Neuropathies, Peripheral

Key Features

• Can be categorized on the basis of the structure primarily affected

• Predominant pathologic feature may be axonal degeneration (axonal or neuronal neuropathies) or paranodal or segmental demyelination

• Distinction may be possible on the basis of neurophysiologic findings

Clinical Findings

• Common mononeuropathies

  • Lead to a sensory, motor, or mixed deficit that is restricted to the territory of the affected nerve

  • A similar clinical disturbance is produced by peripheral nerve tumors, but these are rare except in patients with neurofibromatosis type 1

  • Multiple mononeuropathies suggest a patchy multifocal disease process such as

    • Vasculopathy (eg, diabetes, arteritis)

    • Infiltrative process (eg, leprosy, sarcoidosis)

    • Radiation damage

    • Immunologic disorder (eg, brachial plexopathy)

• Diffuse polyneuropathies

  • Lead to a symmetric sensory, motor, or mixed deficits, often most marked distally

  • Examples include

    • Hereditary, metabolic (eg, diabetic, hyperthyroidism and hypothyroidism, amyloidosis), infectious (eg, syphilis), and toxic (eg, alcohol, lead) disorders

    • Idiopathic inflammatory polyneuropathy (Guillain-Barré syndrome)

    • Nonmetastatic complication of malignant disease (paraneoplastic antineuronal antibodies)

  • Tendon reflexes are depressed or absent

  • Paresthesias, pain (dysesthesia, neuralgia), and muscle tenderness may also occur

Diagnosis

• Blood glucose, serum gamma glutamyl transferase (GGT), thyroid stimulating hormone (TSH), serologic test for syphilis, heavy metals screen, antibodies associated with neoplasia (eg, anti-Hu antibodies, also known as anti-neuronal nuclear antibody type 1 [ANNA-1])

• Nerve conduction velocity and electromyography

  • Motor and sensory conduction velocity are measured in accessible segments of peripheral nerves

  • In axonal neuropathies

    • Nerve conduction velocity is normal or only mildly reduced

    • Needle electromyography provides evidence of denervation in affected muscles

  • In demyelinating neuropathies

    • Nerve conduction velocity may be slowed considerably in affected fibers

    • In more severe cases, conduction is blocked completely, without accompanying electromyographic signs of denervation

• Sural nerve biopsy may be required to establish a pathologic diagnosis in some conditions (eg, amyloidosis, hereditary neuropathies)

Treatment

• Treatment is directed at underlying disease process (eg, control of blood glucose in diabetes; surgery, chemotherapy, immunotherapy, and/or radiation for malignancy)

• Agents useful in control of dysesthesia and neuralgia include

  • Gabapentin, 300–3600 mg orally daily in divided doses

  • Tricyclic antidepressants (eg, desipramine, 25–50 mg orally nightly)

  • Pregabalin, 50–100 mg orally three times daily

  • Duloxetine, 60–120 mg orally daily

  • Opioid agent (submaximal dose particularly in combination with submaximal dose of gabapentin)