What Is Peripheral Neuropathy: Causes, Symptoms, and Treatment

This article is for informational purposes only. Consult a qualified healthcare professional for medical advice, diagnosis, or treatment.

What Is Peripheral Neuropathy?

Peripheral neuropathy refers to damage or dysfunction of one or more nerves outside the brain and spinal cord—the peripheral nervous system. The peripheral nervous system is responsible for transmitting motor commands from the central nervous system to muscles, carrying sensory information from skin and organs back to the brain, and regulating autonomic functions such as heart rate, digestion, and perspiration. When peripheral nerves are damaged, this communication breaks down, producing a wide spectrum of symptoms that affect sensation, movement, and organ function. Peripheral neuropathy affects approximately 20 million people in the United States and is present in about 50% of people with diabetes.

Structure and Function of Peripheral Nerves

Peripheral nerves are bundles of axons—the long projections of neurons—wrapped in myelin sheaths that accelerate electrical conduction. Nerves are classified by what they carry: sensory nerves (afferent), motor nerves (efferent), or autonomic nerves. They can also be classified by fiber size: large, myelinated A-beta fibers carry touch and vibration; small, thinly myelinated A-delta and unmyelinated C-fibers carry pain and temperature. Neuropathy can preferentially damage any of these fiber types, explaining the diverse presentations.

Classification by Pattern

Major Causes

More than 100 different diseases can cause peripheral neuropathy. The most important include:

• Diabetes mellitus: The leading cause worldwide. Chronic hyperglycemia damages nerve blood vessels (vasa nervorum) and triggers sorbitol accumulation and oxidative stress within nerve cells. About 50% of people with diabetes develop neuropathy over their lifetime.
• Nutritional deficiencies: Vitamin B12, thiamine (B1), B6, and vitamin E deficiencies all cause neuropathy. B12 deficiency is particularly common in the elderly and in strict vegans.
• Alcohol use disorder: Directly toxic to nerve cells and causes nutritional deficiencies. Alcoholic neuropathy typically presents as a painful, symmetric, length-dependent polyneuropathy.
• Chemotherapy: Cisplatin, oxaliplatin, paclitaxel, and vincristine are frequent culprits for chemotherapy-induced peripheral neuropathy (CIPN).
• Autoimmune conditions: Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), lupus, rheumatoid arthritis, and Sjogren's syndrome.
• Infections: HIV, Lyme disease, hepatitis C, and leprosy damage peripheral nerves directly or through immune mechanisms.
• Hereditary neuropathies: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy, affecting 1 in 2,500 people.
• Toxic exposures: Heavy metals (lead, mercury, arsenic), industrial chemicals, and certain medications (metronidazole, statins at high doses, amiodarone).

Symptoms

The specific symptoms depend on which types of nerve fibers are affected. General categories include:

• Sensory symptoms: Numbness, tingling (paresthesias), burning pain, electric shock sensations, or hypersensitivity to touch. Loss of balance and proprioception (position sense) leads to unsteady gait and falls.
• Motor symptoms: Weakness in the hands or feet, muscle wasting (atrophy), foot drop, loss of fine motor coordination, and reduced reflexes.
• Autonomic symptoms: Orthostatic hypotension (dizziness on standing), gastroparesis, bladder dysfunction, sexual dysfunction, abnormal sweating, and heart rate irregularities.

Diagnosis

Nerve conduction studies (NCS) and electromyography (EMG) are the primary electrophysiological tests: NCS measures the speed and amplitude of electrical signals in peripheral nerves; EMG assesses electrical activity within muscles. Together they can distinguish axonal damage (reduced amplitude) from demyelinating disease (slowed conduction velocity). Blood tests evaluate for diabetes, vitamin deficiencies, thyroid disease, kidney disease, and autoimmune markers. Skin punch biopsy measuring intraepidermal nerve fiber density is sensitive for small fiber neuropathy, which NCS cannot detect.

Treatment Approaches

Prognosis and Prevention

The prognosis depends heavily on the underlying cause and whether it can be corrected. Nutritional neuropathies often partially or fully recover with supplementation. Diabetic neuropathy can stabilize but rarely reverses significantly once established, underscoring the importance of early and strict glucose control. Hereditary neuropathies are progressive but often slowly so, allowing many decades of meaningful function with appropriate support. Fall prevention measures—including balance training, appropriate footwear, and home hazard reduction—are critical for patients with significant sensory loss or weakness.