Approach to the Patient: Peripheral Neuropathy

Peripheral neuropathy (PN) refers to a peripheral nerve disorder of any cause. Nerve involvement may be single (mononeuropathy) or multiple (polyneuropathy); pathology may be axonal or demyelinating. An approach to pts with suspected neuropathy appears in Fig. 193-1.

Seven initial questions:

1. What systems are involved? Determine if symptoms and signs are predominantly motor, sensory, autonomic, or a combination of these. If only weakness is present without sensory or autonomic dysfunction, consider a motor neuropathy, neuromuscular junction disorder, or myopathy; myopathies usually have a proximal, symmetric pattern of weakness.
2. What is the distribution of weakness? Polyneuropathy involves widespread and often symmetric dysfunction of the peripheral nerves that is usually distal more than proximal; mononeuropathy involves a single nerve, usually due to trauma or compression; multiple mononeuropathies (mononeuropathy multiplex) can be a result of multiple entrapments, vasculitis, or infiltration.
3. What is the nature of the sensory involvement? Temperature loss or burning/stabbing pain suggests small fiber involvement. Vibratory or proprioceptive loss implicates large fibers.
4. Is there evidence of upper motor neuron involvement? The most common cause is combined system degeneration with B₁₂ deficiency, but should also consider copper deficiency, HIV infection, severe hepatic disease, and adrenomyeloneuropathy.
5. What is the temporal evolution? Most neuropathies are insidious and slowly progressive. Rapidly evolving neuropathies are often inflammatory, including acute inflammatory demyelinating polyneuropathy (AIDP) or Guillain-Barré syndrome (GBS); subacute evolution suggests an inflammatory, toxic, or nutritional cause; chronic neuropathies that are long-standing over years may be hereditary.
6. Is there evidence for a hereditary neuropathy? Consider in pts with a slowly progressive distal weakness over many years with few sensory symptoms but significant sensory deficits on clinical examination. Most common is Charcot-Marie-Tooth disease (CMT; look for foot abnormalities such as high or flat arches and hammer toes as well as scoliosis).
7. Does the pt have other medical conditions? Inquire about associated medical conditions (e.g., diabetes, systemic lupus erythematosus); preceding or concurrent infections (e.g., diarrheal illness preceding GBS); surgeries (e.g., gastric bypass and nutritional neuropathies); medications (toxic neuropathy); over-the-counter vitamin preparations (B₆); alcohol, dietary habits; and use of dentures (because fixatives contain zinc that can lead to copper deficiency).

Based on the answers to these seven key questions, neuropathic disorders can be classified into several patterns based on the pattern of sensory, motor, and autonomic involvement (Table 193-1).