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.
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Myosin Heavy Chain Myopathy (MYHM) : Quarter Horse-related breeds are particularly susceptible to complications 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)
- Overo Lethal White syndrome
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 nonexertional rhabdomyolysis ?
Some horses with the MYH1 mutation develop acute severe muscle damage that is not triggered by exercise.
Rather than muscle atrophy, horses show signs of stiffness and swelling of back and rump muscles, with high levels of CK and AST. Reluctance to move, difficulty rising, tachycardia, tachypnea, +/- fever.
Exact mechanism is unknown, possibly an immune-response similar to IMM or the mutation may change the interaction of myosin with actin during muscle contractions. Strepto equi or Anaplasma phagocytophilum can trigger nER.
Homozygous more severely affected.
DDX of rhabdomyolysis in QH
- PSSM 1
- Malignant hyperthermia
- MYHM →Non exertional rhabdomyolysis / IMM
- Nutritional myodegeneration (white muscle disease)
- Toxic myopathy - sycamore maple
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
How is diagnosed PSSM 2 ?
Muscle biopsy :
- PAS stains for glycogen reveal aggregates of amylase-sensitive material clumped in the cytoplasm of the muscle fiber and under the cell membrane.
- A false-positive diagnosis can occur if the muscle biopsy is crushed with forceps resulting in abnormal glycogen, and a false-negative diagnosis can occur if samples are not kept chilled and shipped quickly to the lab, because glycogen is degraded while the muscle biopsy is in transport.
- There is also overlap in the appearance of muscle biopsies of horses with PSSM2 and RER.
- About 80% of cases of PSSM diagnosed by biopsy in WB are PSSM2; 70% in QH.
What are the signs of PSSM2 in horses?
- In Arabian and QH with PSSM2, the most common clinical signs is tying-up (muscle pain, stiffness, reluctance to move) with increased serum CK and AST → ressembling with RER.
- In Warmblood, tying-up is occasionaly reported with high serum CK, but the most common clinical signs are poor performance without elevations in serum CK. Gait abnormalities, painful firm back and hindquarter muscles, reluctance to engage the hindquarters, and drop in energy level, unwillingness to perform after 5-10 min of exercise. Mean age of onset → 8 - 11 yo with low CK and AST.
Both diet (low NSC, higher protein content with high quality aa, fat supplementation) and training (avoir rest, daily turn out, slowly reintroducing exercise, prolonged warm-up with adequate stretching) must be changed to see a beneficial effect. With diet and exercise recommendations, about 70% of WB improved in clinical signs and many return to acceptable levels of performance.
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 why 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
Is PSSM2 the same disease as MFM ?
The clinical features of PSSM2 overlap features of MFM in Arabian and Warmblood horses and it may be that PSSM2 is an early feature of MFM, but this is not completely clear at this time.
If horses have muscle biopsy findings consistent with both PSSM2 and MFM, we use the term MFM to describe these horses as it is a more specific diagnosis.
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.
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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.
Which breed has the highest prevalence of MYHM ?
QH population, particularly in reining QH
VetClinics 20
Prevalence of the E321G MYH1 variant in Brazilian Quarter Horses
evj 22
A 5-year-old Quarter Horse gelding, Rocky, has been diagnosed with the MYH1E321G mutation after presenting with muscle atrophy and stiffness. The owner reports that Rocky was recently vaccinated and had a mild gastrointestinal illness approximately 3 months before the symptoms became noticeable. Based on a recent study evaluating the prevalence and triggers of muscle atrophy in horses with the MYH1E321G mutation, which of the following is most likely regarding Rocky’s condition?
A. Homozygous My/My horses are the most likely to experience rapid muscle atrophy and less likely to recover compared to heterozygous My/N horses.
B. Vaccination and gastrointestinal illness are strongly associated with the onset of muscle atrophy in horses with the MYH1E321G mutation.
C. Stiffness is significantly more common in homozygous My/My horses, with 40% showing stiffness compared to heterozygous My/N horses and homozygous N/N horses.
D. The performance of horses with the MYH1E321G mutation is significantly reduced across all genotypes, with fewer My/My horses achieving expected performance levels.
A. Homozygous My/My horses are the most likely to experience rapid muscle atrophy and less likely to recover compared to heterozygous My/N horses.
Explanation:
The study outlined in the abstract shows that:
- Homozygous My/My horses (80%) experience more frequent and severe muscle atrophy than heterozygous My/N (17%) or homozygous N/N (11%) horses. Moreover, these horses tend to have rapid atrophy, and their symptoms are less likely to resolve compared to My/N horses.
- B. Vaccination and respiratory or gastrointestinal illness were found to be observed 3 months before the episode of atrophy and illness in 47% of MYH1 horses, meaning that inciting causes such as vaccination and infection are inapparent in over half of cases.
- C. Stiffness was common across genotypes and was the most common with My/My (40%), compared with My/N (18%), and N/N (17%), but was not significant (p=0.1)
- D. Performance: the study found no significant difference in performance levels across the genotypes, with a fair number of My/N horses achieving high performance, including national and world championships. In contrast, fewer My/My horses were competing due to the severity of their symptoms.
Thus, A is the most accurate interpretation of the study’s results.
Prevalence of clinical signs and factors impacting expression of myosin heavy chain myopathy in Quarter Horse-related breeds with the MYH1E321G mutation
jvim 22
True or False:
The study found a significant association between the commercial genetic test variants for PSSM2/MFM (P2, P3, and P4) and a histopathological diagnosis of myopathy in Warmblood (WB) and Arabian (AR) horses.
False
Explanation:
The study found no significant association between the PSSM2/MFM genetic test variants (P2, P3, and P4) and a histopathological diagnosis of PSSM2/MFM in Warmblood and Arabian horses.
Additionally, there was no difference in the total number of loci with alternative alleles or in total alternative alleles between control and myopathic horses. Because of these findings, the study concluded that these genetic variants should not be used for selection, breeding, prepurchase examination, or diagnosis of myopathy.
Commercial genetic testing for type 2 polysaccharide storage
myopathy and myofibrillar myopathy does not correspond to a
histopathological diagnosis
evj 21
True or False:
The study found that the P2, P3, and P4 genetic variants associated with human myofibrillar myopathy (MFM) were significantly associated with a histopathological diagnosis of PSSM2 in Quarter Horses (QH)
False
Explanation:
The study found no significant association between the P2, P3, and P4 genetic variants and a histopathological diagnosis of PSSM2 in Quarter Horses. These variants were present in both healthy control-QH (57%) and PSSM2-QH (61%), with no significant differences in genotype or allele frequencies. Additionally, the use of these variants would lead to incorrect diagnoses of PSSM2/MFM in 57% of healthy QH and would fail to diagnose PSSM2 in 40% of affected QH with histopathological evidence.
Absence of myofibrillar myopathy in Quarter Horses with a histopathological diagnosis of type 2 polysaccharide storage myopathy and lack of association with commercial genetic tests
evj 23
True or False:
The study found that Quarter Horses (QH) diagnosed with PSSM2 exhibited histopathological features of myofibrillar myopathy (MFM).
False
Explanation:
The study found that histopathological features of MFM were absent in all Quarter Horses (QH) diagnosed with PSSM2. Despite testing for genetic variants commonly associated with MFM (P2, P3, P4), the horses did not exhibit the muscle pathology typical of MFM, indicating that PSSM2 and MFM are distinct conditions in this breed.
Absence of myofibrillar myopathy in Quarter Horses with a histopathological diagnosis of type 2 polysaccharide storage myopathy and lack of association with commercial genetic tests
evj 23
True or False:
The study identified a monogenic variant in genes known to cause glycogen storage disorders as the cause of PSSM2 in Quarter Horses (PSSM2-QH).
False
Explanation:
The study did not identify a monogenic variant in genes associated with glycogen storage disorders as the cause of PSSM2 in Quarter Horses (PSSM2-QH). Despite analyzing 12 candidate genes related to muscle glycogenoses, none of the 29 predicted high or moderate impact genetic variants were found to be present exclusively in PSSM2-QH and absent in control-QH.
This indicates that PSSM2-QH is a novel glycogen storage disorder with an unknown genetic basis, distinct from known muscle glycogenoses in other species.
Type 2 polysaccharide storage myopathy in Quarter Horses is a novel glycogen storage disease causing exertional rhabdomyolysis
evj 23
True or False:
PSSM2-QH is a novel glycogen storage disorder with an unknown genetic basis, distinct from known muscle glycogenoses in other species.
True
Type 2 polysaccharide storage myopathy in Quarter Horses is a novel glycogen storage disease causing exertional rhabdomyolysis
evj 23
What equine diseases are directly affected by a deficiency of vitamin E ?
In foals :
- Nutritional muscle degeneration
- eNAD/EDM
In adults :
- Vita E responsive myopathy
- EMND
What is nutritional myodegeneration ?
NMD or white muscle disease affects skeletal or cardiac muscle of rapidly growing, active foals and is primarily due to dietary deficiency of selenium beginning in the uterus +/- vitamin E deficiency.
Muscle weakness, difficulty rising, trembling of the limbs, stiffness, depression, tachycardia, pneumonia, sudden death.
Cardiac form of NMD is fatal.
Diagnosis : may include elevated serum CK and AST, whole blood selenium < 0.07 µg/mL +/- serum alpha-tocopherol < 2 µg/mL.
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 .
What is the best supplementation of vitamin E?
What is the recommended dose and risk of excessive supplementation ?
RRR ⍺-tocopherol is natural
> dl-⍺-tocopherol is synthetic
> d-⍺-tocopherol acetate
In case of deficiency, 10 IU/kg btw is recommended.
Upper safe supplementation is 20 IU/kg btw → above this level, blood clotting and impaired bone mineralization.
What are the 5 genetic tests for equine myopathies ?
- HYPP (codominant)
- PSSM1 (dominant)
- MH (dominant)
- MYHM (codominant)
- GBED (recessive)
True or False:
Horses affected by HYPP typically present with episodic muscle weakness, tremors, and in severe cases, paralysis, which can be triggered by factors like stress, diet, or exercise.
Answer:
True
Explanation:
Horses affected by HYPP (Hyperkalemic Periodic Paralysis) exhibit episodic muscle weakness, tremors, and in more severe cases, paralysis.
These episodes are typically triggered by factors such as stress, diet (high potassium intake), and exercise.
The condition is caused by a mutation in the SCN4A gene that encodes for sodium channels, that results in a failure of a subpopulation of sodium channels to inactivate when serum potassium concentrations are increased. Failure of inactivation results in membrane depolarization, which manifests as muscle fasciculations and can eventually lead to depolarization block manifesting as muscular paresis or paralysis.
Affected horses are typically genotyped to confirm the presence of the mutation, and management strategies focus on dietary modifications, stress reduction, and exercise control to minimize episodes.
What is the typical phenotype of a horse affected by HYPP ?
HYPP affects QH, American paint horses, Appaloosas, and QH-crossbred animals worldwide that are descendants of the stallion Impressive. There seems to be selection for the heavily muscled phenotype associated with HYPP in the halter horse performance group, where 56% of horses possess the HYPP mutation.
What are the clinical signs of HYPP ?
Episodes of HYPP begin with a brief period of twitching or delayed relaxation of muscles and can include prolapse of the third eyelid. Sweating and muscle fasciculations commonly occur in the flanks, neck, and shoulders. Stimulation and attempts to move can exacerbate muscle tremors, with some horses developing severe muscle cramping. Episodes usually last for 15 to 60 minutes.
Respiratory distress caused by paralysis of upper respiratory muscles can occur in N/H and H/H horses during episodes and can require a tracheostomy to prevent death from anoxia. After an episode of HYPP subsides, the horse appears normal.
Foals homozygous for HYPP usually show clinical signs of disease in the first few days of life that include dysphagia, respiratory stridor, periodic obstruction of the upper respiratory tract, and respiratory distress. Adults that are H/H usually have more frequent and severe episodes of HYPP compared with N/H horses and more severe signs of upper airway obstruction during an episode.
Photo : Impressive stallion
How to manage a HYPP episode ?
During episodes of muscle fasciculations, most horses have hyperkalemia (6–9 mEq/L), hemoconcentration, and mild hyponatremia with normal acid-base balance. Serum potassium concentration returns to normal quickly after the cessation of clinical signs.
Mild episodes of HYPP can be aborted early on by feeding grain or corn syrup to stimulate insulin-mediated movement of potassium into cells and by initiating light exercise. Other acute treatment options include administration of epinephrine.
In severe cases, administration of calcium gluconate can produce immediate improvement. An increase in extracellular calcium concentration increases the muscle-membrane threshold potential, which attenuates membrane hyperexcitability.
Alternatively, to reduce serum potassium level, IV dextrose alone or combined with sodium bicarbonate can be used to enhance intracellular movement of potassium.
With severe dyspnea caused by laryngeal or pharyngeal obstruction, a tracheostomy can be necessary.
Which factors have been associated with an increased risk of atypical myopathy ?
- Being pastured for over 12h daily
- Fall season
- Lack of supplemental hay in pasture
- Sparse pasture with short grass
- Presence of trees with dead wood on the ground
- Heavy wind or rain in the week preceding clinical signs
- Introduction of a horse onto a pasture for its first season
Which muscles are mostly affected by hypoglycin A ?
Highly oxidative type I muscle fibers, which are abundant in respiratory, cardiac and postural muscles → acute myonecrosis and lipid storage myopathy caused by inhibited mitochondrial β-oxidation and multiple acyl-CoA dehydrogenase deficiency (MADD)
A retrospective case series on Atypical Myopathy (AM) in horses described the clinicopathological data and outcomes. Based on the findings, which of the following factors were associated with nonsurvival in horses hospitalized with AM?
A. Lower blood lactate concentrations and serum creatine kinase (CK) activities on admission.
B. Higher blood lactate concentrations and serum CK activities on admission.
C. Decreased triglyceride concentrations during hospitalization.
D. No association between serum CK activity and triglyceride concentrations with survival.
Answer:
B. Higher blood lactate concentrations and serum creatine kinase (CK) activities on admission.
Explanation:
- A. False. The study found that survivors had lower blood lactate concentrations and serum CK activities on admission compared to nonsurvivors. Therefore, lower lactate and CK levels on admission were associated with survival, not nonsurvival.
- B. True. Higher blood lactate concentrations and serum CK activities on admission were associated with nonsurvival. Specifically, nonsurvivors had higher blood lactate (median 7.3 mmol/L) and serum CK levels (median 172,687 U/L) compared to survivors (median 3.5 mmol/L and 38,369 U/L, respectively).
- C. False. The study found that increasing triglyceride concentrations during hospitalization were associated with nonsurvival, not decreased concentrations.
- D. False. The study clearly found an association between admission CK activity, lactate concentrations, and the outcome. Additionally, increasing CK activity and triglyceride concentrations during hospitalization were associated with nonsurvival.
This MCQ assesses key clinical findings from the study, such as lactate, CK activity, and triglyceride concentrations, which are important prognostic indicators in horses with Atypical Myopathy.
Atypical myopathy in the South-East of England: Clinicopathological data and outcome in hospitalised horses
eve 2020
In a study investigating the presence of Sapindaceae family toxins in mare’s milk, which of the following substances were detected in the milk of a mare with atypical myopathy?
A. Only hypoglycin A and methylenecyclopropylglycine were detected in the mare’s milk.
B. The study found no toxins in the mare’s milk.
C. Hypoglycin A and associated metabolites, including methylenecyclopropylacetyl glycine and carnitine, were detected in the mare’s milk.
D. The milk contained only methylenecyclopropylformyl glycine.
Answer:
C. Hypoglycin A and associated metabolites, including methylenecyclopropylacetyl glycine and carnitine, were detected in the mare’s milk.
Explanation:
- A. False. While hypoglycin A was detected in the mare’s milk, the study also found several associated metabolites, such as methylenecyclopropylacetyl glycine and carnitine, along with increased concentrations of several acylcarnitines. Therefore, the presence of only hypoglycin A is incorrect.
- B. False. The study clearly found the presence of toxins and their metabolites in the mare’s milk, contradicting the idea that there were no toxins detected.
- C. True. The mare’s milk contained hypoglycin A (0.4 μg/L) and its associated metabolites, including methylenecyclopropylacetyl glycine (18.5 μg/L) and carnitine (24.6 μg/L), as well as several other acylcarnitines. Additionally, methylenecyclopropylformyl glycine (0.8 μg/L) and carnitine (60 μg/L) were also detected in the milk.
- D. False. While methylenecyclopropylformyl glycine was detected in the milk, it was not the only substance present. The study also found hypoglycin A and several metabolites like methylenecyclopropylacetyl glycine and carnitine.
This MCQ tests knowledge on the findings related to the vertical transmission of toxins from mares to foals, which could have clinical implications for both veterinary and human medicine, especially regarding the Sapindaceae family toxins (ackee or litchi).
Detection of maple toxins in mare’s milk
jvim 21
In a study developing a rapid LCMS (liquid chromatography-mass spectrometry) method for detecting hypoglycin A (HGA) and its toxic metabolite methylenecyclopropylacetic acid (MCPA)-carnitine, which of the following statements is true regarding the validation and performance of the new diagnostic test for atypical myopathy (AM)?
A. The method was not validated for use in muscle tissue, as it only focused on serum samples.
B. The test was highly specific for atypical myopathy but did not work well for assessing toxin exposure in cograzing horses.
C. The stability of the analytes was significantly affected by storage at different temperatures, limiting the test’s usability in field settings.
D. The test was successfully validated for the detection of both HGA and MCPA-carnitine in serum and muscle.
Answer:
D.The test was successfully validated for the detection of both HGA and MCPA-carnitine in serum and muscle.
Explanation:
- A. False. The method was indeed validated for both serum and muscle tissue. The abstract mentions that the test was successfully validated for detection of HGA and MCPA-carnitine in both serum and muscle, so this option is incorrect.
- B. False. The test is not limited to atypical myopathy (AM) cases. It is also intended for risk assessment of toxin exposure in cograzing horses and to assess horses with undiagnosed myopathies, making this option incorrect.
- C. False. The test’s stability was not significantly affected by storage at different temperatures. The abstract specifically mentions that stability was unaffected by a range of temperatures, so this option is incorrect.
- The serum-based test should also enable risk assessment of toxin exposure in cograzing horses and assessment of horses with undiagnosed myopathies.
- While the tissue detection test should help to confirm cases post-mortem and to determine toxin distribution, metabolism and clearance across different tissues.
Detection of hypoglycin A and MCPA-carnitine in equine serum and muscle tissue: Optimisation and validation of a LC-MS–based method without derivatisation
evj 21
Based on the findings of an experimental study evaluating the effect of mowing and herbicidal spraying on the hypoglycin A (HGA) content of sycamore seedlings and processed haylage and silage, which of the following statements is correct?
A. Mowing temporarily increases the HGA content of sycamore seedlings, and no significant reduction in HGA content was observed in sprayed seedlings over 2 weeks.
B. Mowing or herbicidal spraying significantly reduces the HGA content of sycamore seedlings, thus providing an effective strategy to mitigate the risk of hypoglycin A toxicity in horses.
C. Both mowing and spraying sycamore seedlings with herbicides completely eliminate the risk of HGA exposure to horses within 2 weeks of treatment.
D. Processed hay and silage from pastures contaminated with sycamore material pose no risk of HGA intoxication, as HGA is eliminated during storage.
Answer:
A. Mowing temporarily increases the HGA content of sycamore seedlings, and no significant reduction in HGA content was observed in sprayed seedlings over 2 weeks.
Explanation:
- A. True. The study observed that mowing caused a temporary rise in HGA content of sycamore seedlings. Additionally, no significant reduction in HGA was noted in the sprayed seedlings (whether sprayed with dimethylamine-based or picolinic acid-based herbicides) after 2 weeks.
- B. False. The study found that mowing did not significantly reduce HGA content in seedlings; in fact, it temporarily increased HGA content in the seedlings. Herbicidal spraying also did not significantly reduce the HGA content of sycamore seedlings. Therefore, mowing and herbicidal spraying were not effective in reducing HGA levels.
- C. False. The study did not show that mowing or herbicidal spraying eliminated the risk of HGA exposure. No significant reduction in HGA content was achieved through either mowing or spraying, making this statement incorrect.
- D. False. The study found that HGA was still present in sycamore material even after 6-8 months of storage in both hay and silage, indicating that processed hay and silage from contaminated pastures can still pose a risk of HGA intoxication.
Key Takeaways:
- Option A is correct because it accurately reflects the study’s findings that mowing temporarily increased HGA levels and spraying did not significantly reduce HGA content in sycamore seedlings.
- Option A is incorrect because mowing and herbicidal spraying did not significantly reduce HGA levels.
- Option C is incorrect because neither mowing nor spraying eliminated the risk of HGA toxicity.
- Option D is incorrect because the study demonstrated that sycamore material in hay and silage still contains HGA, posing a risk to horses even after long-term storage.
Atypical myopathy-associated hypoglycin A toxin remains in sycamore seedlings despite mowing, herbicidal spraying or storage in hay and silage
evj 19
True/False Question:
In horses with suspected septic synovitis, the combination of penicillin and gentamicin is not effective as empirical antimicrobial treatment, according to the results of a study on antimicrobial susceptibility patterns.
False.
Explanation:
The study found that 92% of gram-positive bacteria isolated from adult horses and 94% of bacteria isolated from foals were susceptible to either penicillin, gentamicin, or both. Therefore, the combination of penicillin and gentamicin would be an effective empirical treatment for most horses with septic synovitis while awaiting the results of bacterial culture and susceptibility testing.
Most common in adult horses → gram-positive bacteria
Most common in foals → gram-negative bacteria
Antimicrobial susceptibility patterns of bacterial isolates cultured from synovial fluid samples from horses with suspected septic synovitis: 108 cases (2008–2017)
javma 20
Which of the following factors was associated with lower survival rates in Thoroughbred foals with septic arthritis, according to the study?
A) Older age at the time of admission
B) Concurrent multisystemic disease
C) Longer duration of clinical signs
D) Foals treated with arthroscopic lavage
Answer:
B) Concurrent multisystemic disease
Explanation:
The study found that foals with concurrent multisystemic disease were six times less likely to be discharged alive (P = 0.02). Additionally, foals < 26 days old at the time of admission were five times less likely to survive (P = 0.003).
For this cohort, foals that survived to discharge had a similar ability to race as their maternal siblings.
Factors associated with survival and racing performance of 114 Thoroughbred foals with septic arthritis compared with maternal siblings (2009-2015)
evj 21
What is the main cause of racing-associated fatalities in Norwegian and Swedish harness racehorses ?
Traumatic injuries accounted for 14.5%, while sudden death for 85.5% of fatalities. The number of starts within the last 30 days increased the risk of sudden death (5 starts odds ratio (OR) 228.80). An opposite non-linear effect was observed in number of starts the last 180 days (>10 starts OR 0.12).
Acute circulatory collapse because of suspected cardiac or pulmonary failure or both was recorded in 30 horses, while major hemorrhage after vessel rupture was the primary cause of death in 10 cases.
Racing-associated fatalities in Norwegian and Swedish harness racehorses: Incidence rates, risk factors, and principal postmortem findings
jvim 22
Which of the following statements is true regarding the impact of dynamic upper airway obstruction (DUAO) on fitness parameters in Standardbred racehorses?
A) Horses with mild DUAO (medial deviation of the aryepiglottic folds or epiglottic entrapment) had significantly reduced speed at a heart rate of 200 bpm (V200) compared to horses with no DUAO.
B) Horses with severe (DDSP, nasopharyngeal collapse, dynamic laryngeal collapse, or epiglottic retroversion) or multiple DUAOs showed lower speed at a heart rate of 200 bpm (V200) and at a lactate concentrations of 4 mmol/L (vLa4) compared to the no-DUAO group.
C) There was no significant difference in peak lactate concentrations between horses with mild DUAO and those with severe or multiple DUAOs.
D) Horses with multiple DUAOs had higher V200 speeds and lower lactate concentrations compared to the no-DUAO group.
Answer:
B) Horses with severe or multiple DUAOs showed lower speed at a heart rate of 200 bpm (V200) and lactate concentrations compared to the no-DUAO group.
Explanation:
- Option A is incorrect because the study did not mention a significant reduction in speed for horses with mild DUAO compared to those with no DUAO. According to the study, mild forms of DUAO do not affect athletic capacity.
- Option B is correct. Horses with severe or multiple DUAOs showed lower V200 (speed at a heart rate of 200 bpm) and VLa4 (speed at lactate concentration of 4 mmol/L) compared to horses without DUAO.
- Option C is incorrect. Horses with multiple DUAOs had higher peak lactate concentrations compared to those without DUAO, not no significant difference.
- Option D is incorrect. Horses with multiple DUAOs had higher peak lactate concentrations compared to the no-DUAO group, not lower.
Association between dynamic upper airway obstructions and fitness parameters in Standardbred racehorses during high-speed treadmill exercise
javma 22
What are the main causes of poor performance in nonlame SB trotters ?
- MEA
- EGUS
- EIPH
- DUAO
Medical causes of poor performance and their associations with fitness in Standardbred racehorses
jvim 23
True or False:
Horses racing while on furosemide medication had a 62% increased odds of sudden death compared to horses not on furosemide.
True
Explanation:
The study found that horses racing while on furosemide medication had a 62% increased odds of sudden death. The study also found an association between previous injury and sudden death, suggesting preexisting pathology could contribute in some cases.
Fifteen risk factors associated with sudden death in Thoroughbred racehorses in North America (2009–2021)
javma 22
Which of the following conclusions was supported by the study regarding intravenous calcium supplementation to resuscitation fluids in endurance horses?
A) Calcium supplementation had no significant effect on heart rate or gastrointestinal sounds.
B) Calcium supplementation improved gastrointestinal sounds in the treatment group compared to the control group.
C) Calcium supplementation decreased heart rate 45 minutes after starting the infusion.
D) Plasma phosphorus concentration decreased significantly after calcium supplementation.
Answer:
C) Calcium supplementation decreased heart rate 45 minutes after starting the infusion.
Explanation:
The study found that calcium supplementation was associated with a lower heart rate 45 minutes after the infusion began (P = 0.002), but gastrointestinal sounds were less likely to improve in the calcium group compared to the control group (P = 0.005).
There was an increase in plasma phosphorus concentration (P = 0.03) associated with calcium administration, not a decrease.
Ccl° : Intravenous calcium supplementation to endurance horses eliminated from competition after development of metabolic problems may decrease heart rate but impairs improvement in gastrointestinal sounds.
Effects of calcium supplementation to resuscitation fluids in endurance horses: A randomized, blinded, clinical trial
jvim 23
What was the main conclusion of the study on sodium chloride (NaCl) pellets supplementation in exercising horses?
A) NaCl supplementation caused significant gastric mucosal damage in the horses.
B) NaCl supplementation did not adversely affect the gastric mucosa or significantly alter hematologic and serum biochemical variables.
C) NaCl supplementation increased urinary creatinine concentrations significantly.
D) The placebo treatment caused more severe gastric lesions than the NaCl supplementation.
B) NaCl supplementation did not adversely affect the gastric mucosa or significantly alter hematologic and serum biochemical variables.
Explanation:
The study concluded that NaCl supplementation did not cause damage to the gastric mucosa and did not significantly alter hematologic and serum biochemical variables. The urine creatinine concentration decreased, and urinary sodium concentrations increased after supplementation, but there were no adverse effects on the gastric mucosa.
Daily NaCl pellet supplementation is a palatable and safe way to replace electrolyte losses from sweating in exercising horses and has no negative effects on the gastric mucosa.
The effects of feeding sodium chloride pellets on the gastric mucosa, acid-base, and mineral status in exercising horses
jvim 23
What is the main energy source in long-lasting endurance ride between lipid and carbohydrate metabolism ?
Long-lasting physical exertion may trigger the metabolism to switch the main energy source from carbohydrates to lipids due to higher caloric content.
Molecular insights into the lipid-carbohydrates metabolism switch under the endurance effort in Arabian horses
evj 24
Which of the following risk factors was NOT associated with an increased risk of exertional heat illness (EHI) in racehorses according to the study?
A) High wet-bulb globe temperature (WBGT) index
B) Older horses (≥5 years old)
C) Horses with high body weight
D) Longer race distances (>1600 m)
Answer:
C) Horses with high body weight
Explanation:
The study identified that low bodyweight (not high bodyweight) was associated with an increased risk of exertional heat illness (EHI) in racehorses. Other risk factors for EHI included high WBGT index (>28°C), sex (gelding and female horses), older horses (≥4 years old), and longer race distances (>1600 m).
The highest incidence risk was in July.
Risk factors for exertional heat illness in Thoroughbred racehorses in flat races in Japan (2005–2016)
evj 20
