Fiber properties

Chronic partial denervation
Reinnervation: Fiber type grouping
Grouped atrophy
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


NADH stain
Target Fibers
  Clear central regions
  Surrounded by layers with varied staining

NADH stain

NADH stain
Target fibers
  • Clinical correlations
    • Often seen with acute or subacute denervation & reinnervation
    • Rare with diffuse denervation
    • May also occur with tenotomy
    • ? Related to stretching of muscle fibers
  • Histochemistry
    • Targets more common in: Gastrocnemius muscle
    • Shape
      • Transverse view: Rounded, polygonal or irregular
      • Extend longitudinally along length of muscle fiber: Up to 500 μM
      • Not generally from end-to-end
    • NADH stain
      • Best visualization of target architecture
      • Architecture
        • Typical: 3 zones with 3 concentric zones
        • May have clear, dark, or loculated centers
      • Fiber size
        • Targets most commonly in normal-sized or hypertrophied muscle fibers
        • ALS: Targets common in small muscle fibers
      • Differences from cores
        • Central regions: Non-homogeneous; Several different regions; Central area may be dark or light
        • Periphery: Often dark stained
        • Cores occur in all or most muscle fibers, rather than the regional pattern of targets
        • LC3 aggregates: Smaller or absent in cores
    • SDH stain
      • Most sensitive for targets: Internal clear regions in muscle fibers
      • Doesn't stain internal architecture
    • Cytoplasmic bodies (or ? Rods): Mzay occur within, or around, targets
  • Targets: Molecular components
  • "Targetoid" fibers: NADH stain
    • Irregular internal clear regions in muscle fibers
    • Less distinct regional organization than targets
    • Contain similar molecular components to targets

NADH stain

NADH stain
Targetoid fibers

Gomori trichrome stain

Targets: Varied forms

NADH stain

NADH stain
Target fibers

NADH stain

NADH stain

Targets: Varied stages of development

NADH stain

Targets: May be visible on H&E stain as aggregates (Above) or internal clear regions (Below)

H&E stain


Targets: May be visible on ATPase

ATPase pH 9.4 stain
Target & Targetoid fibers

NADH stain

Gomori trichrome stain

Gomori trichrome stain
  May be visible on Gomori trichrome and VvG stains as rounded aggregates with pale surround

VvG stain

VvG stain

Targets: AMPDA
  Targets are visible on AMPDA stain
  AMPDA is present inside targets

AMPDA stain

  May be associated with Cytoplasmic bodies (or Rods)

Gomori trichrome stain




Aggregated LC3 in Target formations

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


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

ATPase pH 4.3 stain
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

ATPase pH 4.3 stain

Early reinnervation: Intermediate staining fibers on ATPase pH 9.4

ATPase pH 9.4 stain

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