NSVN

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

Pathology features

Nerve
- Epineurium: Vessels
  - Inflammation
    - Surrounds small epineurial vessels
    - Histiocytes in vessel walls
  - Structure: Damaged wall & Smoooth muscle layer
  - Neovascularization
- Axons
  - Wallerian degeneration
  - Loss: Differential fascicular
- Endoneurium
  - Loss of ATPase stain
  - Edema: Subperineurial & Endoneurial
Muscle
- Denervation, subacute

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

Perivascular Inflammation
Surrounds small epineurial vessels (Below; Arrow)
Larger epineurial arteries & veins: Varied pathology

H&E stain

H&E stain

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

CD4 stain

CD8 stain

Histiocytes in & near Epineurial Vessel walls

Acid Phosphatase stain

MHC Class I
Expressed by epineurial cells & connective tissue

MHC Classs I stain

NSVN Vessel Damage: Smoooth Muscle Layer
Varied at different levels
Irregular width & Damaged (Above; Arrow)
More normal: Dark stained in vessel wall (Below)
Inflammation
Cells surround epinerial vessels
Neovascularization
Below damaged vessel

ATPase pH 4.3 stain

VvG stain

NSVN Vessel Damage: Epineurial Neovascularization
Increased numbers of smaller epineurial vessels

UEA I stain

NSVN: Endoneurium

H&E stain

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

Gomori trichrome stain

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

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

ATPase pH 4.3 stain

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

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

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

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

VvG stain

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)

Wallerian degeneration
Acid phosphatase stains myelin & some phagocytic endoneurial cells