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Subperineurial Edema

Associations Differential diagnosis Hemorrhage Histochemistry Plastic sections Vessels, Endoneurial Ultrastructure

Subperineurial edema (Arrows) Variable severity   in different fascicles

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Subperineurial edema: Contents

• Better visualized with plastic or frozen sections than fixed sections
• Granular material: May stain with Alcian blue (Mucopolysaccharides)
  
• Cells: Few & Scattered; Fibroblasts; Mast cells; Macrophages
  
• Endoneurial microvessels: May have thick wall & Large endothelium
  

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Subperineurial edema: Diferential Diagnosis

• Systemic
  • Thiamine deficiency
  • Leprosy
  • Ischemic (Atherosclerotic) disease
• Immune
  • CIDP: Pathology
  • CIDP, Subacute
  • AIDP
  • Vasculopathies, Immune
    • Eosinophilic Vasculitis
• Toxic
  • Lead
  • Ipilimumab
• Hereditary
  • CMT 1E

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Subperineurial Edema: General Clinical Associations ¹

• May occur with: Either axonal or demyelinating neuropathies
• More area with: Shorter disease duration in inflammatory disorders
• May persist despite previous immunmodulation treatment
• Possible cause: Leakage through blood-nerve barrier

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SUBPERINEURIAL EDEMA ± INFLAMMATION

H&E stain	Gomori trichrome stain	Subperineurial edema (Narrow arrow) In neighboring fascicle Inflammation Near a small epineurial vessel (Wide arrow)
Clear space between the perineurium and endoneurial contents (arrows).

H&E stain	H&E stain
Clear space contains hyaline material and occasional vessels and cells.

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Toluidine blue stain	Toluidine blue stain
Subperineurial space contains wispy material, clear space, vessels and cells. There may be a variable degree of axon loss within fascicles.

Toluidine blue stain

Toluidine blue stain

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Subperineurial Edema (Arrow): Contents

Alcian blue stain

Alcian blue stain

Subperineurial Edema: Contents
  Background: Irregular & punctate clusters of mucopolysacharides (Alcian blue positive)
  Cells: Large nuclei; Some have Alcian blue positive cytoplasm

Alcian blue stain

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Subperineurial Edema: Subperineurial vessels

Toluidine blue stain

Toluidine blue stain

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Subperineurial Edema: Endoneurial vessels

Gomori trichrome stain	Gomori trichrome stain
Endoneurial vessels: Large with large endothelial nuclei
Gomori trichrome stain	Gomori trichrome stain

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Toluidine blue stain

Toluidine blue stain

Toluidine blue stain

Endoneurial vessels: Large with large endothelial nuclei

Toluidine blue stain

Toluidine blue stain

Toluidine blue stain

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C5b-9 stain C5b-9 complement: Deposited on endoneurial microvessels (capillaries)

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Subperineurial Edema: Ultrastructure
  Contains
    Granular, Proteinaceous fluid
    Cells: Fibroblasts & Macrophages, Few
  Bordered by
    External: Perineurium
    Internal: Endoneurial collagen, axons & Schwann cells
Subperineurial space: Contains
  Granular material
  Collagen: Small amounts
  Fibroblasts & Macrophages, Rare
  Endoneurial microvessels: May have thick wall & Large endothelium

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Endoneurial microvessel (capillary) within region of subperineurial edema
  Contains
    Endothelial cell (Large): In lumen
    Pericyte: In vessel wall (Above)
    Fibroblast: Outside vessel (Below)

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Subperineurial edema
  Space under perineurium: Contains granular, mostly acellular material

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Subperineurial edema
  Axon loss pattern: Differential fascicular
    Varies within and among fascicles
    Some regions (Left fascicle) have complete loss of large and small axons
    Other regions (Right) have relatively preserved populations of large and small axons.

Neurofilament stain

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Subperineurial Edema & Hemorrhage

Toluidine blue stain

Hemorrhage in subperieurial space

Toluidine blue stain

Hemorrhage may also be in perineurium

Toluidine blue stain

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References
1. Muscle Nerve 2016;53:705-710

8/8/2018