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  • Updated 08.19.2023
  • Released 05.12.1999
  • Expires For CME 08.19.2026

Clinical evaluation of peripheral neuropathies



Peripheral neuropathy is responsible for significant disability worldwide. However, a comprehensive diagnostic evaluation of this common condition is cumbersome and costly. A methodical approach is essential for proper localization and characterization of neuropathy and to develop targeted diagnostic testing. In this article, the authors review the clinical phenotype and classification of neuropathy and appropriate diagnostic testing.

Key points

• Detailed history, including onset and progression of symptoms, the pattern of involvement, social history, family history, medical history, surgical history, review of systems, and review of medications and supplements can help characterize the type of neuropathy and minimize unnecessary testing.

• A detailed neurologic examination, including motor system, sensory testing, tendon reflexes, and gait examination, is essential to understand the pattern of involvement.

• Anatomic classification of neuropathy includes (1) fiber type (motor vs. sensory, large vs. small, somatic vs. autonomic), (2) component of fiber affected (axon vs. myelin), and (3) distribution of nerves affected (length-dependent, length-independent, focal, and multifocal).

• Initial screening for distal symmetric neuropathy usually includes fasting blood glucose, comprehensive metabolic panel, liver function test, complete blood count and differential, serum vitamin B12, and serum immunofixation electrophoresis (IFE). If fasting blood glucose is normal, consider a 2-hour oral glucose tolerance test.

• Nerve conduction studies and needle electromyography (EMG) are valuable in evaluating large fiber polyneuropathy diagnosis. They aid in distinguishing axonal and demyelinating components, assessing neuropathy severity, following progression or response to treatment, and helping exclude mimics of polyneuropathy such as myopathy, neuronopathy, plexopathy, or polyradiculopathy.

• Skin biopsy that assesses epidermal nerve fiber density and sweat gland nerve fiber density is helpful for small fiber neuropathy diagnosis.

• Nerve biopsy is most useful in acute/subacute, asymmetric, multifocal, and progressive neuropathy. It should not be performed in routine cases.

• The majority of neuropathies, except some autoimmune neuropathies, are not curable, and treatment is targeted at offering symptomatic relief. Acquired demyelinating polyneuropathies, although rare, are often treatment responsive.

Historical note and terminology

Peripheral neuropathy refers to any acquired or hereditary condition with damaged peripheral nerves. The associated motor and sensory symptoms can be disabling in some patients, leading to falls, limited ambulation and daily activities, and impaired quality of life. The prevalence of polyneuropathy is 5.5% based on the Rotterdam Study, which increases from up to 25.4% to 31.2% among patients over the age of 70, even in the absence of diabetes (33; 37). Given the wide variety of peripheral neuropathies, and an even higher number of potential etiologies, a structured diagnostic approach and management plan may potentially improve patient care (37; 66).

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