Neuromuscular

PERIPHERAL NERVE: Normal features

Age changes
  Pi granules
Endoneurium
  Myelinated axons
    Schmidt-Lanterman Cleft
    Node of Raniver
  Unmyelinated axons
Epineurium
Perineurium

Morphology
  Sural nerve
    Adults
      Axons
        Unmyelinated
      Schwann cells
      Epineurial Vessels
      Node of Ranvier
      Schmidt-Lanterman Cleft
  Infraorbital nerve
  Sciatic nerve (Adult)
  Myelin
    Sciatic
    Sural

NCAM stain
Non-Myelinating Schwann cell clusters stained by NCAM
Mild staining is also present in some myelin sheaths


Epineurium
Perineurium
Endoneurium

Adults: Sural nerve

Structure
Fascicles

Nerve Structure

H&E stain
Normal endoneurium, perineurium, epineurium & vessels

Nerve fascicles
Contain normal numbers of myelinated axons in endoneurium

VvG stain

Gomori trichrome stain


VvG stain

H&E stain

Nerve (Sural): Axons
Normal
Large & Small axons in endoneurium
Large axons: Surrounded by clear myelin halos
Small axons: Clustered among large myelinated axons

Neurofilament stain

Axon morphology: 3 size populations
• Large: Thick myelin sheath
• Intermediate: Thin myelin sheath
• Small: Unmyelinated axons


Toluidine Blue stained plastic section

Electron micrograph (Robert E Schmidt MD)

Unmyelinated axons
  Surrounded by
    Schwann cells



Electron micrograph
  (Robert E Schmidt MD)

Nerve (Sural): Schwann cells, Non-myelinating

NCAM1 stain
Neural Cell Adhesion Molecule (NCAM1)
  NCAM is abundant in non-myelinating Schwann (Remak) cells that surround Unmyelinated axons
  NCAM is also present in
    Adaxonal Schwann cell cytoplasm around myelinated axons
    Myelin sheaths of some larger axons
Myelinated axons: Are generally smaller than in the more proximal sciatic nerve

NCAM stain

Epineurial vessels & Supporting cells in endoneurium

ATPase pH 4.3 stain

Epineurial Vessels

VvG stain
Epineurial vessels: Normal
Artery (Black arrow): Linear fibrils near lumen; Thick wall
Vein (White arrow): Interlaced, thin fibrils around outside of vessel; Thin wall


Toluidine blue stain

Gomori trichrome stain

Myelinated axons: Normal numbers
Epineurial vessels
  Intermediate-size & Small
  Alkaline phosphatase: Stains endothelium in some epineurial and endoneurial vessels

Alkaline phosphatase stain

Congo red stain

Nodes of Ranvier
  • Non-myelinated axon segment
      between 2 myelin internodes
  • Anatomy
    • Axon at node
      • Diameter: Reduced
      • Organelle density
        • Increased
      • Length: ~ 1 μm
    • Schwann cells
      • Loops around axon
      • No myelin

Electron micrographs
  (Robert E Schmidt MD)

Schmidt-Lanterman Cleft (Incisure)

Pi (Reich) Granules


Electron micrograph (Robert E Schmidt MD)
Pi Granules

Location
  Myelinating Schwann cells
  Subcellular
    Often adjacent to nucleus
    Some near paranode
Staining
  Metachromatic: Toluidine blue, Hirsch–Peiffer & Methylene blue stains
  Frozen sections: Acid phosphatase, Sudan black & PAS
Size: 1 μM
Structure: Lamellar; 5 nm periodicity
Age
  More common in older patients
  Not present < 8 years of age
Disease associations
  Non-specific
  Not present in recently remyelinated axons
Pi granules: Few or many in cytoplasm of myelinating Schwann cell

Mast cell

Myelin & Schwann cells: Sural nerve


NCAM in Non-myelinating Schwann cells
  Surrounds most small unmyelinated axons (Yellow)
  Not present around large, myelinated axons (Green)
  May occur in the center of larger axons (Yellow)

Neurofilament stain (Green)
NCAM stain (Red)
Overlap (Yellow)

P0 (Red)
  Prominent in myelin around most (large & small) myelinated axons
  Smallest axons (Green), often in clusters, have no myelin or associated P0 staining

Neurofilament stain (Green)
P0 stain (Red)

Myelin basic protein (MBP) in Myelin (Red)
  Most prominent in myelin around largest myelinated axons
  In myelin around fewer axons than P0 (Above)

Neurofilament stain (Green)
Myelin basic protein stain (Red)

Nerve: Sciatic


Neurofilament stain
Large & small axons: Non-uniform distribution within a fascicle

NCAM1 stain


Neurofilament stain
Large & small axons: Non-uniform distribution among fascicles

NCAM1 stain

Nerve: Sciatic

Neurofilament stain
  Regions with varied numbers of large & small axons

Neurofilament stain

Neurofilament stain


NCAM1 stain
  Regions with varied numbers of NCAM+ Schwann cells

NCAM1 stain


Neurofilament stain

Neurofilament stain

Myelin Components



Neurofilament stain (Green)
P0 stain (Red)
P0 (Red)
  Prominent in myelin around most (large & small) myelinated axons
  Smallest axons (Green), often in clusters, have no myelin or associated P0 staining

Neurofilament stain (Green)
P0 stain (Red)

Myelin basic protein (MBP) (Red)
  Most prominent in myelin around largest myelinated axons

Neurofilament stain (Green)
Myelin basic protein stain (Red)

P0 vs Myelin Basic Protein (MBP)


P0 stain (Green)
Myelin basic protein stain (Red)
P0 protein
  Associated with large & small axons
  More around periphery of myelin sheath
Myelin basic protein
  Mainly associated with largest axons
  More toward inside of myelin sheath

P0 stain (Green)
Myelin basic protein stain (Red)

Nerve: Infraorbital (Branch of Trigeminal)



H&E stain
Myelinated Axons: Abundant all through endoneurium

Gomori trichrome stain

VvG stain
Myelinated Axons: Abundant all through endoneurium

H&E stain

Gomori trichrome stain


Acid phosphatase stain
Infraorbital Nerve
  Acid phosphatase positive cells scattered in endoneurium (Above)
  Alkaline phosphatase positive vessels: Few in endoneurium (Below)

Alkaline phosphatase stain

ATPase activity: Abundant in endoneurial cells

ATPase pH 4.3 stain

Infraorbital Nerve
  Larger myelinated axons: Many
  Small unmyelinated axons: Fewer than in sural nerve

Neurofilament stain


NCAM stain
Infraorbital Nerve
  Non-myelinating Schwann (Remak) cells : Fewer than in sural nerve

NCAM stain
NCAM: Present in Schwann cells
  Non-myelinating Schwann (Remak) cells
  Myelinating Schwann cells: Adaxonal & Abaxonal cytoplasm

NCAM stain

Infraorbital Nerve
  Larger myelinated axons (Green): No associated NCAM; Many
  Small unmyelinated axons (Yellow): Fewer than in sural nerve

Neurofilament stain (Green)
NCAM stain (Red)

Infraorbital Nerve: P0 (Red)
  Prominent in myelin (Red) around most (large & small) myelinated axons
  Smallest axons (Green) have no myelin or associated P0 staining

Neurofilament stain (Green)
P0 stain (Red)

Infraorbital Nerve
  Myelin basic protein (MBP) is markedly reduced in myelin around axons compared to sural nerve

Neurofilament stain (Green)
Myelin basic protein stain (Red)


P0 stain (Green)
Myelin basic protein stain (Red)



Nerve: Children


Nerve from child
Axons are smaller &
  myelin sheaths thinner.

Nerve from neonate
Few axons are myelinated.
Fibroblasts are prominent.

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3/21/2017