Clinical evaluation of peripheral neuropathies

Howard W Sander MD (

Dr. Sander of the NYU Grossman School of MedicineLangone Medical Center received honorariums from Grifols and CSL for consulting work.

Mordechai Z Smith MD (

Dr. Smith of the NYU Grossman School of Medicine Langone Medical Center has no relevant financial relationships to disclose.

Louis H Weimer MD, editor. (

Dr. Weimer of Columbia University has received consulting fees from Roche.

Originally released May 12, 1999; last updated March 31, 2020; expires March 31, 2023


Peripheral neuropathy is responsible for significant disability worldwide. However, a comprehensive diagnostic evaluation of this common condition is cumbersome and costly. A structured clinical approach is necessary for efficient localization and characterization of neuropathy and targeted diagnostic testing. In this article, the authors review the classification of neuropathy, aspects of the clinical history and physical examination, and diagnostic testing, including serum, electrodiagnostic biopsy, and other studies. An updated list of neuropathy-provoking drugs has been included.

Key points


• Detailed history including onset and progression of symptoms, 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.


• Evaluation of peripheral neuropathy includes thorough neurologic examination, including positive and negative motor signs, small and large fiber sensory testing, tendon reflexes, gait examination, and autonomic signs.


• Anatomic classification of neuropathy includes (1) fiber type (motor vs. sensory, large vs. small, somatic vs. autonomic), (2) portion 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, hepatic panel, complete blood count and differential, serum vitamin B12, thyroid stimulating hormone, erythrocyte sedimentation rate, 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 the standard for 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 should not be performed until adequate clinical, laboratory, and electrodiagnostic evaluation is performed. It is most useful in acute/subacute, asymmetric, multifocal, and progressive neuropathy.


• Treatment of neuropathy is targeted at treating the underlying etiology and also reducing symptoms. Acquired demyelinating polyneuropathies, although less common, are often treatment responsive; however, these occur less commonly.

Historical note and terminology

Peripheral neuropathy refers to any condition that injures peripheral nerves, whether acquired or hereditary, systemic or restricted to peripheral nerves, or mildly symptomatic or disabling and severe. The prevalence of these conditions in the general population ranges from 1% to 7% depending on location and age group (Hanewinckel et al 2016). Because the recognized number of causes of peripheral neuropathy exceeds 200, a structured approach to patient evaluation enhances efficiency and minimizes the clinical and economic perils of a wrong diagnosis or an unrecognized but treatable underlying condition.

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.

Find out how you can join MedLink Neurology