Clinical evaluation of peripheral neuropathies

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By Howard W Sander MD and Harpaul S Bhamra MD

Peripheral neuropathy is responsible for significant disability worldwide. However, a comprehensive diagnostic evaluation of this condition is cumbersome and costly. A structured clinical approach is necessary for efficient localization and characterization of neuropathy and targeted diagnostic testing. In this clinical summary, Howard W Sander MD and Harpaul Bhamra MD of NYU School of Medicine 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 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, while less common, are often treatment responsive.


In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited