Neuromuscular

DENERVATION OF MUSCLE

Fiber properties

Chronic partial denervation
Reinnervation: Fiber type grouping
  Early
  Late
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



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
  • Targets: 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


Denervation-Reinnervation: Sub-Acute


Partial Denervation with Reinnervation: Recent
  Many intermediate-size angular muscle fibers
  Larger fibers are normal-size to slightly large

Partial Denervation with Reinnervation: Recent
  Smaller angular fibers: Stain dark; Contain targets

Partial Denervation with Reinnervation: Recent
  Fiber type changes

  Early fiber type grouping
    Incomplete type switching
      Many fibers in groups are type 2C
      Intermediate staining with ATPase pH 4.3 &9.4

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12/22/2014