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Peripheral neuropathies can be classified as mononeuropathy (affecting one nerve), mononeuropathy multiplex (affecting multiple individual nerves), and polyneuropathy (affecting peripheral nerves diffusely). Mononeuropathies of the upper and lower extremities are discussed in Chapters 16 and 17, and mononeuropathy multiplex is discussed in Chapter 15. This chapter focuses on polyneuropathy.


Polyneuropathies can be classified by:

  • Modality affected: sensory, motor, sensorimotor, autonomic

  • Fiber type affected: large fiber (proprioception/vibration) versus small fiber (pain/temperature)

  • Pathophysiology: axonal versus demyelinating

Sensory symptoms can include negative symptoms (numbness), positive symptoms (paresthesias, pain), and/or sensory ataxia due to impaired proprioception (see “Distinguishing Cerebellar Ataxia From Sensory Ataxia” in Chapter 8). Neuropathies affecting motor fibers lead to weakness with lower motor neuron features (see “Upper Motor Neuron Lesions Versus Lower Motor Neuron Lesions” in Chapter 4). Autonomic neuropathy can lead to orthostatic hypotension, bowel/bladder dysfunction, impaired sweating, erectile dysfunction, and/or pupillary abnormalities.

The etiologies of peripheral polyneuropathy include:

  • Metabolic causes: diabetes, uremia, vitamin B12 deficiency

  • Medications:

    • Chemotherapy: platins, taxanes, bortezomib (see “Chemotherapy-Induced Peripheral Neuropathy” in Chapter 24)

    • Antiretrovirals: didanosine, stavudine, zalcitabine (see “Antiretroviral-Associated Neuropathy” in Chapter 20)

    • Antibiotics: metronidazole, linezolid, quinolones, nitro-furantoin

    • Antimycobacterials: isoniazid, dapsone

    • Amiodarone

  • Toxins: heavy metals (e.g., mercury, arsenic, lead), alcohol

  • Inflammatory processes:

    • Primary neurologic inflammatory disorders: acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and chronic inflammatory demyelinating polyneuropathy (CIDP)

    • Inflammatory neuropathies secondary to systemic inflammatory disease: Sjögren’s syndrome, lupus, sarcoidosis

  • Malignancy:

    • Paraprotein-associated neuropathies: myeloma, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), secondary amyloidosis (see Table 27–1)

    • Paraneoplastic (see “Paraneoplastic Syndromes of the Nervous System” in Chapter 24)

  • Infections: HIV, leprosy (see “HIV-Associated Distal Symmetric Neuropathy” and “Leprosy” in Chapter 20)

  • Hereditary diseases: Neuropathy may be the only (or predominant) feature of hereditary conditions (e.g., Charcot-Marie-Tooth disease) or may be one component in a multisystem hereditary disease (e.g., Tangier disease, Fabry’s disease, acute intermittent porphyria) (see Table 27–3)

TABLE 27–1Paraprotein-Associated Neuropathies.

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