Clinical evaluation of peripheral neuropathies

Howard W Sander MD (Dr. Sander of NYU Langone Medical Center received honorariums from Baxter and Grifols for consulting and speaking engagements, and from Kaba Fusion for speaking engagements.)
Patrick M Kwon MD (Dr. Kwon of NYU School of Medicine 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 September 1, 2017; expires September 1, 2020

Overview

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, 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, assess severity, can follow progression or response to treatment, and may help exclude mimics of polyneuropathy, such as myopathy, neuronopathy, plexopathy, or polyradiculopathy. Skin biopsy for 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, and will prove most useful in acute/subacute, asymmetric, multifocal, 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.

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 approaches 10% of the general population, and the condition is responsible for significant disability worldwide (Italian General Practitioner Study Group 1995). 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.

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