Definition

Peripheral neuropathies are a collection of disorders characterized by the generalized dysfunction of peripheral nerves. This group of diseases is heterogeneous, including those that predominantly affect the nerve axon, others that primarily affect the myelin sheath, and still others that involve both parts of the nerve simultaneously. In addition, some peripheral neuropathies affect only small, unmyelinated fibers, whereas others predominantly involve only large myelinated ones. Table 142.1 contains a list of the most frequently encountered forms of peripheral neuropathy.

Peripheral neuropathy is common; one Italian study suggested a prevalence of about 3.5% in the general population [1]. In diabetes, one study demonstrated clinical peripheral neuropathy affecting 8.3% of individuals compared with a control population, in whom 2.1% of individuals were affected [2]. After 10 years, 41.9% of the diabetic patients had peripheral neuropathy compared with 6% of the control subjects.

Defining peripheral neuropathy remains no simple task. Members of the American Academy of Neurology along with those of the American Association of Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation have developed a formal case definition for distal symmetric polyneuropathy (the most common form) [3]. The authors chose to use a combination of symptoms, signs, and electrodiagnostic testing results to formulate an ordinal ranking system to identify the likelihood of the disease in a given patient. Although it is a useful tool for future research studies, the necessity of applying such a complex approach underscores the difficulty in attempting to define peripheral neuropathy in any simple fashion.

Symptoms

Patients with peripheral neuropathy present with a number of specific sensory complaints, including decreased sensation often associated with pain, tingling (paresthesias), and burning. They may complain of a “sock-like” feeling in the feet or that the feet are persistently cold. Some patients, usually with more advanced disease, will note atrophy of the intrinsic foot muscles and some weakness, especially with the development of partial footdrop. Walking difficulties usually also develop once sensation is significantly impaired. Sensory symptoms in the hand (paresthesias and reduced tactile sensation) usually develop once an axonal peripheral neuropathy has progressed up to about the level of the knees. In patients with generalized demyelinating peripheral neuropathies, more generalized symptoms of weakness and sensory loss are often present, although distally predominant paresthesias often occur. The history includes a detailed past medical history, review of systems, and any prior exposure to toxins (Table 142.2).

Physical Examination

The physical examination demonstrates distinct abnormalities that depend on the form of peripheral neuropathy present. Most commonly, patients present with a sensorimotor axonal peripheral neuropathy. In this condition, decreased sensation to pinprick, vibration, light touch, and temperature may be identified distally in the lower extremities with normal sensation more proximally. Of note, vibration sensation testing with a tuning fork has been shown to be reliable [4]. Some weakness of toe or foot extension and flexion may also be apparent. Deep tendon reflexes will be hypoactive distally (e.g., ankle jerks decreased relative to knee jerks).