Muscle Disease

Question 1

Type I myofibers

Answer 1

High in oxidative activity, low in glycolytic capacity, red grossly (from myoglobin and mitochondrial cytochromes), contracts slowly, capable of continuous and repeated contraction

Question 2

Type II myofibers

Answer 2

Low in oxidative activity, high in glycolytic activity, white grossly, fast contracting, cannot maintain repeated contraction

Question 3

Neurogenic atrophy clinical clues

Answer 3

Nerve damage often with associated sensory features

Question 4

Neurogenic atrophy histopathological features

Answer 4

Fiber type grouping, group atrophy

Question 5

Neurogenic atrophy etiology

Answer 5

Motor nerve damage

Question 6

Disuse/steroid atrophy clinical clues

Answer 6

Bedridden/ICU, corticosteroids (long term use), hypothyroidism

Question 7

Disuse/steroid atrophy histopathological features

Answer 7

Type II myofiber atrophy

Question 8

Disuse/steroid atrophy etiology

Answer 8

Atrophy of fast twitch fibers

Question 9

Dystrophin related myopathy clinical clues

Answer 9

Childhood onset

Question 10

Dystrophin related myopathy histopathological features

Answer 10

Myofiber size variability, necrosis, regeneration, endomysial fibrosis, fatty replacement

Question 11

Dystrophin related myopathy etiology

Answer 11

Hereditary abnormalities of dystrophin or related proteins

Question 12

Inflammatory myopathy clinical clues

Answer 12

Adult onset, associated rheumatologist features

Question 13

Inflammatory myopathy histopathological features

Answer 13

Inflammation (usually T-cells), necrosis and regeneration

Question 14

Inflammatory myopathy etiology

Answer 14

Autoimmune

Question 15

Congenital myopathy clinical clues

Answer 15

Onset at birth, floppy baby

Question 16

Congenital myopathy histopathological features

Answer 16

Wide variety of specific changes, inclusions, etc. (nemaline rods, central cores)

Question 17

Congenital myopathy etiology

Answer 17

Variable

Question 18

Channelopathies clinical clues

Answer 18

Myotonia, intermittent symptoms

Question 19

Channelopathies histopathological features

Answer 19

May be normal

Question 20

Channelopathies etiology

Answer 20

Muscle sodium channel protein SCN4A defect

Question 21

Myopathic patterns

Answer 21

Often associated with scattered myofiber necrosis and regeneration

Question 22

Inflammatory myopathies pattern

Answer 22

Myopathic but also characterized by inflammatory infiltrates and/or intracellular inclusions

Question 23

Neuropathic changes

Answer 23

Fiber type grouping or group atrophy

Question 24

Type II myofiber atrophy from disuse

Answer 24

Due to any cause for prolonged immobilization, results in focal or generalized muscle atrophy, tends to affect type II more than type I

Question 25

Type II myofiber atrophy glucocorticoids

Answer 25

History of exposure, either exogenous or endogenous (as in Cushing syndrome), can cause muscle atrophy

Question 26

Dystrophinopathies

Answer 26

Duchenne and Becker muscular dystrophy

Question 27

Broad definition of muscular dystrophies

Answer 27

Diseases associated with the dystrophin-glycoprotein complex

Question 28

Dystrophin-glycoprotein complex function

Answer 28

Skeletal muscle membrane associated proteins involved in the mechanical stabilization and signaling interactions between the cytoskeleton, membrane, and extracellular matrix

Question 29

Duchenne muscular dystrophy clinical course

Answer 29

Evident around 5 years, wheelchair-bound by teenagers, death in early adulthood

Question 30

Clinical features of DMD

Answer 30

Gower’s sign in children, clumsiness, inability to keep up with peers, weakness begins in pelvic girdle and then shoulder, calf muscles enlarged (pseudohypertrophy), high serum creatine kinase levels early on but fall as muscle mass is lost

Question 31

Clinical features of BMD

Answer 31

Appears later in childhood or adolescence, slower and more variable progression, live well into adulthood with nearly normal life span

Question 32

Histologic changes in dystrophinpathologies

Answer 32

Ongoing myofiber necrosis and regeneration, progressive replacement of muscle tissue by fibrosis and fat, variation in myofiber size and abnormally placed internal nuclei (all of these in both BMD and DMD, but BMD is more mild), dystrophin sarcolemmal staining pattern negative (DMD) or reduced (BMD)

Question 33

Pathogenesis of dystrophinopathies

Answer 33

Loss of function mutations in dystrophin gene on the short arm of the X chromosome (Xp21)

Question 34

Congenital myopathy examples

Answer 34

Central core disease, nemaline myopathy, centronuclear myopathy

Question 35

Congenital myopathy patterns

Answer 35

Perinatal or early childhood presentation and often result in relatively static deficits

Question 36

Channelopathy patterns

Answer 36

Myotonia, relapsing episodes of hypotonic paralysis associated with abnormal serum potassium levels

Question 37

Hyperkalemic periodic paralysis

Answer 37

Mutations in gene encoding skeletal muscle sodium channel protein SCN4A, which regulates sodium entry during contraction

Question 38

Metabolic myopathy (glycogen synthesis abnormalities)

Answer 38

Detected with PAS and myophosphorylase

Question 39

Metabolic myopathy (lipid abnormalities)

Answer 39

Detected with Oil Red O

Question 40

Mitochondrial myopathies

Answer 40

Mutations in mitochondrial or nuclear genomes, usually manifest in early adulthood with proximal muscle weakness and sometimes severe involvement of ocular musculature, ragged red fibers on histology from aggregates of mitochondria

Question 41

Inflammatory myopathy examples

Answer 41

Polymyositis, dermatomyositis, inclusion body myositis

Question 42

Polymyositis

Answer 42

Autoimmune disorder associated with T-cells and increased expression of MHC class I on myofibers, endomysium damaged, responds to corticosteroids and immunosuppressive agents

Question 43

Dermatomyositis

Answer 43

Autoimmune disorder, presents with malar rash, rash on upper eyelids, red papules on elbows, knuckles, knees, on histology there is myofiber damage in a paraseptal or perifascicular pattern

Question 44

Inclusion body myositis

Answer 44

Typically in patients older than 60, morphologic hallmark is presence of rimmed vacuoles, might be a degenerative disorder of aging, myopathic changes, mononuclear cell infiltrates, endomysial fibrosis, fatty replacement, chronic and progressive course, does not respond well to immunosuppressive agents

Question 45

Toxic myopathy (thyroxine)

Answer 45

Acute or chronic proximal muscle weakness, show myofiber necrosis and regeneration, associated with thyrotoxicosis

Question 46

Toxic myopathy (ethanol)

Answer 46

After an episode of binge drinking, degree of rhabdomyolysis may be severe (can lead to acute renal failure secondary to myoglobinuria), patients present with acute muscle pain (generalized or localized to a group), myocyte swelling, necrosis, regeneration

Question 47

Toxic myopathy (drug)

Answer 47

Most commonly drugs from the statin family, affected muscles show evidence of myopathic injury usually without an inflammatory component