Dysmyelination

DYSMYELINATION
Metachromatic Leukodystrophy (MLD) (& Krabbe)

Histochemistry
Myelin sheath thin: TB; EM
Onion bulbs
Prismatic inclusions (Macrophages)
Schwann cells
Debris
Molecular features
Tuffstone bodies

Metachromatic Leukodystrophy (MLD)

Toluidine blue stain

Hypomyelinated axons

Metachromatic Leukodystrophy (MLD)
Schwann cells
Contain cytoplasmic debris, particulate & clear
Axons surrounded by
Thin myelin sheaths & Onion bulbs, small

Toluidine blue stain

Myelinating Schwann cells
Contain particulate & clear debris in cytoplasm
Onion Bulbs: Small

MLD Histochemistry

Hypomyelination
Lysosomal activation: Some endoneurial cells
Storage material
- Most reliably assessed on frozen tissue
- Stains
  - Brown-Yellow metachromatic material
    - Hirsch-Peiffer (Acidified Cresyl Violet)
      - Polarized light: Produces yellow-green dichromism
      - Also stains: Reich (Pi) granules
    - Toluidine blue
  - PAS positive

H&E stain

Endoneurium
Pale
Increased space between axons

H&E stain

Gomori trichrome stain

Reduced staining for myelinated axons

Gomori trichrome stain

Larger axons
Increased space between axons

VvG stain

Larger axons: Normal to mildly reduced numbers
Smaller axons: Reduced numbers in some endoneurial areas

Neurofilament stain

Lysosomal activity in some endoneurial cells

Acid phosphatase stain

Schwann Cell Types

Bungner Bands (Yellow)
Contain both P0 & NCAM
Scattered in endoneurium

NCAM stain (Green)
P0 stain (Red)

Neurofilament stain (Green)
NCAM stain (Red)

Neurofilament stain (Green)
MBP stain (Red)

Neurofilament stain (Green)
P0 stain (Red)

P0 stain (Green)
MBP stain (Red)

MLD: Reduced or Absent Myelin Sheath

Unmyelinated axons: Surrounded by Schwann cells

Axons with thin, or folded, myelin sheath

Onion bulb: Small, single layer of basal lamina around axons & Schwann cells

MLD: Schwann cell inclusions

Axons: Moderately or Severely thin myelin sheath
Schwann cells: Contain myeloid debris in secondary lysosomes

Schwann cells: Cytoplasm contains Tuffstone inclusions & Myeloid debris

Schwann cells with Cytoplasmic inclusions

MLD: Tuffstone Bodies

Tuffstone bodies
Electron dense: Sharply demarcated
Most common in Schwann cells of myelinated & unmyelinated axons
Contain
Irregularly oriented granular material
Areas with 5.8 nm periodicity
Peripheral lamellae oriented perpendicular to surface
Vacuoles: Electon lucent