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Nerve Specific (Non-Systemic) Inflammatory Vasculopathic Neuropathy (NSVN)

Pathology features

• Nerve
  • Epineurium
    • Inflammation: Surrounds small epineurial vessels
    • Neovascularization
  • Axons
    • Wallerian degeneration
    • Loss: Differential fascicular
  • Endoneurium
    • Loss of ATPase stain
    • Edema: Subperineurial & Endoneurial
• Muscle
  • Denervation, subacute

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H&E stain

Perivascular Inflammation
  Surrounds small epineurial vessels (Below; Arrow)
  Larger epineurial Arteries & Veins: Varied pathology
    May be Normal (Below) or Damaged (Above)
  Epineurium: May have neovascularization (Above; White Arrow))

Congo red stain

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H&E stain

Perivascular Inflammation
  Surrounds small epineurial vessels (Below; Arrow)
  Larger epineurial arteries & veins: Varied pathology
    May be Normal (Below) or Damaged (Above)
  Epineurium & Vessel walls: May have neovascularization (Above)

H&E stain

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H&E stain

Perivascular Inflammation: T-cells
  Surrounds small epineurial vessels
  Contains CD4 & CD8 lymphocytes

CD4 stain

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CD8 stain

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Histiocytes in & near Epineurial Vessel walls

Acid Phosphatase stain

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NSVN: Neovascularization

H&E stain

H&E stain

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NSVN: Large vessel damage

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NSVN: Endoneurium

H&E stain

NSVN: Nerve Edema
  Present in subperineurial & endoneurial regions between fascicles

Gomori trichrome stain

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NSVN: Axons

VvG stain

NSVN: Differential Fascicular Involvement
  Varied Loss (Above) & Degeneration (Above & Below) of myelin & axons within & among fascicles
  VvG (Above) shows: Irregular staining of damaged myelin
  Acid phosphatase (Below) stains: Damaged myelin sheaths
Epineurium
  Damged structure in some regions

Acid Phosphatase stain

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ATPase stain pH 4.3
  Ischemia: Reduced staining in endoneurium
  Vessels in endoneurium are normally stained

ATPase pH 4.3 stain

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NSVN: Wallerian degeneration
  Axons: Degeneration & Loss
  Myelin: Pathology, Phagocytosis & Loss

Neurofilament stain

Axon loss: Acute
  Granular, punctate staining in areas that previously contained large myelinated axons

Neurofilament stain

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Axon loss: Large & Small
  Differential intrafascicular loss of both large and small axons (bottom right of image).
    The many empty non-myelinating Schwann cell (NCAM; Red) sheaths show loss of small axons.
    Large axons (Green) are also lost in the damaged region compared to the more intact area (upper left)

Neurofilament (Green) + NCAM (Red) stain

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Differential Intrafascicular Axon loss
  More loss in lower regions
  Involves both Large (Empty myelin sheaths (Red)) & Small (Green) axons
Ongoing axon loss: Punctate neurofilament staining within P0 myelin sheaths
Complete axon loss: Some P0 myelin sheaths have no neurofilament-stained axon

Neurofilament (Green) + P0 (Red) stain

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Wallerian degeneration, Early: Myelin pathology
  Damaged myelin sheaths: Irregularly stained by VvG

VvG stain

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Wallerian degeneration, Early: Myelin pathology
  Schwann cells associated with abnormal myelin around degenerating myelinated axons abnormally express NCAM

NCAM stain Wallerian degeneration, Early

NCAM (Green) + P0 (Red) stain   Schwann cells associated with abnormal myelin around degenerating myelinated axons abnormally co-express NCAM (Green) & P0 (Red)

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Wallerian degeneration
  Acid phosphatase stains myelin & some phagocytic endoneurial cells

Acid Phosphatase stain

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Toluidine blue stain

Wallerian degeneration
  Phagocytic endoneurial Schwann cells & Histiocytes contain myelin debris & lipid droplets

Toluidine blue stain

Toluidine blue stain

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NSVN: Acutely denervated muscle
  Muscle fibers: Midly small; Myonuclei are mildly large
NSVN: Acutely denervated muscle
  Muscle fibers: Irregular staining of cytoplasm
NSVN: Acutely denervated muscle
  Muscle fibers: Irregular internal architecture

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Endomysial histiocytes near capillaries

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Return to Muscle biopsies

1/8/2024