type 2X muscle fibers, the fastest contracting muscle fibers (> 50% of the locomotor muscles in QH).
- MYHM presents as two overlapping clinical syndromes → immune-mediated myositis (IMM) and nonexertional rhabdomyolysis (nER).
- MYHM is present about 7% of QH → autosomal dominant mutation. Heterozygotes are clinical and homozygotes seem to have more frequent and severe symptoms.
What is immune-mediated myositis ?
- IMM is one of the forms of MYHM, when the immune system attacks the type 2X fibers in skeletal muscles along the back and rump causing a rapid muscle atrophy.
- Caused by a loss of self-tolerance of the immune system, usually triggered by certain infectious agent (Strepto equi) or vaccines (flu/rhino). Possible mimicry between the M protein of S equi and the type 2X myosin.
- MYHM is present about 7% of QH → autosomal dominant mutation. Heterozygotes are clinical and homozygotes seem to have more frequent and severe symptoms.
- Clinical signs : rapid epaxial and gluteal muscle atrophy in 1-3 days, depression, loss of appetite, stiffnes. Horses < 8yo or > 17 yo are more likely to develop IMM.
How is IMM diagnosed ?
- History : recent history of respiratory infection or vaccination
- Blood analysis : increase in serum CK and AST up to 10,000 U/L
- Genetic testing : MYH1 mutation, autosomal dominant
- Muscle biopsy : rarely necessary with the genetic testing, but samples of the gluteal or epaxial muscles can be submitted → extensive WBC infiltration and inflammed blood vessels, accompanied by regenerating and/or atrophied muscle fibers.
Photo : lymphocytic infiltration of myofibers (arrows), anguloid atrophy of myofibers, and internalization of myonuclei are present.
What is glycogen branching enzyme deficiency ?
- GBED is found in QH-related breeds and causes late-term abortion, still birth, or death of foals by a few months of age. Weakness and hypothermia at birth, tachypnea, weakness, contracted tendons. Hypoglycemia, high CK, AST and GGT.
- Allele frequency in QH : 10%. Autosomal recessive → tissular glycogen lacks the normal branched structure and thus cannot effectively store sugar molecules (liver, skeletal muscles, myocardium, brain).
- Diagnosis : muscle or hepatic biopsy with a characteristic PAS staining pattern. Note globules of abnormal polysaccharide with the absence of normal background pink staining in the GBED biopsy (A. normal ; C. GBED). Genetic test
What is equine myofibrillar myopathy ?
- MFM is a disruption of the orderly alignment of myofibrils, with clumps of desmin near the breaks.
- In Arabians, particularly those competing in endurance, the most common clinical sign of MFM is intermittent tying up (episodes of muscle pain, stiffness, reluctance to move). The severity of muscle stiffness can be much milder than that seen with classic tying-up (exertional rhabdomyolysis). Increased serum CK and AST levels can occur but may not be as high as in classic forms of tying-up.
-
Warmblood horses with MFM may have a history of satisfactory performance as young animals but decline in performance as they reach 8 -10 yrs of age. Tying-up is usually very intermittent or absent in Warmbloods. The most common clinical signs of MFM in Warmbloods are related to poor performance without elevations in serum CK and AST activity. Reluctance to collect and
engage the hindquarters, poor rounding over fences, poor quality of the canter and slow onset of muscle wasting (atrophy), especially when out of work. Not specific to MFM, need a thorough evaluation for lameness. - MFM in Arabians appears to involve altered cysteine metabolism. Cysteine is an amino acid that is a key structural component of proteins and a necessary component of many antioxidants in muscle. Endurance horses have a high capacity to oxidize fatty acids which can create oxidative stress during aerobic exercise. A deficiency of cysteine-containing antioxidants could cause chronic oxidation and aggregation of key proteins such as desmin.
How to diagnose MFM ?
A diagnosis of MFM requires immunohistochemical stain for desmin in a gluteal/semimembranosus muscle biopsy → abnormal amounts and shapes of desmin, likely as a reaction to instability of the myofibrils.
A false positive diagnosis of MFM can occur if the muscle biopsy is taken from a horse with actively regenerating muscle fibers.
False-negative diagnosis can occur if a horse is too young, the muscle samples are too small, the muscle biopsies are not kept chilled during shipping, or shipping is too slow.
In some MFM horses, PAS stains for glycogen reveal aggregates of amylase-sensitive or amylase-resistant PAS positive material resembling PSSM2 diagnostic criteria. We believe pooling of glycogen between the breaks in myofibrils is the reason many cases of MFM were previously
diagnosed with PSSM2.
*No genetic test validated for MFM. *
Photo : A. MFM (abnormal red clumping of desmin occurs in scattered muscle fibers)
B. control
How to manage a horse with MFM ?
- Exercise : Core strengthening exercises, lots of stretching and long, low warm-ups is important for MFM horses (the frame is very important). Many owners of MFM horses have found that three days of work then two days off works best for MFM horses. To strengthen core muscles, hill work, poles and cavaletti can all be introduced gradually.
-
Diet : Rations should focus on providing quality protein and specific amino acids to aid the horse in making proteins necessary to rebuild the contractile proteins. Additionally, oxidative stress is likely involved in the degenerative process, thus antioxidants or precursors of antioxidants are important to support cellular mitochondria.
Currently, there is no evidence supporting extremely low-starch and sugar, high-fat diets are needed by Warmbloods with MFM.
Arabian endurance horses are typically fed higher fat diets, as Arabians depend more on fat oxidation than Thoroughbreds during exercise. However, since MFM in Arabian endurance horses is related to oxidative stress resulting from fat oxidation, it is questionable whether these horses need extremely high levels of fat intake (>15% total
digestible energy intake).
Concentrates for MFM horses should include higher levels of protein (12-14% CP) containing high-quality amino acids and** moderate levels of nonstructural carbohydrates (20-30%) with fat at 4-8%**. If horses are easy keepers and require lower caloric intakes, a ration balancer that contains vitamins, minerals and at least 20% protein may suffice. - Amino acid supplements are recommended, especially whey-based proteins rich in cysteine.
Prognosis :
- WB → In most cases to date, horses have not been able to achieve the level of dressage or 1 meter jumping
performance originally envisioned by their owners.
- Arabian → Several top-level endurance horses with this condition are being managed by their owners to reduce episodes of tying-up. Both daily exercise and diet changes are important for endurance horses and the use of a walker or exercise machine can be of great assistance to avoid complete inactivity. Some MFM Arabian endurance horses with MFM have been retired and used successfully as trail horses.
What is the difference between VEM and EMND ?
VEM :
- muscle atrophy and weakness without evidence of damage to motor nerves. Loss of muscle mass, toe dragging, poor performance, weakness.
-Histo : abnormal ‘moth-eaten’ mitochondrial staining of fresh sacrocaudalis dorsalis muscle in the absence of neurogenic angular atrophy of muscle fibers.
- TT : horses respond remarkably to alpha-tocopherol supplementation and can make a complete recovery
EMND :
- acquired neurodegenerative disorder affecting motor nerves supplying highly oxidative type 1 muscle fibers. EMND is associated with low plasma concentrations of alpha-tocopherol and a dietary deficiency of alpha-tocopherol of at least 18 months duration.
- Generalized muscle wasting, muscle fasciculation, shifting weight, low head carriage, prolonged periods of recumbency.
- Diagnosis : histo evidence of the degeneration of myelinated axons upon biopsy of the ventral branch of the spinal accessory nerve or the finding of neurogenic atrophy of predominantly type 1 muscle fibers in sacrocaudalis dorsalis medialis muscle biopsy.
- TT : 5000-7000 IU/day → 40% of cases with clinical improvement in 6 weeks, but return to performance may result in deterioration. Approximately 40% will stabilize, but remain permanently disfigured, while 20% will deteriorate .
