Published on October 28, 2018
1. Muscle disorders Dr Anu Priya J
2. Muscle disorders Diseases affecting neuromuscular junction • Myasthenia gravis • Lambert-Eaton syndrome Effects of denervation of muscle • Fibrillation • Fasciculation • Muscle atrophy • Denervation hypersensitivity Muscle dystrophies Muscle hypertrophy Metabolic myopathies Muscle paralysis
3. Myasthenia gravis • Myo=muscle; asthenia=weakness; gravis= serious Pathogenesis • Autoimmune disease • Formation of circulating antibodies which destroy the nicotinic Ach(acetylcholine) receptors on the postsynaptic membrane of neuromuscular junction Clinical features • Skeletal muscles are weak & fatigued • Rare, serious & sometimes fatal
4. Myasthenia gravis Investigations • Radioimmunoassay – Ach receptor antibodies detected in 90% of patients • Histology – decreased number of subneural clefts, widening of the synaptic cleft, hyperplasia of thymus gland.
5. Myasthenia gravis Treatment • Neostigmine – drug of choice – reversible AchE inhibitor • Immunosuppression – suppress antibody production – steroid - high dose of cortisol • Thymectomy – as excessive synthesis of thymic hormone is one of the contributing factors • Plasmapheresis
6. Lambert-Eaton syndrome • Autoimmune disease • Autoantibodies against one of the voltage gated calcium channels in the nerve ending at neuromuscular junction • Decreased calcium influx at the synaptic knob that causes Ach release, leading to decreased acetylcholine release • Muscle weakness
7. Fibrillation • In the intact body, skeletal muscle contracts only if its motor nerve supply is stimulated • Destruction of this nerve supply leads to abnormal excitability of the muscle & fine, irregular contractions of the individual fibres called fibrillation
8. Fibrillation • Fibrillation is seen for several weeks after injury, and then ceases as the muscle cells atrophy. • Fibrillation also ceases if the motor nerve regenerates.
9. Fibrillation • Due to denervation hypersensitivity • Classical picture of LMN lesion • Such contractions are not visible grossly, but fibrillation potentials can be recorded by EMG using needle electrodes.
10. Fasciculations • Jerky, visible contractions (twitching) of groups of muscle fibres • As a result of pathological, spontaneous discharge of spinal motor neurons • Seen in diseases affecting the anterior horn cells • Example : Poliomyelitis
11. Muscle atrophy • Atrophy/ Muscle wasting • When there is permanent loss of nerve supply to a muscle, the muscle shows flaccid paralysis & atrophy.
12. Muscular dystrophy • Term used to denote a group of degenerative diseases that cause progressive weakness of skeletal muscle. • Mild or severe or fatal depending on the type of muscular dystrophy • Causes – depends on the type of muscular dystrophy; mostly genetic - mostly mutations in the genes coding for the various components of the dystrophin- glycoprotein complex. • Dystrophin gene is one of the largest in the body, & mutations can occur at many different sites in it.
13. Muscular dystrophy Duchenne muscular dystrophy • X linked recessive disease; males affected • Mutation in the gene coding for dystrophin- glycoprotein complex • Serious form of muscular dystrophy; usually fatal by the age of 30 • Dystrophin protein is absent from the muscle
14. Muscular dystrophy Duchenne muscular dystrophy • Typical feature – the child uses his hands to climb up, while getting up from the floor. • Wheelchair by age 12 • Fatal by age 30
15. Muscular dystrophy Duchenne muscular dystrophy • Progressive muscle weakness, that becomes apparent by age 4 • Muscle hypertrophy especially calf & pelvifemoral muscles • Cardiomegaly
16. Muscular dystrophy Duchenne muscular dystrophy • Enlargement occurs due to gradual degeneration & necrosis of muscle fibers that are replaced by more fibrous & fatty tissue.
17. Muscular dystrophy Becker muscular dystrophy • X linked genetic disease • Mutation in the gene coding for dystrophin- glycoprotein complex • Milder form of muscular dystrophy; not very fatal • Dystrophin protein is present in the muscle but altered or reduced in amount
18. Muscular dystrophy Other muscular dystrophies • Mutations in the gene coding for titin, desmin, sarcoglycans & other components of the dystrophin-glycoprotein complex, etc.,
19. Normal protein
21. Breakage in cell membrane following muscle contractions
22. Entry/leakage of calcium from ECF to ICF
23. Calcium activates proteases that breakdown proteins in the muscle
24. Action of proteases in normal levels
25. When protease conc inc
26. Leakage of CK – inc CK
27. Males affected
28. Metabolic myopathies • Mutations in genes that code for enzymes involved in the metabolism of carbohydrates, fats, and proteins to CO2 and H2O in the muscle and production of ATP • Exercise intolerance and possibility of muscle breakdown due to accumulation of toxic metabolites • Ex: McArdle’s disease
29. Muscle channelopathies • Calcium release channels – RYR – malignant hyperthermia
30. Muscle sprain • Due to overstretching or forced extension of an active muscle. • Often during sports activity or physical labor • Injury at the myotendinous junction or separation of the fibers • Pain, soreness, weakness & swelling • Treat – ice packs, rest, immobility • Drugs for pain relief • Surgery – if required, to correct the damage
31. Muscle cramp • Generation of nerve action potential at a very high rate • Painful condition • Involuntary tetanic contraction of the skeletal muscle • Mechanism: Electrolyte imbalances in the ECF surrounding both the muscle and nerve fibers • Excessive exercise or persistent dehydration • Other causes of electrolyte disturbances
32. EMG • The process of recording the electrical activity of muscle • Electromyography • Surface or needle electrodes • Study the activation of motor units Uses: • Diagnosis of certain muscle disorders. Example: Fibrillation potentials – can be recorded using EMG; not visible grossly over the muscle. • Research
33. Thank you
34. Denervation hypersensitivity • Seen following nerve injury • Increased number and sensitivity of receptors in the postsynaptic membrane following denervation • The muscle becomes hypersensitive to the neurotransmitter substance that is released by its nerve terminals
35. • Muscle rigor gan ebk pg 122 • Myotonia