Pathology of Skeletal Muscle

Question 1

What is associated with fascicles and contribute to muscle degeneration?

Answer 1

Satellite cells - small pool of tissue stem cells.

Question 2

Type 1 muscle fiber type

Action
Activity type
Resistance to fatigue
Power
Color

Answer 2

Action: sustained force.
Activity type: aerobic exercise.
Resistance to fatigue: high.
Power: low.
Color: red.

Question 3

Type 2 muscle fiber type

Action
Activity type
Resistance to fatigue
Power
Color

Answer 3

Action: fast movement.
Activity type: anaerobic exercise.
Resistance to fatigue: low.
Power: high.
Color: white/pale/tan.

Question 4

What occurs in dermatomyositis?

Answer 4

Peri-fascicular atrophy.

Question 5

Prolonged corticosteroid treatment and disuse causes atrophy of which fibers?

Answer 5

Type 2 fibers.

Question 6

Regenerating muscle fibers are rich in…

Thus, they stain:

Answer 6

RNA

Basophilic

Question 7

What age is common in Dermatomyositis?

What is the distinctive skin rash?

What are Grotton lesions?

What are the symptoms? (4)

What are the auto-antibodies involved? (3)

Answer 7

Adults: 4th-6th decade.

Iliac or heliotrope discoloration of eyelids associated with periorbital edema. Telangiectasias may also exist.

Scaly erythematous eruptions or dusky patches over knuckles, elbows and knees.

Proximal muscle involvement first.
1/3 develop dysphagia.
10% develop ILD.
Cardiac involvement is common.

Anti-Mi2 (rash and papules)
Anti-Jo1 (“mechanic’s hands”)
Anti-P155/P140 (paraneoplastic and juvenile)

Question 8

Dermatomyositis increases the risk for what?

What is seen on histology and is classic?

Answer 8

Increased risk of visceral cancer.

“Peri-fascicular atrophy”.

Question 9

Juvenile dermatomyositis onsets when?

What is classically involved?

What is seen on histology? (2)

Answer 9

Approx. 7 y/o.

GI tract.

Calcinosis and Lipodystrophy.

Question 10

What is the presentation of Polymyositis?

How is it different than Dermatomyositis?

What are the distinct histological findings? (2)

Answer 10

Myalgia and weakness with symmetrical proximal involvement.

No cutaneous involvement.

Endomysial mononuclear infiltrate.
Random distribution of affected fibers (not perifascicular like in DMM).

Question 11

What age is common for Inclusion Body Myositis?

What is the presentation?

What is the classic histological finding?

Answer 11

Late adulthood; > 50 y/o (most common inflammatory myopathy in patients > 65 y/o).

Slowly progressive muscle weakness that is most severe in Quads and distal UEs. Dysphagia due to esophageal and pharyngeal n. involvement.

Rimmed vacuoles.

Question 12

What is first-line therapy for Dermatomyositis and Polymyositis?

What is given if they can’t take these drugs?

Which inflammatory myopathy does not respond to the first and second-line therapies?

Answer 12

Steroids.

Immunosuppressive drugs.

Inclusion body myositis responds poorly to steroids and immunosuppressives.

Question 13

Chloroquine and Hydroxychloroquine cause what kind of myopathy?

Answer 13

Slowly progressive muscle weakness; type 1 fiber affected.

Question 14

Thyrotoxic myopathy is characterized as…

Answer 14

Acute or chronic proximal muscle weakness.

Question 15

What myopathy can be produced by alcohol?

Answer 15

Rhabdomyolysis -> myoglobinuria.

Question 16

What are the X-linked muscular dystrophies? (2)

Answer 16

Duchenne muscular dystrophy (DMD) - more common, more severe.

Becker muscular dystrophy (BMD) - same genetic locus.

Question 17

DMD is associated with which gene? Which protein?

How many are familial?

What is the progression of female carriers of DMD?

Answer 17

Xp21, loss of function of dystrophin.

2/3 are familial.

Increased CK, which increases the risk of CM.

Question 18

How common is DMD?

When do symptoms onset?

Answer 18

1/3500 live male births.

Symptoms onset before 5 y/o; wheelchair by 10-12 y/o.

Question 19

BMD onsets when?

What is the progression of the disease?

What is the amount of dystrophin in BMD?

Answer 19

Late childhood adolescence.

Nearly normal lifespan, but with cardiac disease.

Decreased, but not gone (like DMD).

Question 20

What is Pseudohypertrophy of muscles?

Answer 20

Enlargement of muscles of lower leg associated with weakness; *increased bulk due to increased size initially, but leads to increased fat and CT.

Question 21

What is Myotonia? How is it elicited?

What are the symptoms?

What is the inheritance of the disease? What protein is affected?

What is seen on histology?

Answer 21

Sustained involuntary contraction of a group of muscles. It can be elicited by percussion of the thenar eminence.

Skeletal muscle weakness (stiffness, problems releasing grip), cataracts, endocrinopathy and CM.

AD; CTG repeats of DMPK gene.

“Ring fiber” and “sarcoplasmic mass”.

Question 22

What is the progression of Myotonic Dystrophy symptoms?

Answer 22

Gait first, then atrophy of facial muscles: ptosis and “hatchet face”, cataracts and CM.

Question 23

Emery-Dreifuss Muscular Dystrophy (EMD) is associated with mutations in genes that encode what?

What is the triad of symptoms?

What are the 2 inheritance patterns?

Answer 23

Nuclear lamina proteins.

(1) Slowly humeroperoneal weakness, (2) CM w/ conduction defects, (3) early contractures of Achilles t., spine and elbow.

X-linked (EMD1) and AD (EMD2).

Question 24

What is affected in Limb-Girdle Muscular Dystrophy?

What is the inheritance patterns?

The age of onset and severity of diseases…

Answer 24

Muscle weakness that preferentially involves proximal muscle groups.

Multiple AD and AR entities.

Vary greatly.

Question 25

What is the most common disease of lipid or glycogen metabolism?

What are the symptoms?

Answer 25

Carnitine palmitoyltransferase II deficiency.

Episodic muscle damage w/ exercise + fasting.

Question 26

What enzyme is deficient in McArdle disease?

What are the symptoms?

Answer 26

Myophosphorylase deficiency (a glycogen storage disease).

Episodic muscle damage w/ exercise.

Question 27

What characterizes Pompe disease?

Answer 27

Generalized glycogenesis of infancy.

Question 28

Acid maltase deficiency is considered to be…

Answer 28

A milder adult form of enzyme deficiency that affects respiratory and trunk muscles.

Question 29

What is seen in Mitocondrial Myopathies? (4)

Answer 29

Weakness
Elevated serum CK
Rhabdomyolysis
EOM involvement

Question 30

What is seen on histology in Mitochondrial Myopathies? (2)

Answer 30

Ragged red fibers (red w/ + trichrome stain).

Paracrystalline “parking lot” inclusions.

Question 31

What is Spinal Muscular Atrophy?

What is it AKA?

The DDx includes: (6)

Answer 31

A neuropathic disorder and loss of motor neurons -> muscle weakness and atrophy.

“Floppy infant” - infantile hypotonia.

Primary diseases of skeletal muscle.
Congenital myotonia.
Congenital myopathies.
Congenital muscular dystrophies.
Brain abnormalities.
Neuronopathies - spinal muscular atrophy is the prototype!

Question 32

Spinal Muscular Atrophy causes destruction of…

What is the inheritance? What gene is involved?

What is the Wernig-Hoffman variant?

Answer 32

Anterior horn cells of spinal cord.

AR (1/6K); SMN1 gene.

Wrnig-Hoffman (SMA type 1) - most common.

• onset at birth, floppy baby, death at < 3 y/o.
• muscular weakness of the truncal and extremity muscles first, followed by swallowing and breathing difficulties.

Question 33

“Panfasicular atrophy” =

Answer 33

Spinal muscular atrophy

Question 34

What is the inheritance of most Channelopathies?

What are the symptoms?

Answer 34

AD.

Epilepsy, migraine, movement DOs w/ cerebellar dysfunction w/ peripheral n. and muscle diseases.
It can lead to hypotonia or hypertonia.

Question 35

RYR1 mutation =

What are the symptoms?

What triggers this?

What is the molecular cause?

Answer 35

Malignant hyperthermia.

Tachycardia, tachypnea, muscle spasms and hyperpyrexia.

Halogenated inhalational agents.

Increased efflux of Ca++ from SR.