Peripheral Neuropathy Management in the Primary Care Setting: A Guide

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A neurologic examination is a very important component in the diagnosis of peripheral neuropathy.
A neurologic examination is a very important component in the diagnosis of peripheral neuropathy.

Peripheral neuropathy is a neurologic condition that affects approximately 8% of adults over the age of 55.1 Although it is one of the most common neurologic problems seen in the primary care setting, recognizing and evaluating peripheral neuropathy in a patient can be challenging due to its diverse presentations.

Because peripheral neuropathy is associated with significant morbidity and decreased quality of life, it is imperative for primary care providers to efficiently diagnosis and manage patients with suspected neuropathy. In a recent review, Doughty and Sadjadi discussed a standardized approach to evaluate, diagnose, and manage a patient with suspected neuropathy.

Diagnosing a patient with peripheral neuropathy typically involves obtaining a thorough patient history, conducting a neurologic examination, and possibly confirming findings with nerve conduction studies and/or an electromyography (EMG).1 Use of neuroimaging and electrodiagnostic evaluation is debatable for most patients with suspected neuropathy, however, is recommended for patients where no definite diagnosis can be made.

Although assessing symptoms alone has a poor diagnostic accuracy, it is important for a provider to evaluate both the type of symptoms present as well as the pace of their progression.1 Table 1 lists common signs and symptoms seen in patients with peripheral neuropathy. Typically, sensory signs and symptoms present prior to motor and autonomic ones. Although rare, autonomic symptoms may be the most prominent or only symptoms a patient has which indicate neuropathy.

A neurologic examination is also a very important component in the diagnosis of peripheral neuropathy.1 Table 2 summarizes examination findings based on the type of peripheral neuropathy present. The provider should determine the anatomic areas affected, the degree of motor and sensory impairment, as well as the presence or absence of reflexes. The motor examination should assess weakness and/or muscle atrophy while the sensory examination should evaluate vibration, proprioception, pain, and temperature sensation. Screening tools that are often utilized during the examination include the Romberg sign to assess sensory ataxia, the 10-g Semmes-Weinstein monofilament to evaluate large fiber sensory dysfunction, and the 128-Hz tuning fork to evaluate vibratory sensation. 

Following an established diagnosis of neuropathy, it is important for the provider to determine the underlying etiology of the disease.1 To exclude external factors, providers should begin by reviewing the patient's medications, family history, and occupational exposures, as well as consider screening for alcohol abuse. The diagnostic work-up and appropriate laboratory tests vary based on the type of neuropathy a patient has. For example, laboratory tests that are recommended for a patient with distal symmetric polyneuropathy include hemoglobin A1c and/or oral glucose tolerance test, vitamin B12, methylmalonic acid, serum protein electrophoresis with immunofixation, TSH, and a comprehensive metabolic panel complete blood count. If the initial work-up does not yield a definite diagnosis, additional testing tailored to the specific patient should be considered.

Managing patients with peripheral neuropathy involves providing both supportive care as well as symptomatic management.1 Although pharmacologic therapy can slow the progression of neuropathy, chronic residual symptoms typically persist in most patients. Supportive care includes routine foot care and surveillance of wounds for patients with sensory loss in their feet, orthotic devices for patients with weakness, and balance training and/or exercises when a patient's gait is affected.

First-line treatment options for the management of neuropathic pain are listed in Table 3.1 An agent should be chosen based on the patient's comorbidities, concomitant medications, as well as medication cost. An agent should be increased to the goal dose prior to concluding therapeutic failure. If a medication fails or is not tolerated, initiating another agent from a different medication class is the next step. In addition, combination therapy has been shown to be more effective compared to monotherapy, therefore should be attempted prior to initiating a second-line agent.

Peripheral neuropathy is a common neurologic disorder with diverse presentations.1 A recent review by Doughty and Sadjadi discussed the importance of utilizing a standardized approach to evaluate, diagnose, and manage a patient with suspected neuropathy. Treatment of peripheral neuropathy includes both supportive care as well as symptomatic treatment.

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Doughty CT, Sadjadi R. Approach to peripheral neuropathy for the primary care clinician [published online February 1, 2018]. Am J Med. doi: 10.1016/j.amjmed.2017.12.042

Table 1 – Signs and Symptoms of Peripheral Neuropathy1

Type Comments Signs & Symptoms
Sensory • Typically observed first
• Include large diameter fibers (mediate vibratory sensation, proprioception) and small diameter fibers (mediate sensations of pain, temperature)
• Numbness
• Pain
• Loss of coordination/falls
• Ataxia, sensory ataxia
• Paresthesias
• Decreased/loss of vibratory, pain, and temperature sensations
• Proprioception
• Pseudoathetosis
• Areflexia
Motor • Typically observed later • Weakness
• Atrophy
• Fasciculations
• Areflexia
Autonomic • Typically observed later
• May be only or most prominent sign/symptom (rare)
• Dizziness
• Dry eyes, mouth, or skin
• Blurry vision
• Hair loss
• Changes in the skin
• Early satiety
• Coldness, flushing
• Impotence
• Bladder dysfunction
• Orthostatic hypotension
• Hyperemia
• Cold, pale feet

Table 2 – Types of Peripheral Neuropathy & Exam Findings1

Type Comments/Exam Findings
Distal Symmetric Polyneuropathy • Length-dependent: diffuse involvement, affects distal segments first
• Symptoms occur below the knees prior to affecting fingers
• Most common cause: diabetes
Mononeuropathy • Symptoms restricted to distribution of single nerve, myotome, or dermatome
• Asymmetric reflexes
Mononeuropathy Multiplex • Occurrence of several concurrent mononeuropathies
• Vasculitic etiology
Hereditary Neuropathies • Distal calf atrophy, hammertoes, pes cavus
• Motor deficits ≥ sensory deficits
• Diffuse areflexia
Radiculopathy • Degenerative disease affecting cervical or lumbosacral spine
• Asymmetric reflexes
• Lower back pain, pain radiating to legs, bladder/bowel dysfunction
Myelopathy • Disease affecting spinal cord
• Hyperreflexia, spasticity, sensory deficits occurring in the trunk

Table 3 – Pharmacologic Options for Peripheral Neuropathy1

Medcation Goal Dose Evidence Comments
Gabapentin 300mg TID • Not more effective than placebo • Good for patients with a seizure disorder; avoid in patients with renal insufficiency
• AEs: dizziness, drowsiness, balance/gait disturbance, confusion, peripheral edema
Pregabalin 150mg BID • More effective than placebo
• Similar efficacy to TCAs
Amitriptyline and Nortriptyline 50-100mg at bedtime • Found to be more effective than placebo
• Similar efficacy to pregabalin and SNRIs
• Good for patients with insomnia, migraine; avoid in patients with cardiac issues or taking serotonergic medications
• AEs: dry mouth, drowsiness, dizziness, confusion, QT prolongation, orthostatic hypotension
Duloxetine 60mg/day • More effective than placebo and pregabalin
• Similar efficacy to TCAs
• Good for patients with anxiety, depression, or fibromyalgia; avoid in patients with hepatic failure or taking serotonergic medications or anticoagulants
• AEs: nausea, indigestion, constipation, dizziness, dry mouth, hyperhidrosis, sexual dysfunction
Venlafaxine 150mg daily (XR) • More effective than placebo and pregabalin
• Similar efficacy to TCAs
• Good for patients with anxiety or depression; avoid in patients with uncontrolled hypertension or taking serotonergic medications
• AEs: nausea, indigestion, drowsiness, nervousness, hypertension, sexual dysfunction
Opiates • Not effective in the treatment of painful diabetic neuropathy • Associated with increased rates of depression, medication dependence, overdose, use of gait assist-devices
• Found to worsen functional status
Atypical Opiates (tramadol, tapentadol) • More evidence to support use versus typical opiates • Can be used if first-line agents fail
Topical Therapies (capsaicin cream/ patches, lidocaine patches, percutaneous electrical nerve stimulation, botulinum toxin)
• Second-line agents if pain is localized
• Lower risk of systemic AEs and drug interactions

Abbreviations: AEs (adverse events); BID (twice daily); TID (three times daily); SNRIs (serotonin-norepinephrine reuptake inhibitors); TCAs (tricyclic antidepressants)

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