Metachromatic Leukodystrophy (MLD) (& Krabbe)

Myelin sheath thin: TB; EM
Onion bulbs
Prismatic inclusions (Macrophages)
Schwann cells
  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)
        • Toluidine blue
      • PAS positive

H&E stain
  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
    Irregularly oriented granular material
    Areas with 5.8 nm periodicity
    Peripheral lamellae oriented perpendicular to surface
    Vacuoles: Electon lucent

Tuffstone bodies

MLD: Macrophages

Prismatic ("Herringbone") inclusions
  Commonly in endoneurial macrophages
  Stacks of lamellar disks

MLD: Muscle

Muscle fiber sizes: Mild variation; No denervation

Muscle fiber types
  Fiber type grouping: Mild
  Type 2C: Increased numbers

Krabbe disease: Globoid cells

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