Dysmyelination

DYSMYELINATION
Metachromatic Leukodystrophy (MLD) (& Krabbe)

Histochemistry
Myelin sheath thin: TB; EM
Onion bulbs
Macrophages
Prismatic inclusions
Schwann cells
Debris & Inclusions
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 Cells & Myelin

NCAM stain (Green)
P0 stain (Red)

Myelin (Red)
Contains patches of NCAM stain (Yellow)
Bungner Bands (Few) (Yellow)
Contain both P0 & NCAM
Scattered in endoneurium

Small Axons (Yellow)
Nearly normal numbers

Neurofilament stain (Green)
NCAM stain (Red)

Neurofilament stain (Green)
MBP stain (Red)

Myelin
MBP stains myelin around both large and small axons
Normals mainly have MBP in mnyelin around larger axons

Neurofilament stain (Green)
P0 stain (Red)

Axons
Near normal numbers of myelinated (Yellow) and unmyelinated (Green) axons

P0 stain (Green)
MBP stain (Red)

Myelin: Immature
Most myelin, even around smaller axons contains both P0 and MBP (Yellow)
Some myelin sheaths have only MBP (Red)

MLD: Reduced or Absent Myelin Sheath

Unmyelinated axons: Surrounded by Schwann cells

Axons with thin, or folded, myelin sheath

Rudimentary Onion bulb
Small, single layer of basal lamina & Schwann cell processes surrounds axons & Schwann cells

MLD: Schwann cell inclusions

Myelin: Compact layers (Thin) interrupted by Schwann cell cytoplasm containing debris (Above)
Axons: Moderately or Severely thin myelin sheath
Schwann cells: Contain myeloid debris in secondary lysosomes

Myelin sheath: Normal
Schwann cell cytoplasm: Contains myeloid debris in secondary lysosomes

Schwann cells: Cytoplasm contains Tuffstone inclusions & Myeloid debris
Myelin sheath: Thin

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