Tingling or numbness in the hands and feet is a common sign of peripheral neuropathy, a condition caused by damage to the peripheral nerves. If several peripheral nerves are damaged, you may have polyneuropathy. Many health conditions can cause polyneuropathy, including a type of amyloidosis called transthyretin amyloidosis polyneuropathy (ATTR-PN).

How do you know if that odd sensation means you have ATTR-PN or something else? Only a healthcare professional can diagnose you using a systematic evaluation, and they’ll rule out many other conditions along the way. This article provides an overview of polyneuropathy and some defining characteristics of ATTR-PN.

Polyneuropathy Symptoms

Polyneuropathy symptoms vary depending on which nerves are affected. Damaged nerves can interfere with many body functions, such as digestion, or cause symptoms like pain, numbness, or tingling.

The nerves farthest from the brain tend to be affected first, so symptoms often begin in the feet. Because the longest nerve fibers in the body require the most energy to stay healthy, damage often begins in the toes and feet before gradually moving up the legs and may eventually affect the hands. This pattern is called length-dependent neuropathy.

Polyneuropathy symptoms may include:

• Pain that feels sharp, burning, or throbbing
• Pain from touch or activities that normally wouldn’t be painful
• Numbness, tingling, or a pins-and-needles feeling that starts in the hands and feet and may spread up the arms and legs
• Poor coordination, which may lead to falls
• Muscle weakness, muscle cramps, or overactive reflexes
• Atrophy (muscle wasting)
• Reduced sensation in the hands and feet, sometimes making it feel as though you’re wearing gloves or socks
• Paralysis (inability to move certain parts of the body)
• Poor heat tolerance
• Increased or decreased sweating
• Changes in blood pressure that may make your heart beat faster or cause dizziness when you stand up
• Constipation or diarrhea
• Bladder control problems
• Blurred vision
• Swelling
• Changes in skin color
• Sexual dysfunction

Polyneuropathy Causes

Polyneuropathy is often caused by chronic (long-term) conditions that affect the entire body. Injuries can also damage multiple nerves.

Common causes of polyneuropathy include:

• Genetic conditions, including hereditary transthyretin amyloidosis (hATTR amyloidosis)
• Autoimmune disorders like lupus and rheumatoid arthritis
• Type 2 diabetes
• Certain medications or exposure to toxins
• Tumors
• Vitamin deficiencies
• Alcohol use disorder
• Poor circulation
• Infections
• Physical injuries
• Surgery
• Cancer treatments

When healthcare professionals can’t identify the cause of nerve damage, it’s called idiopathic neuropathy or cryptogenic neuropathy. Between 25 percent and 46 percent of polyneuropathy cases are idiopathic.

What Are the Types of Polyneuropathy?

According to the National Institute of Neurological Disorders and Stroke, there are more than 100 types of neuropathy. Healthcare professionals group them into several broad categories, and some types fit into more than one category.

One way to classify neuropathy is by the type of nerve that is affected:

• Motor — Nerves that control voluntary muscle movements, such as walking or picking up an object
• Autonomic — Nerves that control automatic body functions, such as blood pressure, digestion, heart rate, and sweating
• Sensory — Nerves that carry information about touch, temperature, pain, and body position to the brain

Neuropathy can also be described as inherited or acquired:

• Inherited neuropathy — Caused by changes (variants) in genes that are passed down through families (for example, hATTR amyloidosis, Charcot-Marie-Tooth disease, and Friedreich ataxia)
• Acquired neuropathy — Triggered later in life because of another condition or outside factor, such as diabetes, vitamin deficiencies, certain infections, chemotherapy, or amyloid light-chain (AL) amyloidosis

Neuropathy may also be described as chronic, meaning it develops slowly or lasts a long time, or acute, meaning it develops suddenly over days or weeks.

Healthcare professionals may also describe peripheral neuropathy by its underlying cause or its main features. Common examples include:

• Amyloid neuropathy — Caused by amyloid deposits that damage peripheral nerves
• Diabetic neuropathy — Develops when high blood sugar damages nerves, usually starting in the feet and legs before sometimes affecting the hands
• Inflammatory neuropathy — Occurs when the immune system mistakenly attacks the nerves, such as in Guillain-Barré syndrome
• Painful neuropathy — Refers to neuropathy in which nerve pain is a major symptom, including many types such as in diabetic neuropathy and amyloid neuropathy
• Toxic neuropathy — Results from exposure to substances that damage nerves, such as certain chemotherapy drugs, heavy metals, or other toxins

Many other terms may be used to describe polyneuropathy based on its cause, the nerves involved, or how it affects the body. A neurologist can explain the specific type of polyneuropathy you have and what it means for your care.

How Does ATTR-PN Differ From Other Types?

The underlying cause of ATTR-PN sets it apart from other types of neuropathy. ATTR-PN develops when transthyretin (TTR) proteins become unstable, misfold, and build up as amyloid deposits in tissues throughout the body. These amyloid deposits damage nerves directly and can also reduce the blood supply that nerves need to stay healthy, leading to nerve damage over time.

Proteins also play a role in some other types of neuropathy, but in different ways. For example, monoclonal gammopathy of undetermined significance (MGUS) causes the body to make an abnormal protein. In some people, this protein can damage nerves and cause neuropathy.

MGUS can also progress to AL amyloidosis. It’s important to tell AL amyloidosis apart from ATTR-PN because their treatments are very different.

Types of Nerves Affected

Some neuropathies mainly affect one type of nerve. These are called pure motor neuropathy, pure autonomic neuropathy, or pure sensory neuropathy.

ATTR-PN usually affects several types of peripheral nerves. Sensory nerves are often affected first, but motor and autonomic nerves may also become involved as the disease progresses.

Prognosis and Treatment

ATTR-PN is a progressive disease, meaning it tends to get worse over time if left untreated. Unlike some other forms of polyneuropathy, ATTR-PN doesn,t have a cure.

Treatment for ATTR-PN focuses on slowing or stopping the buildup of amyloid. Disease-modifying therapies approved by the U.S. Food and Drug Administration (FDA), including eplontersen (Wainua) and vutrisiran (Amvuttra), reduce the liver’s production of TTR, helping slow nerve damage.

Because polyneuropathy has many different causes, treatment depends on the underlying condition. Medications, physical therapy, and other supportive treatments may also help manage symptoms and improve quality of life.

How Do Doctors Tell Different Types of Polyneuropathy Apart?

Healthcare professionals use several tests to determine the cause of polyneuropathy.

Your doctor will begin by asking about your symptoms, medical history, and family medical history. Your diet, medications, and lifestyle may also provide important clues.

Next, they’ll perform a physical and neurological exam. They’ll check for sensation in your hands and feet and look for muscle weakness, balance problems, or changes in your walking pattern.

Blood tests, nerve conduction studies, and imaging tests may help pinpoint the cause of polyneuropathy. To diagnose ATTR-PN, your doctor may also recommend genetic testing and, in some cases, a tissue biopsy or specialized heart imaging to look for amyloid deposits.

Even with today’s diagnostic tools, sometimes the cause of polyneuropathy remains a mystery.

Why Does the Correct Diagnosis Matter?

Treating polyneuropathy is much easier when healthcare professionals know what’s causing it. Finding the underlying cause also helps doctors predict how the condition may progress and what parts of the body may be affected.

For people with ATTR-PN, getting an early diagnosis is especially important. Disease-modifying therapies work best when started early, before nerve damage occurs. Starting treatment early may help slow disease progression, preserve nerve function, and maintain quality of life for longer.