Applied Evidence

An easy approach to evaluating peripheral neuropathy

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Ask what, where, when, and in what setting to narrow your search.



Practice recommendations
  • Pain described by patients as electric shocks, burning, freezing, tightness, or throbbing suggests toxic, metabolic, or ischemic causes of neuropathy (C).
  • When motor and sensory symptoms appear together, rank them in order of symptom predominance. Motor symptom supremacy may indicate an immune-related disorder (C).
  • When measuring sensory thresholds, keep in mind that they normally increase with the patient’s age and height. Vibration sensation in the toes of elderly persons is often said to be decreased, when in fact it is only an age-related change (C).

Polyneuropathy has an estimated prevalence of about 2% in the general population.1,2 Despite being common, polyneuropathy remains a diagnostic challenge for most clinicians for many reasons, including the large number of potential causes and the fact that a specific cause often cannot be identified even after appropriate testing. These factors can contribute to uncertainty about the direction and level of aggressiveness of the evaluation. The result is often a “one size fits all” strategy—from an unnecessarily expensive “shotgun” approach to a “defeatist” attitude that too quickly deems a neuropathy as idiopathic.

A number of experts have developed algorithms for the evaluation of neuropathy.1,3-8 We have incorporated and modified many of these suggestions to develop a simple, user-friendly approach; one that characterizes the neuropathy using “what?”, “where?”, “when?” and “what setting?” parameters (FIGURE).

The focus of this article is on the polyneuropathy that presents with widespread sensory or sensorimotor symptoms and signs. We will not discuss the evaluation of other peripheral neuropathic processes—eg, mononeuropathies, plexopathies, or motor neuronopathies such as amyotrophic lateral sclerosis. We emphasize the fundamental step of determining whether the polyneuropathy is a distal, symmetrical, sensory or sensorimotor polyneuropathy, in which case metabolic/toxic, inherited and idiopathic causes are more probable. In contrast, alternative presentations suggest immune-mediated and infectious causes.

What: Sensory, motor, or autonomic?

The first step is to assign the patient’s complaints and your examination findings to specific nerve fiber types of the peripheral nervous system: sensory, motor, or autonomic.5

Characterizing your patient’s neuropathy

Sensory findings help narrow your search

Once you have ruled out a nonneuropathic process (eg, arthritis) as the cause of sensory symptoms and signs, turn your attention to distinguishing between peripheral or central nervous system dysfunction. When the pathology resides in the central nervous system (eg, multiple sclerosis) accompanying symptoms and signs usually assist in localization. If a patient acknowledges clinical features suggesting past or present involvement of cerebellar, urinary, or visual (eg, optic neuritis) systems, for example, magnetic resonance imaging rather than electrodiagnostic testing may be warranted.

In a patient with peripheral nervous system dysfunction, sensory abnormalities help exclude neuromuscular diseases not associated with sensory dysfunction, such as myopathies, neuromuscular transmission disorders, or disease of the motor neuron.

Positive neuropathic sensory symptoms suggest acquired polyneuropathies. Patients may describe “prickling,” “tingling,” “swelling,” “asleep-like numbness,” or a sensation of “bunched-up socks.” Patients with acquired polyneuropathies usually complain of positive neuropathic sensory symptoms (PNSS), whereas patients with inherited polyneuropathies only rarely do (FIGURE).

Pain suggests toxic, metabolic, or ischemic causes. Patients may describe “electric shocks,” “burning,” “freezing,” “tightness,” or “throbbing.” They may complain of discomfort or pain to sensory stimuli that under normal circumstances would not be painful (allodynia)—eg, discomfort evoked by a bed sheet resting on the feet. They may also describe exaggerated pain to stimuli that would normally evoke low levels of discomfort or pain (hyperalgesia).

A painful neuropathy narrows the differential diagnosis to diseases that affect smaller nerve fibers, which generally convey pain and temperature input. Causes may be toxic, metabolic, ischemic, or idiopathic. For example, a pure “small-fiber” polyneuropathy commonly occurs in patients aged >60 years and typically causes painful feet. It is often idiopathic, but diabetes or impaired glucose tolerance and alcohol toxicity should be explored.9 Patients with painful neuropathy usually also exhibit reduced or absent sensation of pinprick and temperature in the distribution of their sensory complaints.

Negative neuropathic sensory symptoms. In addition to positive neuropathic symptoms, patients may complain of “negative” symptoms such as loss of sensation and imbalance. Examination usually reveals abnormalities of proprioception and sensation to vibration with reduced or absent deep tendon reflexes and ataxia. These features can occur in acquired or inherited causes of neuropathy.

Important sensory tests. Test sensation on the toes and fingertips, and more proximally (eg, ankle and shin) if any abnormality is found at these distal sites. Test vibration with a 128 Hz tuning fork, pinprick with disposable safety pin, and light touch with a cotton swab.


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