What is the appropriate workup for peripheral neuropathy?

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Last updated: March 25, 2025View editorial policy

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From the Guidelines

The workup for peripheral neuropathy should begin with a thorough history and physical examination, including assessment of temperature or pinprick sensation and vibration sensation using a 128-Hz tuning fork, as well as annual 10-g monofilament testing to identify feet at risk for ulceration and amputation, as recommended by the most recent guidelines 1. The assessment for distal symmetric polyneuropathy should include a careful history and physical examination, with a focus on identifying symptoms and signs of autonomic neuropathy, such as orthostatic dizziness, syncope, or dry cracked skin in the extremities 1. The following tests may be used to assess small- and large-fiber function and protective sensation:

  • Small-fiber function: pinprick and temperature sensation
  • Large-fiber function: vibration perception and 10-g monofilament
  • Protective sensation: 10-g monofilament Electrophysiological testing or referral to a neurologist is rarely needed, except in situations where the clinical features are atypical or the diagnosis is unclear 1. In all patients with diabetes and peripheral neuropathy, causes of neuropathy other than diabetes should be considered, including toxins, neurotoxic medications, vitamin B12 deficiency, hypothyroidism, renal disease, malignancies, infections, chronic inflammatory demyelinating neuropathy, inherited neuropathies, and vasculitis 1. The workup should be tailored to the clinical presentation, as identifying the underlying cause is crucial for appropriate management of peripheral neuropathy. Some of the key points to consider in the workup of peripheral neuropathy include:
  • A thorough history and physical examination
  • Assessment of temperature or pinprick sensation and vibration sensation using a 128-Hz tuning fork
  • Annual 10-g monofilament testing to identify feet at risk for ulceration and amputation
  • Consideration of causes of neuropathy other than diabetes
  • Electrophysiological testing or referral to a neurologist in selected cases
  • A tailored approach to the workup, based on the clinical presentation and individual patient needs.

From the FDA Drug Label

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From the Research

Diagnostic Approach

The appropriate workup for peripheral neuropathy involves a stepwise approach, starting with a detailed history of symptoms, family and occupational history, and a neurological as well as general physical exam 2. This initial assessment helps in pattern recognition of various neuropathies, which can be categorized as acute versus chronic, primary demyelinating versus axonal, hereditary versus acquired, asymmetric versus symmetric, and presence of facial palsies, sensory or motor predominant, and presence of prominent autonomic symptoms.

Laboratory Tests and Diagnostic Tools

  • Nerve conduction studies and electromyography (NCS/EMG) are essential diagnostic tools in the evaluation of patients with large-fiber polyneuropathy 2, 3, 4, 5.
  • Laboratory workup includes serum studies, such as complete blood count, comprehensive metabolic profile, fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels 3, 5.
  • Specialized tests, such as genetic studies, immunological markers, and fat pad biopsy, may be ordered if clinically indicated 2, 3, 4.
  • Skin biopsy may be used to assess intraepidermal nerve fiber density if small-fiber neuropathy is suspected 2.
  • Nerve biopsy may be useful in select cases 2.
  • Magnetic resonance imaging and neuromuscular ultrasound have also shown promise in the evaluation of peripheral neuropathy 2.

Clinical Patterns and Differential Diagnosis

The diagnosis of peripheral neuropathy requires careful clinical assessment, judicious laboratory testing, and electrodiagnostic studies or nerve biopsy if the diagnosis remains unclear 3. A systematic approach begins with localization of the lesion to the peripheral nerves, identification of the underlying etiology, and exclusion of potentially treatable causes. Five common basic clinical patterns of peripheral neuropathy can be recognized, allowing for differential diagnostic pathways to establish the underlying cause 4.

Treatment and Management

Treatment of peripheral neuropathy focuses on managing the underlying etiology, correcting any nutritional deficiencies, and providing symptomatic treatment 3, 5. Several classes of medications, including gabapentinoids and antidepressants, can help alleviate neuropathic pain 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

A Clinician's Approach to Peripheral Neuropathy.

Seminars in neurology, 2019

Research

Diagnosis of peripheral neuropathy.

Neurological research and practice, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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