Peripheral Nerve Neuropathology
What You'll Learn
- The two fundamental reaction patterns — axonal degeneration vs segmental demyelination — and how the biopsy shows them
- Immune/inflammatory neuropathies (GBS, CIDP, vasculitic) on tissue
- Hereditary neuropathies and their signatures (onion bulbs, tomacula)
- Infiltrative causes — amyloid, leprosy, sarcoid — and the biopsy tools that reveal them
The neuropathology view of nerve biopsy. Clinical evaluation of neuropathy lives in the Neuromuscular / Peripheral Nerve notes.
- Axonal degeneration: Wallerian change with myelin ovoids / digestion chambers; teased fibers show linear myelin debris; loss of large myelinated fibers.
- Segmental demyelination & remyelination: thinly myelinated axons and “onion-bulb” Schwann-cell whorls; teased fibers show internodal myelin loss with preserved axon.
- Vasculitic neuropathy: asymmetric (mononeuritis multiplex), axonal with epineurial vessel wall inflammation + fibrinoid necrosis; wallerian degeneration of varying age.
- Amyloid neuropathy: Congo red apple-green birefringence in endoneurium/vessels (ATTR or AL).
- Onion bulbs = chronic demyelinating (CMT1 / CIDP); tomacula (sausage-like myelin thickenings) = HNPP.
Reaction Patterns
| Pattern | Histology | Teased fiber / EM |
|---|
| Axonal degeneration | Loss of myelinated fibers; digestion chambers (myelin ovoids); denervated bands of Büngner | Linear rows of myelin debris; axon lost |
| Segmental demyelination | Thinly myelinated fibers; onion bulbs with chronicity | Internode with myelin loss, axon intact |
| Regeneration | Regenerating clusters (small thinly myelinated fibers grouped) | — |
Immune / Inflammatory Neuropathies
| Entity | Pathology | Clue |
|---|
| Guillain-Barré (AIDP) | Endoneurial edema + macrophage-mediated segmental demyelination, perivascular lymphocytes; roots/proximal | Post-infectious; albuminocytologic dissociation |
| CIDP | Chronic demyelination/remyelination, onion bulbs, endoneurial edema; patchy | Relapsing/progressive >8 wk |
| Vasculitic neuropathy | Epineurial vessel transmural inflammation + fibrinoid necrosis → ischemic axonal loss; wallerian degeneration of differing ages, asymmetric fascicular involvement | Mononeuritis multiplex; PAN, ANCA-vasculitis |
Hereditary Neuropathies
| Entity | Pathology | Gene / signature |
|---|
| CMT1 (demyelinating) | Prominent onion bulbs, thin myelin, “hypertrophic” nerve | PMP22 duplication; slow conduction |
| CMT2 (axonal) | Chronic axonal loss, regenerating clusters | MFN2 and others; normal-ish conduction |
| HNPP | Tomacula (focal sausage-shaped myelin thickenings) + segmental demyelination | PMP22 deletion |
| Metachromatic / Krabbe | Metachromatic granules (toluidine blue) / globoid cells; demyelination | ARSA / GALC (also CNS) |
Infiltrative & Infectious
| Entity | Pathology | Stain |
|---|
| Amyloid neuropathy | Amorphous deposits in endoneurium & vessel walls; axonal loss (small fiber early) | Congo red apple-green; typing (ATTR/AL) |
| Leprosy | Granulomatous (tuberculoid) or foamy-macrophage (lepromatous) nerve infiltration | Acid-fast (Fite) bacilli in nerve |
| Sarcoid | Non-caseating epineurial/perineurial granulomas | Exclusion; organisms negative |
Biopsy Tools
- Sural nerve (sensory) is the standard site; combine with muscle when vasculitis is suspected.
- Paraffin H&E (architecture, inflammation) + semithin toluidine-blue sections (fiber density/myelin) + teased fibers (axonal vs demyelinating) + EM (unmyelinated fibers, tomacula, amyloid fibrils).
- Congo red for amyloid; Fite for leprosy.
| Finding | Diagnosis |
|---|
| Digestion chambers / myelin ovoids | Axonal (Wallerian) degeneration |
| Onion bulbs | Chronic demyelination (CMT1 / CIDP) |
| Tomacula | HNPP (PMP22 deletion) |
| Epineurial vessel fibrinoid necrosis | Vasculitic neuropathy |
| Congo red apple-green in endoneurium | Amyloid neuropathy |
| Fite+ bacilli in nerve | Leprosy |
References
- Midroni G, Bilbao JM. Biopsy Diagnosis of Peripheral Neuropathy.
- Love S, et al. Greenfield's Neuropathology. 9th ed. 2015.
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