Peripheral nerve injury: axonal vs demyelinating
- Mechanism
A nerve can fail because its axon dies, because its myelin is stripped, or because its neuron body dies. Where the damage lies sets the symptoms.
What it is
Peripheral neuropathies damage either the axon, the myelin made by Schwann cells, or the neuron cell body in the anterior horn or dorsal root ganglion. Axonal neuropathies (from toxins, metabolic disease, ischaemia or transection) cause Wallerian or distal 'dying-back' degeneration and recover slowly by regrowth. Demyelinating neuropathies (immune, inherited) strip myelin in segments, slow conduction and can recover quickly by remyelination; repeated cycles create onion bulbs. Neuronopathies kill the cell body and leave no chance of regrowth. The anatomic pattern, from symmetric length-dependent polyneuropathy to mononeuritis multiplex, points to the cause.
Structure
- Teased fibres and plastic sections: axonal degeneration shows myelin ovoids and loss of large fibres; regeneration shows clusters of small thinly myelinated axons.
- Segmental demyelination: internodes of absent or thin myelin with intact axons; remyelinated segments are short and thin.
- Onion bulbs: whorls of Schwann cell processes and collagen around a central axon; the nerve may be visibly enlarged.
- Neuronopathy: loss of neurons in dorsal root ganglia or anterior horns with secondary loss of their axons.
Step by step
- Axonal injury cuts the axon off from the cell body's supply of proteins and mitochondria.
- The distal axon degenerates and Schwann cells and macrophages clear the debris (Wallerian degeneration).
- Schwann cells line up in bands of Büngner and guide a regrowing sprout from the proximal stump.
- In demyelination, Schwann cells or myelin are attacked while the axon survives, so conduction slows or blocks.
- Schwann cells remyelinate the bare segments with thinner, shorter internodes; repeated cycles build onion bulbs.
Patterns of peripheral nerve disease
| Pattern | Distribution | Typical causes |
|---|---|---|
| Distal symmetric polyneuropathy | Stocking-glove, feet first, length-dependent | Diabetes, alcohol, B12 deficiency, uraemia, chemotherapy, HIV |
| Mononeuropathy | One nerve | Entrapment (carpal tunnel), trauma, diabetes |
| Mononeuritis multiplex | Several separate nerves in sequence | Vasculitis, diabetes, leprosy, HIV |
| Polyradiculoneuropathy | Proximal and distal, roots involved | Guillain-Barré syndrome, CIDP, CMV in AIDS |
| Plexopathy | Brachial or lumbosacral plexus | Trauma, tumour infiltration, radiation, diabetes |
| Sensory neuronopathy | Non-length-dependent sensory loss, ataxia | Sjögren disease, anti-Hu paraneoplastic, cisplatin |
Clinical notes
- Nerve conduction studies separate axonal from demyelinating disease and guide the search for a cause.
- Nerve biopsy (usually the sural nerve) is used when vasculitis, amyloid or leprosy is suspected.
- Small-fibre neuropathies cause burning pain with normal conduction studies; skin biopsy counts epidermal nerve fibres.
Test yourself
Think of the answer, then tap the question to see it.
What happens to the axon distal to a nerve transection?
It undergoes Wallerian degeneration: axon and myelin break into ovoids cleared by macrophages.
How do nerve conduction findings differ in axonal vs demyelinating neuropathy?
Axonal: low amplitudes with near-normal velocity. Demyelinating: slow velocities, prolonged latencies and conduction block.
What is an onion bulb?
Concentric layers of Schwann cell processes around an axon after repeated demyelination and remyelination.
Which pattern suggests vasculitis?
Mononeuritis multiplex, with separate nerves affected in sequence.
Elsewhere in DurgiPedia
- Peripheral nerve: endoneurium, perineurium, epineurium; myelin
- Nerve injury and regeneration (Wallerian degeneration)
- The nerve action potential
- Types of nerve fibers
- Upper versus lower motor neuron lesions
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Peripheral Neuropathy | MedlinePlus (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.