CIDP Subacute

Immune Demyelinating Polyneuropathy: Subacute Onset (SIDP)

Note: Patient & Laboratory features

Clinical
- 55 & 70 yo females
- Onset: Progressive over 6 to 8 weeks
- Weakness
  - Severe
  - Proximal & Distal
  - Legs > Arms
- Sensory loss: Panmodal
- Course: Monophasic; Improvement to normal strength
NCV
- Demyelination
  - Conduction velocities, motor: Variably slowed (12 to 31 M/s)
  - Distal latencies: Long
  - Temporal dispersion
- Axon loss
  - SNAPs: Reduced amplitude or Absent
Pathology
- Demyelinated Axons
  - Distribution: Diffuse or Patchy
  - Axons
    - Demyelinated
    - Partial Remyelination (Thinly myelinated)
    - Small onion-like bulbs
- Axons with Myelin present
  - Myelin structure: Irregular
  - Myelin staining: Reduced (Gomori trichrome)
  - Hypomyelination: Very thin myelin sheaths
- Axon loss
  - Varied among & within fascicles
  - Active loss: Wallerian degeneration may be present
- Subperineurial edema
- Vessels
  - Endoneurial: Diameter enlarged; Endothelial cells large
  - Epineurial: Normal structure; No immune cells
- Muscle

Nerve: Axon loss, Varied; Myelin loss, Varied or Diffuse

Neurofilament stain
Axons (Same nerve as on right )
Axon loss: Varied loss of large & small axons within & among fascicles
Large axons:
Demyelinated
Preservation of some large axons without surrounding clear myelin rim

Toluidine blue stain
Myelinated axons
Nearly complete loss of myelin in some fascicles
Subperineurial edema

VvG stain

Differential fascicular involvement
Varied loss of myelinated axons among & within fascicles

Gomori trichrome stain

Myelin Pathology

H& E stain

Myelin Sheaths
Scattered sheaths with pale staining

Gomori trichrome stain

Myelin Sheaths
Scattered sheaths with pale (loss of red) staining

Gomori trichrome stain

Myelin Sheaths
Some have irregular structure (Arrow)

VvG stain

Myelin Sheaths
Remaining Large Myelin Sheaths: Abnormal molecular structure
Many sheaths have MBP (Red) present in regions without P0
Few sheaths have normal co-staining of MBP + P0 (Yellow)
Small Myelin Sheaths: Normal pattern of P0 without MBP (Green)

P0 (Green) + MBP (Red)

Myelin Sheaths
Remaining Large Myelin Sheaths
Abnormal molecular structure: Some have NCAM (Yellow) costaining with P0
Büngner bands, Scattered: NCAM-P0 costained (Yellow) non-myelinating Schwann cells

NCAM (Green) + P0 (Red)

Myelin Sheath Structure

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

Nerve
Varied loss of Large Axons
Moderate loss of Small Axons

Neurofilament stain

Neurofilament stain

Axon Loss
Some fascicles have more loss of large (thick) axons (Right) than others (Left)
Small axons are generally moderately reduced
Empty Non-myelinating Schwann cells (Red; Below)

Neurofilament (Axons; Green) + NCAM (Non-myelinating Schwann cells; Red)

Axon Loss
Small axons
Generally moderately reduced in number
Many Non-myelinating Schwann cells have no axon (Red)
Some remaining small axons have abnormal beaded structure

Neurofilament (Axons; Green) + NCAM (Non-myelinating Schwann cells; Red)

Ongoing Axon Loss + Demyelinated Axons
Some MBP myelin sheaths (Red)
Are irregularly shaped
Have no associated axon: Indicates active, recent axon loss (Wallerian degeneration)
Large axons (Green): Demyelinated
Many have no MBP myelin sheath
Some have MBP costaining (Yellow) indicating association with immature Schwann cells that do not produce myelin

Neurofilament (Axons; Green) + MBP (Myelin; Red)

From: R Schmidt

Wallerian Degeneration: Autophagic Schwann Cell
Myelin breakdown products within Schwann cells, especially outside myelin sheath
Degenerating axon inside damaged myelin sheath
Macrophage (Top right)
Processes surround Schwann cell

From: R Schmidt

Wallerian Degeneration
Schwann cell cytoplasm contains
Degenerated myelin (Ovoid)
Pi granules

Large axons: Demyelinated & Poorly formed small onion bulb-like structures (Pseudo-onion bulbs)

Toluidine blue stain

Toluidine blue stain

Demyelinated axons: Pseudo-onion bulbs
Demyelinated, or thinly myelinated axons, may be surrounded by poorly formed onion bulbs & Schwann cell nuclei (Arrow)

From: R Schmidt

Pseudo-Onion-Bulbs
Center: Schwann cell with large nucleus surrounds thinly myelinated axon
Surround: Layers of interdigitated Schwann cell processes are separated by collagen

From: R Schmidt

From: R Schmidt

Pseudo-Onion-Bulbs
Center: Schwann cell process surrounds thinly myelinated axon
Surround: Layers of interdigitated Schwann cell processes are separated by collagen

Large axons: Demyelinated

Neurofilament (Axons; Green) + P0 (Myelin (Red)

Demyelination of Large Axons that are normally myeliniated
Many large axons have no associated myelin (Green; Arrow)
Small Unmyelinated Axons
Moderately reduced in number
Remaining small axons often have irregular or beaded structure

From: R Schmidt

Demyelinated Axon
Surrounded by multiple Schwann cell processes
No myelin

From: R Schmidt

From: R Schmidt

Demyelinated Axon
Axon contents
Closely packed filaments (Above)
Moderately separated filaments (Below)
Surrounded by Schwann cell processes
No myelin

From: R Schmidt

Demyelinated Axon
Immediately surrounded by Schwann cell process
Neighboring large Schwann cell contains multiple pi granules

From: R Schmidt

Remyelination

Remyelinated small axon (Above)
Very thin myelin sheath
Axon with thick but irregular myelin sheath (Below)
Schwann cell cytoplasm contains Pi granules
Büngner Band, Small (Top Right)

From: R Schmidt

Remyelinated small axon (See Above)
Myelin sheath: Very thin
Schwann cell cytoplasm contains multiple mitochondria

From: R Schmidt

From: R Schmidt

Remyelinated small axons
Myelin sheath: Very thin

From: R Schmidt

From: R Schmidt

Remyelinated small axon
Myelin sheath: Very thin

Subperineurial Edema

H & E stain
Subperineurial Edema: Clear region beneath long area of perineurium

Toluidine blue stain
Subperineurial Edema & Few normally myelinated axons

H & E stain
Region of subperineurial edema:
Contains amorphous material and small vessels

Toluidine blue stain
Intrafascicular septa:
Widened & Cellular
Contains enlarged endoneurial vessel
Myelinated Axons: Few remaining; Small

Endoneurial microvessels: Large size; Abnormal endothelial cells with large nuclei

H&E stain

Endoneurial microvessels: Enlarged with large endothelial cells

VvG stain

Gomori trichrome stain

Gomori trichrome stain

Endoneurial microvessels: Enlarged with large endothelial cells

H&E stain

Endoneurial Microvessels
Normal Alkaline phosphatase staining

Alkaline phosphatase stain

From: R Schmidt

Endoneurial microvessels
Walls have layers of concentric cell processes separated by connective tissue

From: R Schmidt

From: R Schmidt

Endoneurial microvessel
Wall has layers of concentric cell processes separated by connective tissue

Endoneurial Autophagic/Phagocytic cells

Acid phosphatase stain

Endoneurial Cells
Scattered small & punctate acid phosphatase stained cells
Relatively little staining of myelin
Some histiocytes may be lacated near a subperineurial endoneurial microvessel (Below, Left)
Compare to: Active Demyelination

Acid phosphatase stain

Acid phosphatase stain

Macrophage, Endoneurial
Surrounded by collagen
Two small unmyelinated axons & a Büngner band with a collagen pocket, but without an axon, are also present

From: R Schmidt

From: R Schmidt

Schwann cell, Autophagic (Above)
Contains lipid droplets, vesicles & pi granules
Macrophage (Below)
Has: Small processes extennding from surface; Large nucleus