Neuromuscular

DENERVATION OF MUSCLE

Fiber properties

Chronic partial denervation
Fiber type grouping
Grouped atrophy
  Large
  Small
  ALS
Pyknotic nuclear clumps
Target fibers

Denervating disorders
  Amyotrophic lateral sclerosis (ALS)
  Bulbospinal Muscular atrophy
  Spinal muscular atrophy



Denervated muscle fibers: General properties


PYKNOTIC NUCLEAR CLUMPS: Denervation of muscle fibers without reinnervation

   
H&E stain
Angular fibers: Esterase
Non-specific esterase stain
Pyknotic nuclear clumps
  • Clumps of myonuclei
    • End product of denervation atrophy
    • Larger in muscles with fiber hypertrophy
  • The remainder of the myofiber largely disappears
    • Contractile apparatus
    • Cytoplasm
  • Pyknotic nuclear clump distribution
    • May occur alone (Left)
    • Part of a region of grouped muscle fiber atrophy (Center)
  • Pyknotic nuclear clumps often stain for esterase (Right)
  • Disease associations


TARGET FIBERS



NADH stain
Target fibers
  • Often seen with acute denervation & reinnervation.
  • Histochemistry
    • Best visualized on NADH stain
    • May have clear, dark, or loculated centers.
    • Central clear regions with mitochondrial stains
    • Cytoplasmic bodies or Rods may occur within, or around, targets
  • More common in
    • Gastrocnemius muscle
    • ALS
  • Molecular components

NADH stain

 



Gomori trichrome stain

Targets: May be visible on H&E

H&E stain

 

Targets: May be visible on ATPase

ATPase pH 9.4 stain

NADH stain

Targets: May be associated with Cytoplasmic bodies (or Rods)


Gomori trichrome stain

 

 

 

Aggregated proteins in Target formations
  Caveolin-3 (Left) & LC3 (Right)

Disordered sarcomeres in targets (Top half of images)
  Disorganization of Z-disks



GROUPED ATROPHY OF MUSCLE FIBERS


H&E stain

NADH stain

ATPase pH 9.4 stain

Non-specific esterase stain
  • Small angular muscle fibers in clusters
    • Often basophilic on H&E stain (Top left)
    • Stain darkly with NADH and esterase.
    • May also stain with desmin, spectrin & Leu-19 (myoblast & satellite cell related antigen)
  • Atrophic groups contain small angular fibers.
  • Small rounded fibers in groups may be seen with chronic denervation.
  • Denervation in ALS: Grouped atrophy with little type grouping (ATPase)
    • Many esterase positive small angular fibers
    • Multiple small regions of grouped atrophy
    • Both type I & type II atrophic fibers occur in a single group
  • Denervation in SMA
    • Atrophic groups: Larger
    • Small fibers: Often rounded
    • Ramaining large muscle fibers: Often type I


Return to Muscle biopsies
Return to Biopsy illustrations
Return to Neuromuscular home page
Return to Polyneuropathy Index

3/5/2014