Polyneuropathy, Chronic

Key Features

Essentials of Diagnosis

• Insidious onset of weakness and fatigability of the limbs, sometimes with pain or numbness; decreased strength and reflexes

General Considerations

• Causes

  • Toxins (lead, arsenic, mercurials, vincristine, and benzene)

  • Systemic disorders (diabetes mellitus, chronic uremia, recurrent hypoglycemia, porphyria, polyarteritis nodosa, and lupus erythematosus)

  • Inflammatory states (chronic inflammatory demyelinating polyneuropathy and neuritis associated with mumps or diphtheria)

  • Hereditary, often degenerative conditions, which in some classifications include certain storage diseases, leukodystrophies, spinocerebellar degenerations with neurogenic components, and Bassen-Kornzweig syndrome

  • Hereditary sensory or combined motor and sensory neuropathies

Clinical Findings

• Onset is usually insidious

• Condition is slowly progressive

• Disturbances of gait and easy fatigability in walking or running are presenting symptoms

• Weakness or clumsiness of the hands is seen slightly less often

• Pain, tenderness, or paresthesias are mentioned less frequently

• Neurologic examination discloses muscular weakness, greatest in the distal portions of the extremities, with steppage gait and depressed or absent deep tendon reflexes

• Cranial nerves are sometimes affected

• Sensory deficits occur in a stocking-and-glove distribution

• Muscles may be tender

• Trophic changes such as glassy or parchment skin and absent sweating may occur

• Rarely, thickening of the ulnar and peroneal nerves may be felt

• In sensory neuropathy, the patient may not feel minor trauma or burns, and thus allows trauma to occur

• Chronic inflammatory demyelinating neuropathy (CIDP)

  • Most common chronic motor neuropathy of insidious onset

  • Often has no identifiable cause

  • Assumed to be immunologically mediated and may have a relapsing course

  • Sometimes facial weakness occurs

  • CSF protein levels are elevated

  • Nerve conduction velocity is slowed

  • Nerve biopsy findings may show round cell infiltration

Diagnosis

• Electrophysiologic testing confirms diagnosis

• CSF protein levels are often elevated, sometimes with an increased IgG index

• Nerve biopsy, with teasing of the fibers and staining for metachromasia, may demonstrate loss of myelin, and to a lesser degree, loss of axons and increased connective tissue or concentric lamellas (so-called onion bulb appearance) around the nerve fiber

• Muscle biopsy may show the pattern associated with denervation

• Screening for heavy metals as well as for metabolic, renal, or vascular disorders may need to be done

Treatment

• Corticosteroid therapy is used first when the cause is unknown or neuropathy is considered to be due to chronic inflammation

• Prednisone

  • Initiated at 2–4 mg/kg/d orally, with tapering to the lowest effective dose

  • May need to be reinstituted when symptoms recur

  • Should not be used for treatment of hereditary neuropathy

• Immunomodulating therapy may be safer or "steroid-sparing"; options include

  • IVIg

  • Plasmapheresis

  • Mycophenolate mofetil

  • Rituximab

Outcome

Prognosis

• Varies with the cause and the ability to offer specific therapy

References