Causes

The two most common causes of a typical length-dependent peripheral neuropathy are diabetes and alcohol use.

Other causes:

• Inflammatory process: Guillain-Barré syndrome (acute), CIDP (chronic), diphtheria (acute)
• Critical illness
• Metabolic: uremia, liver disease, B12 or folate deficiency, thiamine deficiency, B6 deficiency or overuse, porphyria
• Infectious/granulomatous: HIV/AIDS, leprosy, Lyme, sarcoid
• Vasculitis: lupus, polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis, Sjogren’s syndrome, cryoglobulinemia
• Neoplastic/paraneoplastic (esp. paraproteinemic)
• Toxin: drugs (esp. platinum and vinca alkaloid based chemotherapy, amiodarone, antiretrovirals), metals (e.g. mercury, arsenic, and thallium), shellfish
• Hereditary
• Entrapment (more common in diabetes, hypothyroidism, RA, amyloidosis, acromegaly)

Evaluation

• Nerve distributions of motor/sensory disturbances (symmetric vs. asymmetric? distal vs. proximal? small fiber vs. large fiber?), reflexes, autonomic symptoms, time course, and age of onset

• Note that Guillain-Barré syndrome presents with sudden ascending weakness and hypo/areflexia

• Labs: consider CBC, CMP, HbA1c, TSH, B12, ESR, TSH, HIV, 24 hour urine for heavy metals, SPEP/UPEP, rheumatoid factor, and ANA
• EMG and nerve conduction studies are helpful in most patients to distinguish between axonal vs. demyelinating neuropathy
• In selected cases, a lumbar puncture may be helpful in looking for protein and/or signs of inflammation

Hughes RA.  Peripheral neuropathy.  BMJ 2002 Feb 23;324:466-469.