Peripheral neuropathy is one of the most common neurologic problems encountered by family physicians.^1,2 Peripheral neuropathy can be classified clinically by the anatomic pattern of presenting symptoms and, if indicated, by results of electrodiagnostic studies for axonal and demyelinating disease.^2,3 Peripheral nerves consist of motor, sensory, and autonomic nerve fibers. It is important to differentiate peripheral neuropathy from other disorders with similar presentations and to identify and address potential causes.

Epidemiology

The prevalence of peripheral neuropathy in the general population ranges from 1% to 7%, with higher rates among those older than 50 years.^4,5 The most common identifiable causes of peripheral neuropathy include diabetes mellitus, nerve compression or injury, alcohol use, toxin exposure, hereditary diseases, and nutritional deficiencies.

Peripheral neuropathy affects 25% to 50% of patients with diabetes, depending on factors such as the patient's age, number of years with diabetes, and level of diabetes control.^6,7 Peripheral neuropathy is idiopathic in 25% to 46% of cases, and this is more common with increasing patient age.^8,9

Evaluation

The pathophysiology of peripheral neuropathy results from injury to small- or large-diameter nerve fibers. Damage can occur to the cell body, axon, myelin sheath, or a combination of these, leading to symptoms such as numbness, tingling, pain, and weakness.^3,10 Large nerve fibers mediate motor, sensory, vibration, and proprioception functions. Small nerve fibers mediate pain, temperature, and autonomic functions.¹

A systematic approach should be used to evaluate and manage patients with symptoms of peripheral neuropathy (Figure 1).¹¹ Distinguishing peripheral neuropathy from central nervous system (CNS) and other pathology is an important first step. CNS lesions should be suspected in patients with speech disturbance, ataxia, visual disturbance, cranial nerve involvement, or bowel and bladder incontinence. Evaluation for nerve compression, radiculopathy, or peripheral nerve root lesions should be considered in patients with symptoms that are asymmetrical; follow a dermatomal pattern; or are associated with numbness, imbalance, falls, ataxia, and paresthesias.

If peripheral neuropathy is suspected, a differential diagnosis should be formulated through a history and physical examination.¹² The anatomic distribution of peripheral neuropathy symptoms can be categorized as focal, multifocal, or symmetrical (Table 1¹³ ). Symmetrical peripheral neuropathy can be further classified as distal or proximal. Less common patterns of peripheral neuropathy involve the cranial nerves, autonomic nerves, and nerves of the upper extremities.

History

A detailed history of symptoms is essential. Symptom onset and timing may be most helpful in narrowing the differential diagnosis. Location and distribution help distinguish focal, multifocal, and symmetrical patterns. Aggravating and remitting factors can be clues to exogenous causes, and a complete review of systems should be performed to evaluate for autonomic and vasomotor symptoms.

Early peripheral neuropathy may present as sensory alterations that are often progressive, including sensory loss, numbness, pain, or burning sensations in a “stocking and glove” distribution of the extremities.³ Later stages may involve proximal numbness, distal weakness, or atrophy.³ One-third of patients with peripheral neuropathy have neuropathic pain.¹ Other common presenting symptoms include a stabbing or electric shock sensation, allodynia, hyperalgesia, and hyperesthesia.^1,4,13,14 Patients may also report autonomic symptoms such as orthostatic intolerance, gastroparesis, changes in bowel and bladder function, erectile dysfunction, and blurry vision, or vasomotor symptoms such as dryness of the eyes, mouth, or skin, and burning or flushing.¹