Myopathy

This topic is an important subject with the fact that it is usually misdiagnosed. It is very important to clear our basics on this topic.

1. MYOPATHY Dr Bipul borthakur Prof & head Dept. of orthopaedics Silchar medical college

2. LEARNING OBJECTIVES INTRODUCTION SYMPTOMS CLASSIFICATION LABORATORY INVESTIGATIONS. INDIVIDUAL MYOPATHY. TREATMENT

3. MYOPATHY These are disorders with structural changes or functional impairment of muscle.

4. I NTRODUCTION Skeletal muscle is made up of large number of multinucleated muscle fibres with outer membrane and cytoplasm (sarcoplasm). The fibres are separated by connective tissue( endomysium ) and arranged in bundles(fasciculi). Each fasciculus has a connective tissue sheath(perimysium).

5. STRUCTURE OF SKELETAL MUSCLE

6. HISTOLOGY

7. GROUP OF SYMPTOMS Motor manifestations- 1)weakness- bilateral ,symmetrical affecting certain group of muscles (proximal). 2) Hypotonia . 3) Change in muscle bulk( pseudohypertrophy ).

8. Pain- It is rare complaint in primary muscle disease. No sensory manifestations. No sphincter dysfunction.

9. CLASSIFICATION Primary - Progressive muscle dystrophy. Secondary – 1)Inflammatory. 2)Metabolic, periodic familial paralysis. 3)Endocrinal, thyrotoxic, cushing . 4)Drug induced- corticosteroid, statin. 5) Miscellaneous, carcinomatous.

10. CLASSIFICATION OF PROGRESSIVE MUSCLE DYSTROPHY X-LINKED DISORDERS A) Duchenne’s muscular dystrophy. B) Becker’s muscular dystrophy. 2) AUTOSOMAL RECESSIVE DISORDERS A) Limb- Girdle muscular dystrophy.

11. AUTOSOMAL DOMINANT DISORDERS Fascio-scapulo - humeral muscular dystrophy. Distal myopathy. Ocular myopathy. Oculo -pharyngeal myopathy.

12. MYOPATHY BASED ON WEAKNESS/MUSCLE INVOLVEMENT PROXIMAL WEAKNESS(LIMB GIRDLE) Limb girdle , myotonic dystrophy type 2,rare FSHD. Congenital myopathies. Metabolic myopathies(glycogen and lipid storage) Mitochondrial myopathies. Inflammatory myopathies. Toxic myopathy. Neuromuscular junction disorders(myasthenia gravis, LEMS etc).

13. BASED ON DISTAL WEAKNESS Distal muscular dystrophies/ Myofibrillar dystrophy. Late onset centronuclear and nemaline rod myopathy. Metabolic like Glycogen storage ( McArdle disease) Lipid storage disease(neutral lipid storage myopathy) NMJ disorders (myasthenia gravis etc ).

14. SCAPULOPERONEAL/HUMEROPERONEAL WEAKNESS Facioscapulohumeral muscular dystrophy(FSHD). Emery- Dreifuss muscular dystrophy(EMMD). Bethlem myopathy.

15. DISTAL ARM/PROXIMAL LEG WEAKNESS Inclusion body myositis. Myotonic dystrophy.

16. AXIAL MUSCLE WEAKNESS Inflammatory( cervico -brachial). Isolated neck extensor myopathy/Bent spine syndrome. FSHD Late onset central core(RYR 1 MUTATION). Late onset pompe disease.

17. EYE MUSCLE WEAKNESS PTOSIS WITHOUT OPHTHALMOPARESIS A) Myotonic dystrophy. b) Congenital myopathies. PTOSIS WITH OPTHALMOPARESIS A) Oculopharyngeal dystrophy. b) Mitochondrial myopathy.

18. MUSCLE STIFFNESS Myotonia congenital. Paramyotonia congenital. Hyperkalemic periodic paralysis with myotonia . Schwartz – jampel syndrome. Brody disease.

19. SYMPTOMS Muscle weakness – A) Intermittent weakness. B)Persistent weakness Myalgia ,cramps and stiffness.

20. LABORATORY EVALUATION Serum enzymes 1)CREATINE KINASE- most sensitive. 2) CK-MB 3)AST,ALT and LDH 4)ALDOLASE 5)GAMMA GLUTAMYL TRANSFERASE

21. ELECTRODIAGNOSTIC STUDIES EMG(ELECTROMYOGRAPHY) NCS(NERVE CONDUCTION STUDIES) REPETITIVE NERVE STIMULATION .

22. EMG AND NCS

23. GENETIC TESTING IS THE GOLD STANDARD. FOREARM EXERCISE TEST. MUSCLE BIOPSY- mainly from most affected muscle is taken.

24. DUCHENNE MUSCULAR DYSTROPHY It is the most common muscular dystrophy affecting 1 in 3500 males born worldwide. Females are carriers. Son of carrier mother has 50% chance of inheriting mutated gene.

25. PATHOGENESIS Disorder is caused by mutation in DYSTROPHIN gene,the largest gene on human x chromosome. Muscles undergo repeated cycles of necrosis and regeneration. Mitochondrial dysfunction occurs due to excess calcium penetration in sarcolemma.

26. PATHOGENESIS

27. CLINICAL FEATURES Age of onset – 2 to 6 yrs. Difficulty in climbing upstairs . Difficulties in running. Hypertrrophy of muscles particularly in calves. Mental Retardation and cardiomyopathy occurs. Cardiomyopathy usually occurs by 2 nd or 3 rd decade.

28. GOWERS SIGN S

29. LABORATORY EVALUATION Serum ck levels are elevated(50 to 100 times). Western blot analysis of muscle biopsy samples . demonstrate absent dystrophin . Deletions within or duplications of the dystrophin .

30. HISTOLOGY

31. TREATMENT Glucocorticoids slows progression in DMD. There is NO CURE yet for DMD. Positional Aids. Nutritional counselling . Psychological counselling.

32. BECKER MUSCULAR DYSTROPHY X LINKED recessive muscular dystrophy. Muscle weakness due to DYSTROPHIN. Age of onset(10 to 13) yrs. Subtle form of DMD. Cardiopathy starts around 4 th or 5 th decade. Physical and occupational therapy are helpful.

33. LIMB GIRDLE MUSCULAR DYSTROPHY Males =Females Pelvic and Shoulder girdle musculature are affected. Immunohistochemistry differentes diff. types( sarcoglycans,dysferlin,alpha dystroglycans ). LGMD2L,the most common cause of LGMD is associated with marked scapular winging,lack of calf muscle hypertrophy.

34. EMERY-DREIFUSS MUSCULAR DYSTROPHY EMERIN and FHL1 mutations are due to X LINKED inheritance. AUTOSOMAL dominant type associated with LAMIN A/C gene. Muscle weakness affects humeral and peroneal muscles>limb girdle . Atrial fibrillation and atrioventricular heart block can occur.

35. Serum ck increased. Muscle biopsy- Myofibrillar myopathy. Supportive care and stretching of contractures. Use of defibrillators or cardiac pacemakers for cardiomyopathy and arrhythmias .

36. MYOTONIC DYSTROPHY Two types myotonic dystrophy type 1 and 2 (known as proximal myotonic myopathy). Type 1 have hatched faced appearance. Complete heart block and sudden cardiac death can occur. DM2 affects proximal muscle. CK inc,muscle biopsy shows internalised nuclei combined with many atrophic fibres with pyknotic nuclear clamps.

37. Cardiac pacemaker or implantable cardioverter defibrillator should be considered. Molded ankle foot orthoses used in foot drop. BiPAP and modafinil may be beneficial.

38. FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY Type 1 and type 2(95 and 5%) respectively. Presents in childhood,facial weakness is initial manifestation. Loss of scapular stabilizers . COATS disease with telangiectasia,exudation and retinal detachment occurs. NO specific treatment ,ankle foot orthosis are helpful.

39. OCULOPHARYNGEAL DYSTROPHY Includes progressive external ophthalmoplegia . Pupil is spared,has late onset. Presents with ptosis or dysphagia. On electron microscope,feature of OPMD is presence of 8.5nm tubular filament in muscle cell nuclei. Autosomal dominant,affects (French-Canadian and Ashkenazi jews ) Cricopharyngeal myotomy improves swallowing.

40. DISTAL MYOPATHIES Welander,Udd and Merkesbery -Griggs type distal myopathies are late onset usually begins after 40 yrs. Laig distal myopathy and myofibrillar myopathies presents with diatal weakness. In Miyoshi myopathy Gastrocnemius Muscles are affected.

41. Laing and Miyoshi myopathy,rimmed vacuoles can be seen . Occupational therapy for loss of hand function,ankle foot orthoses for lower limb support.

42. DISORDERS OF MUSCLE ENERGY METABOLISM GLYCOGEN STORAGE AND GLYCOLYTIC DEFECTS 1) Pompe disease-alpha glucosidase or acid maltase deficiency(type 2 glycogenosis ) - usually infants are affected,childhood form resembles DMD. -DEATH by 1.5 yrs. 2) Debranching enzyme deficiency(type 3 glycogenesis)

43. Branching Enzyme deficiency(type 4 glycogenosis ).

44. DISORDERS OF GLYCOLYSIS CAUSING EXERCISE INTOLERANCE McArdle disease caused by myophosphorylase deficiency. Carnitine Palmitoyltransferase 2 deficiency is the most common cause of recurrent myoglobinuria .

45. MITOCHONDRIAL MYOPATHY Kearn -Sayre syndrome. Progressive external ophthalmoplegia . Myoclonic Epilepsy with Ragged Red fibres(MERRF). Mitochondrial Myopathy,Encephalopathy,Lactic acidosis and stroke like episodes.(MELAS) Mitochondrial DNA depletion Syndromes.

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