Myopathies Flashcards

Question

Recurrent exertional rhabdomyolysis (RER) -diagnosis

Answer 1

History and signalment ○ Soon after onset of exercise, or shortly after cessation of exercise Marked CK and AST elevation Muscle biopsy ○ Often performed to rule out other myopathies ○ Chronic, non-specific changes In vitro contracture studies ○ Gold standard, use intercostal muscle ○ Not performed in clinical practice really

Answer 2

Low starch Use fat for extra calories diet ○ E.g. RE-LEVE by Saracen ○ Competition animals: meet high calorie requirement Access to a salt block Vitamin E +/- selenium

Answer 3

Don’t exercise beyond scope of training Avoid rest days Minimise stress Appropriate training When in recovery period from myopathy, put in small pen so can walk around more than in a stable - loosening of stiffness and improvements to circulation. Rather than box rest.

Answer 4

Diet and exercise important Dantrolene * RYR1 antagonist -> inhibits calcium release from sarcoplasmic reticulum * Detection time 48hrs (BHA) - not helpful from a competing point of view

Answer 5

Heritable: Quarter horses, Connemara, Warmbloods…

Answer 6

Commonly triggered by exercise (can be less than 20min)

Answer 7

Accumulate polysaccharide (abnormal glycogen) in the myofibre Energy source is locked away in muscle cells

Answer 8

Recurrent episodes may be mild (stretching out, ‘lazy’, may look like shifting lameness) to severe (sweating, reluctance to move, recumbency)

Answer 9

GYS1 gene mutation (autosomal dominant) Increases glycogen synthase activity Glycogenolysis doesn’t work as well -> less glucose -> less energy Can see abnormal granules sitting in the cell Myokinase reaction used for energy - inefficient

Answer 10

a disease of abnormal polysaccharide storage -But we don’t know why/mechanism… Likely to be a group of conditions Altered staining on a biopsy for glycogen, but absence of GYS1 mutation

Answer 11

May have persistently elevated muscle enzymes ○ Exercise test to challenge if muscle enzymes not elevated ○ Threefold increase in CK 4hrs after exercise Biopsy semimembranosus muscle ○ Increased skeletal muscle glycogen Gold standard – test for GYS1 mutation on hair roots/blood

Answer 12

Limit glycogen synthesis (reduce insulin activity) Promote breakdown of glycogen Low starch, high fat Provide 1.5-2% BWT as roughage < 10% Digestible energy as non structural carbohydrates >13 % fat Vegetable oil up to 1ml/kg/day Supplemental Vitamin E +/- selenium Commercial diets Lose weight if overweight

Answer 13

Maintain regular work/turn out routine Avoid days off Minimise stress Minimise changes in management Don’t exercise beyond scope of training Prognosis fair if managed correctly

Answer 14

disease in Arabians and warmblood horses

Answer 15

there is a disruption of the orderly alignment of myofibrils and aggregates of desmin (cytoskeletal protein) are identified using special stains

Answer 16

Clinical signs are predominantly those consistent with an exertional rhabdomyolysis in Arabians and non-specific poor performance in warmblood horses May not have increased CK/AST

Answer 17

Recent advice is that horses seem to do best if ridden work is kept to 30-45min, and a long/low lunging warm up for 10-15min is incorporated prior to ridden exercise

Answer 18

Acute, severe rhabdomyolysis, affects horses at pasture caused by hypoglycin A toxicity Seeds and seedlings of some Acer trees UK: Sycamore (Acer pseudoplatanas)

Answer 19

Hypoglycin A forms toxic metabolite (MCPA), which binds to FAD. MCPA deficiency, because they can’t use FAD as a cofactor. This means that mitochondrial aerobic metabolism is impaired. This deprives muscle of an energy source. Type 1 muscle fibres are worst affected, so clinical signs are consistent with postural muscle disease.

Answer 20

Autumn and spring Wet and windy weather Presence of Sycamore trees (UK) Access to pasture Often poor body condition, young, or not being fed supplementary feed when on pasture May be mistaken for cases of colic, severe laminitis, botulism (neurological exam normal in AM) Intrinsic horse factors? Variable concentrations in different parts of the plant (even if from the same tree)? Likely multiple factors

Answer 21

Weakness, reluctance to move, may be found recumbent Painful, firm muscles may be appreciated on palpation Myoglobinuria Tachycardia, tachypnoea, congested mucous membranes Distended bladder on rectal palpation

Answer 22

High muscle enzymes on serology Myoglobinuria Submit plasma for acylcarnitine/serum for hypoglycin A and conjugated MCPA Confirmation takes 48-72h via RVC Neuromuscular Lab You cannot wait this long before implementing treatment Postmortem: samples of masseter/intercostal muscle

Answer 23

Start treatment before definitive diagnosis if suspected Require intensive supportive care and nursing Fluid therapy (monitor renal function) Add glucose (5% glucose to provide alternative energy source) Analgesia Vitamin E and selenium, riboflavin, oral carnitine

Answer 24

Very hard to predict – survival rates are improving ↓ prognosis: hypoxia, dyspnoea, tachypnoea, hypothermia, bladder distension, absence of intestinal sounds, remaining recumbent ↑ vitamin and anti-oxidant administration (advised for all cases, including subclinical ones that are diagnosed alongside index clinical case)

Answer 25

QH, Paint, Appaloosa

Answer 26

Gene mutation alters voltage-dependent skeletal muscle sodium channel = persistent depolarisation of muscle cells

Answer 27

variable (muscle spasms and trembling)

Answer 28

Genetic testing (commercially available) Hyperkalaemia and suggestive clinical signs, no/little change in CK

Answer 29

Localised rather than generalised myopathy Hard, hot, swollen muscles ○ Gluteals, epaxial muscles, triceps Onset may be delayed Compartment syndrome ○ ↑ pressure within muscle -> ischaemia -> muscle swelling ->↑ pressure Careful consideration RE positioning on table ○ Dorsal recumbency: symmetrical ○ Lateral recumbency: extend lower forelimb forwards/hindlimb back Monitor and maintain blood pressure under anaesthesia Symptomatic and supportive treatment

Answer 30

QH/paints (and pigs!) RYR1 (ryanodine receptor) gene mutation ○ Dramatic increase in intracellular calcium -> contraction -> muscle heat and necrosis Exercise or anaesthesia induced ○ Worth screening before anaesthetising these breeds? ○ Pre-treat with dantrolene ○ Marked hyperthermia and acidosis

Answer 31

Effects of a deficiency in Vitamin E and Selenium result in the destruction of cell membranes and proteins leading to a loss of cellular integrity. The precise interrelationships among selenium/Vit E, other metabolic factors and triggering mechanisms in NMD are not fully understood because some deficient animals do NOT have disease. Selenium appears to be the most important in foals however, and deficiencies in this nutrient are more likely to lead to NMD than vitamin E.

Answer 32

Cardiac form and skeletal form Dyspnoea, weakness, stiffness, trembling, recumbency, sudden death, irregular tachydysrhythmia Aspiration pneumonia common secondary to tongue necrosis Tongue, gastrocnemius, semimembranosus/tendinosus, biceps femoris, lumbar, gluteals, neck affected

Answer 33

Clinicopathologic abnormalities ○ CK/AST elevation ○ Myoglobinuria ○ Electrolyte derangements Low selenium (whole blood), GSH-Px, α-tocopherol (vit E) (plasma) Gross pathology ○ Pale, oedematous muscle, calcification ○ Hypercontracted muscle fibres

Answer 34

Cardiorespiratory disease -> poor prognosis Skeletal muscle disease -> better prognosis ○ usually see improvement quickly Selenium injections IM ○ irritant, can dilute before injection Oral α-tocopherol supplementation Supportive nursing

Answer 35

Disease in its own right? Precursor to EMND? Presence of myopathic not neuropathic change in SCDM biopsy

Answer 36

Weakness, narrow-base stance Animals with disease of postural muscles often look better when you get them walking. May look worse when asked to stand still, weight shift and look uncomfortable. Muscle atrophy Trembling and muscle fasciculations Weight shifting

Answer 37

SCDM biopsy May have normal serum α-tocopherol

Answer 38

Oral α-tocopherol supplementation Not powders, needs to be v bioavailable Is diet deficient, or can horse not absorb it? Re-test. As with EMND could be because diet is deficient, often stabled animals. Might consider glucose absorption test if suspect primary absorption issue.

Answer 39

Minimise continued muscle damage - rest - NSAIDs - ACP - Antioxidants Analgesia Correct fluid deficit/diurese

Answer 40

NSAIDs Opioids ○ Buprenorphine/butorphanol licensed for horses ○ Methadone more potent but use on cascade ○ Morphine commonly used, not licensed in any veterinary spp. Paracetamol ○ Use as an adjunct, not sole analgesic Lidocaine infusion ○ Logistics require hospitalisation Ketamine infusion ○ Requires hospitalisation (scheduled drug and logistics require hospitalisation)