Diseases of the muscles

1. MUSCLE DISEASES

2. 1- Disorders in which there is a structural or functional abnormality
of skeletal muscle
2- About 50000 people / 60 million in the UK have a primary muscle
disease ( hereditary or acquired )( ~ 1/1000 )
3- Many more have muscle symptoms related to drugs or systemic
diseases
4- Some of these conditions are treatable
Introduction
Rosette Jabbour, MD 2

3. DIAGNOSIS
1st STEP: confirm the MYOGENIC SYNDROME
differentiate from ▪ a neurogenic syndrome:
- peripheral nerve disease
- motor neuron disease (neuronopathy, anterior horn)
▪ myasthenic syndrome (neuromuscular junction)
based on clinical findings, labs, neurophysiology
2nd STEP: look for the ETIOLOGY
clinical findings ( personal and family history, physical findings )
complete laboratory work-up
tests for metabolic diseases
neurophysiology testing
MRI of the muscles
muscle biopsy
genetic testing Rosette Jabbour, MD 3

4. myofibril
MUSCLE STRUCTURE
1- A muscle fiber is made of a large
number of myofibrils
2- Several muscle fibers
are arranged in fascicles
endomysium
3- several fascicles
form a muscle
epimysium
perimysium
endomysium
Rosette Jabbour, MD 4

5. nucleus
mitochondria
myofibrils
Basal lamina
Sarcoplasmic
membrane
Sarcoplasmic
reticulum
sarcoplasm
MUSCLE FIBER
Rosette Jabbour, MD 5

6. Transversal
Section
Longitudinal
section
Rosette Jabbour, MD 6

7. SECTION OF NORMAL MUSCLE
Section of normal adult muscle stained
With hematoxylin and eosin. Muscle fibers
Are uniform in size and stain pink with eosin.
Their nuclei stain blue with hematoxylin
Section of normal adult muscle stained
With Gomori trichrome stain.
Muscle fibers are stained greenish blue
And nuclei are dark red
Rosette Jabbour, MD 7

8. Type I: red fibers (myoglobin)
slow contraction
tonic activity
not easily tired
rich in mitochondria
Aerobic metabolism
(oxydation of glucose:
succinodehydrogenase,
cytochrome c oxidase)
Type II: white fibers
( A,B) rapid contraction
phasic activity
easily tired
Anaerobic metabolism
(glycolysis, ATPase,
phosphorylase)
DIFFERENT TYPES OF FIBERS
Rosette Jabbour, MD 8

9. DISTRIBUTION OF HISTOCHEMICAL FIBER TYPES IN
NORMAL MUSCLE ( TYPE I, 2A, 2B ). ATPase stain pH 4.6
( glycolytic enzyme activity )
Rosette Jabbour, MD 9

10. 2A
1
2B
1
NORMAL DISTRIBUTION OF OXIDATIVE ENZYME
ACTIVITY IN NORMAL MUSCLE FIBERS.
TYPE I FIBERS CONTAIN MORE MITOCHONDRIA
THAN TYPE 2 FIBERS, AND STAIN DARKER.
Cytochrome c oxidase stain
Rosette Jabbour, MD 10

11. TYPE 2 MUSCLE FIBER ATROPHY ( darker staining )
ATPase stain pH 9.4
Rosette Jabbour, MD 11

12. MUSCLE FIBERS IN DENERVATION ATROPHY
LARGE GROUPS OF ATROPHIC FIBERS OF ALL
HISTOCHEMICAL TYPES. ATPase stain pH 4.6
Rosette Jabbour, MD 12

13. SITE OF THE MUSCLE LESION
Muscle channel: sodium, potassium, chloride
( modification of the action potential )
Muscle structure: proteins in the membrane and sarcoplasm
( modification of the structure and trophicity of the fibers )
or the interstitial tissue
( secondary alteration of the myofibrils )
Muscle metabolism: source of energy: glycogen, lipids, mitochohondria
( modification of the function of the fibers )
Neuromuscular junction: postsynaptic acetylcholine receptors
( alteration of the neuromuscular transmission )
Rosette Jabbour, MD 13

14. DEPOLARIZATION
REPOLARIZATION
AFTER POTENTIALS
Rosette Jabbour, MD 14

15. Sarcoplasmic membrane
Extracellular Matrix
collagen
actine
dystrophin
α
β
sarcoglycans
sarcoplasm
dystroglycans
dysferlin
laminin
syntrophins
sarcospan
STRUCTURAL PROTEINS
Rosette Jabbour, MD 15

16. CLASSIFCATION OF MYOPATHIES
HEREDITARY
MUSCULAR DYSTROPHIES without myotonia
Duchenne and Becker muscular dystrophy ( DMD / BMD )
Emery - Dreifus muscular dystrophy
Limb girdle muscular dystrophy ( LGMD )
Facioscapulohumeral dystrophy ( FSMD )
Oculopharyngeal muscular dystrophy
MUSCULAR DYSTROPHIES with myotonia
Myotonic dystrophy (classic form ) DM1 ( steinert )
Proximal myotonic dystrophy ( DM2 )
CHANNELOPATHIES
Myotonia congenita
Hyperkalemic periodic paralysis
Hypokalemic periodic paralysis
METABOLIC MYOPATHIES
Glycogen storage diseases
Lipid storage diseases
Mitochondrial myopathies
CONGENITAL MYOPATHIES
Congenital muscular dystrophies
Congenital myopathies (nemaline, myotubular, central core )
Malignant hyperthermia
Rosette Jabbour, MD 16

17. CLASSIFICATION OF MYOPATHIES
ACQUIRED
Inflammatory myopathies ( PM-DM )
Inclusion body myopathies ( IBM )
Endocrine myopathies
Myopathies associated with systemic disease (critical illness, trichinosis,
amyloidosis..)
Drug induced myopathies / toxic
Rosette Jabbour, MD 17

18. CLINICAL FINDINGS IN MYOPATHY
NEGATIVE
1- weakness
2- muscle atrophy
3- exercise intolerance
and fatigue
POSITIVE
1- myalgias
2- cramps
3- myotonia
4- stiffness
5- muscle hypertrophy
6- myoglobinuria
7- contractures
8- tendon reflexes
Rosette Jabbour, MD 18

19. WEAKNESS
1- PROXIMAL MUSCLE WEAKNESS
Difficulty climbing stairs, arising from a chair, brushing hair,
lifting objects overhead
2- DISTAL MUSCLE WEAKNESS
Difficulty opening jars, turning a key, tripping
3- CRANIAL MUSCLE WEAKNESS
dysphagia, dysarthria, diplopia (rare), ptosis, difficulty whistling,
blowing up balloons, using a straw, sleeping with eyes open
Rosette Jabbour, MD 19

20. FUNCTIONNAL ASSESSMENT OF WEAKNESS
Rosette Jabbour, MD 20

21. GOWER’S SIGN
Rosette Jabbour, MD 21

22. MUSCLE ATROPHY AND HYPERTROPHY
Atrophy with time without fasciculations
Hypertrophy, true: in MYOTONIA CONGENITA due to repetitive activity
Hypertrophy, pseudo: in DMD, BMD, some LGMD, due to connective tissue
proliferation
MYALGIAS, CRAMPS AND EXERCISE INTOLERANCE
Constant in most of inflammatory myopathies (myalgias)
Frequent in drug-induced and hypothyroidism (myalgias, cramps)
in electrolytes disturbances (cramps)
Episodic, after or during exercises in metabolic and mitochondrial
myopathies (myalgias and cramps)
Rosette Jabbour, MD 22

23. PSEUDOHYPERTROPHY
TRUE HYPERTROPHY
Rosette Jabbour, MD 23

24. MYOTONIA
Muscle stiffness and difficulty in muscle relaxation due to repetitive
depolarization of the muscle membrane
Active and passive
Worsening with rest and cold, improving with exercise: myotonia congenita
Exacerbation with exercise and cold: paramyotonia congenita
Some drugs exacerbate myotonia: β-blockers
Rosette Jabbour, MD 24

25. REFLEXES AND CONTRACTURES
DTR :
- preserved in pure myopathy
- may be lost when there is advanced wasting
- lost if there is a myopathy + neuropathy
Contractures :
- early in Emery- Dreifus and some LGMD
- late in most myopathies: fixed contractures
Rosette Jabbour, MD 25

26. MYOGLOBINURIA
Discoloration of urine:
brown-black ( like cola ), due to liberation of myoglobin from the muscle
Causes :
- Excessive exercise - Inflammatory myopathies
- Viral/Bacterial infection - Metabolic myopathies:
- Drugs and toxins glycogen: Mc Ardle
- Neuroleptic malignant syndrome lipid: CPT deficiency
- Heat stroke - LGMD 2C-F
- Malignant hyperthermia
- Prolonged fever
- Prolonged immobilization
- Metabolic disturbances
Rosette Jabbour, MD 26

27. NON MYOPATHIC FEATURES
CNS, eyes ( retina ), GI, liver, endocrine, kidneys, blood, skin
Cardiac: arrhythmias, heart failure
Respiratory: due to diaphragm and respiratory muscle involvement
Rosette Jabbour, MD 27
Muscular dystrophy
Congenital
myopathies
Inflammatory
myopathies

28. CARDIAC COMPLICATIONS
Rosette Jabbour, MD 28
Arrythmia
CHF
Congestive

29. LABORATORY WORK-UP MUSCLE ENZYMES
Rosette Jabbour, MD 29
CK
LEV
ELS

30. DIFFERENTIAL DIAGNOSIS OF CK ELEVATION
HIGH CK
WITH
WEAKNESS
HIGH CK
WITHOUT
WEAKNESS
Rosette Jabbour, MD 30

31. MAGNITUDE OF
CK ELEVATION
Rosette Jabbour, MD 31

32. DRUGS-ASSOCIATED HIGH CK
Rosette Jabbour, MD 32

33. CLASSIFCATION OF MYOPATHIES
HEREDITARY
MUSCULAR DYSTROPHIES without myotonia
Duchenne and Becker muscular dystrophy
Emery - Dreifus muscular dystrophy
Limb girdle muscular dystrophy
Facioscapulohumeral dystrophy
Oculopharyngeal muscular dystrophy
Rosette Jabbour, MD 33

34. DUCHENNE MUSCULAR DYSTROPHY
■ Incidence: 1/3000-4000 male births. X – linked
.
■ Near total loss of dystrophin
 structural protein bound to the sarcolemma providing structural integrity to the muscle membrane
 Abnormal dystrophin gene located on chromosome Xp21
 female carriers or spontaneous mutations
■ Clinical features:
 new born: normal – high CK
 babies: slight delay in walking( 18 months )
 3-5 yrs: progressive weakness, proximal more than distal, pelvic girdle more than scapular
 12-15 yrs: wheelchair
 20-25 yrs: respiratory and cardiac complications
Other musculoskeletal:
 calf hypertrophy
 heel cord shortening
 hyperlordosis and kyphoscoliosis
Extra-muscular:
 cardiomyopathy with arrhythmias and congestive heart failure
 gastro paresis and pseudo obstruction
Rosette Jabbour, MD 34

35. ■ Laboratory features:
1- CK markedly elevated ( 50-100X )
2- EMG: abnormal polyphasic MUP
normal NCV
3- Histopathology:
a- muscle fibers degeneration and regeneration
( variation in size )
b- increased connective tissue
c- marked reduction of dystrophin on immunostaining and
on western blot analysis
■Treatment:
1- steroids - creatine
2- supportive therapy- bracing- surgery
DUCHENNE MUSCULAR DYSTROPHY
Rosette Jabbour, MD 35

36. DMD
Rosette Jabbour, MD 36

37. DMD- HE stain: cluster of necrotic and regenerating fibers
Rosette Jabbour, MD 37

38. Dystrophin immunostaining
Rosette Jabbour, MD 38

39. BECKER MUSCULAR DYSTROPHY
Incidence: 1/20000 male births. X – linked
Abnormal dystrophin ( reduced amount and abnormal function )
Phenotype similar to that of DMD, but delayed expression
Severity variable, usually mild
Life expectancy reduced but significantly longer than DMD
Rosette Jabbour, MD 39

40. BECKER MUSCULAR DYSTROPHY
HE stain: chronic myopathic changes: variation of fiber
Sizes, endomysial fibrosis, internal nuclei.
Rosette Jabbour, MD 40

41. EMERY- DREIFUS MUSCULAR DYSTROPHY
X – linked
Much less severe weakness ( humero – peroneal )
Contractures ( Achilles tendons, elbows, posterior cervical muscles )
Cardiomyopathy with conduction defects: stroke and arrhythmias
Abnormal structural protein of the nuclear membrane: Emerine
Mutation in a gene located on chromosome Xq28
Rosette Jabbour, MD 41

42. LIMB GIRDLE MUSCULAR DYSTROPHY
Incidence: 6-7/100000 births
Autosomal recessive: LGMD-2 A, B, C,…
Autosomal dominant : LGMD-1 A, B, C...
( less common )
Spontaneous mutations on different chromosomes 5, 1, 3, 6, 7…
Abnormal structural proteins of the membrane and the cytoplasm
of the muscular fiber: Sarcoglycans (α, β, γ..), dysferlin, merosin,..
Dystrophin is normal
Clinical features not specific: early scapular, or early pelvic
early onset, rapid progression
late onset, slow progression
Differential with other myopathies: inflammatory, metabolic,..
or neurogenic ( SMA )
Rosette Jabbour, MD 42

43. LGMD
Rosette Jabbour, MD 43

44. Rosette Jabbour, MD 44

45. FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
Incidence: 4/million
Autosomal dominant with variable degree of penetrance of clinical
findings within families
Gene not yet isolated. Could be present on the chromosome 4q35
Clinical features:
age of onset variable: 5 to 45 years
facial muscles are affected the earlier ( incomplete eye closure )
scapular winging
weakness of biceps and triceps
weakness of tibialis anterior: foot drop
pelvic girdle later: hyperlordosis
Normal life span
Rosette Jabbour, MD 45

46. OCULOPHARYNGEAL MUSCULAR DYSTROPHY
Autosomal dominant
Mutations on the chromosome 14q11
Clinical features:
 in fourth to six decades
 bilateral ptosis
 difficulty in swallowing 1/4
 extra ocular muscles affected 1/2 ( usually without diplopia)
 mild weakness of the neck and proximal limbs (sometimes)
Slow progression and normal life span
CK normal or mildly elevated
Rosette Jabbour, MD 46

47. CLASSIFCATION OF MYOPATHIES
HEREDITARY
MUSCULAR DYSTROPHIES without myotonia
Duchenne and Becker muscular dystrophy
Emery - Dreifus muscular dystrophy
Limb girdle muscular dystrophy
Facioscapulohumeral dystrophy
Oculopharyngeal muscular dystrophy
MUSCULAR DYSTROPHIES with myotonia
Myotonic dystrophy (classic form )( DM1)
( STEINERT disease )
Proximal myotonic dystrophy ( DM2 )
Rosette Jabbour, MD 47

48. MUSCULAR DYSTROPHIES with MYOTONIA
MYOTONIC DYSTROPHY ( classic form) STEINERT DISEASE
Incidence: 1/8000. most frequent dystrophy in adults
Autosomal dominant
Chromosome 19q13.2- increased number of repetition of CTG
coding the myotonin protein kinase
Clinical features:
 myotonia
 weakness and atrophy:
- limbs: distal lower part of the forearm, intrinsic muscles of the hands,
peroneal muscles.
- head: ptosis, wasting of temporalis and masseter muscles
orbicularis oris (eversion of the lower lip), sternocleidomastoid,
tongue, pharyngeal and laryngeal muscles, abnormal voice
Rosette Jabbour, MD 48

49. MYOTONIC DYSTROPHY
Extra muscular manifestations:
 Frontal balding
 Sub scapular cataract
 Atrophy of testicles, impotence with high FSH and preserved sexual
characters
 Cardiac conduction defects (long PR – AV block )
 Dysphagia and chronic pseudo obstruction
 Hypoventilation (diaphragm, intercostal muscles) decreased central
drive with sleep apnea
 Cognitive impairment, mental retardation
Life span reduced
Rosette Jabbour, MD 49

50. MYOTONIC DYSTROPHY
Rosette Jabbour, MD 50

51. STEINERT- Gomori trichrome stain: increase in the number of
fibers containing Internal nuclei
Rosette Jabbour, MD 51

52. MYOTONIC DYSTROPHY
Rosette Jabbour, MD 52

53. CLASSIFCATION OF MYOPATHIES
HEREDITARY
MUSCULAR DYSTROPHIES without myotonia
Duchenne and Becker muscular dystrophy
Emery - Dreifus muscular dystrophy
Limb girdle muscular dystrophy
Facioscapulohumeral dystrophy
Oculopharyngeal muscular dystrophy
MUSCULAR DYSTROPHIES with myotonia
Myotonic dystrophy (classic form ) STEINERT
CHANNELOPATHIES
Myotonia congenita
Hyperkalemic periodic paralysis
Hypokalemic periodic paralysis
Paramyotonia congenita
Central core disease
Anderson - Tawil syndrome
Rosette Jabbour, MD 53

54. MYOTONIA CONGENITA
Mutation of CLCN1 (chloride channel gene) on chromosome 7q35
Autosomal dominant: Thomsen
Autosomal recessive: Becker
Clinical features:
 Myotonia: improving by repetition of movements (warm up phenomenon)
 Muscle hypertrophy: athletic, herculean appearance
 Muscle stiffness
 No weakness
Recessive :
 Myotonia worse
 Proximal weakness
Life span normal
Lab: CK normal or slightly elevated
EMG: myotonic discharges
Rosette Jabbour, MD 54

55. Rosette Jabbour, MD 55

56. HYPOKALEMIC PERIODIC
PARALYSIS
Age at onset: puberty
Duration of episodes: hours- days
Weakness: episodic, possibly permanent later
in life
Myotonia: absent
Precipitants: cold, rest after exercise,
carbohydrate loading
Alleviating factors: potassium loading,
exercise
Inheritance, gene mutation: AD, CACNL1A,
SCN4A, 17q23
Remark:
always look for hyperthyroidism
Age at onset: infancy-early childhood
Duration of episodes: minutes-hours
Weakness: episodic, possibly permanent
later in life
Myotonia: possibly ( between episodes of
weakness) EMG (+)
Precipitants: potassium loading, cold,
fasting, rest after exercise
Alleviating factors: carbohydrate loading,
exercise
Inheritance, gene mutation:
AD, SCN4A, 17q23
HYPERKALEMIC PERIODIC
PARALYSIS
Rosette Jabbour, MD 56

57. CLASSIFCATION OF MYOPATHIES
HEREDITARY
MUSCULAR DYSTROPHIES without myotonia
Duchenne and Becker muscular dystrophy
Emery - Dreifus muscular dystrophy
Limb girdle muscular dystrophy
Facioscapulohumeral dystrophy
Oculopharyngeal muscular dystrophy
MUSCULAR DYSTROPHIES with myotonia
Myotonic dystrophy (classic form ) STEINERT
CHANNELOPATHIES
Myotonia congenita
Hyperkalemic periodic paralysis
Hypokalemic periodic paralysis
METABOLIC MYOPATHIES
Glycogen storage diseases
Lipid storage diseases
Mitochondrial myopathies
Rosette Jabbour, MD 57

58. GLYCOGEN STORAGE DISEASES
► Glycogen storage disease type II: Acid maltase deficiency:
1- Autosomal recessive ( 17q23-25 )
2- Lysosomal enzyme(α-glycosidase: conversion of glycogen to glucose)
3- Severe infantile form: Pompe’s disease
cardiomyopathy, hepatomegaly, hypotonia,
feeding and respiratory weakness
4- Less virulent juvenile or adult type =
Limb girdles
► Glycogen storage disease type V: Mc Ardle disease
1- Autosomal recessive
2- Muscular phosphorylase
3- Cramps, stiffness pain on exertion, myoglobinuria
Rosette Jabbour, MD 58

59. Vacuoles, subsarcolemma, containing PAS (+) material ( glycogen )
Rosette Jabbour, MD 59

60. EM: accumulation of glycogen in the sub sarcolemma
Rosette Jabbour, MD 60

61. LIPID STORAGE DISEASES
CPT1 and CPT2 ( carnitine- palmityl transferase ) deficiency:
Enzymes required for the active transport of long chain fatty acids into mitochondria
For β-oxidation which is a process of aerobic energy production converting these FA
To acetyl –CoA which then used to generate ATP
Episodic exercise-induced myalgia, myoglobinuria and weakness
Myalgias occur after exercise, or during prolonged exercices and fasting
( glcogen storage diseases: during exercises )
Myalgias without cramps and myoglobinuria
Muscle biopsy may show lipid accumulation
CK normal between attacks
Rosette Jabbour, MD 61

62. Gomori trichrome stain: vacuoles containing lipids
Rosette Jabbour, MD 62

63. Red oil stain: vacuoles filled with lipids ( red material )
Rosette Jabbour, MD 63

64. EM: lipid droplets
Rosette Jabbour, MD 64

65. MITOCHONDRIAL MYOPATHIES
Multisystem diseases, sometimes confined to muscle (brain, liver, kidneys)
Autosomal recessive, dominant or X-linked
DNA mutations responsible for enzyme deficiency, or structural abnormalities
CLINICAL MANIFESTATIONS :
- non specific: mild weakness, episodic weakness with acidosis,
precipitated by infection, alcohol or exercise. Myalgia, exercise-induced cramps,
rhabdomyolysis, myoglobinuria.
- specific presentations: Chronic progressive external ophtalmoplegia
Kearns-Sayre syndrome: ptosis, ophtalmoplegia,
pigmentary retinopathy, with heart block or high
protein in CSF, or cerebellar ataxia
- other presentations: MELAS: mitochondrial encephalomyopathy with lactic
acidosis and stroke like episodes
MERRF: myoclonic epilepsy with ragged red fibers
Leber’s hereditary optic neuropathy
Leigh’s syndrome
LAB: CK normal, high lactate on aerobic exercise
muscle biopsy with immunostaining and electron microscopy
genetic testing in blood, urine and muscle.
Rosette Jabbour, MD 65

66. Ragged-red fibers with increased sub sarcolemmal red staining
membranous material ( accumulation of mitochondria )
Gomori trichrome stain
Rosette Jabbour, MD 66

67. EM: collections of abnormal mitochondria containing abnormal
inclusions
Rosette Jabbour, MD 67

68. Cytochrome oxidase negative fibers
( cytochrome c oxidase stain )
Rosette Jabbour, MD 68

69. CONGENITAL MYOPATHIES
Myopathic disorders presenting preferentially at birth
But not exclusively
CONGENITAL MUSCULAR DYSTROPHIES
1- Hypotonia + arthrogryposis +abnormal myelination ( mental retardation)
2- Some are related to deficit in merosine ( membrane of the muscle fiber )
OTHER CONGENITAL MYOPATHIES
1- Less severe
2- Neonatal onset or delayed
3- Specific :
• Nemaline myopathy
• Myotubular myopathy
• Central core disease
Rosette Jabbour, MD 69

70. Rosette Jabbour, MD 70

71. MALIGNANT HYPERTHERMIA
Incidence: 1/7000-1/50000 anesthetics given
50% had previous anesthesia without clinically manifesting the disorder
Autosomal dominant. at least 6 different genes identified
Mutations in RyR1(ryanodine receptors) on chromosome 19q13
Activation of mutant receptors causes calcium release from sarcoplasmic reticulum stores,
leading to excessive muscle contraction, overproduction of heat, fever and
rhabdomyolysis.
Precipitated by depolarizing muscle relaxants( succinylcholine ), and halogenated inhalation
anesthetic agents ( isoflurane )
Other conditions that predispose: myotonia congenita, periodic paralysis, myotonic dystrophy,
Duchenne and Becker dystrophies, mitochondrial disorders, CPT deficiency.
Clinical manifestations: severe muscle rigidity, myoglobinuria
fever, tachycardia, arrhythmias
Testing: genetic
susceptibility test (fresh muscle sample with halothane or caffeine)
Rosette Jabbour, MD 71

72. CLASSIFICATION OF MYOPATHIES
ACQUIRED
Inflammatory myopathies ( PM-DM )
Inclusion body myositis
Endocrine myopathies
Myopathies associated with systemic disease (critical illness, trichinosis,
amyloidosis..)
Drug induced myopathies / toxic
Rosette Jabbour, MD 72

73. INFLAMMATORY MYOPATHIES
GENERAL REMARKS:
Characterized by: muscle weakness, high CK, inflammation on biopsy
3 major groups:
► Idiopathic inflammatory myopathies ( of unknown etiology )
■ Dermatomyositis (the most common in childhood and adulthood)
■ Polymyositis (rare, overdiagnosed, many turn out to be IBM, or DM
with minimal rash, or muscular dystrophy with inflammation)
■ Inclusion body myositis( most common in patients older than 50 yrs)
► Myositis associated with connective tissue disease (SLE, Sjogren, RA, ..)
► Myositis due to infection (virus, HIV, trichinosis,..)
PAYHOPHYSIOLOGY:
DM: humoral mediated microangiopathy of the skin and muscle. Weakness is
related to ischemia/infarction of muscles
PM: cell mediated autoimmune attack against specific antigen in muscle fibers
IBM: unclear
cell mediated like PM
inflammation secondary to a degenerative myopathy ?
(poor response to immunosuppression)
Rosette Jabbour, MD 73

74. CLINICAL FEATURES:
DM:
1- acute or insidious onset of proximal greater than distal
2- skin rash: heliotrope, forehead and malar regions, chest and neck,
extensor surface of extremities and joints
3- other organs: interstitial lung disease(10-20%), myocarditis, GI bleeding, arthritis.
4- increased risk of malignancy
PM:
1- same as DM
2- with no rash
IBM:
1- Insidious onset of proximal and distal weakness
2- early involvement of wrist and fingers flexors with relative sparing of deltoids, and
of quadriceps and ankle dorsiflexion
3- weakness is often asymmetric
4- cranial muscles spared except for dysphagia, sometimes
5- no increased risk of malignancy
Rosette Jabbour, MD 74

75. IBM
Rosette Jabbour, MD 75

76. LABORATORY FEATURES:
DM/PM:
1-CK can be normal early or when onset is insidious
more commonly high ( more than 10X )
2-CK not a good indicator of disease activity
3-ANA positive when underlying CTD
4-Anti-jo-1 positive when ILD
IBM:
1-CK normal or mildly elevated ( less than 10X )
2-Autoantibodies uncommon and non significant
ELECTRODIAGNOSTIC FEATURES:
1-Increased spontaneous activities ( fibrillation potentials, positive sharp waves )
2-MUP: small amplitude, short duration, polyphasic with earl recruitment .
Rosette Jabbour, MD 76

77. HISTOLOGIC FEATURES:
DM: a- infiltration by inflammatory mononuclear cells of the perimysium and
the perivascular space
b- perifascicular atrophy
c- immune complex deposition on small blood vessels
d- no endomysial inflammation and no invasion of non necrotic fibers
PM: a- infiltration by inflammatory mononuclear cells of the endomysium and
invasion of non necrotic muscle fibers
IBM: a- infiltration by inflammatory mononuclear cells of the endomysium and
and invasion of non necrotic fibers
b- presence of rimmed vacuoles in the muscle fibers
c- mitochondrial abnormalities
d- EM: 15-21 nm tubulofilamants in the cytoplasm of vacuolated fibers,
and less commonly in nuclei
e- 20-30% will not demonstrate all these findings leading to erroneous
diagnosis of PM ( importance of the clinical pattern )
Rosette Jabbour, MD 77

78. DM- HE stain: inflammatory infiltrates in the perimysium - perivascular
Rosette Jabbour, MD 78

79. DM- HE stain: perifascicular atrophy
Rosette Jabbour, MD 79

80. PM- HE stain: inflammatory infiltrates present at several endomysial sites
Rosette Jabbour, MD 80

81. PM- HE stain: focal invasion of a non-necrotic fiber by inflammatory cells
Rosette Jabbour, MD 81

82. IBM- Gomori trichrome stain: inflammatory cells focally invade
a non-necrotic muscle fiber
Rosette Jabbour, MD 82

83. IBM- Gomori trichrome stain: muscle fibers with rimmed vacuoles
Rosette Jabbour, MD 83

84. IBM- EM: filamentous inclusions near an autophagic vacuole
containing degenerating membranous material with myeloid figures
Rosette Jabbour, MD 84

85. IBM- EM: intranuclear filamentous inclusions
Rosette Jabbour, MD 85

86. ENDOCRINE MYOPATHIES
Important role of the endocrine system in controlling the structure
and the function of the muscle.
1- HYPERTHYROIDISM
2- HYPOTHYROIDISM
3- HYPERCORTICISM
4- HYPOCORTICISM
Signs are not specific
Proximal weakness of variable intensity
Muscular atrophy, cramps, slow relaxation
Periodic paralysis
Rosette Jabbour, MD 86

87. DRUGS INDUCING MYOPATHIES
Rosette Jabbour, MD 87

88. DRUG-INDUCED- Necrotizing myopathy
Rosette Jabbour, MD 88

89. SPECIFIC TREATMENT FOR MUSCLE DISEASE
Rosette Jabbour, MD 89

90. SPECIFIC TREATMENT FOR MUSCLE DISEASE
conditions Specific treatment
Rosette Jabbour, MD 90