Causes of nerve thickening
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Nerve thickening (peripheral nerve enlargement) has several causes - leprosy is the classic one, but there are others including hereditary neuropathies and infiltrative conditions.
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Here is a structured, textbook-based overview of the causes of nerve thickening (peripheral nerve hypertrophy/enlargement):
Causes of Nerve Thickening (Peripheral Nerve Enlargement)
Palpation of peripheral nerves is an important part of the neurological examination. Nerve enlargement can be focal/single nerve or generalized/multifocal, and the pattern points toward different diagnoses.
Pattern 1: Single Nerve Thickening
| Cause | Notes |
|---|---|
| Neurofibroma | Benign nerve sheath tumor; single or multiple (in NF1) |
| Schwannoma | Benign tumor arising from Schwann cells |
| Malignant peripheral nerve sheath tumor (MPNST) | Often in NF1; rapidly enlarging, painful |
| Localized perineurial hypertrophic neuropathy (perineurioma) | Focal fusiform enlargement; slowly progressive painless mononeuropathy; affects young adults; cannot be localized to typical entrapment sites |
| Déjérine-Sottas disease (focal form) | Localized enlargement at the wrist; tender painful mass due to hypertrophic interstitial neuropathy |
Pattern 2: Generalized or Multifocal Nerve Thickening
These are the classic causes of diffuse palpable nerve enlargement:
| Cause | Key Features |
|---|---|
| Leprosy (Mycobacterium leprae) | Most common cause worldwide; thickened, tender peripheral nerves (ulnar, common peroneal, greater auricular, radial cutaneous, sural); one of the 3 cardinal diagnostic signs |
| Neurofibromatosis (NF1) | Multiple neurofibromas along nerve trunks; cafe-au-lait spots |
| Charcot-Marie-Tooth (CMT) disease - Types 1 and 3 | Hereditary demyelinating neuropathy; "onion bulb" formation on nerve biopsy due to repeated demyelination/remyelination |
| Refsum disease (phytanic acid storage disease) | Autosomal recessive; elevated serum phytanic acid; hypertrophic neuropathy with onion bulbs on sural nerve biopsy; associated with retinitis pigmentosa, ichthyosis, overriding toes |
| Acromegaly | Nerve enlargement from hypertrophic neuropathy; also causes carpal tunnel syndrome |
| CIDP (Chronic inflammatory demyelinating polyneuropathy) | Rarely causes palpable nerve thickening |
| Amyloidosis | Nerve infiltration by amyloid deposits |
Pattern 3: Specific Contextual Causes
- Carpal tunnel syndrome (CTS): Proximal nerve thickening on ultrasound at the wrist (secondary, not primary nerve enlargement)
- Hypothyroidism / Acromegaly / Mucopolysaccharidosis / Rheumatoid arthritis: Connective tissue thickening around nerves causing compression (e.g., CTS), as noted in - Adams and Victor's Principles of Neurology
- Déjérine-Sottas (HMSN III): A severe hypertrophic demyelinating neuropathy
Memory Aid (Generalized Nerve Thickening - "LNCRAR")
- L - Leprosy
- N - Neurofibromatosis
- C - CMT (types 1 & 3)
- R - Refsum disease
- A - Acromegaly
- R - Rarely CIDP
Key teaching point: A single thickened nerve trunk suggests a neoplastic process or localized perineurioma. Generalized or multifocal nerve thickening points toward leprosy, neurofibromatosis, CMT types 1/3, acromegaly, Refsum disease, or (rarely) CIDP. - Bradley and Daroff's Neurology in Clinical Practice
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