69. NMJ/Muscle Diseases

Question 1

epimysium v. perimysium v. endomysium

Answer 1

Epimysium: c.t. around multiple muscle fascicles
Perimysium: c.t. around one muscle fascicle
Endomysium: c.t. around individual muscle fibers

Question 2

How does muscle respond to injury?

What are signs of myopathy on histo?

Answer 2

Injury: muscle fiber necrosis, collagen/fat deposits, vacuolation (accumulation of deposits), regeneration (peripheral nuclei proliferate in), hypertrophy

Histo: small, ROUND fibers, fiber splitting, internalized nuclei, fatty infiltration, more c.t./inflammatory infiltrates, ragged red fibers/vacuoles

Question 3

Distinguish between the three diseases of inflammatory myopathy:
Dermatomyositis
Polymyositis
Inclusion Body Myositis

Answer 3

DM: symmetric proximal muscle weakness

• with SKIN sx (heliotrope red rash on eyelids, Gottron’s papules on knuckles, chest rash)
• onset in children/adults
• Humoral-mediated injury (immune complex deposition in capillaries around muscle)
• Histo: Perifascicular Atrophy, Scattered Necrotic Fibers, Inflammatory Infiltrates (perivascular/perimysal)
  tx: steroids/IVIG

PM: symmetric proximal muscle weakness

• onset >20 years (only adults)
• Cell-mediated injury (antigens on muscle fibers)
• Histo: fiber size variability, scattered necrotic fibers, inflammatory infiltrate (endomysial)
• tx: steroids/IVIG

IBM: weak finger/wrist flexors and quads

• onset ~50 years
• labs: elevated CK
• Histo: RIMMED VACUOLES
  tx: steroids/IVIG DO NOT WORK

Question 4

What is the function of dystrophin?

Answer 4

protein that connects actin cytoskeleton to sarcolemma - c.t. around sarcomere - needed to transmit contraction force external to muscle

Question 5

Distinguish between Duchenne Muscular Dystrophy and Becker Muscular Dystrophy

Answer 5

DMD: XLR Dystrophin mutation (NO dystrophin)
sx: waddling gate (2-6yo), wheelchar (12yo), death in 20s due to resp/cardiac involvement
signs: calf pseudohypertrophy, proximal weakness, Gower sign (needs hands to stand up)
labs: high CK
Tx: supportive, prednisone slows rate of deterioration

BMD: milder mutation (LESS dystrophin)
sx: wide spectrum, later onset difficulty walking, reduced life expectancy due to cardiac/resp impairments

BOTH
Histo: small round fibers and more endomysial c.t.
MRI: more fat/c.t. where muscle should be

Question 6

Myotonic Dystrophy

• what is myotonia
• pathogenesis
• features
• histo

Answer 6

Myotonia: delayed relaxation of skeletal muscle after contraction
P: expansion of DMPK gene - disrupts target proteins - abnormal excitability (severity of myopathy correlates with size of expansion - ANTICIPATION)
F: DISTAL weakness, onset any age, “Hatchet Face” (puckered up), mild reduction in cognitive abilities
Histo: lots of internalized nuclei, atrophic fibers, fiber size variability

Question 7

Disorders of Carbohydrate Metabolism: Pompe vs. McArdle Disease
What stain do you use on biopsy?

Disorders of Lipid Metabolism: Carnitine Deficiency
What stain do you use on biopsy?

Answer 7

PAS (periodic Acid-Schiff) Stain to view glycogen deposits!
Pompe: deficiency of acid alpha-glucosidase (cant break down glycogen) - limb girdle weakness in adults (tx with enzyme replacement)
McArdle: deficiency of myophosphorylase (more common) - can’t P glycogen to break it down - “second wind” phenomenon, exercise intolerance (tx with oral sucrose before exercise)

Oil Red O Stain to view lipid deposits
Carnitine: can’t transport LCFA into mito. - progressive muscle weakness (tx oral carnitine supplement)