Causes of nerve thickening

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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

CauseNotes
NeurofibromaBenign nerve sheath tumor; single or multiple (in NF1)
SchwannomaBenign 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:
CauseKey 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 3Hereditary 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
AcromegalyNerve enlargement from hypertrophic neuropathy; also causes carpal tunnel syndrome
CIDP (Chronic inflammatory demyelinating polyneuropathy)Rarely causes palpable nerve thickening
AmyloidosisNerve 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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