General Approach to Muscle Disease PDF

G E N E R A L A P P R OA C H TO M U S C L E D I S EA S E Dr Charlotte Maile BVetMed BSc PhD FHEA MRCVS Lecturer in Veterinary Clinical Sciences (Equine) LEARNING OBJECTIVES Relate the anatomy and physiology of muscle activity to common presentations and investigations of muscle disea...

G E N E R A L A P P R OA C H TO M U S C L E D I S EA S E Dr Charlotte Maile BVetMed BSc PhD FHEA MRCVS Lecturer in Veterinary Clinical Sciences (Equine) LEARNING OBJECTIVES Relate the anatomy and physiology of muscle activity to common presentations and investigations of muscle disease Understand the common clinical presentations in animals presenting with muscle disease. Outline the diagnostic approach to disorders of skeletal muscle, using a problem based clinical methodology. Describe the potential long term implications of myopathies and outline the factors that influence the prognosis of muscle disease #universityofsurrey 2 R O L E O F S K E L E TA L M U S C L E 1. Maintains posture 2. Movement: generates power; strength and speed 3. Precise co-ordination 4. Active metabolic organ Rivero, J.L. and Piercy, R.J., 2008. Muscle physiology: responses to exercise and training. Equine exercise physiology: the science of exercise in the athletic horse M U S C L E A N ATO M Y #universityofsurrey  Paula_Radciffe_NYC_Marathon_2008.jpg: fergie lancealotderivative work: Hydrox, CC BY 2.0 , via Wikimedia Commons Paula Radcliffe VO2 max 70ml/kg/min Matthew Pinsent #universityofsurrey VO2 max 75ml/kg/min P H Y S I O LO GY: AT H L E T I C C A PA C I T Y https://caferoubaix.com/2014/03/18/oskar-svendsen-i-can-become-a-gc-rider/ Oskar Svendson VO2 max 97.5ml/kg/min 5 W H AT A B O U T H O R S E S ? VO2 max 140-180ml/kg/min 55% of a Thoroughbred is muscle #universityofsurrey W H AT C A N G O W R O N G W I T H M U S C L E S ? Diseases of skeletal muscle can develop due to disorders of the: I.Neuromuscular input II.Muscle cell membrane III.Proteins of myofibre IV.Metabolic function Acquired vs hereditary #universityofsurrey 7  A P P R O A C H TO I N V E S T I G AT I N G M U S C L E D I S E A S E Clinical History Signalment List of common myopathies is quite different across species Equine: Exertional rhabdomyolysis, metabolic disorders, atypical myopathy Dog: Autoimmune disorders, inherited disorders Livestock: Infectious myositis, white muscle disease Porcine malignant hyperthermia Breed Inherited disorders often associated with particular breeds Diet Nutritional myopathies – most common = selenium/Vit E deficiency (white muscle disease) Access to pasture – Atypical myopathy in horses Exercise and husbandry Other recent disease #universityofsurrey 8 A P P R O A C H TO I N V E S T I G AT I N G M U S C L E D I S E A S E Establishing the problem Onset of clinical signs Acute vs chronic Activities being undertaken prior to/at onset of signs Nature of clinical signs Weakness? Exercise intolerance? Gait abnormalities? Loss of muscle mass – atrophy or wasting? Progression Other signs of illness/comorbidities #universityofsurrey 9 A P P R O A C H TO I N V E S T I G AT I N G M U S C L E D I S E A S E Clinical signs associated with muscle disease: Pain, heat, and/or swelling on palpation of muscle Muscular cramping Abnormal limb position e.g. muscle tears Gait abnormalities Weakness Fatigue/poor performance Muscle fasciculation Muscle atrophy Sweating Myoglobinuria #universityofsurrey 10 A PROBLEM-BASED APPROACH 1. Muscular cramping in association with exercise Firm, swollen or painful muscles during or after exercise Overexertion Electrolyte depletion/abnormalities Energy depletion Exertional rhabdomyolysis ‘Tying up’, Common syndrome in horses Racing greyhounds Myotonia congenita Hereditary chloride channel defect Delayed relaxation of contracted muscles Fainting goats. #universityofsurrey 11 A PROBLEM BASED APPROACH 2. Persistent or permanent gait abnormalities Muscular injury Muscle tear Muscle strain Fibrotic myopathy Can occur in any species Fibrotic change in muscle after severe injury 12 #universityofsurrey A PROBLEM BASED APPROACH 3. Episodic or progressive weakness More likely to be neurological or neuromuscular Upper motor neuron lesions Spinal trauma Lower motor neuron lesions Equine motor neuron disease Diseases of the neuromuscular junction Myasthenia gravis Disorders of cell membrane function Selenium/Vitamin E deficiency Hypokalaemia (cats with CKD) Hypothyroidism #universityofsurrey 13  A PROBLEM-BASED APPROACH 4. Muscle wasting or atrophy Neurogenic atrophy Disuse atrophy Examples: Equine motor neuron disease (EMND) Immune mediated polymyositis Infectious myositis (e.g. Lyme disease) Usually a sign of a chronic disorder rather than acute #universityofsurrey 14  A PROBLEM-BASED APPROACH 5. Acute rhabdomyolysis Acute, often severe muscle degeneration/destruction releasing myoglobin into circulation → Myoglobinuria Examples: Exertional rhabdomyolysis Infectious myonecrosis (Clostridial myositis) Can be very rapidly fatal Toxicities Eg, Atypical Myopathy (hypoglycin A) Ionophore poisoning (Monensin) Circulatory disturbances post-anaesthetic myopathy #universityofsurrey 15 DIAGNOSIS OF MUSCLE DISEASE Serum muscle enzyme activity Increased because of defect in integrity of myofibre membrane and sarcolemma Creatine kinase (CK) Found in muscle (skeletal and cardiac) and brain Serum levels are muscle specific Aspartate transferase (AST) Amino acid metabolism enzyme Not muscle specific Also found in hepatocytes #universityofsurrey 16 SERUM MUSCLE ENZYME ACTIVITY CK Peaks rapidly (4-6 post injury) Half life 2-4 hours AST Peaks around 24 hrs Half life 7-10 days Normal levels (100,000 seen in acute myopathies Magnitude of increase does not directly correlate with the degree of muscle damage #universityofsurrey 17  POST-EXERCISE MUSCLE ENZYME ACTIVITY “Exercise-test” to detect exercise-associated muscle disease Most often used in equine cases Some physiological increase in CK & AST will occur after exercise, especially strenuous exercise. Test looks to detect exaggerated responses to non-strenuous exercise Measure CK before and 4 hours after 15-20 minutes of sub-optimal exercise Most healthy horses show no change in CK levels Significant increase in CK indicative of underlying pathology Even modest rises could be relevant #universityofsurrey 18  DIAGNOSIS OF MUSCLE DISEASE Urinalysis Myoglobinuria Myoglobin released into serum from damaged muscle cells Filtered by kidney → Presence of myoglobin pigment in urine Pigment is nephrotoxic Gross examination or dipstick analysis Haematuria or pigmenturia? Haematuria will sediment, pigmenturia will not Erythrocytes will settle out pH. Need laboratory analysis to differentiate between haemoglobinuria and myoglobinuria Collect blood simultaneously for fractional excretion of electrolytes #universityofsurrey 19 DIAGNOSIS OF MUSCLE DISEASE Specific blood tests Vitamin E/ Selenium assays Vitamin E/Selenium deficiency leads to white muscle disease Common in farm animals grazing on selenium deficient pasture Occurs in foals born to dams that consumed selenium-deficient diets during gestation. Plasma sample to measure selenium levels GSH-Px correlates with selenium levels (selenium incorporated into GSH-Px) GSH-Px measured in whole blood (heparinised sample) Vitamin E (-tocopherol) requires plasma sample to be stored on ice and in the dark Electrolytes Serum electrolytes and fractional excretion of urinary electrolytes #universityofsurrey 20 DIAGNOSIS OF MUSCLE DISEASE Immunology testing Myasthenia Gravis – anti-AChR antibody titre Genetic tests: require DNA Usually extracted from EDTA blood or hair roots Polysaccharide Storage Myopathy type 1 (PSSM1) Hyperkalaemic periodic paralysis (HYPP) Myosin heavy chain myopathy (MYHM) Glycogen Branching Enzyme Deficiency (GBED) Malignant hypothermia (MH) #universityofsurrey 21  DIAGNOSIS OF MUSCLE DISEASE Diagnostic imaging Ultrasonography: Evaluate muscle structure Best for assessing injuries/foci of infection (abscesses) MRI: More commonly for small animals Visualise muscles in finer detail Visualise muscles that cannot be palpated or scanned externally #universityofsurrey 22  DIAGNOSIS OF MUSCLE DISEASE Muscle biopsy Most often used in horses Histopathological analysis Biochemical analysis Surgical incisional biopsy Percutaneous ‘Bergstrom’ Needle Muscle selection will depend on: Focal or generalised myopathy? Fibre composition of muscle Differential diagnoses https://www.rvc.ac.uk/Media/Default/Comparative%20Neuromuscular%20Diseases%20Laboratory/Muscle-biopsy- procedure-1.pdf #universityofsurrey 23  MUSCLE BIOPSIES Postural muscles Locomotor muscles Fibre type Mainly type I Mainly type 2a/2x DDx EMND, nutritional myodegeneration RER, PSSM Location Sacrocaudalis dorsalis medialis Semimembranosus #universityofsurrey 24 M U S C L E H I S TO PAT H O LO GY Vacuolar myopathy-Equine Centronuclear myopathy-Canine Taken from Massey et al, 2013 Taken from Walmsley et al, 2017) Normal healthy muscle Polysaccharide storage myopathy type 1 #universityofsurrey Taken from McCue et al, 2008 25 LONG TERM SEQUELAE OF MUSCLE DISEASE Fibre necrosis Loss of fibre number Fibrosis of muscle tissue Reduced contractile and expansile function #universityofsurrey 26 P R O G N O S I S F O R PAT I E N T S W I T H M U S C L E DISEASE Generally favorable with appropriate management Depends on: Underlying condition Severity of muscle pathology and clinical signs Use of animal e.g. athlete vs. companion Implication of breeding hereditary conditions? See next lecture… #universityofsurrey 27 SUMMARY Understanding the anatomy and physiology of muscle can help us to investigate, diagnose, manage and comment on the prognosis of myopathies in domestic animals Species, signalment and breed, along with thorough clinical history and examination are important factors in establishing the cause of a myopathy. Myopathies can cause a wide range of clinical signs, from poor performance through to severe, debilitating cramp and pain. Diagnostics including serum muscle enzymes, muscle biopsy, urinalysis, genetic testing and imaging amongst others may be required to reach a diagnosis. #universityofsurrey 28 REFERENCES & ACKNOWLEDGEMENT Acknowledgements: Dr R Naylor, Dr M Cathcart, Dr R Lewis References: Aleman, M., 2008. A review of equine muscle disorders. Neuromuscular disorders, 18(4), pp.277-287. Naylor, R., 2014. Managing muscle disease in horses. In Practice, 36(8), p.418. Rivero, J.L. and Piercy, R.J., 2008. Muscle physiology: responses to exercise and training. Equine exercise physiology: the science of exercise in the athletic horse, p.463. Royal Veterinary College Comparative Neuromuscular Disease Laboratory; https://www.rvc.ac.uk/research/laboratories/comparative-neuromuscular-diseases-laboratory Accessed 6/11/2018. Sjaastad, O.V., Hove, K. and Sand, O., 2010. Physiology of domestic animals. Scan. Vet. Press. #universityofsurrey 29