
Am Fam Physician. 2020;102(12):732-739
Author disclosure: No relevant financial affiliations.
Peripheral neuropathy, a common neurologic problem encountered by family physicians, can be classified clinically by the anatomic pattern of presenting symptoms and, if indicated, by results of electrodiagnostic studies for axonal and demyelinating disease. The prevalence of peripheral neuropathy in the general population ranges from 1% to 7%, with higher rates among those older than 50 years. Common identifiable causes include diabetes mellitus, nerve compression or injury, alcohol use, toxin exposure, hereditary diseases, and nutritional deficiencies. Peripheral neuropathy is idiopathic in 25% to 46% of cases. Diagnosis requires a comprehensive history, physical examination, and judicious laboratory testing. 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. Later stages may involve proximal numbness, distal weakness, or atrophy. Physical examination should include a comprehensive neurologic and musculoskeletal evaluation. If the peripheral nervous system is identified as the likely source of the patient's symptoms, evaluation for potential underlying etiologies should initially focus on treatable causes. Initial laboratory evaluation includes a complete blood count; a comprehensive metabolic profile; fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; and serum protein electrophoresis with immunofixation. If the initial evaluation is inconclusive, referral to a neurologist for additional testing (e.g., electrodiagnostic studies, specific antibody assays, nerve biopsy) should be considered. Treatment of peripheral neuropathy focuses on managing the underlying etiology. Several classes of medications, including gabapentinoids and antidepressants, can help alleviate neuropathic pain.
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.

Recommendation | Sponsoring organization |
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Do not order a magnetic resonance imaging scan of the spine or brain for patients with only peripheral neuropathy (without signs or symptoms suggesting a brain or spine disorder). | American Association of Neuromuscular and Electrodiagnostic Medicine |
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.
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.

Focal | |||
Acromegaly Amyloidosis Direct trauma to nerves, such as repeated minor trauma, traction, injection, cold exposure, burns, radiation Entrapment/compressive neuropathies | Ischemic lesions Leprosy Myxedema Neoplastic infiltration Rheumatoid arthritis Sarcoidosis | ||
Symptoms | |||
Sensory and motor symptoms | |||
Predominantly sensory symptoms, including pain and paresthesias | |||
In severe or chronic cases, motor symptoms may include weakness and atrophy | |||
Multifocal | |||
Connective tissue diseases | Infections (HIV/AIDS) | ||
Diabetes mellitus | Leprosy | ||
Hereditary predisposition to pressure palsies | Vasculitis | ||
Symptoms | |||
Sensory and motor symptoms are asymmetrical and affect multiple areas of the body | |||
Sensory symptoms include pain, paresthesias, vibration, and proprioception | |||
Motor symptoms may include weakness and atrophy | |||
Autonomic symptoms may be present | |||
Symmetrical distal sensorimotor | |||
Acromegaly Alcohol use Amyloidosis Celiac disease Chronic kidney disease Connective tissue diseases Cryoglobulinemia Diabetes Gouty neuropathy Hypothyroidism/hyperthyroidism Infections (HIV/AIDS, Lyme disease) Inherited diseases (Charcot-Marie-Tooth disease, familial amyloidosis) | Liver disease Malignancy Medication induced (see Table 2) Nutritional deficiencies (vitamins B6, B12, and E; thiamine; folate; copper; phosphate) Postgastrectomy syndrome Toxin exposure (heavy metals, carbon monoxide, acrylamide, hexacarbons, ethylene oxide, glue) Vasculitis Whipple disease | ||
Symptoms | |||
Distal sensory and motor symptoms involve both sides symmetrically | |||
Sensory symptoms include pain, paresthesias, vibration, and proprioception | |||
Motor symptoms may include weakness and atrophy | |||
Autonomic symptoms may be present | |||
Symmetrical proximal motor | |||
Acute arsenic poisoning Chronic inflammatory demyelinating polyradiculoneuropathy Diabetes Guillain-Barré syndrome Hypothyroidism | Infections (HIV/AIDS, Lyme disease, diphtheria) Malignancies Porphyria Vincristine exposure | ||
Symptoms | |||
Motor symptoms include weakness and atrophy of proximal muscles in a symmetrical anatomic distribution | |||
Less common patterns | |||
Neuropathies with cranial nerve involvement | |||
Diabetes Guillain-Barré syndrome Infections (HIV/AIDS, Lyme disease, diphtheria) | Neoplastic invasion of the skull base or meninges Sarcoidosis | ||
Symptoms | |||
Sensory and motor symptoms involve the cranial nerves, such as problems with speech, swallowing, taste, and sensory or autonomic functions; coughing; head, pharyngeal, or neck pain; and weakness of the trapezius, sternocleidomastoid, or tongue muscles | |||
Neuropathies predominant in upper extremities | |||
Diabetes Guillain-Barré syndrome Hereditary amyloid neuropathy type II Hereditary motor sensory neuropathy | Lead toxicity Porphyria Vitamin B12 deficiency | ||
Symptoms | |||
Sensory and motor symptoms predominantly involve the upper limbs | |||
Sensory symptoms include pain, paresthesias, vibration, and proprioception | |||
Motor symptoms may include weakness and atrophy | |||
Neuropathies with autonomic involvement | |||
Amyloidosis | Paraneoplastic neuropathy | ||
Diabetes | Porphyria | ||
Lymphoma | Thallium, arsenic, or mercury toxicity | ||
Symptoms | |||
Autonomic symptoms may include orthostatic intolerance, gastroparesis, bowel and bladder changes, erectile dysfunction, and blurry vision |
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
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