• Clinical science



Polyneuropathy is a disorder that involves damage to multiple peripheral nerve fibers. The condition can be caused by diabetes mellitus, alcoholism, hereditary diseases, toxins, infection, or other inflammatory conditions. The classic presentation is a symmetric distal burning or loss of sensation. Further clinical features depend on whether an axonal or demyelinating nerve injury has occurred. Diagnostic tests such as electrodiagnostic studies are indicated in the case of atypical clinical features, unknown etiology, and/or severe or rapidly progressive symptoms. Management involves treatment of the underlying disorder and symptomatic therapy (e.g., control of neuropathic pain).



Clinical features


  • Symmetric distal sensory loss (glove and stocking pattern)
  • May be accompanied by neuropathic pain, paresthesias, and motor weakness
  • Atrophy and paresis of muscles: e.g., “stork legs” in the case of HMSN type I
  • Sensory ataxia: e.g., sensory ataxia due to vitamin B12 deficiency
  • Deep tendon reflexes

Axonal vs. demyelinating

Axonal Demyelinating
Chronic Acute Chronic Acute


  • Slow decline over years
  • Months to years of slow, yet incomplete recovery
  • Variable (periods of recovery, stabilization, exacerbations, or slow decline)
  • Variable
  • Affects longer axons first (begins in lower extremities → sternum (intercostal nerves) → head)
  • Early disease: sensory symptoms > motor symptoms
  • Similar, but symptoms more severe
  • Significant pain
  • Early disease: motor symptoms = sensory symptoms
  • Early disease: motor symptoms > sensory symptoms
  • Distal muscle wasting: feet, lower legs, hands (severe cases)
  • Distal sensory loss (pain, temperature, proprioception, vibration)
  • Reduced or absent distal reflexes (usually begins in the ankles)
  • Generalized muscle weakness: distal > proximal
  • Diffusely reduced or absent reflexes
Associated conditions


Subtypes and variants

Diabetic polyneuropathy

Alcoholic polyneuropathy

Hereditary motor sensory neuropathies

  • Definition: progressive hereditary peripheral nerve disorders due to impaired Schwann cell growth and function
  • Etiology
  • Characteristic feature: ascending flaccid paralysis; and atrophy, which begins distally; sensory deficits may occur later (type I, III, and IV cause hypertrophic neuropathy)
  • Important types
    • HMSN type I (Charcot-Marie-Tooth disease)
      • Distal symmetric sensorimotor polyneuropathy with atrophy of the calf muscles (“stork legs”) and pes cavus deformity (sensory loss occurs late)
      • Intrinsic hand musculature may become involved after several years.
      • May be associated with sleep apnea
      • Nerve biopsy: repeated demyelination and remyelination evident in large nerve fibers (onion peel appearance)
      • Nerve conduction studies: ↓ impulse conduction velocity
    • HMSN type IV (Refsum disease)
    • HMSN type V
      • Associated with hereditary spastic paraplegia
      • Combination of spastic spinal paralysis, type VI and VII HSMN, and ocular symptoms
      • Nerve conduction studies: normal or mildly ↓ nerve conduction
  • Treatment: See “Treatment” below.



Further tests are usually indicated in patients with atypical clinical features, an unknown etiology, and/or severe or rapidly progressive symptoms.

  • Electrodiagnostic studies
    • Nerve conduction studies on the sural nerve: to determine the type of neuropathy and with it the possible cause
      • Primary demyelination: ↓ impulse conduction velocity, normal amplitude
      • Axonal degeneration: normal impulse conduction velocity, ↓ amplitude
    • Electromyography (EMG): e.g., spontaneous electrical activity at rest (denervation potentials) in the case of axonal degeneration
  • Laboratory tests (selection depends on the suspected underlying disorder)
  • If necessary: nerve-muscle biopsies (useful to identify a small fiber sensory neuropathy or infiltrative disorders), skin biopsy (useful to identify small fiber sensory neuropathies), molecular genetic tests for suspected hereditary disorders


Differential diagnoses

Differential diagnosis of impaired sensation and sensory ataxia

Polyneuropathy Multiple sclerosis Subacute combined degeneration Tabes dorsalis Compressive myelopathy


  • Acute or chronic demyelination and/or axonal degeneration due to:
Impairment of sensation
  • Symmetrical distal loss of all the types of sensation (stocking-and-glove distribution)
  • Loss of all the types of sensation is possible (distribution depends on the lesion).
  • Loss of position and vibration sense below the level of the lesion
  • Loss of position and vibration sense below the level of the lesion
  • Loss of pain and temperature sensation below the level of compression is most common.
Motor neuron signs
  • None
Other features


The differential diagnoses listed here are not exhaustive.


Treatment efficacy can only be assessed after 2–4 weeks of therapy! Since complete pain relief is often not possible, a tolerable level of pain can be an acceptable treatment goal!